Skip to main content
NCBI home page
PLOS One logoLink to PLOS One
. 2023 Sep 1;18(9):e0291090. doi: 10.1371/journal.pone.0291090

Impact of COVID-19 vaccination on mortality after acute myocardial infarction

Mohit D Gupta 1,*,#, Shekhar Kunal 2,#, Girish M P 1, Dixit Goyal 1, Rajeev Kumar Malhotra 3, Prashant Mishra 1, Mansavi Shukla 1, Aarti Gupta 1, Vanshika Kohli 1, Nitya Bundela 1, Vishal Batra 1, Ankit Bansal 1, Rakesh Yadav 4, Jamal Yusuf 1, Saibal Mukhopadhyay 1
Editor: Robert Jeenchen Chen5
PMCID: PMC10473468  PMID: 37656727

Abstract

Background

COVID-19 vaccines are highly immunogenic but cardiovascular effects of these vaccines have not been properly elucidated.

Objectives

To determine impact of COVID-19 vaccination on mortality following acute myocardial infarction (AMI).

Methods

This was a single center retrospective observation study among patients with AMI enrolled in the the North India ST-Elevation Myocardial Infarction (NORIN-STEMI) registry. In all the enrolled patients, data regarding patient’s vaccination status including details on type of vaccine, date of vaccination and adverse effects were obtained. All enrolled subjects were followed up for a period of six months. The primary outcome of the study was all-cause mortality both at one month and at six months of follow-up. Propensity-weighted score logistic regression model using inverse probability of treatment weighting was used to determine the impact of vaccination status on all-cause mortality.

Results

A total of 1578 subjects were enrolled in the study of whom 1086(68.8%) were vaccinated against COVID-19 while 492(31.2%) were unvaccinated. Analysis of the temporal trends of occurrence of AMI post vaccination did not show a specific clustering of AMI at any particular time. On 30-day follow-up, all-cause mortality occurred in 201(12.7%) patients with adjusted odds of mortality being significantly lower in vaccinated group (adjusted odds ratio[aOR]: 0.58, 95% CI: 0.47–0.71). Similarly, at six months of follow-up, vaccinated AMI group had lower odds of mortality(aOR: 0.54, 95% CI: 0.44 to 0.65) as compared to non-vaccinated group.

Conclusions

COVID-19 vaccines have shown to decrease all-cause mortality at 30 days and six months following AMI.

Introduction

The unprecedented emergence of COVID-19 pandemic saw accelerated development of treatment strategies including drugs and vaccines [1]. Most of the vaccines were developed in a shorter time frame however, still had high efficacy and safety. In India, “Emergency use authorization” was granted to two vaccines viz. COVISHIELD (Serum Institute of India Limited, India) and COVAXIN (Bharat Biotech Limited, India) [2]. The universal vaccination against COVID-19 in India began in January 2021 and within a span of 2 years, 2.2 billion doses of COVID-19 vaccine (COVISHIELD: 79.3%; COVAXIN: 16.5%) has been administered [3]. Several large-scale studies and clinical trials have established the efficacy and safety of COVID-19 vaccines. However, most of these studies and trials were conducted in ideal settings among homogenous and limited population groups far away from the real-world scenario [4]. The adverse effects (AEs) of COVID-19 vaccine have mostly been mild, transient and self-limiting. However, concerns have been raised regarding the cardiovascular adverse effects of these vaccines. Any side effect can have catastrophic effect especially in large densely populated countries such as India. Data from the COVID-19 vaccination trials reported that adverse cardiovascular effects were largely isolated with an incidence of <0.05% [5, 6]. However, recent real-world data have highlighted increasing frequency of cardiovascular AEs with COVID-19 vaccines. A majority of these AEs were cases of myocarditis caused by mRNA-based vaccines [7, 8]. With increasing concerns regarding cardiovascular AEs especially acute coronary syndrome (ACS), there is a greater hesitancy to get vaccinated thereby affecting vaccination rates and prolonging the COVID-19 pandemic. This is of greater concern especially with emergence of newer potent variants of SARS-CoV-2 which have been associated with greater reinfection rates and worse outcomes. Previous studies among patients with heart failure have shown that COVID-19 vaccination was associated with significant reduction in all-cause hospitalization rates and mortality [9]. However, data regarding occurrence and impact of acute myocardial infarction (AMI) following COVID-19 vaccination is sparse. We studied timeline of occurrence of AMI after COVID-19 vaccination and its impact on all-cause mortality in these patients.

