On 2022-12-15 10:49:12, user Author wrote:
We would like to reply to a comment entitled “Japan preprint on myocarditis used inadequate methods to suggest COVID-19 vaccines cause more myocarditis deaths”: a review by Health Feedback (Editor: Ms. Flora Teoh). <br />
https://healthfeedback.org/...
We thank them for commenting on our paper. We understand their main points of criticism were three summarised as followings:
1. Comparison of pre-pandemic and post-pandemic rates of myocarditis death (their 2nd point)
2. No examination of history of myocarditis death and ignored COVID-19 as the cause (their 1st point)
3. Sample size was too small to discuss causality
1. comparison of pre-pandemic and post-pandemic rates of myocarditis death (their 2nd point)
Their 2nd point is based on the fundamental misunderstanding on the methods of our study. They erroneously stated "The authors' association of change in the risk of myocarditis death associated with COVID-19 vaccines was based on comparing pre-pandemic and post-pandemic rates of myocarditis death". <br />
We compared myocarditis mortality in the SARS-CoV-2 VACCINATED population with that of the 2017-2019 (pre-pandemic period: reference) population; we did NOT compare myocarditis mortality between POST-PANDEMIC and pre-pandemic periods.<br />
Because of the misunderstanding the fundamental methods of our study, the following criticism have no sense:<br />
“But this assumes that the only thing that changed between the two periods is the availability of the COVID-19 vaccines. It excludes, without justification, the possibility that COVID-19 itself could produce an increase in myocarditis deaths. No reason was given by the authors for excluding COVID-19 as a potential explanation, despite the fact that COVID-19 is a more likely explanation than COVID-19 vaccines for an increase.” “This is because we know—based on previous published studies—that COVID-19 is more likely to lead to cardiac complications than the vaccines [1,2]. Therefore, the alleged causal association rests on the assumption that only COVID-19 vaccines can explain the change in myocarditis mortality, which isn’t true.”<br />
However, we would like to comments on “COVID-19 is more likely to lead to cardiac complications than the vaccines” referring reports by Block et al [1], and Patone et al [2,3].<br />
It is important to consider following three points; vaccines are not given to dying persons and to persons with fever or other acute diseases. Hence vaccinated people are relatively healthier than the non-vaccinated (healthy vaccinee effect) [4]. Conversely, vulnerable persons (frail, suppressed immunity due to stress or sleep debt etc) are more likely to be infected with SARS-CoV-2 (vulnerability confounding bias: VCB) [5].
Patone et al. [1] stated in the discussion section as follows: “Of note, the estimated IRRs were consistently <1 in the pre-exposure period before vaccination. ---- This was expected because events are unlikely to happen shortly before vaccination (relatively healthy people are receiving the vaccine).” This is exactly the same as the healthy vaccinee effect [4] and it is the lowest at day 0 of vaccination [2]: for example, IRR of arrhythmia at day 0 of BNT162b2 vaccination was 0.33 (0.29 to 0.37) compared with 0.72(0.70 to 0.73) during -28 to -1 days before vaccination [2]. <br />
Paton et al [1] also discussed that the estimated IRRs were consistently >1 in the pre-risk period before a SARS-CoV-2–positive test. They thought that events are more likely to happen before a SARS-CoV-2–positive test (as a standard procedure, patients admitted to the hospital are tested for SARS-CoV-2). But they missed to discuss that IRRs on day 0 of vaccination are the most prominent (with 10 times more than that in the pre-risk period, because standard testing of SARS-CoV-2 is mostly done on the day of admission). Hence, constant IRR >1 during -28 to -1 days before vaccination may be another cause. It may be explained by the vulnerability confounding bias [5].<br />
We estimated the effect of vulnerable person’s susceptibility to infection (vulnerability confounding bias: VCB) from the pre-risk period (-28 to -1 days) of the SARS-CoV-2 test-positive group: 2.84 (1.89 to 4.28) for myocarditis and 4.82 (4.68 to 4.97) for arrhythmia. When applied these data for the index of VCB, VCB-adjusted IRRs are 3.44 (2.11 to 5.59) and 1.11 (1.07 to 1.16) which are similar to or less than the healthy vaccinee effect adjusted IRRs of myocarditis (3.97: 3.05 to 5.16) and arrythmia (2.70: 2.38 to 3.05) respectively [4].<br />
It is not possible to estimate the healthy-vaccinee effect and VCB directly from the report of Block et al [3], however, post-SARS-CoV-2 infection/post-vaccination myocarditis risk ratios may be less than 1.00 in almost half of those listed when above adjustments were applied.
2. No examination of history of myocarditis death and ignored COVID-19 as the cause (their 1st point)
This point is also derived from the fundamental misunderstanding on the methods of our study. We did NOT compare myocarditis mortality between POST-PANDEMIC and pre-pandemic periods BUT compared SARS-CoV-2 VACCINATED population for 28 DAYS after vaccination with pre-pandemic periods. <br />
Therefore, as a rule, deaths following SARS-CoV-2 infection were not included in this study. In fact, none had COVID-19 listed in the death cause column of cases included in this analysis.<br />
Moreover, in the MHWL list we referred; most deaths included brief medical history as well as the cause of death. We clearly stated that “these were myocarditis death cases reported by physicians as serious adverse reactions to the vaccine” in the Methods section.<br />
Furthermore, as we stated in the discussion section, myocarditis deaths in the 2017-2019 (reference) population were also based on a doctor's diagnosis, with no other medical history known. Mevorach et al [6] also analysed using the same methodology and already published as a peer reviewed paper.
3 Sample size is too small to discuss causality
This point is also derived from the fundamental misunderstanding on the methods of our study. We compared SARS-CoV-2 VACCINATED population for 28 DAYS after vaccination with pre-pandemic periods. Hence this sample size was enough to demonstrate increased myocarditis mortality rate ratio after vaccination.<br />
As we stated in the end of the discussion section and in supplemental Table S6, all of the Modified US Surgeon General criteria for causal were satisfied.
Sincerely,<br />
Watanabe and Hama.
References<br />
[1] Block JP, Boehmer TK, Forrest CB, et al. Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination - PCORnet, United States, January 2021-January 2022. MMWR Morb Mortal Wkly Rep 2022; 71:517-23. DOI: http://dx.doi.org/10.15585/...<br />
[2] Patone M, Mei XW, Handunnetthi L, et al. Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex. Circulation. 2022; 146(10):743-54. doi:10.1161/CIRCULATIONAHA.122.059970<br />
[3] Patone M, Mei XW, Handunnetthi L, et al. Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection. Nat Med. 2022; 28(2):410-22. doi:10.1038/s41591-021-01630-0<br />
[4] Hama R and Watanabe S. The risk of vaccination may be higher by considering “healthy vaccinee effect” Response to Husby et al: https://doi.org/10.1136/bmj... (Published 16 December 2021)<br />
Available at: https://www.bmj.com/content...<br />
(Accessed 30 November 2022)<br />
[5] Hama R and Watanabe S. Vulnerability confounding bias should be taken into account in assessing risk of post SARS-CoV-2 infection: an opposite concept of healthy-vaccinee effect (Under submission)<br />
[6] Mevorach D, Anis E, Cedar N, et al. Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel. N Engl J Med. 2021; 385(23):2140-49. doi:10.1056/NEJMoa2109730