Adverse events following COVID‐19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia

Background and Objectives Since publishing successful clinical trial results of mRNA coronavirus disease 2019 (COVID‐19) vaccines in December 2020, multiple reports have arisen about cardiovascular complications following the mRNA vaccination. This study provides an in‐depth account of various cardiovascular adverse events reported after the mRNA vaccines' first or second dose including pericarditis/myopericarditis, myocarditis, hypotension, hypertension, arrhythmia, cardiogenic shock, stroke, myocardial infarction/STEMI, intracranial hemorrhage, thrombosis (deep vein thrombosis, cerebral venous thrombosis, arterial or venous thrombotic events, portal vein thrombosis, coronary thrombosis, microvascular small bowel thrombosis), and pulmonary embolism. Methods A systematic review of original studies reporting confirmed cardiovascular manifestations post‐mRNA COVID‐19 vaccination was performed. Following the PRISMA guidelines, electronic databases (PubMed, PMC NCBI, and Cochrane Library) were searched until January 2022. Baseline characteristics of patients and disease outcomes were extracted from relevant studies. Results A total of 81 articles analyzed confirmed cardiovascular complications post‐COVID‐19 mRNA vaccines in 17,636 individuals and reported 284 deaths with any mRNA vaccine. Of 17,636 cardiovascular events with any mRNA vaccine, 17,192 were observed with the BNT162b2 (Pfizer−BioNTech) vaccine, 444 events with mRNA‐1273 (Moderna). Thrombosis was frequently reported with any mRNA vaccine (n = 13,936), followed by stroke (n = 758), myocarditis (n = 511), myocardial infarction (n = 377), pulmonary embolism (n = 301), and arrhythmia (n = 254). Stratifying the results by vaccine type showed that thrombosis (80.8%) was common in the BNT162b2 cohort, while stroke (39.9%) was common with mRNA‐1273 for any dose. The time between the vaccination dosage and the first symptom onset averaged 5.6 and 4.8 days with the mRNA‐1273 vaccine and BNT162b2, respectively. The mRNA‐1273 cohort reported 56 deaths compared to the 228 with BNT162b2, while the rest were discharged or transferred to the ICU. Conclusion Available literature includes more studies with the BNT162b2 vaccine than mRNA‐1273. Future studies must report mortality and adverse cardiovascular events by vaccine types. We aim to summarize the events of cardiac complications following the mRNA coronavirus disease 2019 vaccine, providing an in‐depth analysis of their occurrences, and their implications. The review includes 69 case reports/case series, 4 studies with data obtained from electronic medical records (hospital surveillance data, national database, VAERS/VigiBase), and 8 observational studies including prospective/retrospective cohort.

Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia.

BACKGROUND AND OBJECTIVES: Since publishing successful clinical trial results of mRNA coronavirus disease 2019 (COVID-19) vaccines in December 2020, multiple reports have arisen about cardiovascular complications following the mRNA vaccination. This study provides an in-depth account of various cardiovascular adverse events reported after the mRNA vaccines' first or second dose including pericarditis/myopericarditis, myocarditis, hypotension, hypertension, arrhythmia, cardiogenic shock, stroke, myocardial infarction/STEMI, intracranial hemorrhage, thrombosis (deep vein thrombosis, cerebral venous thrombosis, arterial or venous thrombotic events, portal vein thrombosis, coronary thrombosis, microvascular small bowel thrombosis), and pulmonary embolism. METHODS: A systematic review of original studies reporting confirmed cardiovascular manifestations post-mRNA COVID-19 vaccination was performed. Following the PRISMA guidelines, electronic databases (PubMed, PMC NCBI, and Cochrane Library) were searched until January 2022. Baseline characteristics of patients and disease outcomes were extracted from relevant studies. RESULTS: A total of 81 articles analyzed confirmed cardiovascular complications post-COVID-19 mRNA vaccines in 17,636 individuals and reported 284 deaths with any mRNA vaccine. Of 17,636 cardiovascular events with any mRNA vaccine, 17,192 were observed with the BNT162b2 (Pfizer-BioNTech) vaccine, 444 events with mRNA-1273 (Moderna). Thrombosis was frequently reported with any mRNA vaccine (n = 13,936), followed by stroke (n = 758), myocarditis (n = 511), myocardial infarction (n = 377), pulmonary embolism (n = 301), and arrhythmia (n = 254). Stratifying the results by vaccine type showed that thrombosis (80.8%) was common in the BNT162b2 cohort, while stroke (39.9%) was common with mRNA-1273 for any dose. The time between the vaccination dosage and the first symptom onset averaged 5.6 and 4.8 days with the mRNA-1273 vaccine and BNT162b2, respectively. The mRNA-1273 cohort reported 56 deaths compared to the 228 with BNT162b2, while the rest were discharged or transferred to the ICU. CONCLUSION: Available literature includes more studies with the BNT162b2 vaccine than mRNA-1273. Future studies must report mortality and adverse cardiovascular events by vaccine types.