Methods

This was a single center retrospective observational study conducted in the Department of Cardiology at a tertiary care medical center. All patients ≥18 years of age with ST-Elevation Myocardial Infarction (STEMI) who were registered in the North India ST-Elevation Myocardial Infarction (NORIN-STEMI) registry [10] and had consented to be a part of the study were enrolled from August 2021 up till August 2022. In all these patients, STEMI was diagnosed based on the European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force for the Fourth Universal Definition of Myocardial Infarction [11]. In all the enrolled patients following a written informed consent, baseline demographic data, risk factors and presenting symptoms were recorded in an electronic questionnaire. The details of the treatment given were also recorded. Data regarding the patient’s vaccination status against COVID-19 which included details on the type of vaccine, date of vaccination (first dose and second dose) and adverse effect following immunization (AEFI). Patients with non-ST-elevation myocardial infarction (NSTEMI), history of previous MI or coronary revascularization, congenital heart disease, previous structural heart disease, recent surgery, absence of vaccination details, unwilling for follow-up or non-consenting to be a part of the study were excluded. Subjects were labelled as vaccinated if they had received either one or both the doses of COVID-19 vaccine while unvaccinated population included those who had not received a single dose of the vaccine (Fig 1). In order to determine the temporal association between vaccination and occurrence of AMI, time-lines were drawn which included 0–30 days, 30–90 days, 90–150 days, 150–210 days, 210–270 days, 270–330 days and beyond.

Fig 1. Central figure highlighting the impact of vaccination on all-cause mortality in acute myocardial infarction (AMI) patients.

Fig 1

Open in a new tab

Abbreviations: NORIN-STEMI: North Indian ST-Segment Elevation Myocardial Infarction; STEMI: ST-Segment Elevation Myocardial Infarction; MACE: major adverse cardiac events; CAD: coronary artery disease; NSTEMI: non ST-Segment Elevation Myocardial Infarction.

Outcomes

The primary outcome of the study was major adverse cardiac events (MACE) in terms of all-cause mortality both at one month and at six months of follow-up. Outcome data were collected from the medical records and via telephonic interview.

Consent and ethical issues

A written informed consent was obtained from all the enrolled patients. The present study was approved by the institutional ethics committee [EC number: F.1/IEC/MAMC/ (85/04/2021/No 486)] and was conducted in accordance with the ethical principles as per the Declaration of Helsinki and are consistent with Good Clinical Practice and all local regulations.

Statistics

Continuous data was expressed as median and categorical data as proportions. Normality of distribution of continuous variables were assessed using the Kolmogorov-Smirnov test. Chi-square test was used for unweighted comparison. In order to account for differences in the baseline patients’ characteristics, a propensity-weighted score logistic model using the inverse probability of treatment weighting (IPTW) was used. The propensity score (PS) was determined using logistic regression with vaccination as the dependent variable and age, sex, diabetes, hypertension, and smoking as covariates. The vaccinated individuals were weighted with 1/PS and nonvaccinated patients with 1/(1-PS). The imbalance of covariates before and after IPTW was assessed with P-value and considered balanced if P<0.05. A two-sided P value of < 0.05 was considered to be statistically significant. SPSS version 24.0 (IBM Corp, Armonk, NY) and R-software was used for statistical analysis.

Results

A total of 1700 patients with AMI were initially screened of whom vaccination data was not available for 122 subjects and they were excluded from the study (Fig 1). Of the 1578 subjects enrolled in the study, a majority of them were males (1273;80.7%) with a median age of 55 years (IQR: 46–62 years). A total of 1086 patients (68.8%) were vaccinated against COVID-19 while 492 subjects (31.2%) had not received a single dose of COVID-19 vaccine and were labelled as unvaccinated. Among the vaccinated group, 1047 (96.4%) had received two doses of the vaccine while 39 (3.6%) had received only a single dose. Majority of them (1002 [92.3%]) had been vaccinated with COVISHIELD while 84 (7.7%) had received COVAXIN. The demographics and baseline characteristics in the vaccinated and unvaccinated group were comparable (Table 1). Analysis of the temporal trends of occurrence of AMI following vaccination did not show a specific clustering of AMI after the vaccination at any particular time. The numbers of events according to the timeline are shown in Fig 2. A total of 185 (11.7%) of STEMIs occurred within 90–150 days of vaccination while 175 (11.1%) occurred between 150–270 days. Only 28 (1.8%) of AMI cases occurred within first 30 days of COVID-19 vaccination.

Table 1. Baseline patients characteristics of vaccinated and unvaccinated AMI patients.

Variable Vaccinated (n = 1086) Unvaccinated (n = 492) P-value (Unweighted) P-value (Weighted)
Sex
Male 895(82.4%) 378(76.8%) 0.009 0.944
Female 191(17.6%) 114(23.2%)
Age, Median(IQR), yrs 55[46–62] 56[48–65] <0.001 0.939
18–39 yrs 112(40.3%) 33(6.7%)
40–64 yrs 760(70.0%) 325(66.1%)
≥65 yrs 214(19.7%) 134(27.2%)
Co-morbidities
Diabetes 233(21.5%) 114(23.2%) 0.446 0.924
Hypertension 347(32.0%) 156(31.7%) 0.923 0.992
COPD 35 (3.2%) 15 (3.0%) 0.854
CKD 03 (0.27%) 01 (0.20%) 0.789
Heart failure 30 (2.7%) 18 (3.6%) 0.336
Dyslipidaemia 42(3.9%) 24(4.9%) 0.353 0.961
Smoking 474(43.6%) 184(37.4%) 0.020 0.958
Physical Activity 484(44.6%) 217(44.1%) 0.864
Family History 261(24.0%) 120(21.4%) 0.878
Revascularization 52 (10.6%) 139 (12.1%) 0.208 0.894
Open in a new tab

Abbreviations: AMI: acute myocardial infarction; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; IQR: inter-quartile range; yrs: years

Fig 2. Histogram showing the timeline for distribution of AMI patients following COVID-19 vaccination.

