On 2021-12-21 11:23:13, user Shallee Page wrote:

These descriptive data provide really useful data for thinking about LC and the visualizations are good.

It seems like there is a lot of room for more caveats for this self-selected groups.

The speculation about why so many tested negative for COVid seems shoddy. Primer sets are not the main problem here. There is a subset of respondents where there is little evidence that their symptoms are caused by SARS-CoV2. The number of negatives is higher than the false negative rates reported by the molecular biologists. Consulting some would be wise because I think timing of virus load is much more likely to be the problem than some primer pair problems that tests suffered from in early 2020.

On 2021-12-25 16:37:09, user Markus wrote:

In the light of the negative vaccine efficiency, why do they conclude that there is the need for massive rollout of vaccinations and booster vaccinations? The vaccines appear to undermine the natural immunity.

On 2021-12-25 15:01:12, user Aaron Snyder wrote:

I love that it cites the results of a completely different study in the middle of analysis simply because it showed higher efficacy. I wonder if that study cited this one and said the opposite? The last line is also truly remarkable. Would it be so hard for science to admit the obvious that mass vaccination is not the conclusion here?

On 2021-06-02 08:09:56, user Le Bon wrote:

The idea of looking at patients who had at least a substantial cumulated dose is great, but there is an important immortal time bias, since the patients can't die the first 10 days in the HCQ group, as seen on the Kaplan-Meïer

I suggest to calculate again the results with excluding the first 10 days death in the control group.

Due to the small group size, you will probably loose significance, but it still will be usefull for pooled analysis.

On 2020-04-28 04:37:59, user Choplifter wrote:

I applaud the authors for publishing this study. It is not without its flaws, obviously you can pick apart whether the sample was reprsentative of the community given the limited way testing candidates were solicited, but it is important to get tests like this out to the public quickly rather than wait months to get statistically perfect data. I suspect the estimate of fatality rate they give is a little low, but the scale is consistent with similar studies out of NYC and elsewhere, all suggesting that the fatality rate from COVID-19 is far, far, far less than the terrifying 5% that continues to be touted on the CDC website and by people who support contined lockdowns. The real rate is likely well under 0.4%, making it worse then seasonal flu (even the historically virulent 2017-2018 flu season) but still orders of magnitude less than the 5% Armageddon numbers that were used to scare the public into accepting complete lockdowns and the widespread ruin to economies and livelihoods, that they caused.

On 2020-04-17 20:13:28, user AM wrote:

thanks for the information. you did not specify if you found the IgM or the IgG antibody which would allow us to know what stage they are in on the time frame of when someone sero-converts. it would be great to conduct the same study now, or even 2 weeks from now to see the changes and the transition to herd immunity. ideally, you have kept track of all the people you tested. we could derive a wide range of conclusions from this one time test. nonetheless, thanks for taking the time to conduct these tests.

https://uploads.disquscdn.c...

On 2020-04-23 05:48:38, user G.O.B. wrote:

20-25% increase in overall deaths in Santa Clara County in March 2020 compared to same time last year. We are missing a lot of covid19 deaths in our current counts.

https://www.mercurynews.com...

On 2020-04-18 18:45:15, user S. MonDragon wrote:

Dear Dr. Jay et al.,

I am curious about a couple of other scenarios related to your study. Do those that have SARS-CoV-2 antibodies, also show any other antibodies that might be of particular research interest? And further, how many of these people actually had any symptoms? For example, how many of those who had COVID-19 antibodies also had antibodies for other types of coronaviruses, including SARS-CoV-1. Did the presence or absence of these other antibodies seem to have an effect on symptom severity? I guess what I am asking is, why do some people have such severe symptoms while others can walk around without even knowing that they may have the virus? And, can your samples help us to answer some of these questions?

On 2020-04-23 23:47:11, user Tesla Coil wrote:

In addition to the criticisms raised in other comments, I see a fatal flaw in the study's "Statistical Analysis" that I believe has not been raised (apologies if I have missed it).

The authors appear to first re-weight the sample by demographic factors, and only then adjust for test sensitivity and specificity. This appears to me to be the obviously incorrect order.

If, say, in the unweighted sample, true false positives of the test were 1.5% (which is within the 95% confidence interval of 0.1% to 1.7% calculated by the authors), and the authors only found 1.5% positive samples, the actual true positives would be 0%. So for the unweighted sample, the lower bound for prevalence of antibodies should be 0% true positives. Any further re-weighting of the sample cannot change this and the lower bound must remain 0%.

However, as the authors re-weight the sample first, they apply the false positive rate of 0.1% to 1.7% to their re-weighted estimate of 2.8% positive samples.

On 2020-04-23 15:59:44, user gmshedd wrote:

If we take the observed fatalities (by residence) in the Bronx (2258 as of 4-22) and Queens (3432), and apply the suggested infection fatality rates of 0.12% to 0.20%, we can infer that between 80% and 133% of Bronx residents have already been infected, and that between 76% and 127% of Queens residents have also been infected. Therefore, Bronx and Queens residents have achieved herd immunity, so they can re-open everything immediately. This is such great news! Oh, but you say, these populations aren't similar. OK, so I'll use Nassau County (Long Island)--median income $111k vs $116k in Santa Clara County. 1431 Nassau County residents have died, from which we would infer that between 53% and 88% of the 1,356,924 county residents have been infected. My point is that the suggested infection fatality rates don't pass the eye test, and, since they are derived from the infection rates that are at the center of the controversy, it would seem that the publication's Santa Clara County infection rates are higher than seems reasonable for the NYC area--unless California COVID-19 has a significantly lower infection fatality rate than New York COVID-19.

On 2020-09-03 00:54:02, user Joseph Miano wrote:

This is an important study and is the direction we need to be going for this and future pandemics. Great work!!

On 2020-07-29 18:21:23, user Alen Stojanac wrote:

When I've first noticed that anomaly in charts, my first thought was on the line of some of the comments - that it had something to do with the way reports were made. But this gives far more plausible explanation. Thank you.

On 2020-04-05 18:23:54, user Sinai Immunol Review Project wrote:

Summary: Authors evaluate clinical correlates of 10 patients (6 male and 4 female) hospitalized for severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). All patients required oxygen support and received broad spectrum antibiotics and 6 patients received anti-viral drugs. Additionally, 40% of patients were co-infected with influenza A. All 10 patients developed lymphopenia, two of which developed progressive lymphopenia (PLD) and died. Peripheral blood (PB) lymphocytes were analyzed – low CD4 and CD8 counts were noted in most patients, though CD4:CD8 ratio remained normal.

Critical analysis: The authors evaluated a small cohort of severe SARS-CoV-2 cases and found an association between T cell lymphopenia and adverse outcomes. However, this is an extremely small and diverse cohort (40% of patients were co-infected with influenza A). These findings need to be validated in a larger cohort. Additionally, the value of this data would be greatly increased by adding individual data points for each patient as well as by adding error bars to each of the figures.

Significance: This study provides a collection of clinical data and tracks evolution of T lymphocyte in 10 patients hospitalized for SARS-CoV-2, of which 4 patients were co-infected with influenza A.

Review by Katherine E. Lindblad as part of a project of students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine at Mount Sinai.

On 2020-04-28 11:01:19, user Henry Lahore wrote:

I do not understand the author's matrix pool testing process..

On 2020-04-16 18:03:55, user Sinai Immunol Review Project wrote:

This retrospective study evaluated the use of intravenous methylprednisolone to treat severe COVID-19 pneumonia in a cohort of 46 patients. The severity of the disease was determined according to version 5 of the Coronavirus Pneumonia Diagnosis and Treatment Plan by the National Health Committee of the People's Republic of China. The percentage of patients with comorbidities was 32%, and it was reported similar between methylprednisolone treated and untreated groups. The results showed that the group of patients that received methylprednisolone (n=26) had a shorter number of days with fever than patients that did not received methylprednisolone (n=20); they also had a faster improvement of peripheral capillary oxygen saturation (SpO2), and better outcomes in follow-up CT scans of the lungs. The dosage of methylprednisolone was reported to be 1-2mg/kg/d for 5-7 days, although there is no information about the concrete dosages for each patient. From the 46 patients, 43 recovered and were discharged, while 3 cases were fatal. Patients without administration of methylprednisolone needed longer periods of supplemental oxygen therapy, though there is no reference to the number of patients requiring mechanical ventilation. Interestingly, there were no significant differences in leucocyte and lymphocyte counts nor in the levels of IL-2, IL-4, IL-6 or IL-10 after treatment with methylprednisolone.

Some of our main criticisms to this study are also pointed-out by the authors themselves: it is a retrospective single-center study with no validation cohort and without mid- and long-term follow-ups. The reported mortality was 7% (3/46) and did not appear to be affected by corticosteroid treatment: one patient died in the group that did not receive methylprednisolone, while two patients died in the methylprednisolone treatment group. Additionally, although the authors mention that patients received cotreatments, such as antiviral therapy and antibiotics, there is no mention of differences between the prevalence of other medications between the two groups. Unfortunately, there is also no indication on whether the patients receiving methylprednisolone were discharged earlier; the authors merely refer that the symptoms and signs improved faster.

Corticosteroid have been widely used as therapy for acute respiratory distress syndrome (ARDS), including in infections by SARS-CoV, so these findings in COVID-19 patients are not unexpected. The implications of this study for the current pandemic due to SARS-CoV-2 require evaluation in future clinical trials, especially in a randomized way and in combination with and comparison to other immunosuppressive and immunomodulatory agents, including hydroxychloroquine. Nevertheless, based on this report, the intravenous application of methylprednisolone with the intention of strengthening the immunosuppressive treatment and controlling the cytokine storm appears to be safe in COVID-19 patients, and it might successfully shorten the recovery period.

This review was undertaken by Alvaro Moreira, MD as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai

On 2025-09-08 05:55:10, user Harvy Joy Liwanag wrote:

This scoping review has been published in Social Science & Medicine and the following is the complete citation with the correct DOI:

Frahsa A & Liwanag HJ [joint 1st authors], Betancourt CK, Ipekci AM, Minder B, Schow D. A scoping review of community participation in public health research and action during the COVID-19 pandemic: Exploring approaches on the continuum between utilitarianism and empowerment. Soc Sci Med. 2025 Sep 6. https://doi.org/10.1016/j.socscimed.2025.118556

On 2021-10-17 14:04:46, user BouncingKitten wrote:

The article mentions "All data is available in the supplementary file" but doesn't provide a link to the file.

Could you update the paper with a link to the supplementary file please?

On 2024-04-20 08:35:56, user matthieuboisgontier wrote:

This article has been accepted for publication in PTJ: Physical Therapy & Rehabilitation Journal published by Oxford University Press.

On 2020-05-09 21:20:43, user erkin wrote:

Those people who had no reasons to got infected but just wanted to be sure that they didn't, might have felt compelled to take the test. So this might even create a bias towards the oportion of the population who is not infected yet. So may be the infection rate is even higher.

On 2024-04-27 22:04:26, user Linette Roungchun wrote:

I am a TSW sufferer and this work is important. I have suffered with TSW on and off since the young age of 3, so to see the science backing up the fact that TSW is in fact, a separate entity from Eczema is so validating and healing. Huge thank you to Kelly, Kathy, and Dr. Ian Myles!

On 2020-04-16 09:05:11, user Stef Verlinden wrote:

Please study the paper thorougly before jumping to conclusions. Standard of care means that (most of the) patients were also treated with lopinavir-ritonavir, arbidol, oseltamivir, virazole, entecavir, ganciclovir and/or interferon-alpha.

The autors also did a post-hoc subanalyses with patients who did not get other medications other than HCQ in the treatment group or nothing in the SOC group. And, for what it is worth, here they found ‘a significant efficacy of HCQ on alleviating symptoms’.

What also could be of interest is that patients treated with HCQ showed a significantly higher reduction of CRP. One of the proposed MOA for HCQ is an anti-inflammatory one.

All in all a very weak study from wich not much can be concluded

On 2021-08-18 13:24:26, user Justin -O'Sullivan wrote:

We have a povidone iodine product 0.58% (zero surfactant) which showed in vitro inactivation of SarsCoV2 published with the awareness of public health England. Can't understand why this strategy not used more. Would be interested to know what final volume of irrigation fluid was and was it standardised in protocol?

On 2021-08-25 16:22:39, user Sajjad Nasiri wrote:

I am wondering if you considered manually sniffing nasal saline irrigation?

On 2020-04-07 16:22:04, user Kevin Niall wrote:

"All received standard treatment (oxygen therapy, antiviral agents, antibacterial agents, and immunoglobulin, with or without corticosteroids)"

This could play a huge part in the difference considering teh very small sample size and the difference of 8 patients.

On 2023-02-28 18:38:31, user Stéphanie C. Thébault wrote:

Link to published article:

PLoS One. 2023 Jan 12;18(1):e0278388. doi: 10.1371/journal.pone.0278388

On 2020-05-12 07:28:54, user Emily Tang wrote:

could you explain what is the difference between seroprevalence and seroincidence? (Fig 7 and Fig 8)

On 2021-10-16 11:50:49, user Markus Falk wrote:

Very interesting read. Does the unvaccinated group contain persons with a past infection?