Nationwide Analysis of Cardiac Arrest Outcomes During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic had a significant impact on the chain of survival following cardiac arrest. However, large population-based reports of COVID-19 in patients hospitalized after cardiac arrest are limited. The National Inpatient Sample database was queried for cardiac arrest admissions during 2020 in the United States. Propensity score matching was used to match patients with and without concurrent COVID-19 according to age, race, sex, and comorbidities. Multivariate logistic regression analysis was used to identify predictors of mortality. A weighted total of 267,845 hospitalizations for cardiac arrest were identified, among which 44,105 patients (16.5%) had a concomitant diagnosis of COVID-19. After propensity matching, cardiac arrest patients with concomitant COVID-19 had higher rate of acute kidney injury requiring dialysis (64.9% vs 54.8%) mechanical ventilation >24 hours (53.6% vs 44.6%) and sepsis (59.4% vs 40.4%) compared to cardiac arrest patients without COVID-19. In contrast, cardiac arrest patients with COVID-19 had lower rates of cardiogenic shock (3.2% vs 5.4%, P < 0.001), ventricular tachycardia (9.6% vs 11.7%, P < 0.001), and ventricular fibrillation (6.7% vs 10.8%, P < 0.001), and a lower utilization of cardiac procedures. In-hospital mortality was higher in patients with COVID-19 (86.9% vs 65.5%, P < 0.001) and, on multivariate analysis, a diagnosis of COVID-19 was an independent predictor of mortality. Among patients hospitalized following a cardiac arrest during 2020, concomitant COVID-19 infection was associated with significantly worse outcomes characterized by an increased risk of sepsis, pulmonary and renal dysfunction, and death.

A Comparison of COVID-19 and Influenza-Associated Myocarditis: A Nationwide Study in the United States.

We aimed to compare the characteristics and outcomes of adult patients hospitalized with myocarditis and either concomitant corona virus disease 2019 (COVID-19) or influenza, and elucidate clinical predictors associated with adverse outcomes in both groups. The study used the national inpatient sample (NIS) from 2019 to 2020 to identify 27,725 adult myocarditis hospitalizations, of which 5840 had concomitant COVID-19 and 1045 had concomitant influenza. After propensity score matching, the in-hospital mortality from myocarditis was significantly higher in COVID-19 compared to influenza. Patients with myocarditis and COVID-19 were more likely to have cardiovascular comorbidities and be older than those with influenza-associated myocarditis. Predictors of mortality were also different in both groups.

Impact of COVID-19 on Outcomes of Patients Hospitalized With STEMI: A Nationwide Propensity-matched Analysis.

Patients with ST-segment elevation myocardial infarction (STEMI) and concurrent coronavirus disease 2019 (COVID-19) have been reported to have poor outcomes. However, previous studies are small and limited. The National Inpatient Sample database for the year 2020 was queried to identify all adult hospitalizations with a primary diagnosis of STEMI, with and without concurrent COVID-19. A 1:1 propensity score matching was performed. A total of 159,890 hospitalizations with a primary diagnosis of STEMI were identified. Of these, 2210 (1.38%) had concurrent COVID-19. After propensity matching, STEMI patients with concurrent COVID-19 had a significantly higher mortality (17.8% vs 9.1%, OR 1.96, P< 0.001), lower likelihood to receive same-day percutaneous coronary intervention (PCI) (63.6% vs 70.6%, P = 0.019), with a trend towards lower overall PCI (74.9% vs 80.2%, P = 0.057) and significantly lower coronary artery bypass grafting) (3.0% vs 6.8%, P = 0.008) prior to discharge, compared with STEMI patients without COVID-19. The prevalence of cardiogenic shock, need for mechanical circulatory support, extracorporeal membrane oxygenation, cardiac arrest, acute kidney injury (AKI), dialysis, major bleeding and stroke were not significantly different between the groups. COVID-19-positive STEMI patients who received same-day PCI had significantly lower odds of in-hospital mortality (adjusted OR 0.42, 95% CI 0.20-0.85, P = 0.017). STEMI patients with concurrent COVID-19 infection had a significantly higher (almost 2 times) in-hospital mortality, and lower likelihood of receiving same-day PCI, overall (any-day) PCI, and CABG during their admission, compared with STEMI patients without COVID-19.