Fig 2

Open in a new tab

Outcomes

(i) 30-day MACE

Of the 1578 patients with AMI, the 30-day all-cause mortality occurred in 201(12.7%) patients (S1 Table). Out of these, 116(57.7%) belonged to the vaccinated group while 85 (42.2%) were non-vaccinated. The adjusted odds of 30-day mortality was significantly lower in the vaccinated AMI population (adjusted odds ratio[aOR]: 0.58, 95% CI: 0.47–0.71) as compared to the non-vaccinated group. Male patients with AMI had a lower likelihood of 30-day mortality as compared to women (OR: 0.41; 95% CI:0.31–0.53). Contrarily, increasing age, diabetics and smokers had higher odds of 30-day mortality (Fig 3A). A lower risk of 30-day mortality in the vaccinated AMI patients was observed in all the sub-groups, albeit some of the factors did not reach statistical significance [Table 2].

Fig 3.

Fig 3

Open in a new tab

A: Forest plot showing the adjusted odds ratio for the factors for 30-days all-cause mortality using the propensity score weighting. B: Forest plot showing the adjusted odds ratio for all-cause mortality between 30-days and six months using the propensity score weighting. C: Forest plot showing the adjusted odds ratio for the factors all-cause mortality using the propensity score weighting at six months.

Table 2. Propensity score weighted logistic regression models for assessing odds ratio of vaccination on 30 days and 6 months mortality.
30-day mortality (n = 201) 6-Month Mortality(n = 276)
Variable Vaccinated (n = 116) Unvaccinated (n = 85) Adjusted Odds Ratio (95% CI) P-value Vaccinated (n = 148) Unvaccinated (n = 128) Adjusted Odds Ratio (95% CI) P-value
Overall* 116 85 0.58 [0.46–0.71] <0.001 148 128 0.54 [0.44–0.66] <0.001
Sub-group Analysis*
 Male 88 57 0.60 [0.49–0.79] <0.001 116 84 0.62 [0.50–0.78] <0.001
 Female 28 28 0.41 [0.25–0.66] 0.0003 32 44 0.30 [0.19–0.47] <0.001
Age*
 18–39 years 8 5 0.36 [0.14–0.82] 0.0198 10 6 0.49 [0.22–1.08] 0.080
 40–64 years 80 48 0.68 [0.52–0.88] 0.0039 101 73 0.64 [0.50–0.82] 0.0003
 ≥65 years 28 32 0.39 [0.25–0.61] <0.001 37 49 0.38 [0.26–0.56] <0.001
Diabetes
 Yes 38 31 0.48 [0.32–0.71] 0.0003 42 39 0.47 [0.31–0.71] 0.0004
 No 78 54 0.60 [0.47–0.78] 0.0001 106 89 0.54 [0.43–0.68] <0.001
Hypertension
 Yes 50 34 0.62 [0.44–0.87] 0.0007 60 51 0.62 [0.44–0.86] <0.001
 No 66 51 0.56 [0.42–0.74] <0.001 88 77 0.51 [0.40–0.65] <0.001
Hyperlipidaemia
 Yes 8 6 1.58 [0.58–4.53] 0.380 8 9 0.61 [0.22–1.69] 0.339
 No 108 79 0.56 [0.45–0.70] <0.001 140 119 0.54 [0.44–0.66] <0.001
Smoking
 Smoker 72 47 0.55 [0.41–0.75] 0.0002 83 61 0.54 [0.40–0.73] <0.001
 Non-smoker 44 38 0.57 [0.42–0.79] 0.0008 65 67 0.52 [0.40–0.69] <0.001
Physical Activity
 Yes 43 23 0.85 [0.59–1.22] 0.3789 65 41 0.64 [0.47–0.86] 0.004
 No 73 62 0.49 [0.37–0.64] <0.001 83 87 0.48 [0.37–0.63] <0.001
Family History
 Yes 27 20 0.54 [0.3–0.84] 0.007 37 26 0.82 [0.53–1.24] 0.345
 No 89 65 0.58 [0.45–0.74] <0.001 111 102 0.48 [0.38–0.60] <0.001
Open in a new tab

*Adjusted for age, sex, comorbidities, smoking, physical activity, and family history (in subgroup analysis respective variable was removed from the model)

(ii) MACE between 30-days and six months

During the period of 30 days to six months, 75 patients had all-cause mortality of whom 43.7% were vaccinated. The adjusted odds of mortality in vaccinated subjects were lower than in the non-vaccinated (aOR: 0.34[0.24–0.48]) [Fig 3B]. Apart from vaccination, increasing age was also significantly associated with higher mortality [S2 Table].