On 2020-06-23 15:26:34, user Gustavo Hernandez wrote:

it will be better to see the analysis as a match case control study instead (Death vs Discharged alive). Doing it as a cohort study makes no sense as its not clear the reason of receiving or not Ivermectin. Contrasting the characteristics of death and discharged alive patients with allow to weight the effect of the studied exposure

On 2021-08-21 21:15:54, user HarryT wrote:

Virus mutation frequency is somewhat constant. Vaccinated human hosts changed the outcome of the selection out of a pool of mutant viruses.

On 2020-09-13 07:59:08, user OxImmuno Literature Initiative wrote:

https://www.immunology.ox.a...

On 2021-11-28 00:33:27, user tommythegrouch wrote:

How can I track when this will be peer reviewed?

On 2021-08-12 21:07:51, user Sam Wheeler wrote:

What about Johnson Johnson = Janssen vaccine? And Sputnik V vaccine?<br /> Janssen recently said their vaccine gives better protection after 8 months compared to 1 month after vaccination. And Janssen was approved based on efficacy after only 2 weeks. So Janssen may be much more efficient than previosly thought!

On 2021-09-03 18:55:26, user Sean Rolnick wrote:

There needs to be a separation of blood types tested. Where these people came from which pre-humans were they from. This has a lot to play on how these subjects play on this study. They all may have a different immune system and work in a different way than has been discovered prior.

On 2020-09-30 16:10:46, user Dan Housman wrote:

The paper is interesting although I would have expected to see some associations between genetic SNPs/genes etc, and certain 'eating types'. There is only one mention I saw of a single gene. Is that type of analysis in the works? I'd be interested to see such an association study.

On 2020-04-13 13:45:53, user Rosemary TATE wrote:

Hi, I dont see the STROBE (for observational studies) guidelines checklist uploaded, although you ticked yes to this<br /> "I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. "<br /> A lot of people seem to ignore these but they are important and any good journal will require them.<br /> Can you please upload? Many thanks.

On 2021-12-07 10:40:57, user S. von Jan wrote:

I feel that some of the assumption that go into the model calculation are overestimated, others are underestimated, and some important further information is not considered. I am referring specifically to v (vaccine uptake), s (susceptibility reduction) and b (relative increase in the recovery rate after a breakthrough infection).

The authors assume a vaccination rate of 65% for the period between 11.10 and 7.11. For the sake of transparency, I think it should be mentioned in the study that in Germany an underestimation of the vaccination rate of up to 5 percentage points is assumed (1), perhaps this should also be considered in the scenarios. Moreover, the recovered cases are not mentioned at all, do they not play a role for the model?

For s in the "upper bound" scenario, a 72% efficacy of the vaccination in Germany is assumed (2), this figure comes from the German Robert Koch Institute (RKI) and is calculated based on the vaccination breakthroughs in Germany, i.e., it only includes the number of symptomatic cases in Germany. The RKI writes on the estimated vaccine effectiveness: "The values listed here must therefore be interpreted with caution and serve primarily to classify vaccination breakthroughs and to provide an initial estimate of vaccine effectiveness" (3, own translation). The vaccine effectiveness estimated here refers to the effectiveness of vaccination against Covid 19 infections with clinical symptoms, not against infection in general. However, there are indications that infections are more often asymptomatic in vaccinated persons ("vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older"(4)), and vaccinated people in Germany must rarely participate in Covid 19 tests. The RKI points out that vaccination would considerably reduce transmission of the virus to other people but assumes that even asymptomatically infected vaccinated people can be infectious: "However, it must be assumed that people become PCR-positive after contact with SARS-CoV-2 despite vaccination and thereby are infectious and excrete viruses. In the process, these people can either develop symptoms of an illness (which is mostly rather mild) or no symptoms at all" (5, own translation). So is the effectiveness of vaccination against symptomatic infections in this setting relevant when it comes to the role of the vaccinated/unvaccinated to the infection incidence?

In the "lower efficacy" scenario, s is given as 50% to 60% based on an English study. This percentage corresponds to the data from another study, which estimates the effectiveness of the Biontech/Pfizer vaccination against infection as 53% after 4 months in the dominant delta variant (6). Would this number not be more plausible for the "upper bound" scenario? The "lower efficacy" scenario could then be calculated with an efficacy of 34%, for example, as suggested by another study on infection among household members (7).

If we consider b, "an average infectious period that is 2/3 as long as this of unvaccinated infecteds" is assumed. This figure seems reasonable based on the available information on the faster decline of the viral load in vaccinated persons. However, there are statements, for example by Prof. Christian Drosten in an interview with the newspaper “Die Zeit”, that make this effect seem less significant: "The viral load - and I mean the isolatable infectious viral load - is quite comparable in the first few days of infection. Then it drops faster in vaccinated people. The trouble is, this infection is transmitted right at the beginning. I'm convinced that we have little benefit from fully vaccinated adults who don't get boostered" (8, own translation). Moreover, there is another issue that is not mentioned in the paper at all, but which I think should be taken into account: Unvaccinated people in Germany have to test themselves much more frequently than vaccinated people (e.g., at the workplace) due to the 3G rules (9, this means vaccinated, recovered or tested). Children and adolescents have a testing frequency of 3 rapid tests a week (10). Even if the effectiveness of the rapid Covid 19 tests for asymptomatic infections should be 58% (i.e., only 58% of infected persons are correctly identified as positive) (11), a test rate of 2 to 3 tests per week would still reduce the duration during which an unvaccinated person is infectious and not in quarantine. This consideration is not included in the model calculation.

Overall, it appears that several central parameters were underestimated or overestimated in the model calculation: The vaccination rate is actually higher, the effectiveness of vaccination against infection is certainly lower than the figure given in the “upper bound” scenario, and the period in which infected persons infect others is shortened for unvaccinated persons by 3G regulations, since they have to go into quarantine if they test positive. As a result, the contribution of the unvaccinated to the infection incidence in Germany is likely to be strongly overestimated in the model calculation, especially in the “upper bound” scenario.

(1) https://www.rki.de/DE/Conte... <br /> (2) For adolescents, s is even estimated at 92%, without explicit data being available here.<br /> (3) https://www.rki.de/DE/Conte.... <br /> (4) https://www.thelancet.com/j...<br /> (5) https://www.rki.de/SharedDo... <br /> (6) https://www.thelancet.com/j... <br /> (7) https://www.thelancet.com/j... <br /> (8) https://www.zeit.de/2021/46... <br /> (9) https://www.bundesregierung... <br /> (10) https://taz.de/Schulen-in-d... <br /> (11) https://www.cochrane.de/de/... This overview work does not yet refer to the delta variant.

On 2021-12-01 21:39:22, user Heinrich Schweizer wrote:

The Title of this paper is very misleading. It is evident, and the authors explicitly state it in the discussion section that: (citation: "The analyses performed here represent model-based estimations that are limited by data quality..."). So I think the title would rather have to be formulated as a question than as the firm statement (lending itself to propagandistic abuse).

On 2021-12-01 21:40:48, user anedabei wrote:

The statement of the paper "unvacs drive it" ist not grounded in reality.

The weekly report of the RKI Report from Nov 25 compares vacs and unvacs in "Tabelle 3"

Unfortunately, it is in German, so some help: The row "Symptomatische COVID-19-Fälle¹ " shows symptomatic cases for the prior 4 weeks.<br /> Adding them up results in 289.953 cases for all age groups. 139.856 of them or 48 % are vac breakthru.

So both vacs und unvacs contribute about the same to drive the pandemia. However, vacs are of course somewhat better protected.

For VE, the vac rate needs to be considered. It is, taken from page 24, 12-17 years 43.0 %, 18-59 years 75.0 % and for 60+ years 87.8 %, resulting in an average rate of 68.1 % for the entire population.

On 2021-08-27 23:09:52, user Raghvendra Mall wrote:

Is there an update on the status of the paper? Has it been published?

On 2021-03-17 14:25:05, user John Smith wrote:

Hi<br /> I look forward to seeing what you come up with for Turkmenistan who have 'officially' recorded no cases of Covid but more than 1000 deaths have been unofficially noted including that of one senior government official and hundreds of medical staff.<br /> The country also has a rule implemented that all grave markers must be flat so as not to be seen from the air which indicates high mortality trying to be hidden.

On 2025-11-11 14:32:38, user Evolutionary Health Group wrote:

We at the Evolutionary Health Group ( https://evoheal.github.io/) "https://evoheal.github.io/)") really enjoyed this paper.

Here are our highlights:

NHANES baseline measures linked to Medicare/NDI to follow incident Alzheimer’s and dementia in >14,000 people, so the risk is tracked over time rather than a one-off snapshot.

The paper centers on cumulative lead (estimated patella/bone lead), which is the right biology for long-term neurotoxicity; the highest vs lowest quartile shows about a 3× higher Alzheimer’s risk (HR 2.96; 95% CI 1.37–6.39).

The same cumulative metric also predicts all-cause dementia, with the highest vs lowest quartile HR 2.15 (95% CI 1.33–3.46), a clean, brief-ready number for policy slides.

Methods-forward and reusable: survey-weighted Cox time-to-event models with up to 30 years of follow-up let the hazard accumulate with aging, exactly the structure we can port to other exposure->dementia questions.

We also like the operational clarity: blood lead showed no association, while cumulative (patella) lead did, pointing action toward lifetime load and legacy remediation rather than one-time screens.

On 2022-01-07 00:38:04, user disqus_8AVEuorTBu wrote:

Given the authors intend to move away from characterizing individual mutations toward representing the "language" of genomes, it may be worth comparing their discrete measure of genetic distintiveness with natural language models often applied to biological sequences (e.g., doi: 10.1101/2021.05.25.445601, 10.1126/science.abd7331, 10.1016/j.csbj.2021.03.022). The continuous distances between the other models' embeddings may provide additional information not captured by this distinctiveness.

On 2020-08-29 10:12:31, user Rebecca Weisser wrote:

@MinSeoKim_MD Your paper of May 18 showed benefit of HCQ +antibiotic to patients with moderate Covid compared to Lopinavir–Ritonavir and standard care. Your paper of July 7 hid that benefit by adding in 173 patients with mild Covid who all recovered without treatment. Why did you do that?

On 2020-08-14 23:07:40, user Luis Carlos Gutiérrez-Negrín wrote:

But even taking into account the probable under-count of Covid 19 active cases and deaths in Kenya in April 30-Jun16, the prevalence of the IgG antibodies in 5% of the population (1 in 20) is astonishly high. These results are, however, compatible with the find of IgG antibodies in seric tests made in other country on samples taken months before the first outbreak of the virus in Wuhan. One sounding alternative explanation could be that one or more older corona viruses, sharing almost the same protein forming their respective peaks, have previously infected Kenya (or certain counties like Nairobi, Mombasa and Kisumu), as well as the country where old IgG antibodies were found.

On 2020-08-13 20:06:24, user Rhyothemis wrote:

Could the low number of deaths in Kenya be at least partly attributable to low per capita protein consumption? It seems as though many countries with low per capita protein consumption rates are reporting relatively low per capita COVID death rates. Mechanistically, such an association (if it exists) could be related to lower baseline mTOR activation.

On 2025-08-20 13:21:16, user Anthony Clanton wrote:

Thank you for the opportunity to comment on your well-constructed manuscript. We appreciate the authors’ efforts to advance the STARD-IONM framework and promote rigor in reporting diagnostic accuracy for IONM. We would like to highlight the importance of clarifying partial recovery scenarios within the STARD-IONM framework. While the manuscript provides valuable discussion on reversible and irreversible signal changes, it does not explicitly define or address partial recovery—cases in which IONM signals improve but do not return to baseline. These common scenarios are clinically relevant and may reflect incomplete injury or partial mitigation. To improve clarity and consistency, we suggest considering the following additions:

• Clearly define “partial recovery” and distinguish it from full recovery and persistent deterioration.<br /> • Include guidance on how to classify and report partial recovery in diagnostic accuracy studies, particularly when calculating sensitivity, specificity, and predictive values.<br /> • Provide illustrative examples or decision frameworks to support consistent interpretation and reduce bias in outcome classification.

We would also like to emphasize that the STARD-IONM checklist does not currently call for authors to specify which muscles, nerves, or anatomical structures were included in the intraoperative monitoring plan, nor does it recommend reporting which signals changed and then recovered or failed to recover. While item 10a under “Test Methods” may implicitly suggest this level of detail, making this expectation explicit would be beneficial. Such information is frequently absent in studies evaluating IONM, yet it is essential for interpreting outcomes and ensuring reproducibility.

Thank you again for your commitment to transparency and community engagement. These additions could further strengthen the STARD-IONM framework and help ensure it serves the entire research community effectively.

Kent Rice, Kevin McCarthy, Anthony Clanton & Adam Doan

On 2020-04-28 15:32:51, user Sinai Immunol Review Project wrote:

Main findings<br /> In this manuscript, the authors describe direct complement system activation through the SARS-CoV-2-N-protein as a common denominator of coronavirus-induced lung injury.