Impact of COVID-19 on Patients Hospitalized With Deep Vein Thrombosis and/or Pulmonary Embolism: A Nationwide Analysis.

The Coronavirus disease 2019 (COVID-19) infection predisposes patients to develop deep vein thrombosis (DVT) and pulmonary embolism (PE). In this study, we compared the in-hospital outcomes of patients with DVT and/or PE with concurrent COVID-19 infection vs those with concurrent flu infection. The National Inpatient Sample from 2019 to 2020 was analyzed to identify all adult admissions diagnosed with DVT and PE. These patients were then stratified based on whether they had concomitant COVID-19 or flu. We identified 62,895 hospitalizations with the diagnosis of DVT and/or PE with concomitant COVID-19, and 8155 hospitalizations with DVT and/or PE with concomitant flu infection. After 1:1 propensity score match, the incidence of cardiac arrest and inpatient mortality were higher in the COVID-19 group. The incidence of cardiogenic shock was higher in the flu group. Increased age, Hispanic race, diabetes, chronic kidney disease, arrhythmia, liver disease, coagulopathy, and rheumatologic diseases were the independent predictors of mortality in patients with DVT and/or PE with concomitant COVID-19.

COVID-19, Heart Failure Hospitalizations, and Outcomes: A Nationwide Analysis.

Heart Failure (HF) patients are at a higher risk of adverse events associated with Coronavirus disease 2019 (COVID-19). Large population-based reports of the impact of COVID-19 on patients hospitalized with HF are limited. The National Inpatient Sample database was queried for HF admissions during 2020 in the United States (US), with and without a diagnosis of COVID-19 based on ICD-10-CM U07. Propensity score matching was used to match patients across age, race, sex, and comorbidities. Multivariate logistic regression analysis was used to identify predictors of mortality. A weighted total of 1,110,085 hospitalizations for HF were identified of which 7,905 patients (0.71%) had a concomitant diagnosis of COVID-19. After propensity matching, HF patients with COVID-19 had higher rate of in-hospital mortality (8.2% vs 3.7%; odds ratio [OR]: 2.33 [95% confidence interval [CI]: 1.69, 3.21]; P< 0.001), cardiac arrest (2.9% vs 1.1%, OR 2.21 [95% CI: 1.24,3.93]; P<0.001), and pulmonary embolism (1.0% vs 0.4%; OR 2.68 [95% CI: 1.05, 6.90]; P = 0.0329). During hospitalizations for HF, COVID-19 was also found to be an independent predictor of mortality. Further, increasing age, arrythmias, and chronic kidney disease were independent predictors of mortality in HF patients with COVID-19. COVID-19 is associated with increased in-hospital mortality, longer hospital stays, higher cost of hospitalization and increased risk of adverse outcomes in patients admitted with HF.

Impact of COVID-19 in patients hospitalized with stress cardiomyopathy: A nationwide analysis.

Stress cardiomyopathy was noted to occur at a higher incidence during coronavirus disease of 2019 (COVID-19) pandemic. This database analysis has been done to compare the in-hospital outcomes in patients with stress cardiomyopathy and concurrent COVID-19 infection with those without COVID-19 infection. The National Inpatient Sample database for the year 2020 was queried to identify all admissions diagnosed with stress cardiomyopathy. These patients were then stratified based on whether they had concomitant COVID-19 infection or not. A 1:1 propensity score matching was performed. Multivariate logistic regression analysis was done to identify predictors of mortality. We identified 41,290 hospitalizations for stress cardiomyopathy, including 1665 patients with concurrent diagnosis of COVID-19. The female preponderance was significantly lower in patients with stress cardiomyopathy and COVID-19. Patients with concomitant COVID-19 were more likely to be African American, diabetic and have chronic kidney disease. After propensity matching, the incidence of complications, including acute kidney injury (AKI), AKI requiring dialysis, coagulopathy, sepsis, cardiogenic shock, cases with prolonged intubation of >24 h, requirement of vasopressor and inpatient mortality, were noted to be significantly higher in patients with COVID-19. Concomitant COVID-19 infection was independently associated with worse outcomes and increased mortality in patients hospitalized with stress cardiomyopathy.