(iii) MACE within six months

Over a period of six months of follow-up, 276 (12.7%) died within six months of the admission to hospital, of whom 148(53.6%) were vaccinated with either dose while 128(46.4%) were non-vaccinated. The adjusted odds of mortality in the first six months were significantly lower in the vaccinated AMI group (aOR: 0.54, 95% CI: 0.44 to 0.65) as compared to the non-vaccinated group. Additionally, males patients with AMI had a lower likelihood of mortality (aOR: 0.45; 95% CI: 0.35–0.58) within six months as compared to females. On the other hand, increasing age, diabetes, hypertension, and smoking increased the odds of six months mortality (Fig 3C). A lower risk of six months mortality in vaccinated AMI patients was observed in all the sub-groups, albeit some of the factors did not reach statistical significance [Table 2].

Discussion

The present study retrospectively investigated the impact of vaccination on occurrence of AMI and all-cause mortality at 30 days and six months. Findings of our study showed that the 30-day and six months all-cause mortality risk was significantly lower in the vaccinated subjects as compared to the unvaccinated population. Additionally, a lack of temporal clustering of AMI cases following COVID-19 vaccination did not suggest a significant association between COVID-19 vaccination and occurrence of AMI. This study is the first to be conducted among a larger population of AMI patients which has shown COVID-19 vaccine to be not only safe but also have a protective effect in terms of reduction of all-cause mortality both on short term as well as at six months of follow-up.

COVID-19 infection has been associated with multiple CV events including acute coronary syndrome (ACS), myocarditis and heart failure [12]. CV effects of COVID-19 infection depends both on the disease severity as well as the presence of co-morbidities. The two COVID-19 vaccines used in India have been shown to generate high neutralizing antibody titres and stronger T-cell response [13]. Data regarding the protective effects of COVID-19 vaccine on CV system is largely limited to a small unpublished study [14]. It reported that COVID-19 vaccination was associated with decreased rates of hospital admission ACS patients undergoing percutaneous coronary intervention. The present study also showed significant reduction over and above the other risk factors in all-cause mortality in vaccinated AMI patients at 30 days and at six months of follow-up.

The exact mechanism regarding the beneficial effects of COVID-19 vaccination in reduction of MACE is unclear. A recent study among patients with heart failure demonstrated protective effects of COVID-19 vaccination in terms of significant reduction in all-cause mortality (HR 0.33; CI 0.23–0.48) on follow-up [9]. Viral infections such as influenza has been shown to increase the predisposition for CV events [15]. This has been attributed to a heightened systemic inflammatory response following infection leading to plaque rupture [15]. Previous studies based on the influenza vaccines have shown to reduce MACE in patients with ACS [16–18]. The proposed hypothesis regarding protective effect of influenza vaccine is the cross-reaction of the vaccine-induced antibodies with the bradykinin receptor thereby leading to increased nitric oxide production and vasodilation [19]. A similar analogy can be thought in terms of the COVID-19 vaccine however, greater research is needed to explore this aspect. Another plausible reason regarding the beneficial effects of COVID-19 vaccination in terms of reduction in all-cause mortality following AMI could be the “healthy user effect” [20]. Individuals who undergo COVID-19 vaccination can be thought of as “healthy users” who are inclined to adopt behaviors that promote their well-being, such as making dietary and lifestyle modifications, and adhering to medication regimens following AMI thereby leading to lower mortality as compared to unvaccinated individuals.

Additionally, vaccination against COVID-19 has been shown to reduce the risk of occurrence of AMI and stroke following COVID-19. Data from the Korean nationwide COVID-19 registry and the Korean National Health Insurance Service involving 231037 patients reported that the adjusted risk for both AMI (aHR: 0.48; 95% CI, 0.25–0.94) and ischemic stroke (aHR: 0.40; 95% CI, 0.26–0.63) following COVID-19 infection was significantly lower in fully vaccinated patients [21]. Similarly, data from the United States National COVID Cohort Collaborative reported that both full (aHR: 0.59; 95% CI: 0.55–0.63) and partial (aHR: 0.76; 95% CI: 0.65–0.89) vaccination against COVID-19 were associated with reduced risk of MACE [22].