The authors refer to previous evidence on SARS-CoV and MERS-CoV in which they showed that the nucleocapsid (N-) protein binds to a variant of MBL-associated serine protease-2 (MASP-2) that under physiologic conditions initiates the lectin pathway of the complement cascade. The authors hypothesized that SARS-CoV-2 activates the complement cascade in severely ill patients through viral N-protein-mediated dimerization and activating auto-cleavage of MASP-2 leading to respiratory failure in some patients.

Following confirmation of MASP-2 binding to the N protein of SARS-CoV, MERS-CoV and SARS-CoV2, the authors show that MASP-2/MBL binding is enhanced and subsequently demonstrate enhanced complement activation in vitro as measured by C4b deposition in a complement deposition assay and enhanced phagocyte activity. Translating these findings into an in vivo model, the authors pre-infected mice with an adenovirus expressing SARS CoV, MERS-CoV and control virus and challenged the animals with LPS to activate the lectin pathway. This effect was abolished when the N-protein was truncated or anti-MASP-2 antibodies or C1 esterase inhibitor (dissociates MASP from MBL) were used. In mice infected with SARS- or MERS-CoV, the authors found significantly higher C4b and C4 deposits in the lungs and showed tremendously worse survival. However, when MASP-2 knockout mice were challenged with the above-mentioned viruses (or C1 esterase inhibitor given), survival was substantially better as compared to virus-infected wildtype mice.

The authors next analyzed lung tissues from deceased COVID-19 patients and found strong IHC stainings of complement components. In the final step, the authors treated two critically ill COVID-19 patients with a monoclonal antibody that binds C5a (differs from the C5 convertase inhibitor eculizumab) as a part of a clinical trial. Both patients showed clinical improvement of their severe pneumoniae.

Limitations<br /> The question if and in how far coronaviruses are capable of activating the complement system has been controversial so far with conflicting data published.

However, the authors performed a thorough and convincing analysis with well-designed in vitro an in vivo experiments showing the ability of the nucleocapsid to enhance MBL initiated complement activation.

The authors performed key experiments using adenoviruses only containing SARS-CoV and MERS-CoV but not SARS-CoV-2. While the assumption that due to the high sequence homology in the N-protein-binding motif and the proven binding of the SARS-CoV-2 N-protein to MASP-2 strongly suggests that the N-protein in SARS-CoV-2 also plays a major role in complement activation in vivo remains to be proven.

MBL induced complement activation is likely to increase C3a and C3b formation as well as C5a and MAC complex deposition. The finding that anti C5a has some clinical benefit is of interest but does not directly support the MBL mechanism shown here (C5a production could occur via alternative or classical pathway activation)

Significance<br /> Anti-inflammatory treatment in patients with severe viral pneumonia is established as a clinical standard procedure. However, most pathophysiologic aspects of immune hyperreactivity in these patients remains unclear. The study reviewed here shows one mechanism by which coronaviruses activate the complement cascade causing or at least aggravating inflammation in the lung. Showing the successful treatment of two patients with a anti-C5a mAb (not available in the US) is promising and supportive of ongoing or planned trials of a cyclic peptide C3 inhibitor or a C5 convertase inhibiting monoclonal antibody (eculizumab) in severely ill COVID-19 patients.

Reviewed by C. Matthias Wilk, MD as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai. Edited by Professor P. S. Heeger, MD

References:<br /> doi: 10.1038/emi.2015.28. Epub 2015 May 6.<br /> doi: 10.1128/mBio.01753-18

On 2021-11-26 12:33:59, user Richard Hockey wrote:

Hi<br /> This is a cohort study so why not calculate Risk Ratios, seems more appropriate given the design.

On 2021-04-12 19:59:24, user Rui Seabra wrote:

The article was published at: http://dx.doi.org/10.3389/f...

On 2020-05-10 06:58:24, user Volker Dowidat wrote:

In 2015 an Australian study showed that 58% of Australians have a vitamin D deficiency. Therefore, sunlight does not seem to guarantee adequate vitamin D levels. This is related to the use of sunscreen and sunblockers. In addition, the skin loses the ability to produce vitamin D as it ages.

On 2021-02-17 17:12:29, user Tim Pollington wrote:

Dear Epke and colleagues,

I would like to share some comments following reading your (v. relevant) paper on impact of COVID on VL in India at the country level. This is the second time I've commented on a preprint like this on medrxiv, and shared an 'open review' so I hope you receive it in the spirit it was intended. As I'm interested in doing similar studies your manuscript was relevant to me. And since I am funded by BMGF I thought it would be a waste of my funded time if I do not share these thoughts with you too, especially since you're at the preprint/pre-accepted stage.

I thought the paper could benefit from an additional author who has field experience of the IRS/ACD activities occurring there to back-up your assumption that "no IRS and ACD take place and that only passive case detection" during an interruption.

Given that the role of Asx in infecting others is still debated (some say recent xeno shows near zero contribution while ours last year did fit estimates consistently when relative Asx infectiousness of 0,1 or 2% were used), your use of the models E1 & E0 is a smart move to err on the cautious side.

Model structure and quantification section<br /> Thanks for much for following best practice and using PRIME-NTD. It is the first time I have seen it and I definitely plan to use it in my next modelling publication and also when initially planning a model re engagement with policymakers.

Given that the model runs for 30 years has population growth been taken into account?

Impact assessment section<br /> Although adding incidence rates in the same period is acceptable, as events share the same 'person time at risk' denominator (and if the events are mutually exclusive), I'm not sure if epidemiologically it's a correct calculation to sum up rates over the 30 years since the population will be changing in this time and thus the denominators are changing. Perhaps one can convert it into absolute cases in each year and then sum those up?

Discussion section - First paragraph<br /> It may help the reader if more emphasis was made on how a 1-year impacted delay by describing how it is amplified. ie How just one year interruption causes growth which needs to be curtailed before it turns over and falls, and the excess cases this generates. This concept of amplification could be strengthened.

Second paragraph<br /> "80% of [VL-endemic???] sub-districts..." Did this cover just Bihar or all 4/5? endemic states.

Third paragraph<br /> I think mortality rates are really relevant but can understand your caution re scant data. I think it's so important now considering the 1%CFR 2021-2030 target. Could this independent review help provide some rough estimates from pages 12-15 & 40? <br /> Even rough estimates from your model on excess VL cases and when they would likely be seen in the coming years, could be a useful starting place for resource planning of drugs.

I think a caveat needs to be noted that this analysis is country-level whereas the threshold targets are at the block-level, to avoid the reader making an ecological fallacy.

I hope that helps and also encourage you to comment on my work if I get to that stage!

All the best, Tim.

On 2022-02-14 08:23:23, user kdrl nakle wrote:

Poorly written paper that looks like a hodge podge and has diagrams lacking clarifications, one has to search in the main body of paper for relevant references.

On 2020-05-30 11:44:57, user Dude Dujmovic wrote:

29,500 reported yesterday May 29, out of your 95% CI. LOL

On 2021-08-27 02:57:37, user Jason Eshleman wrote:

The author's model assumes that the generation time for the variants is the same. This seems to run counter to observations of a markedly shorter incubation period with delta. This analysis absolutely needs to be rerun without that assumption. Are we seeing greater transmission between generations or are we seeing a fitness advantage due to a shorter generation time?

On 2025-01-03 13:38:21, user Ekkehard hewer wrote:

The final version of our article after peer-review is now published in the Journal of Clinical Pathology (J Clin Pathol. 2024 Dec 9:jcp-2024-209695. doi: 10.1136/jcp-2024-209695.)

On 2021-01-14 14:10:21, user Jeroen van Kampen wrote:

Finally peer-reviewed and online.<br /> See: https://www.nature.com/arti...

On 2021-02-09 05:10:52, user David Brewer wrote:

What honey was used in the HNS study?

On 2021-01-08 21:53:07, user Marek J wrote:

Your study says that methylglyoxal contained in honey cause immunostimulatory or pro-inflammatory action via stimulating the production of immunological mediators, also IL-1?. This study https://www.nature.com/arti...<br /> Shows that low levels of IL-1 are linked to lower mortality.<br /> Is it then safe to recommend using honey rich for MGO, e.g. Manuka honey?

On 2020-04-04 01:25:42, user GLB wrote:

The data from Wuhan are used to characterize the influence of social distancing. From the paper "To be specific, the generalizable information from Wuhan was the impact that social distancing had on maximum death rate and time to reach the inflection point.". Many sources have raised doubts about the veracity of the Wuhan data. Does this render the characterization of the efficacy of social distancing methods in the model suspect? Can the model be tested by using a different location (say, Italy) as the training data set to see how the analysis changes?

On 2020-10-28 13:08:33, user juanpa wrote:

I completely agree with what you say about the unintended? "Forgetting" the huge difference in deaths at 4 weeks.

I also agree on the meaning of the "p".

To all this should be added another "forgetfulness": that the percentage of intubations and mechanical ventilations in the active group are 40.9% lower than placebo group in the same time period (2.4 vs 3.3%),

The number of deaths specifically on invasive mechanical ventilation is new to me.

In my opinion there are thre more criticisms to add

1st.- If the study designers wanted to verify the degree of effectiveness of the Raoult method scientifically, they only had to clone it. It is evident that this was never his intention (there is no AZ or Zn, neither the doses nor the timing are the same, the treatment was not started early enough either, ...)

2nd.- The funding agencies should never have financed it until the treatment designed cloned the Marseillais.

3º.- For me, the reasons for the premature suspension of the study were never too clear. Did they think there would not be a 2nd wave? Couldn't they wait for her?<br /> Someone might suspect that the preliminary results were too flattering for the HDQ and that the results should be prevented at all costs from being statistically more significant.

Sorry for my bad english

On 2020-05-11 14:50:43, user Quant wrote:

I published an article Apr 26th with a similar theme that may interest readers. I described this as a Jensen's Inequality effect. It can apply to any source of heterogeneity including population density. Its good to see progress like this paper towards a more nuanced understanding of the turning point of an epidemic. <br /> https://www.linkedin.com/pu...

On 2021-08-19 17:45:40, user BiotechObserver wrote:

How do you now "these ones" will not last 10 years? You measured the B cells of participants? No, I didn't think so.

On 2021-08-16 22:58:15, user Emily Porter wrote:

Well one question is did everyone take the intervention after unblinding? If so they may still have a control group albeit a smaller one.

On 2020-03-22 22:28:02, user The Mad Viking wrote:

I do not understand the use of the words "asymptomatic infection" in this article.? Your 24 patients all had Hubei contacts, where it seems likely they were in contact with a symptomatic individual. I see no evidence that they were infected by an individual that was asymptomatic. But that is what the media is reporting, referencing work like this.

On 2020-08-11 11:14:29, user One bird one cup wrote:

Limited evidence to support effectiveness of quarantine? <br /> SARS: 8,098 cases worldwide. About 5300 in China. "Most included trials had poor design, reporting and sparse events." No difference between N95 and surgical masks? <br /> I'm not buying this.

On 2020-04-13 13:32:07, user Rosemary TATE wrote:

Hi, I dont see the STROBE guidelines checklist uploaded, although you ticked yes to this<br /> "I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. " <br /> A lot of people seem to ignore these but they are important and any good journal will require them.<br /> Can you please upload? Many thanks.

On 2021-08-29 20:22:01, user Holger Lundstrom wrote:

"PCM received funding from the Wellcome Trust [110110/Z/15/Z]."

To quote from:<br /> https://www.bmj.com/content...

"An increasingly clear feature of the covid-19 pandemic is that the public health response is being driven not only by governments and multilateral institutions, such as the World Health Organisation, but also by a welter of public-private partnerships involving drug companies and private foundations."

"These advisory and media activities seem to overlap with Wellcome’s £28bn endowment, which has at least £1.25bn invested in companies working on covid-19 vaccines, therapeutics, and diagnostics: Roche, Novartis, Abbott, Siemens, Johnson & Johnson, and—through its holdings in the investment company Berkshire Hathaway—Merck, AbbVie, Biogen, and Teva.11"

"Yet charities such as Gates and Wellcome—and even drug companies—have generally been praised in the news media during the pandemic for their efforts to solve the public health crisis, with relatively little attention paid to their financial interests and with few checks and balances put on their work."

“What the pandemic is doing is buffing the reputation of organisations like Gates and Wellcome and the drug companies, when I don’t think they really deserve that buffing up,” says Joel Lexchin, professor emeritus of York University’s school of health policy and management in Toronto. “I think they’re acting the way they always have, which is, from the drug companies’ point of view, looking after their own financial interests, and from the point of view of the foundations is pursuing their own privately developed objectives without being responsible to anybody but their own boards of directors.”

On 2020-06-15 01:10:48, user Serge wrote:

There are many inaccuracies in the report that may significantly affect the conclusions.<br /> 1. Diamond Princess analysis: the mortality data (in single digits) is not sufficient for a confident estimate of the mortality per jurisdiction (for some nations there was only a single case). Moreover, most countries started universal BCG vaccination around 1950s plus the effect of WWII would likely compromise any earlier program to a significant extent. That means that regardless of the country of origin, large part of over 70 population would not be protected and thus shouldn't be considered in verification of the hypothesis.<br /> 2. Certainly there can be no expectation that the protection effect would extend equally into a very advanced age, 60 years and longer after vaccination.<br /> 3. What is meant by the statement "BCG was provided mostly in Europe"? This is plain incorrect, please check "BCG World Atlas".<br /> 4. Country analysis: was the population taken into account? It is not clear from the description of diagrams. I would advise to attempt to calculate mortality per capita, from the most current data and compare it between jurisdictions at a similar period of exposure. Note that all countries with the highest M.p.c. adjusted for the time of exposure, never had a BCG program (or equivalent as in Spain where it was provided for 18 years out of 70) there's simply not a single exception.

