The Role of the Immune System on the Cardiac Complications Observed in SARS-CoV-2

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.

Heart failure after dengue infection- a population-based self-controlled case-series study.

BACKGROUND: Major cardiovascular events (MACEs) have been described with dengue infection. Among these MACEs, heart failure (HF) is the most common but has not been thoroughly assessed. This study aimed to evaluate the association between dengue and HF. METHODS: Under the self-controlled case-series study design, we used the Notifiable Infectious Disease dataset linkage with the National Health Insurance claims data to obtain the study subjects. All laboratory-confirmed dengue cases who were hospitalized for HF after dengue infection within one year between 2009 and 2015 in Taiwan were included. We identified the first 7 and 14 days after dengue infection as the risk intervals. The incidence rate ratio (IRR) and 95% confidence interval (CI) for HF were estimated by conditional Poisson regression. RESULTS: Among the 65,906 dengue patients, 230 had admission for HF after dengue infection within one year. The IRR of HF admission within the first week after dengue infection was 56.50 (95% C.I. 43.88-72.75). This risk was highest in >60 years (IRR = 59.32, 95% C.I. 45.43-77.43) and lower in 0-40 years (IRR = 25.82, 95% C.I. 2.89-231.02). The risk was nearly nine times higher among admission (for dengue infection) than among nonadmission cases (IRR 75.35 vs. 8.61, p < 0.0001). The risks increased slightly in the second week 8.55 and became less obvious after the third and fourth week. CONCLUSIONS: Patients with dengue infection have a risk of developing acute heart failure within one week, especially in >60 years, men, and dengue admission subjects. The findings emphasize the awareness of diagnosis and further appropriate treatment of HF.

COVID-19 myocarditis and long-term heart failure sequelae.

PURPOSE OF REVIEW: The clinical syndrome of coronavirus disease 2019 (COVID-19) has become a global pandemic leading to significant morbidity and mortality. Cardiac dysfunction is commonly seen in these patients, often presenting as clinical heart failure. Accordingly, we aim to provide a comprehensive review on COVID-19 myocarditis and its long-term heart failure sequelae. RECENT FINDINGS: Several suspected cases of COVID-19 myocarditis have been reported. It is often not clear if the acute myocardial dysfunction is caused by myocarditis or secondary to generalized inflammatory state of cytokine release or microvascular thrombotic angiopathy. Ischemia may also need to be ruled out. Regardless, myocardial dysfunction in these patients is associated with poor overall prognosis. Laboratory testing, echocardiography, cardiac magnetic resonance imaging, and even endomyocardial biopsy may be needed for timely diagnosis. Several treatment strategies have been described, including both supportive and targeted therapies. SUMMARY: COVID-19 can cause a spectrum of ventricular dysfunction ranging from mild disease to fulminant myocarditis with hemodynamic instability. Future research is needed to understand the true prevalence of COVID-19 myocarditis, as well as to better define various diagnostic protocols and treatment strategies.

Role of Coxsackievirus B3-Induced Immune Responses in the Transition from Myocarditis to Dilated Cardiomyopathy and Heart Failure.

Dilated cardiomyopathy (DCM) is a cardiac disease marked by the stretching and thinning of the heart muscle and impaired left ventricular contractile function. While most patients do not develop significant cardiac diseases from myocarditis, disparate immune responses can affect pathological outcomes, including DCM progression. These altered immune responses, which may be caused by genetic variance, can prolong cytotoxicity, induce direct cleavage of host protein, or encourage atypical wound healing responses that result in tissue scarring and impaired mechanical and electrical heart function. However, it is unclear which alterations within host immune profiles are crucial to dictating the outcomes of myocarditis. Coxsackievirus B3 (CVB3) is a well-studied virus that has been identified as a causal agent of myocarditis in various models, along with other viruses such as adenovirus, parvovirus B19, and SARS-CoV-2. This paper takes CVB3 as a pathogenic example to review the recent advances in understanding virus-induced immune responses and differential gene expression that regulates iron, lipid, and glucose metabolic remodeling, the severity of cardiac tissue damage, and the development of DCM and heart failure.

Special Considerations in Critical Care of the Congenital Heart Disease Patient.