Nationwide Analysis of the Outcomes and Mortality of Hospitalized COVID-19 Patients.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) pandemic has affected people worldwide with the United States (US) with the largest number of reported cases currently. Previous studies in hospitalized COVID-19 patients have been limited by sample size. METHODS: The National Inpatient Sample database which is the largest inpatient database in the US was queried in the year 2020 for the diagnosis of COVID-19 based on ICD-10-CM U07.1 and associated outcomes. Multivariate logistic regression analysis was used to identify predictors of mortality. STATA 16.0 was used for statistical analysis. RESULTS: A weighted total of 1,678,995 hospitalizations for COVID-19 were identified. Median age of admitted patients with COVID-19 was 65 year (51-77) with 47.9% female and 49.2% White. Majority of the patients admitted were >65 years of age (49.3%). Hypertension and diabetes were the most common comorbidities (64.2% and 39.5%, respectively). Overall inpatient mortality was 13.2% and increasing to 55.9% in patients requiring mechanical ventilation. Trend of inpatient mortality was significantly decreasing over the year. Predictors of inpatient mortality included age, male sex, diabetes, chronic kidney disease, heart failure, arrythmia, obesity, and coagulopathy. Despite a lower proportion of patients admitted to hospital with COVID-19, Black, Hispanic, and Native Americans were at an increased adjusted odds of inpatient mortality. Disparity was also noted in income, with low median household income associated with higher risk of mortality. CONCLUSION: In the largest US cohort with >1.6 million hospitalized COVID-19 patients in 2020, overall inpatient mortality was 13.6% with significantly higher mortality in ventilated patients. Significant socioeconomic and racial disparities were present with minorities at higher odds of mortality.

Prevalence of comorbidities and symptoms stratified by severity of illness amongst adult patients with COVID-19: a systematic review.

Introduction: We performed a systematic review of comorbidities and symptoms of adult patients with coronavirus disease 2019 (COVID-19) to evaluate comorbidities, symptoms, and severity. Material and methods: We searched databases and extracted comorbidities and symptoms from the included studies. We stratified the similar signs and symptoms in groups and on the basis of severity and compared them with stratified analysis. Individual case reports and case series with < 5 patients were excluded. Results: A total of 163 studies with 43,187 patients were included. Mean age was 54.6 years. There were significantly fewer women in the study (43.9% vs. 56.1%, p < 0.0001). Prevalent cardiovascular comorbidities were hypertension (31.9%), obesity (27.9%), hyperlipidemia (26.4%), smoking (18.9%), diabetes mellitus (17.2%), atherosclerotic disease (9.2%) and arrhythmia (5.0%). The most frequently reported constitutional symptoms of COVID-19 were fever (73.9%), fatigue (33.4%), malaise (29.9%), myalgia and/or arthralgia (19.2%), generalized weakness (19.0%), and chills (11.3%). For the cardiovascular system, chest pain and/or tightness were most often reported (19.6%), followed by palpitations (5.2%). Hypertension and diabetes were common in severe disease. Obesity and congestive heart failure were not observed in any non-severe cases. Severe cases compared to non-severe cases more frequently had fever (87.8% vs. 58.5%, p < 0.001), shortness of breath (47.4% vs. 20.6%, p < 0.001), cough (66.8% vs. 62.9%, p < 0.001), sputum production (35.4% vs. 26.5%, p < 0.001) and rhinorrhea (32.2% vs. 7.3%, p < 0.001). Conclusions: Hypertension, diabetes, and atherosclerotic diseases are common comorbidities across the world, with obesity as the second most common in the US and more common in men.

Proposed Pathogenesis, Characteristics, and Management of COVID-19 mRNA Vaccine-Related Myopericarditis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus causing coronavirus disease 2019 (COVID-19), has affected human lives across the globe. On 11 December 2020, the US FDA granted an emergency use authorization for the first COVID-19 vaccine, and vaccines are now widely available. Undoubtedly, the emergence of these vaccines has led to substantial relief, helping alleviate the fear and anxiety around the COVID-19 illness for both the general public and clinicians. However, recent cases of vaccine complications, including myopericarditis, have been reported after administration of COVID-19 vaccines. This article discusses the cases, possible pathogenesis of myopericarditis, and treatment of the condition. Most cases were mild and should not yet change vaccine policies, although prospective studies are needed to better assess the risk-benefit ratios in different groups.