On 2020-05-17 19:04:29, user Shreyans Pagariya wrote:

For more detailed predictions on when COVID-19 could end in each state of India using the same model described in the article, take a look at https://covid19quarantine.i...

On 2020-09-04 19:44:32, user Art Framer wrote:

Excuse my ignorance but it seems that the tests for covid 19 are looking for the virus itself. Wouldn't the tests have a higher rate of success if they looked for signs of the body's reaction to the virus?

On 2020-07-28 17:28:54, user Hannes Fischer wrote:

Have you seen some studies with favipiravir results? What drugs show some potential nowadays?

On 2022-01-05 17:26:08, user Terry Baines wrote:

I greatly appreciate this effort of trying to analyze the unique challenges which Tribes and Tribal members in managing COVID-19 when confounding social, medical, and community issues are involved. With the complex challenges Tribes face, unique and robust solutions need to be devised. Thank you for those efforts; I would love to see more like it.

On 2021-05-05 19:46:25, user Kevin Roche wrote:

you do realize that CV-19 has multiple animal hosts. it ain't going nowhere

On 2021-05-27 19:44:53, user Roland wrote:

Note too, how vapor saturation of masks from the wearer's breath increases mask effectiveness. This is out there as well.

I would like to read about that if you can provide a link. It makes more sense to me that as your mask gets coated with spit, it begins to act as a mesh nebulizer to convert the previously harmless big drops into aerosol droplets every time you exhale through the mask's tiny pores. Those can float around for hours and be inhaled by other people. In other words, if you are infected, putting on a mask turns you into a walking covid mosquito fogger.<br /> If masks worked as well as the faithful claim they do, we would see overwhelming correlation between mask use and reduced cases, deaths and hospitalizations. We don't. Ian Miller tweets the non-proof every day.

On 2021-06-10 02:33:11, user baby drumf wrote:

How come countries like Taiwan and South Korea have such low rates of transmission? they are all wearing melt blown polypropylene masks (KF94 & N95 Respirators). Respirators work much better than cloth or surgical type procedure masks.

On 2020-04-25 21:34:02, user Christopher Rentsch wrote:

We believe that Magagnoli et al failed to correctly identify intubation occurring in hospitalized patients testing positive for COVID-19. They used CPT codes 31500, 94002, 94003, and E0463 and ICD-10 procedure codes indicative of assistance with respiratory ventilation, or extracorporeal membrane oxygenation (ECMO). We identified 5,906 COVID-19 patients treated in the Veterans Health Administration between March 1 and April 21, 2020. In addition to the above CPT codes, we identified intubation according to ICD-10 procedure codes for insertion of endotracheal airway, and respiratory ventilation, which were usually concordant. We cross-validated with medications typically used during intubation, such as neuromuscular blocking agents (e.g., succinylcholine, rocuronium) and short acting sedatives (e.g., propofol, midazolam). We also found these intubation codes most frequently in the context of intensive care. We did not find similar evidence of face validity for ventilation assistance codes. No instances of ECMO were found as this procedure is unlikely to be used in the Veterans Health Administration.

We classified 307/5,906 = 5.2% patients as intubated. Using the Magagnoli algorithm, only 96/5,906 = 1.6% patients were said to be intubated. Of these, 37 were classified based on ventilation assistance codes, not indicative of intubation.

List of ICD-10 Procedure codes used to identify intubation

Codes in both Magagnoli and Tate lists<br /> - Respiratory Ventilation (5A1935Z 5A1945Z 5A1955Z)

Codes in Magagnoli list, but not Tate list<br /> - Assistance With Respiratory Ventilation (5A09357 5A09358 5A09359 5A0935B 5A0935Z 5A09457 5A09458 5A09459 5A0945B 5A0945Z 5A09557 5A09558 5A09559 5A0955B 5A0955Z)<br /> - Extracorporeal Oxygenation, Membrane (5A1522F 5A1522G 5A1522H)

Codes in Tate list, but not Magagnoli list<br /> - Insertion of Endotracheal Airway Into Trachea (0BH13EZ 0BH17EZ 0BH18EZ)

Janet P. Tate (Janet.Tate2@va.gov)<br /> Christopher T. Rentsch (@DarthCTR)<br /> Joseph T. King Jr.<br /> Amy C. Justice

VA Connecticut Healthcare System<br /> West Haven, CT

On 2020-04-22 01:19:52, user stickler wrote:

Every news media seems to be including this same sentence: "The nationwide study was not a rigorous experiment," which to trump supporters means that its conclusions are completely untrustworthy and it can be summarily disregarded as a politically motivated product of the deep state. In what way did this study lack rigor? Does there appear to be anything lacking in the design, methodology, data, analysis, interpretation or reporting of results, or is it more a matter of just awaiting peer review?.

On 2020-04-23 12:44:36, user dirk van renterghem wrote:

The problem is the absence of randomisation. Were patients given HC or HC+Azitro at admission, or because they were deteriorating? If so (in some) we cannot compare the deteriorating with the non-deteriorating population... In the HC group 17% had creatinine>5mg/dl, much worse than the no-drug group... , also more anemia an lymphopenia.

On 2020-04-22 00:35:27, user Eric H wrote:

The Hazard Ratio confidence intervals in Table 5 of the report shows that the findings of this study are not significant. That plus the uncertainties in the Propensity Score Matching method make it even worse. I noticed the HCQ group contained a substantially higher proportion of high blood pressure and diabetic w/complications than the control group. Worst of all, they apparently did not interview even one doctor to ascertain the range of Tx criteria used.

On 2024-11-11 04:16:52, user Christopher Penney wrote:

This preprint, "Tucaresol: A Clinical Stage Oral Candidate Drug With Two Distinct Antiviral Mechanisms", was published September 30, 2024 in the refereed journal, Journal of Clinical Review & Case Reports.

CL Penney, Ph.D.

On 2020-10-15 09:13:31, user Ariel ISRAEL wrote:

Our new large population study is out!<br /> We harnessed the power of Clalit unique database to identify drugs that significantly decrease severity of COVID. CoQ-10 with ezetimibe or rosuvastatin helps (a lot):<br /> Systematic analysis of electronic health records identifies drugs reducing risk of COVID-19 hospitalization and severity<br /> https://www.medrxiv.org/con...

On 2021-07-21 07:40:43, user withamk wrote:

No funding? It has to be funded by something, donations of labor and materials, or by Cleveland itself.

On 2021-06-13 21:16:52, user thomas wrote:

I am not in the health field (that may be obvious from the questions I have) but I am very interested in this study because my parents (in their 70's) both had and recoverd from covid. They have not received a vax yet.

1. Why wouldn't having the infection give immunity? Is there something about this specific virus, or this type of virus in general, that it wouldn't be expected to give immunity?

2. If infection doesn't give immunity, how will the vaccines work? I realize some vaccines are mRNA or viral vector, but at least the two Chinese ones, the Indian one, and a new one the French are working on are all based on using a dead/weakened virus. Shouldn't recovering from an actual infection work just as good as the simulated infection of a vaccine?

3. Is 1,359 subjects really considered small? How big where the sample sizes for the initial vaccine studies? What would be an acceptable size? My background is more in the social sciences, and we often see samples in the hundreds.

4. Is it really correct to assume that people who had COVID would be more careful afterwards? I know with my parents, they were almost consumed with fear about catching the disease, but once they did and recovered, much of that went away. I wasn't around to see their behavior, but just based on conversations, I find it hard to believe they were more careful.

When my parents saw the doctor after recovering, he told them they could not get the vaccine for at least 3 months and that they didn't need to get it until after 6 months. So this study seems in line with what the medical establishment was already saying (they had COVID back in March).

On 2021-06-13 21:26:08, user thomas wrote:

As I mentioned in my longer post (please read it once they post it, I'm very interested in this for my parents and have a lot of questions), my parents got and recovered from COVID. Afterwards, they were much less worried about the disease and, if anything, were probably less conscious. I think the people who had very serious cases would be more careful, but for the milder cases (like my parents) it's not necessarily true.

On 2021-03-19 17:23:16, user Jenana Maker wrote:

Thank you so much for doing this study - this is such an important public health topic and will hopefully raise awareness within the country and beyond. The reasons for vaccine hesitancy are certainly complex but will need to start with healthcare providers being "on board" and educating the patients and public about the importance of vaccination...hvala vam za objavu ove studije :-)

On 2020-05-19 12:45:29, user Lynn Wright wrote:

Was the HCQ given alone or with Azithro as is being prescribed in doctor's offices and hospitals? If not, why?

On 2021-03-13 18:13:49, user Sean Patrick Murphy wrote:

This study focuses on hospitalized COVID patients. Many longhaulers were never hospitalized and some were completely asymptomatic. The authors attempt to address this issue with the likely erroneous statement - "Secondly, this is an initially hospitalised cohort so we cannot directly extrapolate to individuals who initial infection did not result in hospitalisation although there is no reason to suggest the effect would be any different." Patient-led research has demonstrated that there are clear subcategories of longCOVID based on symptomatology and to lump these all together is simply wrong.

On 2021-08-21 00:31:20, user Sonia Villapol wrote:

This article has been published in "Scientific Reports" on 09 August 2021, a Nature Publishing Group's open access research journal: <br /> https://www.nature.com/arti... <br /> Thanks! <br /> - Sonia Villapol

On 2024-05-25 16:10:01, user Mark wrote:

Writing that the "simulation demonstrates that repeated boosters, given every few months, are needed to maintain this misleading impression of efficacy" (in their abstract) the authors build upon the assumption that (fully) vaccinated persons are miscategorized as "unvaccinated" for some period of time after they've received a repeated ‘booster’ vaccination.

I wonder if there is any example, research study or country which actually proceeded this way ...

On 2020-06-11 16:22:18, user Keith Gentile wrote:

Is this the study used by the CDC to estimate the covid IFR?

On 2020-11-11 00:17:25, user kdrl nakle wrote:

This paper has no science in it, there is no data in it, mostly typical educational stuff.

On 2020-05-07 12:18:58, user Jean-Baptiste Hazo wrote:

Thank you! Have you been adjusting for smoking status?

On 2020-06-23 19:40:15, user Roman Shein wrote:

In an interview Hendrik Streeck claimed the specificity to be 99%. How? In March, when all mayhem just started to envelop! How were these test verified?<br /> At the same time, the very same Hendrik Streeck has co-authored a paper (published), that the antibody tests are rubbish, not fit to diagnose Covid. The specificity is around 88%. I admit the paper concerns antibody test usage at much earlier stage of the disease, but nevertheless his own assessment seems to contradict the claim about 99%.

• The data from other sources suggests the specificity to be in the region of 85-90%. Due to this it seems reasonable to suggest that out every 15 people in "w antibodies", lets say, 12 (88% specificity, indeed) were, in fact, the false positives. In this case, what is left, 15-12=3% of population w the real immunity, not 15%! By comparison, the official infection rate was stated to be 3%...

On 2020-06-26 22:11:48, user Hilda Bastian wrote:

It's excellent that this trial was done, but the preprint is overly positive: given it's not clear that anyone either working in, or exercising in the gym, was infected, it's not possible to know if the hygiene and social distancing measures worked.

There have been clusters of outbreaks related to gyms (for example in Japan and South Korea), and this needs to be discussed. Given that infected gym employees have been shown to have been the source of clusters, it's problematic that all employees weren't tested and considered more here.

This trial report is missing key methodological information, such as the method of randomization. At one point, the authors refer to the trial's protocol, but do not provide a reference for it. (That level of detail on methodological issues isn't included in the ClinicalTrials.gov entry for the trial.)

I think it's unfortunate that this was a non-inferiority trial, given the known risk of gym clusters. The bar was set too low for this trial. There was too much missing data on testing - nearly 20% of participants and nearly 10% of employees. The authors argue that disease is more critical than infection, but the risk of seeding clusters is a critical concern in gym re-opening.

On 2021-03-25 12:37:30, user Bernhard Brodowicz wrote:

Protocol from one of the labs involved in vienna, the Vienna Covid-19 Detection Initiative (https://www.maxperutzlabs.a... "https://www.maxperutzlabs.ac.at/fileadmin/user_upload/VCDI/News/COVID19_Testing_VCDI_v1.1.pdf)") states that 'Ct values <40 are considered positive' (this is acc. to US CDC EUA protocol, when CDC-N1 and CDC-N2 target are used; for other targets a Ct reference was not reported). <br /> Sensitivity/specificity of the targets are described there as follows:<br /> CDC-N1: Very sensitive; SARS-CoV2-specific; low false-positive rate;<br /> IMP-ORF1b: SARS-CoV2-specific version of HKU-ORF1b-nsp14; very sensitive; low false-positive rate;<br /> CDC-N2: Very sensitive; SARS-CoV2-specific; false positives in presence of genomic DNA;<br /> E_Sarbeco: Sensitive; not SARS-CoV2 specific; reduced sensitivity in 384-well format;<br /> Especially as IMP-ORF1b and CDC-N2, which are described as 'very sensitive' but also false positives are mentioned, the interpretation of high Ct values > 40 as positives could raise questions when validation data (sensitivity, specificity, LOD) is not given and was not verified by individual labs (and different analytical setups) involved.