COVID-19 vaccination was initially implicated in causing AMI without any definitive evidence. This was based on a few case reports [23–26] rather than any systematically conducted study. Few case reports and series did initially ascribe the role of COVID-19 vaccination to the occurrence of AMI [23–26]. Multiple mechanisms that were postulated included (a) vaccine induced thrombocytopenia [27], (b) Kounis syndrome as a part of allergic vasospasm to the components of COVID-19 vaccine [28], (c) myocarditis, (d) stress of obtaining a vaccine among elderly individuals with pre-existing health conditions resulting in demand-supply mismatch ischemia [29]. However, recent studies [30, 31] have failed to establish a definite association of AMI with COVID-19 vaccine. Post-mortem examination and histopathological evaluation of five sudden cardiac deaths following COVID-19 vaccination reported no definitive causal relationship with vaccine administration [30]. Similarly, in a nationwide study from France in individuals ≥75 years, there was no increase in the incidence of AMI 14 days following administration of each dose of the BNT162b2 (mRNA) vaccine [31]. The present study failed to show any temporal clustering of cases of AMI following COVID-19 vaccination.

Limitations

This was a single center retrospective study. This is a main limitation. The findings need to be validated in further larger studies from different ethnic groups. However, as evident by the high immunogenic response generated by these two vaccines shown in different populations across the country, it is likely that the vaccine will show a protective effect. In our study, only all-cause mortality was evaluated on follow-up which is also one of the limitations. All-cause mortality is a hard end point and we have tried to adjust all the possible confounders in our analysis. In this study during covid times, it was extremely challenging to collect data of all possible outcomes in a resource limited country like India.Thirdly, as with any other observational study, there is always a potential for residual confounding factors despite the use of propensity matching. Our results are based on the evaluation of two COVID-19 vaccines (COVISHIELD, COVAXIN), both of which were non-mRNA vaccines, being administered in India. Large scale studies involving different population group and vaccine types (both mRNA and non-mRNA vaccines) are required before the findings can be generalized to geographically diverse populations groups.

Conclusion

In a large, populous and resource limited country such as India, the two indigenous vaccines with good immunogenic response have shown to decrease the mortality at 30 days and 6 months after AMI.

Supporting information

S1 Table. Comparison of patients’ characteristics between 30 days outcome.

(DOCX)

Click here for additional data file. (14.6KB, docx)
S2 Table. Propensity score weighted logistic regression models for assessing the odds ratio of vaccination on mortality during one—six months of follow-up.

(DOCX)

Click here for additional data file. (15.1KB, docx)