Gout Pharmacotherapy in Cardiovascular Diseases: A Review of Utility and Outcomes.

Hyperuricemia and gout have been linked to an increased risk for cardiovascular (CV) disease, stroke, hypertension, heart failure, and chronic kidney disease, possibly through a proinflammatory milieu. However, not all the drugs used in gout treatment improve CV outcomes; colchicine has shown improved CV outcomes in patients with recent myocardial infarction and stable coronary artery disease independent of lipid-lowering effects. There is resurging interest in colchicine following publication of the COLCOT, LoDoCo, LoDoCo2, LoDoCo-MI trials, and COLCORONA trial which will shed light on its utility in COVID-19. Our aim is to review the CV use of colchicine beyond pericardial diseases, as well as CV outcomes of the available gout therapies, including allopurinol and febuxostat. The CARES trial and its surrounding controversies, which lead to the US FDA 'black box' warning on febuxostat, in addition to the recent FAST trial which contradicts this and finds febuxostat to be non-inferior, are discussed in this paper.

Biventricular takotsubo syndrome with COVID-19 in an Asian male.

Coronavirus disease 2019 (COVID-19) has been shown to affect the cardiovascular system, and several cases of takotsubo syndrome (TTS) induced by COVID-19 have been reported. TTS predominantly affects postmenopausal women in western countries, but the prevalence in men is higher in Asian populations. It should be noted that male patients with either TTS or COVID-19 are associated with higher mortality. Despite the higher prevalence of TTS in Asian men, little is known about Asian men with TTS induced by COVID-19. This is a case report of a 60-year-old Asian male with biventricular TTS precipitated by COVID-19. He presented with acute respiratory distress syndrome, cardiogenic shock, and acute kidney injury. He required intubation, multiple vasopressors, and renal replacement therapy. The left ventricular ejection fraction was 15%, but it normalized in 5 weeks. The patient had a prolonged hospital stay in a critical condition, but was eventually discharged alive. The scarce literature about this condition in Asian male populations and the increasing number of COVID-19 cases in Asian countries highlight the rarity and importance of this case. Further studies are warranted to investigate the uneven sex distribution and outcomes of TTS triggered by COVID-19 in an Asian population. .

Management of Thrombotic Complications in COVID-19: An Update.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2), is now a global pandemic. This virus primarily affects the respiratory tract and causes lung injury characterized by acute respiratory distress syndrome. Although the pathophysiology of COVID-19 is not yet clear, the most widely accepted mechanism is systemic inflammation. A clinically significant effect of the inflammation is coagulopathy. As a result of this effect, patients are found to have a high risk of venous thromboembolism. Studies have reported a high incidence of thrombotic complications in critically ill patients with COVID-19. In this review, we discuss the most updated evidence on the pathophysiology, diagnosis, and treatment of the coagulopathy of COVID-19. Prophylactic anticoagulation is recommended for all in-patients with COVID-19. Those with a higher risk of developing thromboembolic events or who have already developed venous thromboembolism should be treated with therapeutic anticoagulation. We also discuss post-discharge prophylaxis for high-risk patients and some newly proposed treatments for the hypercoagulability that could improve the outcomes of the affected patients.

COVID-19 Pandemic: Cardiovascular Complications and Future Implications.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a global pandemic with the highest number of affected individuals in the modern era. Not only is the infection inflicting significant morbidity and mortality, but there has also been a significant strain to the health care system and the economy. COVID-19 typically presents as viral pneumonia, occasionally leading to acute respiratory distress syndrome (ARDS) and death. However, emerging evidence suggests that it has a significant impact on the cardiovascular (CV) system by direct myocardial damage, severe systemic inflammatory response, hypoxia, right heart strain secondary to ARDS and lung injury, and plaque rupture secondary to inflammation. Primary cardiac manifestations include acute myocarditis, myocardial infarction, arrhythmia, and abnormal clotting. Several consensus documents have been released to help manage CV disease during this pandemic. In this review, we summarize key cardiac manifestations, their management, and future implications.