On 2021-07-22 18:07:27, user Ken Jacobie wrote:

What was the average age and INNATE IMMUNE SYSTEM STATUS of these 167 person in this study? How many were CHEMOTHERAPY recipients etc...

On 2019-10-07 13:54:02, user GuyguyKabundi Tshima wrote:

EPIDEMIOLOGICAL SITUATION

EVOLUTION OF THE EBOLA EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI OCTOBER 05, 2019<br /> Sunday, October 06, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,204, of which 3,090 are confirmed and 114 are probable. In total, there were 2,142 deaths (2028 confirmed and 114 probable) and 1004 people healed.<br /> 414 suspected cases under investigation;<br /> No new cases confirmed;<br /> 1 new confirmed death at CTE in Ituri in Komanda;<br /> No one healed out of ETCs;<br /> No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths.<br /> Day 19 without response activities in the Lwemba Health Area in Mandima, Ituri, where the dialogue continues in the community.

NEWS

Reconciliation between displaced people from Lwemba to Biakato and communities left in Lwemba in Mandima in Ituri

The Lwemba communities that moved to Biakato in Mandima in Ituri reconciled on Sunday 06 October 2019 with the communities that had remained in Lwemba in the presence of the response team led by the Deputy General Coordinator, Dr. Justus Nsio Mbeta, head of the Cheffery and Mandima MCZ, coordinator of Mangina's sub-coordination of the response, as well as some partners from the Ministry of Health, including WHO, MSF, UNICEF and United Nations ;<br /> - From this meeting, follows the following recommendations: setting up a community committee to support the response, the local recruitment of sensitizers in the monitoring of community-based surveillance, decontamination and the workforce in the community. burning houses. The Ministry of Health has promised the next supply of drugs to Lwemba;<br /> - The Deputy General Coordinator for the Ebola Virus Epidemic Response, representing the Ministry of Health and the Technical Secretariat of the CMRE, Dr. Justus Nsio Mbeta, took this opportunity to recall the regulatory role of the Ministry of Health and the role of each partner involved in the response;<br /> - For the community victim of the fire, they ask for the guarantee of their security, the emergency humanitarian aid, the compensation of their destroyed property and the reconstruction of their burned houses, the commitment or the hiring of all victims in the various services at all levels, the immediate arrest of all the alleged perpetrators of these uncivil acts and the care of the children affected;<br /> - These fires occurred following the death of a nurse from Lwemba, confirmed with Ebola Virus Disease. His death sparked the uprising of the population to burn down the houses and other property of all the unknowns of Lwemba. This remains the cause, even, the cessation of the activities of the response in this Health Area for more than 15 days;<br /> - The leaders of the Lwemba community also asked for the construction of the houses for the displaced, the organization of an intercommunal dialogue session by the Administrator of the territory or his delegate and the rehabilitation of the road leading to Lwemba ;<br /> - In the response, WHO is responsible for epidemiological surveillance, communication and prevention against infection (IPC) and immunization, UNICEF is in charge of communication, psychosocial care and PCI, MSF and ALIMA take care of the treatment of patients in Ebola treatment center and PCI and psychosocial support within CTE, WFP brings food products to contacts, IOM deals with Entry and Control Points (water supply, soap and chlorine);<br /> - As for the National Institute for Biomedical Research (INRB), Dr. Nsio stated that he is in charge of the diagnosis and gives MSF and ALIMA the medicines to treat patients with CTE.<br /> - The World Health Organization has pledged to rebuild burned houses, to provide community surveillance (community watch) and investigations of all suspected cases, as well as to build a transit center in LWEMBA, while UNICEF has pledged to improve communication and awareness through the use of space, to support ICH, decontamination and psychosocial, to provide water sources and to build latrines in 5 priority schools;<br /> - On the other hand, Médecins Sans Frontières intends to help the community of Lwemba to resume primary health care, to organize triage in the Health Zones present in the village and to break the PCI, as well as to train sensitizers;<br /> - At the end of this Lwemba meeting, all partners, including WHO, UNICEF and MSF, met around the Deputy General Coordinator at the Biakato Reference Health Center to review the joint and shared planning of activities in Lwemba.

VACCINATION

• Since vaccination began on August 8, 2018, 234,108 people have been vaccinated;
• The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

MONITORING AT ENTRY POINTS

• Three high-risk contacts were intercepted on Saturday 05 October 2019 at Maboya Checkpoint (PoC) in Butembo. They are all from the same family and came from the Kabasha Health Area to Kalunguta for Bunyuka in Vuhovi;
• They are all contacts of a confirmed case, died of the Ebola Virus Disease (EVD) of September 30, 2019 in Kabasha;
• The first contact is an unvaccinated 8-year-old girl who presented fever at 38 ° C. She was taken to the CTE of Butembo for the care after validation of the alert was validated;
• The 2nd contact is a 24 year old man vaccinated and asymptomatic. He is the biological father of the first contact;
• 3rd contact, first contact grandmother, 54 years old, unvaccinated and asymptomatic;
• Since the beginning of the epidemic, the cumulative number of travelers checked (temperature measurement ) at the sanitary control points is 102,840,774 ;
• To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these sanitary measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

On 2020-04-26 21:01:22, user reuns wrote:

Important study because it proves the outbreak came from the Highschool (15-18yr plus the teachers and workers)

On 2024-02-26 17:14:48, user Ciarán McInerney wrote:

It is admirable that<br /> the authors followed the STROBE guidelines but this study is not an<br /> observational study. Instead, it is about building a prediction model so a more<br /> appropriate guideline to follow is TRIPOD (doi: 10.7326/M14-0698). The authors<br /> should also follow the guidelines of the PROGRESS framework for researching<br /> clinical outcomes (doi: 10.1136/bmj.e5595, 10. 1371.journal/pmed.1001380, 10.1371.journal/pmed.1001381,<br /> 10.1136/bmj.e5793).

On 2020-12-31 16:42:18, user R Pressinger wrote:

One drawback with this study is it investigates only two parameters of lymphocyte counts - comparing individuals below 900 per cu/mm with those above this range. Normal lymphocyte count is approximately 1,100 to 3,100 for the middle 95% population. 2.5% of us score below this range and 2.5% above. Therefore, the majority of Covid-19 deaths could very well be in the bottom 5-10% range but we would not know if this was occurring from the current study design. Other published studies have shown asymptomatic Covid-19 patients average upwards of approximately 1,700 lymphocytes, which is interesting as this is still in the bottom 1/4th to 1/3rd of the general population. It would be intriguing and far more enlightening to add additional parameters for comparison. For example, comparing Covid-19 fatality rates for those with absolute lymphocytes below 900 to those in the "healthy normal range" (roughly between 1,800 and 2,400). Extrapolating from current findings, this information could possibly result in a dramatic difference in fatality rates. If this was the case, it would identify individuals at near zero risk of severe health outcome for this and future outbreaks and imply these individuals could be at the front line without risk of injury. This would be invaluable information for workers in many professions including medical, nursing home staff and teachers involved in the education of our children.

On 2025-04-06 23:02:55, user carl otto schell wrote:

This article has been published in BMJ Global Health<br /> 25 March 2025 https://gh.bmj.com/content/10/3/e017119#rapid-responses

On 2020-04-04 20:34:04, user Sinai Immunol Review Project wrote:

Title: First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naïve and Experienced COVID-19 Patients

Keywords: Clinical study – HCV protease inhibitor – Danoprevir – Ritonavir – Covid19 treatment

Main findings:<br /> The authors treated 11 Covid-19 patients with Danoprevir, a commercialized HCV protease inhibitor [1], boosted by ritonavir [2], a CYP3A4 inhibitor (which enhances the plasma concentration and bioavailabilty of Danoprevir). Two patients had never received anti-viral therapy before (=naïve), whereas nine patients were on Lopinavir/Ritonavir treatment before switching to Danoprevir/Ritonavir (=experienced). The age ranged from 18 to 66yo.<br /> Naïve patients that received Danoprevir/Ritonavir treatment had a decreased hospitalization time. Patients treated with Lopinavir/Ritonavir did not have a negative PCR test, while after switching to Danoprevir/Ritonavir treatment, the first negative PCR test occurred at a median of two days.

Limitations:<br /> The results of the study are very hard to interpret as there is no control group not receiving Danoprevir/Ritonavir treatment. This was especially true in naïve patients who seemed to have more mild symptoms before the start of the study and were younger (18 and 44yo) compared to the experienced patients (18 to 66yo). The possibility that the patients would have recovered without Danoprevir/Ritonavir treatment cannot be excluded.

Relevance:<br /> The authors of the study treated patients with Danoprevir, with the rational to that this is an approved and well tolerated drug for HCV patients [2], and that it could also target the protease from SARS-CoV-2 (essential for viral replication and transcription). Indeed, homology modelling data indicated that HCV protease inhibitors have the highest binding affinity to Sars-Cov2 protease among other approved drugs [3]. <br /> While this study shows that the combination of Danoprevir and Ritonavir might be beneficial for Covid-19 patients, additional clinical trials with more patients and with better methodology (randomization and control group) are needed to make further conclusions.

1. Seiwert SD, Andrews SW, Jiang Y, et al. Preclinical Characteristics of the Hepatitis C Virus NS3/4A Protease Inhibitor ITMN-191 (R7227). Antimicrob Agents Chemother. 2008;52(12):4432-4441. doi:10.1128/AAC.00699-08
2. Xu X, Feng B, Guan Y, et al. Efficacy and Safety of All-oral, 12-week Ravidasvir Plus Ritonavir-boosted Danoprevir and Ribavirin in Treatment-naïve Noncirrhotic HCV Genotype 1 Patients: Results from a Phase 2/3 Clinical Trial in China. J Clin Transl Hepatol. 2019;7(3):213-220. doi:10.14218/JCTH.2019.00033
3. Nguyen DD, Gao K, Chen J, Wang R, Wei G-W. Potentially highly potent drugs for 2019-nCoV. bioRxiv. February 2020:2020.02.05.936013. doi:10.1101/2020.02.05.936013

Review by Emma Risson part of a project of students, postdocs and faculty at the Immunology Institute of the Icahn school of medicine, Mount Sinai.

On 2021-04-07 10:34:02, user Ariane Fillmer wrote:

The results you present appear to be really interesting. Thank you for sharing this. In order to allow the experienced reader to assess the data you show in a bit more detail, it would be great if you could add some more information on what you actually did: What scanner did you use (field strength does have a massive influence on the appearance of spectra)? What sequence did you use, and what methods did you use to calibrate for optimal data quality? How did you generate the basis sets that you used in LCModel? (Btw. in the data set of the COVID-A patient there is some signal contribution (at both echo times) that is clearly higher than noise but was not accounted for in your model, that might indeed be an interesting finding as well)

To help improve overall reporting standards in MRS and MRSI studies, a few colleagues of mine recently published a consensus paper on minimal reporting standards. This is also meant as a guide to help authors who are somewhat new to the field of MR spectroscopy, and help make the work better comparable to other studies and hence lead to overall improvement of impact of MRS papers: https://doi.org/10.1002/nbm...

On 2025-11-23 17:32:31, user Charlotte Strøm wrote:

In the following “text in italics – inside quotations marks are copy-pasted from the reference in question." Underlining and/or bolded text are done by me.

1. SPIN AND FRAMING<br /> The title of the preprint is: “Randomised trial of not providing booster diphtheria-tetanus-pertussis (DTP) vaccination after measles vaccination and child survival: A failed trial”<br /> 1.1 Framing neutral findings as abnormal or disappointing<br /> The authors consistently imply the results are “unexpected” or “contradictory”, rather than acknowledging that the RCT failed to support earlier observational findings.

Examples<br /> “A failed trial” says the title ->The trial did not “fail”: it ran, randomised 6500+ participants, and produced valid estimates showing no harm of the DTP vaccine. Calling it “failed” is a framing tactic that positions the result as an error rather than what the data showed.

Page 8, lines 11-12: “The was no difference in non-accidental mortality … the HR being 0.84 (0.52–1.37).” ->This is an appropriate stating of results, but the subsequent framing undercuts it.

Page 8, lines 22-24: “Since no beneficial effect of not giving DTP4 was found, contradicting many observational studies… possible interactions were explored…” -> This subtly frames the RCT as problematic because it contradicts earlier observational research, rather than recognizing that RCTs supersede observational evidence.

Page 10, line 2:“The present RCT is therefore an outlier which needs an explanation.” -> This is spin: the RCT is not an "outlier" needing explanation; observational studies - upon which the research hypothesis are based - are know to have confounding and are biased. CONSORT encourages presenting results without exaggeration or defensive justification.

1.2 Causal interpretations of non-significant results<br /> The authors imply meaningful patterns where no statistically reliable findings exist.