Data Availability

Data cannot be shared publicly because of ethical reasons. The Data includes potentially identifiable /sensitive information on covid vaccination details of patients that cannot be made available on public domain as per government rules and regulations of the country. However, data are available on request on drmohitgupta@Yahoo.com or iecmamc@gmail.com (Ethics Committee) for researchers who meet the criteria for access to confidential data.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Kunal S, Ray I, Ish P. Global implication of booster doses of COVID-19 vaccine. Infez Med. 2021;29:643–647. doi: 10.53854/liim-2904-20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Coronavirus | India approves COVID-19 vaccines Covishield and Covaxin for emergency use. The Hindu [Internet]. 2021 Jan 3 [cited 2023 March 2]; Available from: https://www.thehindu.com/news/national/drug-controller-general-approves-covishield-and-covaxin-in-india-for-emergency-use/article33485539.ece [Google Scholar]
  • 3.Ministry of Health and Family Welfare. Co-WIN dashboard. [Internet] [cited 2023 March 2]. Available from: https://dashboard.cowin.gov.in/ [Google Scholar]
  • 4.Chang Y, Lv G, Liu C, Huang E, Luo B. Cardiovascular safety of COVID-19 vaccines in real-world studies: a systematic review and meta-analysis. Expert Rev Vaccines. 2023;22:25–34. doi: 10.1080/14760584.2023.2150169 [DOI] [PubMed] [Google Scholar]
  • 5.Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. ; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383:2603–2615. doi: 10.1056/NEJMoa2034577 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. ; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384:403–416. doi: 10.1056/NEJMoa2035389 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Goyal M, Ray I, Mascarenhas D, Kunal S, Sachdeva RA, Ish P. Myocarditis post-SARS-CoV-2 vaccination: a systematic review. QJM. 2023;116:7–25. doi: 10.1093/qjmed/hcac064 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Paknahad MH, Yancheshmeh FB, Soleimani A. Cardiovascular complications of COVID-19 vaccines: A review of case-report and case-series studies. Heart Lung. 2023;59:173–180. doi: 10.1016/j.hrtlng.2023.02.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Johnson KW, Patel S, Thapi S, Jaladanki SK, Rao A, Nirenberg S, et al. Association of Reduced Hospitalizations and Mortality Rates Among COVID-19-Vaccinated Patients With Heart Failure. J Card Fail. 2022;28:1475–1479. doi: 10.1016/j.cardfail.2022.05.008 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Arora S, Qamar A, Gupta P, Vaduganathan M, Chauhan I, Tripathi AK, et al. Design and rationale of the North Indian ST-Segment Elevation Myocardial Infarction Registry: A prospective cohort study. Clin Cardiol. 2019;42:1140–1146. doi: 10.1002/clc.23278 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. ; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018;138:e618–e651. [DOI] [PubMed] [Google Scholar]
  • 12.Kunal S, Sharma SM, Sharma SK, Gautam D, Bhatia H, Mahla H, et al. Cardiovascular complications and its impact on outcomes in COVID-19. Indian Heart J. 2020;72:593–598. doi: 10.1016/j.ihj.2020.10.005 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Arankalle V, Kulkarni-Munje A, Kulkarni R, Palkar S, Patil R, Oswal J, et al. Immunogenicity of two COVID-19 vaccines used in India: An observational cohort study in health care workers from a tertiary care hospital. Front Immunol. 2022;13:928501. doi: 10.3389/fimmu.2022.928501 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Huang Y, Ni W, Zhou Y, Zhang F, Xu J, Chen C, et al. Association between Non-mRNA COVID-19 Vaccine and Outcomes in Acute Coronary Syndrome after Percutaneous Coronary Intervention. Available at SSRN: https://ssrn.com/abstract=4145576. [Google Scholar]
  • 15.Kwong JC, Schwartz KL, Campitelli MA, Chung H, Crowcroft NS, Karnauchow T, et al. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med. 2018;378:345–353. doi: 10.1056/NEJMoa1702090 [DOI] [PubMed] [Google Scholar]
  • 16.Phrommintikul A, Kuanprasert S, Wongcharoen W, Kanjanavanit R, Chaiwarith R, Sukonthasarn A, et al. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. Eur Heart J. 2011;32:1730–5. doi: 10.1093/eurheartj/ehr004 [DOI] [PubMed] [Google Scholar]
  • 17.de Abajo FJ, Rodríguez-Martín S, Barreira D, Rodríguez-Miguel A, Fernández-Antón E, Gil M, et al. Influenza vaccine and risk of acute myocardial infarction in a population-based case-control study. Heart. 2022;108:1039–1045. doi: 10.1136/heartjnl-2021-319754 [DOI] [PubMed] [Google Scholar]
  • 18.Maniar YM, Al-Abdouh A, Michos ED. Influenza Vaccination for Cardiovascular Prevention: Further Insights from the IAMI Trial and an Updated Meta-analysis. Curr Cardiol Rep. 2022;24:1327–1335. doi: 10.1007/s11886-022-01748-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Veljkovic V, Glisic S, Veljkovic N, Bojic T, Dietrich U, Perovic VR, et al. Influenza vaccine as prevention for cardiovascular diseases: possible molecular mechanism. Vaccine. 2014;32:6569–75. doi: 10.1016/j.vaccine.2014.07.007 [DOI] [PubMed] [Google Scholar]
  • 20.Shrank WH, Patrick AR, Brookhart MA. Healthy user and related biases in observational studies of preventive interventions: a primer for physicians. J Gen Intern Med. 2011;26:546–50. doi: 10.1007/s11606-010-1609-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Kim YE, Huh K, Park YJ, Peck KR, Jung J. Association Between Vaccination and Acute Myocardial Infarction and Ischemic Stroke After COVID-19 Infection. JAMA. 2022;328:887–889. doi: 10.1001/jama.2022.12992 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Jiang J, Chan L, Kauffman J, Narula J, Charney AW, Oh W, et al. ; N3C Consortium. Impact of Vaccination on Major Adverse Cardiovascular Events in Patients With COVID-19 Infection. J Am Coll Cardiol. 2023;81:928–30. doi: 10.1016/j.jacc.2022.12.006 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Aye YN, Mai AS, Zhang A, Lim OZH, Lin N, Ng CH, et al. Acute Myocardial Infarction and Myocarditis following COVID-19 Vaccination. QJM. 2021. Sep 29:hcab252. doi: 10.1093/qjmed/hcab252 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Maadarani O, Bitar Z, Elzoueiry M, Nader M, Abdelfatah M, Zaalouk T, et al. Myocardial infarction post COVID-19 vaccine—coincidence, Kounis syndrome or other explanation—time will tell. JRSM Open. 2021;12:20542704211025259. doi: 10.1177/20542704211025259 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Srinivasan KN, Sathyamurthy I, Neelagandan M. Relation between COVID-19 vaccination and myocardial infarction–Casual or coincidental? IHJ Cardiovascular Case Reports (CVCR). 2021;5:71–4. doi: 10.1016/j.ihjccr.2021.05.003 [DOI] [Google Scholar]
  • 26.Chatterjee S, Ojha UK, Vardhan B, Tiwari A. Myocardial infarction after COVID-19 vaccination-casual or causal? Diabetes Metab Syndr. 2021;15:1055–1056. doi: 10.1016/j.dsx.2021.04.006 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S, et al. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med. 2021;384:2092–2101. doi: 10.1056/NEJMoa2104840 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Kounis NG, Koniari I, Mplani V, Kouni SN, Plotas P, Tsigkas G. Acute Myocardial Infarction Within 24 Hours After COVID-19 Vaccination: Is Kounis Syndrome the Culprit? Am J Cardiol. 2022;162:207. doi: 10.1016/j.amjcard.2021.09.032 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Boivin Z, Martin J. Untimely Myocardial Infarction or COVID-19 Vaccine Side Effect. Cureus. 2021;13:e13651. doi: 10.7759/cureus.13651 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Baronti A, Gentile F, Manetti AC, Scatena A, Pellegrini S, Pucci A, et al. Myocardial Infarction Following COVID-19 Vaccine Administration: Post Hoc, Ergo Propter Hoc? Viruses. 2022;14:1644. doi: 10.3390/v14081644 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Jabagi MJ, Botton J, Bertrand M, Weill A, Farrington P, Zureik M, et al. Myocardial Infarction, Stroke, and Pulmonary Embolism After BNT162b2 mRNA COVID-19 Vaccine in People Aged 75 Years or Older. JAMA. 2022;327:80–82. doi: 10.1001/jama.2021.21699 [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Robert Jeenchen Chen