Examples Page 8–9 (exploring interactions despite explicitly stating low power): “There was one significant interaction … DTP strain … observed only for females.” (p=0.05)

No correction for multiple testing; >20 interactions tested -> This is classic exploratory-analysis spin.

1.3. Hypothesis-confirming language<br /> The manuscript repeatedly positions NSE hypotheses as foundational truths rather than unproven claims.

Example Page 3, lines 5-7: “Several studies inidcated… beneficial non-specific effects… more pronounced in females.” -> These were observational or post-hoc analyses, being framed as established background biases the narrative.

1.4 Framing underpowering as the main explanation<br /> Repeated emphasis that the trial was “strongly underpowered” serves to discount the main finding.

Examples Page 8, lines 13-15: “...the trial was planned with 3% annual expected mortality rate… observed rate was 81% lower… we had 65% fewer deaths…” -> This is accurate but placed repeatedly tthroughout the text to frame the null result as flawed.

Page 9, lines 18-21: “The RCT was strongly underpowered… mortality declined …” -> The authors do not consider that a null finding study is plausible.

2. CONSORT NON-COMPLIANCE <br /> 2.1. Missing or unclear prespecified primary outcome<br /> CONSORT requires explicitly stating primary and secondary outcomes and linking to a prespecified Statistical Analysis Plan (SAP).

Issues: The manuscript says: Page 5, lines 25-27: “The outcomes were all-cause non-accidental mortality and hospitalisation, as well as sex-difference…”<br /> -> It is unclear which of these is the primary outcome. Mortality? Hospitalisation? Sex-differential mortality? AND - there is ...

-> No link to protocol-defined hierarchy.

2.2. Discrepancies between protocolled numbers and intervention<br /> There are discrepancies between numbers stated in the publicly available protocol and study record at http://clinicaltrials.gov and the numbers appearing in the preprint. The intervention described in the preprint is not aligned with the protocol.

These discrepancies are unexplained in the preprint. The preprint states that DTP3 has been reported elsewhere, but the reference that is included in the preprint (2) does not report on mortality data, moreover it includes both DTP3 and DTP4. And these protocol deviations are inadequately accounted for in the preprint.

It remains therefore unexplained what the actual flow of study subjects were, and it remains unclear what the results are from the DTP3+OPV+MV versus OPV + MV only – as stated in the protocol.

2.3. Randomisation procedure is not sufficiently described<br /> CONSORT requires allocation concealment method and sequence generation details

Example Page 5, lines 12-14: “...randomisation lots were prepared by the trial supervisor… kept in envelopes… mother asked to draw envelope…” -> No description of safeguards (opaque, sealed, sequentially numbered). -> Allocation was not blinded, but CONSORT requires explicit reporting of potential bias. DTP3 is not mentioned in the trial flowchart - figure 1.<br /> 2.4. Lack of intention-to-treat analysis <br /> CONSORT requires ITT or explanation for deviations.

Example Page 7, lines 1–3: “All children with follow-up and who received the per-protocol intervention were included in the analyses.”<br /> -> This is per-protocol only, inappropriate for a superiority RCT intended to detect harm.

-> No ITT analysis is presented.

2.5. No reporting of missing data handling<br /> CONSORT requires transparent handling of missing outcome data.

Example Page 7, line 14: “No imputation for missing data was done.” -> But the extent of missing data is not reported for mortality or hospitalization outcomes.

2.6. Discussion includes non-evidence-based explanations, violates CONSORT as Discussion should reflect results, not speculation<br /> The discussion drifts into immunological theory and historical interpretations unsupported by trial data.

Examples: Page 10, lines 4-6:“...likely that immune mediated NSEs are more pronounced when mortality is high…”<br /> Page 9-10 (multiple paragraphs): Repeatedly argues unexpected null results require explanation. -> This is speculative; not based on data reported from this RCT.

2.7. Lack of balanced discussion<br /> CONSORT item 22: discuss both limitations and strengths. -> The manuscript heavily emphasises limitations (underpowering, interventions, etc.), but does not discuss the strength of randomisation or lack of harmful signal which is odd considering the research hypothesis of the trial.

3. OVERALL REFLECTIONS ON THE IMPACT OF SPIN, FRAMING, AND CONSORT DEVIATIONS<br /> Altogether, it seems to be rather unusual for researchers to put the trial down already in the headline, downright devaluating the trial. The authors are known to advocate detrimental effects of the DTP vaccine, a hypothesis that is based on purely observational studies (3, 4), and very small numbers that have not managed to replicate even by the same group of researchers (5).

This preprint reports results from a large-scale randomized trial, outranking observational studies in the hierarchy of evidence. Hence – making use of “A failed trial” appears to be an attempt to frame the results as invalid, which is ethically disturbing and highly inappropriate towards trial participants and readers.

p. 10:“The present RCT is therefore an outlier which needs an explanation. The drop in power due to the declining mortality rate may not only have lowered the possibility of finding significant tendencies; it is also likely that the immune mediated NSEs are more pronounced when mortality is high, so when mortality declines by >80%, the residual deaths may be less likely to be affected by immunological changes.”<br /> There seems to be a deliberate misinterpretation, unsubstantiated, and highly speculative. It is difficult not to read this in any other way than as a deliberate attempt to spin the results, frame them to be perceived according to the authors’ hypothesis about DTP having detrimental effects and increasing child mortality. Spinning results is defined as questionable research practice (6). The study was a null finding study, not an outlier.

There were no signs of more pronounced negative NSE, i.e., higher mortality in the child participants, who got DTP with, or after the measles vaccine. However, the primary outcome analysis demonstrated that this trial is a null finding study and thus the hypothesis was rejected.

3.1.Spinning the facts around other interventions.<br /> Several times in the preprint, the authors argue that other health interventions affected the trial conduct and the results.

Examples<br /> Page 1; “During the trial period many new interventions, including many national health campaigns, were carried out.”<br /> and <br /> “due to the large number of health interventions, not envisioned at the initiation of the trial, a limited part of the follow-up was a comparison between DTP4+OPV4 vs OPV4 as the most recent vaccinations”<br /> Page 6:“Other interventions and interactions. As the number of routine vaccinations and national health campaigns vaccinations increased through the 1990s and the 2000s, it has become increasingly clear that there are numerous interactions between different health interventions, such as vaccines and micronutrient supplementation, which are usually not taken into consideration in planning a vaccination programme. For example, the sequence of vaccinations, the time difference between non-live and live vaccines, and booster exposure to the same vaccines all had impact on the mortality levels. In addition, most vaccines have sex-differential NSEs (16). Since children were enrolled at 18 months of age, there were numerous possibilities for interactions with (a) national health intervention campaigns before enrolment; (b) participation in previous RCTs; and (c) national health campaigns after enrolment in the trial.”

Page 10: “trials of NSEs were planned more or less as vaccine efficacy studies. However, it has become increasingly clear that there are interactions with other routine vaccinations, vaccination campaigns, and other interventions affecting the immune system like vitamin A (16,19,20). Hence, in the present RCT we examined possible interactions with campaigns before enrolment, previous RCTs, and campaigns given after enrolment.”

-> The reader is left with the impression that a series of other factors influenced the trial and possibly invalidated the results. However, this was a randomized trial set-up which to a great extent compensates for any potential confounding effects, ie. other interventions that may have affected the outcome; but they will do so in both the intervention and comparator group.

Moreover, from table 1 of the preprint – Baseline characteristics – it would seem that the authors tend to put too much weight on multiple other factors as the trial appears to be well randomized.

Finally, if it in fact was true that this trial was influenced by other RCTs, health interventions, or campaigns, then this argument applies to all trial data originated from this research group in Guinea Bissau and consequently invalidates all of them.<br /> Again it is remarkable that the authors put down their own trial, spin the data and frame them into letting the reader believe that the trial is worth nothing at all. This is not in accordance with appropriate reporting standards as per CONSORT (7).

3.2. Spinning the facts around the succession of vaccines<br /> p.3 “high-titre-measles-vaccine (HTMV) was protective against measles infection, but surprisingly, it was associated with higher female mortality, when tested against STMV (5,6). Hence, NSEs could be beneficial or deleterious and they were often sex-differential.

References 5 and 6 are self-citations and based on post hoc re-analyses. The hypothesis that the DTP – following HTMV induced higher mortality remain highly speculative and never replicated. A more likely explanation would be that the HTMV was dosed too high resulting in measles infections, attenuated but still, which unfortunately in some cases increased the subsequent risk of mortality. This is notably a specific effect of the vaccine. However, as the authors advocate that the live (attenuated) vaccines are inferring beneficial effects and the non-live vaccines infer detrimental effects, a post-hoc narrative was constructed on the succession of vaccines having relevance. Importantly, this current preprint where the DTP vaccine is given alongside or not a live attenuated vaccine does not support this highly speculative hypothesis. On the contrary: if anything the results pointed towards DTP increasing child survival.

1. OVERALL REFLECTIONS ON ETHICS

4.1. Troubling lack of ethical standards and compliance

p. 7 it is stated that the study was explained to mothers in the following way:

“...though DTP is highly protective against whooping cough, it can occasionally give adverse reactions or limit the effect of measles vaccine….”

This speculative hypothesis seems to be introduced in the study participant / guardian information material, although this was never defined as a research question in the protocol.

Moreover, the protocol states:

“Hypothesis: Not providing DTP together with or after MV is associated with a 35 % reduction in overall mortality and 23% reduction in hospitalizations.

Taking one step back – and reflecting just for a minute – it appears to be the wildest research question ever. How did the Ethics Committee and the relevant authorities allow for this largescale trial to be conducted in the first place? What could possibly justify a RCT of this magnitude based on an outrageous research question like the one that was raised in the protocol: A 35% reduction in mortality is expected from omission of a single shot of vaccine?

4.2. Underpowered or not<br /> The preprint states that the trial was “highly underpowered,” although 109% of the planned study population was enrolled. There seems to be a large contrast between how this trial and a recently reported trial (8) are interpreted based on whether there was a significant finding or not. These discrepancies indeed appear as tendentious framing.

A direct comparison of these two large RCTs conducted by the same research group – with vast discrepancies in the results (enrolment and conduct) as well as interpretation is available at this link: https://www.linkedin.com/pulse/review-preprint-reports-dtp-trial-nct00244673-charlotte-str%25C3%25B8m-awgtf/ <br /> 4.3. Self-citation rate of 95%<br /> Nineteen of 20 references include members of the same author group – and are thus self-citations. This may reflect a general lack outside this group of scientific support to the NSE hypothesis and / or selective citation which is considered to be questionable research practice (6). A rule of thumb is that a self-citation rate above 15% raises suspicion of selective citation.

4.4. Reflections on the “Postscript” of the preprint<br /> It is truly a good thing that these results have finally come to light. The study subjects, their families, and the scientific community have been waiting for these data to be published.

The preprint is concluded by a lengthy postscript explaining the unusual long delay (14 years) in publishing the results from this trial.

"Postscript. We apologise for the late reporting. The implementation of the trial went quite different from the scheduled plans. In this older age group, more children than expected were registered by an ID and address that could not be followed. Funding was lacking for the PhD student to complete the data cleaning and analysis. Before funding could be obtained, the Guinean field supervisor had died which made it difficult to resolve some inconsistencies in data. The senior authors had too many other commitments. Finally, from 2020, the COVID-19 pandemic changed all priorities"<br /> These explanations may very well be seen as a result of hypocrisy, as members of this group of authors have published numerous papers – including reporting of several clinical trials during the past 14 years. Moreover during this delay it has been argued by members of the author group that an RCT with the exact same research hypothesis should be conducted (10):

“Almost 4 years after WHO reviewed the evidence for NSEs and recommended further research, IVIR-AC has now submitted for public comments two protocols of RCTs to measure the NSE impact of BCG and MV on child mortality:<br /> a. A BCG trial will compare mortality between 0 and 14 weeks of age for children randomized to BCG-at birth plus routine vaccines at 6–14 weeks of age vs. placebo at birth and routine vaccines at 6–14 weeks, with BCG at 14 weeks of age.<br /> b. An MV trial will compare mortality between 14 weeks and 2 years of age for children randomized to an additional dose of MV co-administered with DTP3 vs. placebo co-administered with DTP3.”<br /> According to http://clinicaltrial.gov the study hypothesis of NCT00244673.<br /> “DTP3/4+OPV+MV versus OPV+MV or DTP4+OPV4 versus OPV4”<br /> And even worse – it was claimed in the same publication Expert Review of Vaccines, Vol 17, 2018 – Issue 5 (10) that: "Science is also about accounting for all data. ... it has not been possible to conduct RCTs of DTP in high-mortality areas."<br /> There has evidently been a complete lack of willingness from the research group behind this trial to report on this null finding study that rejected the research hypothesis and rejected the hypothesis that the DTP vaccine has detrimental NSE. Such selection bias in reporting trial results on mortality is scientifically troubling and ethically both irresponsible and unacceptable.

References:

1. Agergaard JN, S.; Benn, C.S.; Aaby, P. Randomised trial of not providing booster diphtheria-tetanus-pertussis (DTP) vaccination after measles vaccination and child survival: A failed trial. In: Bandim Health Project IN, Apartado 861, Bissau, Guinea-Bissau; Department of Infectious Diseases, Aarhus University Hospital, Denmark; Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark/Odense University Hospital, Denmark; Danish Institute for Advanced Study (DIAS), University of Southern Denmark, Denmark, editor. 2025.

2. Agergaard J, Nante E, Poulstrup G, Nielsen J, Flanagan KL, Ostergaard L, et al. Diphtheria-tetanus-pertussis vaccine administered simultaneously with measles vaccine is associated with increased morbidity and poor growth in girls. A randomised trial from Guinea-Bissau. Vaccine. 2011;29(3):487-500.

3. Mogensen SW, Andersen A, Rodrigues A, Benn CS, Aaby P. The Introduction of Diphtheria-Tetanus-Pertussis and Oral Polio Vaccine Among Young Infants in an Urban African Community: A Natural Experiment. EBioMedicine. 2017;17:192-8.

4. Aaby P, Mogensen SW, Rodrigues A, Benn CS. Evidence of Increase in Mortality After the Introduction of Diphtheria-Tetanus-Pertussis Vaccine to Children Aged 6-35 Months in Guinea-Bissau: A Time for Reflection? Front Public Health. 2018;6:79.

5. Sørensen MK, Schaltz-Buchholzer F, Jensen AM, Nielsen S, Monteiro I, Aaby P, et al. Retesting the hypothesis that early Diphtheria-Tetanus-Pertussis vaccination increases female mortality: An observational study within a randomised trial. Vaccine. 2022;40(11):1606-16.

6. Bouter LM, Tijdink J, Axelsen N, Martinson BC, Ter Riet G. Ranking major and minor research misbehaviors: results from a survey among participants of four World Conferences on Research Integrity. Res Integr Peer Rev. 2016;1:17.

7. Hopewell S, Chan AW, Collins GS, Hrobjartsson A, Moher D, Schulz KF, et al. CONSORT 2025 explanation and elaboration: updated guideline for reporting randomised trials. BMJ. 2025;389:e081124.

8. Thysen SM, da Silva Borges I, Martins J, Stjernholm AD, Hansen JS, da Silva LMV, et al. Can earlier BCG-Japan and OPV vaccination reduce early infant mortality? A cluster-randomised trial in Guinea-Bissau. BMJ Glob Health. 2024;9(2).

9. Benn CS. Non-specific effects of vaccines: The status and the future. Vaccine. 2025;51:126884.

10. Benn CS, Fisker AB, Rieckmann A, Jensen AKG, Aaby P. How to evaluate potential non-specific effects of vaccines: the quest for randomized trials or time for triangulation? Expert Rev Vaccines. 2018;17(5):411-20.

On 2022-05-10 01:01:58, user Joe Max wrote:

Dear Paglino et al<br /> very nice study but the phrase "mortality disadvantage" is totally opaque to the non specialist (like me) I have no idea what this phrase means; surely you can do better !!

On 2021-07-11 12:09:52, user Radical Rooster wrote:

The article fails the first test of objectivity: SELF COLLECTED SAMPLES. Scientific research must be rigorous, procedures cannot vary from one person to another. Sampling must be done by only a select group of samplers. In this paper, there were 3,975 samplers.

On 2021-07-28 14:18:10, user H. wrote:

5,372 were excluded from study due to infection how many had any vaccine? 795 not considered vaccinated how many had vaccine injection? These are important questions.

On 2020-08-13 12:21:29, user Justin Cotney wrote:

These Cq values are at the very unreliable end of the instrument's detection range. Most biologists and in my own lab do not trust Cq values greater than 35. The instrument will usually report a number even in negative controls as was seen in their table. Performing a melt curve analysis after the PCR reveals if it is the product you were expecting or spurious amplification. Please show qpcr traces and melt curves.

On 2021-02-11 03:05:16, user Another Concerned Resident wrote:

Interesting study! Where can we find the supplementary materials? I'd like to check the ITT Table 1 because the PP Table 1 shows significant baseline differences.

A few questions:<br /> - Could you explain why you did not opt for placebo control and double blind?<br /> - What were the serology results performed at day 28?<br /> - You mention "COVID-19 infection occurred in 94% measured by RT-PCR". How were the extra 6% diagnosed?<br /> - Do you have any data on adverse events?<br /> - For the primary outcome: do you have any information on the reasons for admission?

Thanks

On 2023-11-03 16:41:46, user Dr. Hans-Joachim Kremer wrote:

It is not well described, what exatly is control. The estimates in Figure 1 are not comprehensible given the few details provided. <br /> Fig 1: It is written that Pfizer bivalent vs. Moderna bivalent is shown, however, the text suggests that Pfizer bivalent was compared with its own contol (before vaccination). What is true? If in fact you compared them to their own control: Where are respective details?<br /> It appears that in that Figure the "all" in the first row has a different meaning from the "all" in the third row. Note that the "16" of the first row, denoted as "all", is repeated in the fifth row, but denoted as "new".<br /> Anyhow, the "new" is not explained in the text and the "all" might have a meaning different from common understanding, as it appears that it stands for "after matching", so not really "all".

On 2023-12-07 15:20:52, user Alex Liber wrote:

This article has now been published: Liber AC, Faraji M, Ranganathan R, Friedman AS. How Complete Are Tobacco Sales Data? Assessing The Comprehensiveness Of US Tobacco Product Retail Sales Data Through Comparisons To Excise Tax Collections. Nicotine Tob Res. 2023 Nov 2:ntad214. doi: 10.1093/ntr/ntad214. Epub ahead of print. PMID: 37933997.

On 2021-01-29 18:28:35, user hlritter wrote:

The stated 51% reduction in daily incidence reflects only that half as many cases occurred in the second 12 days as in the first 12. But that does not take into account the fact that the curves don't begin to diverge until 6 days into the second 12-day interval. What's important is the improvement in incidence that occurs after immunity develops, not after the halfway point to some arbitrary date. It appears that only about 1/6 as many new cases occurred in the 6 days after the onset of relative immunity at Day 6 as occurred in any 6-day interval prior to this. This supports an efficacy in the range of 80%-85%, not 51%.

On 2021-09-20 23:38:51, user BaboliDaboli wrote:

The study states: "Symptoms for all analyses were recorded in the central database within 5 days of the positive RT-PCR test for 90% of the patients, and included chiefly fever, cough, breathing difficulties, diarrhea, loss of taste or smell, myalgia, weakness, headache and sore throat." I understand this as follows: 90% of recorded symptomatic COVID-19 cases in the study were first recorded as positive on RT-PCR test. That would mean that any correlation between recorded number of positive RT-PCR tests, recorded symptomatic COVID-19 outcomes, and recorded COVID-19 related hospitalization outcomes may stem from the fact that positive RT-PCR test was a prerequisite for any other outcome to be recorded at all. As there were no fatal outcomes recorded, most hospitalizations recorded in the study might have been due to mild symptoms and a previous positive RT-PCR test (study fails to present the breakdown of hospitalizations by disease severity or duration of hospitalization). An earlier study of the link between hospital load and increased COVID-19 mortality in Israel (Rossman, H., Meir, T., Somer, J. et al. Hospital load and increased COVID-19 related mortality in Israel. Nat Commun 12, 1904 (2021). https://doi.org/10.1038/s41467-021-22214-z) found that between July 15th 2020, and January 1st 2021, on average, almost 60% of people were hospitalized while presenting mild initial clinical state. So, if most breakthrough infections or re-infections in the study never progressed past the mild clinical state, and if such patients wouldn't even be considered for hospitalization in Israel without a positive RT-PCR test, it is quite possible that all study outcomes depend directly on people taking a RT-PCR test and testing positive. While it may be difficult to assess and account for the difference between vaccinated and previously recovered people in terms of their inclination towards taking the test in case of mild or non-existent symptoms, any possible bias in terms of testing policies in Israel should be addressed and accounted for in the study. An example of such potential bias can be found on the Israel Ministry of Health "Testing for COVID-19" webpage (https://www.gov.il/en/departments/general/corona-tests) which states: "As a general rule, save for few exceptional cases, it is not necessary for confirmed patients or recovered patients to take a swab test for coronavirus, unless there is clinical suspicion for repeated infection with the virus." As clinical suspicion depends on severity and combination of symptoms typical for COVID-19, and as the set of symptoms related to delta variant seems to differ slightly from the set of symptoms related to previous variants, some or maybe even many reinfected people never got tested by RT-PCR as they had no symptoms or had only mild symptoms that never progressed beyond that. If that were the case the number of reinfections and related outcomes might be significantly underestimated in this study.

On 2021-09-13 04:36:00, user Steven D. Keirstead wrote:

Your second number point is completely false. The RT-PCR Test for COVID-19 does not generate false positives from influenzas. It cannot amplify cDNA from the RNA of anything but SARS-CoV-2 virus. People misread the guidance from the CDC about discontinuation of the CDC reagents for the PCR test in favor of commercially produced test reagents and kits, which are identical to the CDC formulation with respect to the DNA primers used. The point the CDC made was that their kits were part of the diagnostic criteria to differentiate COVID-19 from influenza or other respiratory diseases, and people misunderstood that. https://www.reuters.com/art...

On 2021-03-20 04:41:11, user Wael wrote:

This work is immense. I appreciate the fact that the research devised 29 objective points to measure the level of Hesitancy, way to go. The methodology is really robust. I know that because I already have two publications using reliability models. In addition, the figures are clear.

On 2023-01-16 01:47:52, user Brian Piper wrote:

This is a timely review on an important topic!

In evaluating the safety of the relaxation of take-homes, it might be helpful to consider that “The number of clients receiving methadone increased from 306,440 in 2011 to 408,550 in 2019 and then decreased to 311,531 in 2020” [1]. This reduction from 2019 to 2020 of 97,019 patients is a 23.7% decline!<br /> The increase in the number of overdoses involving methadone may only appear equivalent to the increase in all opioid overdoses when one does not take this factor (i.e. using the population size and not the number of methadone patients as the more appropriate denominator) into account.

The authors also are encouraged revisit the important policy research in England and Scotland which identified sizable declines in methadone overdoses following implementation of supervised administration [2].

Citations

1. National Survey of Substance Abuse Treatment Services (N-SSATS): 2020 Data on Substance Abuse Treatment Facilities. Table 3.2.

2. Strang et al. Impact of supervision of methadone consumption on deaths related to methadone overdose (1993-2008): analyses using OD4 index in England and Scotland. BMJ 2010;341:c4851.

On 2020-06-04 17:10:24, user Mandy Lyons wrote:

"only 37.4% of suspected SARS-CoV-2 patients seroconverted"<br /> 1) What are the criteria for suspected SARS-CoV-2 patients?

2) Do these suspected cases have SARS-CoV-2, or do they have an infection which mimics SARS-CoV-2?<br /> 3) Is the test testing for the test? I.e. is there something functionally different in the infection causing presumed cases which, if it actually is SARS-CoV-2, would cause the antibody test to be inaccurate?<br /> 4) Is there another illness circulating which mimics SARS-CoV-2 which has heretofore not been identified?<br /> 5) Is there any follow-up or investigation on these negative antibody cases in both the confirmed and suspected cases?

On 2025-04-09 10:34:28, user M. Key wrote:

As someone who has experienced this, I am so grateful this research is being done.

I would like to put forward that, in some cases, what is actually happening is very long Epstein Barr. That is, every exposure reactivates Epstein Barr. Symptoms peak a few weeks after, then slowly resolve after a matter of many months, leaving more residual damage each time. This means that while the experience is chronic, it also makes it possible to trace it directly to certain events like testing positive for covid or getting a booster shot.

As someone who is vehemently pro-vax, I had been getting all the boosters.

If, for some people, this is an extended expression of both covid and EBV, and EBV is also known to create a host of other autoimmune conditions, then it seems like focusing on EBV is important. From the patient end, that seems a bit like a black hole; it doesn't seem like there's an established diagnostic or treatment pathway, so it's ignored. So I hope this focus continues.

On 2020-05-11 09:18:27, user David Sbabo wrote:

Russia and Ukraine in the HCQ group?

Their third death occured in March in both countries. HCQ was autorised in mid April in both countries Unless they can go back in time, HCQ cannot have any influence here.

So the main result of this study is null and void.

On 2025-03-07 14:55:26, user Fatima wrote:

I am so shocked that even a preprint could be published without any evidence-based material. How dare you underestimate one of the most influential, trained medical staff of the Middle East region such as Iran so naive to restrict the import of foreign vaccines into our country. Meanwhile, our honored scientists were preparing Iranian vaccines with efficacy and safety from the very beginning.<br /> It is against humanity to forget our successful safe vaccines Noora and Barekat all of them are Iranian.<br /> Let's shed light on the truth

On 2020-02-12 22:27:46, user Dudley Poole wrote:

Anybody bother to figure out the higher "susceptibility" in males relative to their over representation in the Chinese population?

On 2020-05-03 19:00:29, user John Goodrich wrote:

So the WP has now written about the data from this Yale group. Where’s the report of the study, with the actual data?

On 2021-08-02 15:23:29, user Larry Lewyn wrote:

What does ct stand for please?