3 May 2023

PONE-D-23-07327Impact of COVID-19 Vaccination on Mortality after Acute Myocardial InfarctionPLOS ONE

Dear Dr. Gupta,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise.

Please submit your revised manuscript by Jun 17 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information

3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: At the outset, I would like to congratulate the authors for having taken up this study. In this study, the authors have evaluated two COVID-19 vaccines (COVISHIELD, COVAXIN) available in India. The primary outcome of the study was all-cause mortality both at one month and at six months of follow-up. The authors conclude that COVID-19 vaccines showed a decrease in all-cause mortality at 30 days and six months following AMI.

It is a very elegant study but it must be kept in mind that this is a single centre retrospective observational study.

A few questions for the authors:

• It is not mentioned how many participants received single dose and how many received two doses of vaccine.

• Why the effect of third dose (booster)of COVISHIELD not studied in this study?

• Why only one parameter that is all-cause mortality was evaluated in this study?

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2023 Sep 1;18(9):e0291090. doi: 10.1371/journal.pone.0291090.r002

Author response to Decision Letter 0

10 May 2023

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reply: We thank the learned reviewer for the comments.

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reply: We thank the learned reviewer for the comments.

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reply: We thank the learned reviewer for the comments.

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: At the outset, I would like to congratulate the authors for having taken up this study. In this study, the authors have evaluated two COVID-19 vaccines (COVISHIELD, COVAXIN) available in India. The primary outcome of the study was all-cause mortality both at one month and at six months of follow-up. The authors conclude that COVID-19 vaccines showed a decrease in all-cause mortality at 30 days and six months following AMI.

It is a very elegant study but it must be kept in mind that this is a single centre retrospective observational study.

A few questions for the authors:

• It is not mentioned how many participants received single dose and how many received two doses of vaccine.

Reply: We thank the learned reviewer for the comments. We have now highlighted in our MS regarding the number of participants receiving single and two doses of COVID-19 vaccine.

• Why the effect of third dose (booster)of COVISHIELD not studied in this study?

Reply: We thank the learned reviewer for the comment. The data included in this study was before the launch of the booster dose of COVID-19 vaccines in India and hence enrolled patients had not received the booster dose.

• Why only one parameter that is all-cause mortality was evaluated in this study?

Reply: We thank the learned reviewer for the comment. We had included all-cause mortality as one of the hard end-points for our study. In a resource limited developing country such as India during the COVID-19 pandemic, it was not possible to collect data regarding all other end points. This has been highlighted as one of the limitations of our study.

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (15.1KB, docx)

Decision Letter 1

Robert Jeenchen Chen

21 Jun 2023

PONE-D-23-07327R1Impact of COVID-19 Vaccination on Mortality after Acute Myocardial InfarctionPLOS ONE

Dear Dr. Gupta,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise.

Please submit your revised manuscript by Aug 05 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Very elegant manuscript. Well written and well structured, with a valid hypothesis. Conclusions should be interpreted with caution, with this only being a single centre study.

Reviewer #3: - missing base line characteristics as COPD, heart failure, CKD, are needed.

- no laboratory or imaging data were included.

- missing other variables as type of AMI (Stemi or NSTEMI) would affect the MACE

- the method and timing of revascularization would significantly affect the study results.

Reviewer #4: We have some comments:

1- The authors should defend the rationale on why including only STEMI ACS,

2- In the methodology and to have clear inclusion criteria, the authors should determine the maximum and minimum time interval between vaccination day and occurence of STEMI event needed for enrollment.

3- All cause mortality is a complex outcome with grand multifactorial confounders and is difficult to analyse. The authors should defend and discuss this point properly.

Regards

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes: Rami Riziq Yousef Abumuaileq

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2023 Sep 1;18(9):e0291090. doi: 10.1371/journal.pone.0291090.r004

Author response to Decision Letter 1

27 Jun 2023

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

Authors reply: We thank the learned reviewers for the comments.

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: (No Response)

Authors reply: We thank the learned reviewers for the comments.

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: (No Response)

Authors reply: We thank the learned reviewers for the comments.

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: (No Response)

Authors reply: We thank the learned reviewers for the comments.

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: (No Response)

Authors reply: We thank the learned reviewers for the comments.

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Very elegant manuscript. Well written and well structured, with a valid hypothesis. Conclusions should be interpreted with caution, with this only being a single centre study.

Authors reply: We thank respected reviewer for kind words of appreciation. We agree that all the results have to be interpreted with caution. We have highlighted very clearly in the manuscript that this is a single centre study and results have to be interpreted with caution.

Reviewer #3: - missing base line characteristics as COPD, heart failure, CKD, are needed.

- no laboratory or imaging data were included.

Authors reply: We thank the learned reviewers for the comments. We have now added the data for missing baseline characteristics in the MS (Table 1). Since this was a retrospective review to determine any causality between COVID-19 vaccination and AMI, laboratory and imaging data were not included.

- missing other variables as type of AMI (Stemi or NSTEMI) would affect the MACE

Authors reply: We thank the learned reviewers for the comments. We had categorically looked into occurrence of STEMI following COVID-19 vaccination which we had mentioned in the methods. We sought to study the most severe form of MI after vaccination. Since this was a retrospective review carried out during the pandemic in a resource limited set-up, all comer STEMI cases were included.

- the method and timing of revascularization would significantly affect the study results.

Authors reply: We thank the learned reviewers for the comments. The details of revascularization with PCI have now been included in the manuscript. The figure (Figure 3) and table (table 1) have been modified. There was no impact of revascularization on the protective effect of COVID-19 vaccination. This has now been added in the MS.

Reviewer #4: We have some comments:

1- The authors should defend the rationale on why including only STEMI ACS,

Authors reply: We thank the learned reviewers for the comments. This study was a retrospective analysis of effect of vaccination on STEMI patients. This is the most severe form of coronary artery disease and hence we aimed to see the effect of vaccination on mortality after STEMI.

2- In the methodology and to have clear inclusion criteria, the authors should determine the maximum and minimum time interval between vaccination day and occurence of STEMI event needed for enrollment.

Authors reply: Learned Reviewer have very rightly suggested the mention of time interval. However, we must state that the effect of vaccination on STEMI and the time period after which it may or may not effect is unknown. Hence, we didn’t define any time interval in inclusion, rather we included all the patients who were vaccinated and studied the effect of vaccination in time quartiles to clearly see the time interval when these events occur.

3- All cause mortality is a complex outcome with grand multifactorial confounders and is difficult to analyse. The authors should defend and discuss this point properly.

Authors reply: Learned Reviewer has very rightly pointed out the limitation of using all cause mortality. However, we must state that all cause mortality is a hard end point and we have tried to adjust all the possible confounders in our analysis. In this study during covid times, it was extremely challenging to collect data of all possible outcomes in a resource limited country like India. The same has now been included in the discussion

Attachment

Submitted filename: Reply to reviewers comments.docx

Click here for additional data file. (17.8KB, docx)

Decision Letter 2

Robert Jeenchen Chen

22 Aug 2023

Impact of COVID-19 Vaccination on Mortality after Acute Myocardial Infarction

PONE-D-23-07327R2

Dear Dr. Gupta,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #4: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #4: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #4: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #4: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #4: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #4: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #4: Yes: Rami Riziq Yousef Abumuaileq

**********

Acceptance letter

Robert Jeenchen Chen

25 Aug 2023

PONE-D-23-07327R2

Impact of COVID-19 vaccination on mortality after acute Myocardial Infarction

Dear Dr. Gupta:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Robert Jeenchen Chen

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Comparison of patients’ characteristics between 30 days outcome.

    (DOCX)

    Click here for additional data file. (14.6KB, docx)
    S2 Table. Propensity score weighted logistic regression models for assessing the odds ratio of vaccination on mortality during one—six months of follow-up.

    (DOCX)

    Click here for additional data file. (15.1KB, docx)
    Attachment

    Submitted filename: Response to Reviewers.docx

    Click here for additional data file. (15.1KB, docx)
    Attachment

    Submitted filename: Reply to reviewers comments.docx

    Click here for additional data file. (17.8KB, docx)

    Data Availability Statement

    Data cannot be shared publicly because of ethical reasons. The Data includes potentially identifiable /sensitive information on covid vaccination details of patients that cannot be made available on public domain as per government rules and regulations of the country. However, data are available on request on drmohitgupta@Yahoo.com or iecmamc@gmail.com (Ethics Committee) for researchers who meet the criteria for access to confidential data.

    Articles from PLOS ONE are provided here courtesy of PLOS

    RESOURCES