On 2020-04-18 20:32:07, user BaNe™ Machine wrote:

Does it matter that studies are finding antibodies in 85 times more people than reported being sick? How does this affect the models? If the spread rate is actually 85 times higher? Doesn't that make this nonsense? Thanks, please clarify. Studies out of Stanford Univ.

On 2020-04-01 22:04:32, user Mr. Andrew wrote:

Singapore, Taiwan, Hong kong are litterally next to China and have only double digit death rates, all added, in total. WHY? All vaccinate their kids for BCG versus Tuberculosis. It's not a coincidence, all other countries do not vaccinate for it. Other BCG Vaccinating countries: Romania, Malaysia, Thailand..

check this map bellow (in the link) of countries which never had BCG. In entire Europe, Italy is the only one which never had BCG vaccination. Thus, they have a huge deathrate.

https://www.researchgate.ne...

This is further proved by all countries with BCG at birth. Check out all countries and how bad they are doing with covid 19 by looking at their death rate and serious critical numbers, at the official WHO numbers: https://www.worldometers.in...

Till now all countries which have BCG at birth have extremely low death rate and people in serious critical condition, but huge infection rate (thus small percentage). Singapore, Taiwan Hong Kong were infected way back before Italy was infected.

=

Lets tell people about BCG and pressure more research on this, and if it actually is helpful give every other country which did not get it at birth: a shot. It might be a cure, I am predicting but the data does not lie.It provides viral immunity although its meant for bacteria. As your lungs are stronger. The data shows something, and look at all the countries death rate and serious critical numbers versus infected.

They are soo exceptionally good compared to all others like x30 times better. Would like your help to spread the word of BCG and more research to be done. So countries like Italy which never where vaccinated would get a shot. (the U.S is next, as they never vaccinated for BCG)

On 2025-02-05 20:08:07, user Daniel Corcos wrote:

Gotzsche and Jorgensen claim to have found a high level of overdiagnosis after mammography screening. However, the method they use does not allow them to distinguish between cancers related to overdiagnosis and those caused by X-rays. Yet, when measuring the delay in the appearance of excess cancers, it becomes clear that, in addition to the excess corresponding to the lead time due to detection, there is a significant excess of delayed-onset cancers, which are therefore caused by X-rays ( https://www.biorxiv.org/content/10.1101/238527v1.full ; Corcos D & Bleyer, NEJM, 2020). These cancers explain the failure of screening at decreasing breast cancer mortality observed at 13 years by the authors.

On 2025-02-10 12:39:18, user MINGXIN LIU wrote:

This preprint has been published in International Journal of Medical Informatics and can be accessed at: " https://doi.org/10.1016/j.ijmedinf.2024.105673 ."

The title of the published version has been changed to "Evaluating the Effectiveness of advanced large language models in medical Knowledge: A Comparative study using Japanese national medical examination". Readers are encouraged to refer to the published version for the final peer-reviewed content.

On 2020-05-13 14:21:49, user Sinai Immunol Review Project wrote:

Main Findings: <br /> Given the urgent need for diagnostic testing for COVID-19, this study uses enzyme-linked immunoabsorbent assay (ELISA) to measure serum antibody levels against recombinant spike protein ectodomain as well as its receptor binding domain (RBD) to angiotensin-converting enzyme (ACE2). Twenty RT-PCR confirmed COVID-19 patients as well as 99 healthy donors were tested for IgG titers in their serum. Antibodies to spike protein ectodomain were detected in 17 out of 20 patients, of which 5 showed borderline levels. 15 out of 20 patients tested positive for antibodies against spike RBD, of which 7 indicated borderline levels. These findings suggest that while majority of COVID-19 patients develop antibodies against the RBD, some patient responses may target other epitopes of the spike protein. Furthermore, they show that circulating antibody levels (ie: positive vs borderline) do not correlate with clinical severity or recovery from COVID-19. Strikingly, 1 patient who recovered did not have detectable IgG antibodies against RBD, suggesting a potential role of cellular immunity in the clinical resolution of COVID-19. In addition, they report that 4 out of 10 healthy donor serum collected since January 2020 tested positive. This indicates that apparently healthy individuals may be asymptomatic carriers, which underscores the importance of developing effective methods for community wide testing.

Limitations: <br /> The authors cite a study in their introduction that demonstrates minimal cross reactivity of antibodies between SARS-CoV and SARS-CoV-2 patients suggesting a specific antibody response for each disease. However, their study showed that five out of 89 serum samples collected from healthy donors between 2017 to 2019 tested positive for antibodies against spike protein ectodomain, and acknowledge a possible cross reactivity from prior exposure to other strains of coronavirus. This result also stands in contrast with other recent studies*. Understanding whether or not there is indeed such cross reactivity would be important for interpreting their results and designing vaccines against this specific virus. Furthermore, their thresholds for determining positivity versus borderline antibody levels are arbitrary and can significantly influence the outcome of their assay. It will be critical to obtain a larger cohort to further validate the robustness of their thresholds for determining circulating antibody levels.

Significance: <br /> This study establishes a straightforward assay in testing for circulating antibodies against spike protein in the serum of COVID-19 patients. This is important not only for surveying the population for people with immunity, but also improves sensitivity for diagnosis when combined with RT-PCR. In addition, their finding of a patient who recovered without detectable antibodies against spike protein RBD provides important insights to designing therapies for COVID-19.

Reviewed by Joel Kim as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai.

References:<br /> *Amanat, F., et al. A serological assay to detect SARS-CoV_2 seroconversion in humans. medRxiv preprint (2020)

On 2023-08-28 18:17:04, user Yiran Wang wrote:

This paper has been modified and published in the Journal of Nuclear Medicine. <br /> DOI: https://doi.org/10.2967/jnu... <br /> https://jnm.snmjournals.org...

On 2020-05-11 20:53:16, user Erik Hansson wrote:

Thank you for your work, it is valuable to consider that that people have different social activity levels, but I am concerned that your approach miss two important aspects which will underestimate the herd immunity threshold/make it less valid as an indicator of the risk of new severe epidemic flares:

1. Social distancing recommendations from Swedish authorities likely have different effects on levels of social activity between social strata. R is probably more flexible downwards in more affluent social classes leading to different seroprevalence in different strata when the global disease-induced herd immunity threshold is reached.
2. Post-social distancing (i.e. after achieving disease-induced herd immunity threshold) social interaction will happen primarily within social strata (i.e. within seroprevalence strata).

Lower social classes may be less able to achieve a low level of social activity due to household crowding, dependence on public transportation and inability to work from home due to having manual work. This may lead to higher disease transmission in lower than higher social classes. Add to this the situation in elderly care in which the absence of PPE has probably led to quite intense transmission both from and to workers, who are strongly concentrated to lower social classes in Stockholm.

Outcome data is scarce but there seems to be empirical evidence of such a social gradient in covid-19 transmission both in hospitalized cases and very limited seroprevalence studies (contact Björn Olsen in Uppsala for more details or read media reports from last week - their study found 0% seroprevalence at Östermalm (~Knigthsbridge) in the end of April, n=?). Information from other major cities tell a similar story of a social gradient.

Under "normal" circumstances persons from lower social classes may not necessarily have higher levels of social activity than persons from the more affluent classes. I am concerned it may rather be the opposite as people from higher social classes may more likely engage in several activities less accessible to persons from lower classes, activities that do not happen in a semi-quarantine setting, such as culture and sports events, parties, eating out, bars, office work and meetings, conferences, university education, etc, but that are expected to be possible to do in a society having reached herd immunity.

Furthermore, due to prevailing segregation by class and ethnicity such post-social-distancing activities will likely primarily be done together with other persons likewise having been able to limit their activities during the first phase of the epidemic. There are thus conditions that allow rapid disease transmission within more affluent social strata if these go back to business as usual. It may even be argued that estimating a herd immunity threshold as an average percentage within a strongly segregated city is not especially meaningful. If there are large enough pools of connected susceptible individuals there is still a possibility of epidemics that overwhelm the healthcare system.

Another concern, which is partly related to the present manuscript is the use of quite uncertain and potentially inflated modeled estimates to make predictions of when Stockholm will reach the disease-induced herd immunity threshold, in June 2020, less than 3 weeks from now. This model estimated 26% had been infected by May 1. A critique of this model estimated 5-10% (https://twitter.com/AdamJKu... "https://twitter.com/AdamJKucharski/status/1254084771535376391)"), and the only (to my knowledge) somewhat representative seroprevalence study found 7.5% (Björn Olsen) at that time. Two separate methods that concur so well seems more credible than one modeled estimate.

The combination of estimating an artificially low herd immunity threshold and using potentially exaggerated cumulative infected proportion risk declaring “all-clear” in Stockholm much prematurely.

Erik Hansson, <br /> MD, MSc Epidemiology

On 2020-04-20 17:37:29, user Philip Davies wrote:

The low dose arm of this study is worth following.

The big problem for this study is comparison. It really has not defined the control population at all. The Italian and Chinese references are entirely different. Even the 2 Chinese populations referenced had massively different outcomes because the populations examined were different.

The Italian mortality rate was actually similar to the overall study average here (but much higher than the low dose arm). The Chinese study involved all patients admitted to the two hospitals ... that included a majority of patients with moderate ("ordinary" as the Chinese class it) disease severity. The patients in this Brazilian study were regarded as severe or critical ... such patients (looking at worldwide stats) would attract a mortality of 30-40% plus.

This is the most important factor. Do not compare apples with pears. So far this study points the "swingometer" in favor of benefit versus harm for the use of HQN in patients with advanced disease.

Once again however, we are looking at the potential impact of an orally administered drug to patients with advanced disease. That's a big ask.

For CQ and HCQ the most interesting results will likely come from studies looking at prophylaxis and early treatment (using safe doses, not silly high doses with added drugs that also lengthen QT). We can't yet guess how they will pan out.

Dr Philip Davies<br /> GP<br /> Aldershot Centre For Health, UK<br /> http://thevirus.uk

On 2020-04-09 03:16:28, user Knut M. Wittkowski wrote:

You state that "the central government of the People's Republic of China imposed a lockdown and social distancing measures in this city and surrounding areas starting on January 23 2020", without reference. On that date, travel restrictions were imposed, preventing citizens of Wuhan to leave by train (starting in the morning) or car (starting in the afternoon). Do you have primary references indicating when which social distancing measures were imposed?

On 2021-08-30 15:16:42, user Jeff Brender wrote:

For those wondering about the decrease in PhD respondents from the last version<br /> From the Methods section<br /> "To be included in the analysis sample, participants had to complete the questions on vaccine uptake and intent, and report a gender other than “prefer to self-describe.”. This exclusion was made after discovering that the majority of fill-in responses for self-described gender were political/discriminatory statements or otherwise questionable answers (e.g. Apache Helicopter or Unicorn), and that as a group, those who selected self-described gender (<1% of the sample) had a high frequency of uncommon responses (e.g., Hispanic ethnicity [41.4%], the oldest age group [23.2% >=75 years] and highest education level [28.1% Doctorate]), suggesting the survey was not completed in good faith. "

On 2022-01-28 20:26:50, user Joshua Polgar wrote:

Do you think there would be a similar relationship regarding homicidal intent?

On 2022-01-18 15:16:11, user Dena Schanzer wrote:

Dear Authors:

I suggest looking at the historic trends in the rate ratio, or the relative risk (RR) of testing positive for COVID-19 for vaccinated compared to unvaccinated Ontario populations. The crude rate ratio can be calculated daily for cases, hospital and ICU occupancy from population level data provided by Ontario Public Health (https://data.ontario.ca/en/dataset/covid-19-vaccine-data-in-ontario ). The crude RR dropped below 1 by the end of December 2021 and has since steadied around 0.8 since Ontario closed high risk venues such as bars and restaurants. Hence, as this study suggests, it seems quite clear that the vaccinated population as a whole is currently at higher risk of infection than those who are unvaccinated. And, it is not surprising that a VE calculated as 1-OR, even in the test-negative control design would eventually become negative as well.

The steady decline in the crude RR can likely be explained by the lack of mixing between the vaccinated and unvaccinated populations (accentuated by the vaccine passport) and the higher transmission rate in the vaccinated group. If the effective reproductive number (Re) is higher in the vaccinated group, the RR should continue to decline even if the VE is held constant. It would be very helpful get your infectious disease colleagues (from the Ontario Science Table) to run a few infectious disease model simulations. I suspect that differences in Re were responsible for some of the downward drift in the RR in November when delta dominated. I’d suggest including the control group in the modelling exercise as well. I doubt that the Re gap is the same in the ‘other respiratory virus’ group. If it is (for example if you use the double vaccinated as the control for triple vaccinated), I would expect your test-negative control design would effectively control for biases introduced by the drift in exposure risks.

This study raises interesting questions. In the end, we will have a better understanding of how to monitor epidemics in near real-time. Perhaps monitoring the difference in the week-over-week percentage change in the vaccinated and unvaccinated groups could have provided an early warning indicator that either VE has dropped or contact rates have increased in the vaccinated group to a level where the vaccinated start driving the epidemic growth. Simulation studies should provide valuable insight on how to interpret this data!

Dena Schanzer

On 2021-10-10 05:22:31, user kdrl nakle wrote:

I'll keep this paper in mind, it really looks realistic but so far most of COVID projections turned out completely wrong.