Outcomes of congenital heart disease have improved markedly over the past 20 years, with survival to adulthood now close to 90%. The mean age of admission to an intensive care unit (ICU) is 40 years. The incidence of hospital and critical care admissions have increased significantly as a consequence of this improved survival. Intensivists are now confronted with the management not only of complex adult congenital heart disease (ACHD) lesions from a cardiac perspective, but also of extracardiac organ consequences of years of abnormal circulation after surgical or palliative correction. Kidney and liver dysfunction and respiratory and hematologic abnormalities are very common in this population. ACHD patients can present to the ICU for a vast number of reasons, classified in this review as medical noncardiac, medical cardiac, and surgical. Community/hospital-acquired infections, cerebrovascular accidents, and respiratory failure, alongside arrhythmias and heart failure, are responsible for medical admissions. Surgical admissions include postoperative management after correction or palliation, but also medical optimisation and work-up for advanced therapies. ICU management of this large heterogeneous group requires a thorough understanding of the pathophysiology in order to apply conventional adult critical care modalities; left ventricular or right ventricular dysfunction, pulmonary hypertension, intracardiac, extracardiac, and palliative surgical shunts can be present and require additional consideration. This review focuses on the pathophysiology, long-term sequelae, and different treatment modalities to supply a framework for the ICU physician caring for these patients. Successful outcome, especially in complex lesions, depends on early involvement of specialised ACHD centres.

Oxygenated right ventricular assist device as part of veno-venopulmonary extracorporeal membrane oxygenation to support the right ventricle and pulmonary vasculature.

COVID-19 infection can lead to severe acute respiratory distress syndrome (ARDS), right ventricular (RV) failure and pulmonary hypertension. Venovenous extracorporeal membrane oxygenation (V-V ECMO) has been used for patients with refractory hypoxemia. More recently dual-lumen right atrium to pulmonary artery oxygenated right ventricular assist devices (Oxy-RVAD) have been utilized in the severe medical refractory COVID ARDS setting. Historically, animal data has demonstrated that high continuous non-pulsatile RVAD flows, leading to unregulated and unprotected circulation through the pulmonary vessels is associated with an increased risk of pulmonary hemorrhage and increased amount of extravascular lung water. These risks are heightened in the setting of ARDS with fragile capillaries, left ventricular (LV) diastolic failure, COVID cardiomyopathy, and anticoagulation. Concurrently, due to infection, tachycardia, and refractory hypoxemia, high V-V ECMO flows to match high cardiac output are often necessary to maintain systemic oxygenation. Increase in cardiac output without a concurrent increase in VV ECMO flow will result in a higher fraction of deoxygenated blood returning to the right heart and therefore resulting in hypoxemia. Several groups have suggested using a RVAD only strategy in COVID ARDS; however, this exposes the patients to the risk of pulmonary hemorrhage. We present one of the first known cases using an RV mechanical support, partial flow pulmonary circulation, oxygenated Veno-venopulmonary (V-VP) strategy resulting in RV recovery, total renal recovery, awake rehabilitation, and recovery.

Acute heart failure due to COVID-19 related myocardial injury and de novo hypertensive cardiomyopathy: a challenging diagnosis.

We report a COVID-19 case with acute heart and kidney failure in a healthy young male. Echocardiography showed severe systolic and diastolic left ventricle dysfunction, with diffuse myocardial thickening. Cardiac MRI showed aspects of focal myocarditis, and hypertensive cardiomyopathy. Renal biopsy demonstrated limited acute tubular injury, and hypertensive kidney disease. Coronary angiography excluded critical stenoses. Unlike what we initially suspected, myocardial inflammation had a limited extent in our patient; severe hypertension causing cardiomyopathy and multi-organ damage, not diagnosed before, was primarily responsible for severe illness. Correct diagnosis and guidelines-directed treatment allowed a favorable course.

Natriuretic Peptides as Biomarkers: Narrative Review and Considerations in Cardiovascular and Respiratory Dysfunctions.

Natriuretic peptides (NPs) encompass a family of structurally related hormone/paracrine factors acting through the natriuretic peptide system regulating cell proliferation, vessel tone, inflammatory processes, neurohumoral pathways, fluids, and electrolyte balance. The three most studied peptides are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-Type natriuretic peptide (CNP). ANP and BNP are the most relevant NPs as biomarkers for the diagnosis and prognosis of heart failure and underlying cardiovascular diseases, such as cardiac valvular dysfunction, hypertension, coronary artery disease, myocardial infarction, persistent arrhythmias, and cardiomyopathies. Cardiac dysfunctions related to cardiomyocytes stretching in the atria and ventricles are primary elicitors of ANP and BNP release, respectively. ANP and BNP would serve as biomarkers for differentiating cardiac versus noncardiac causes of dyspnea and as a tool for measuring the prognosis of patients with heart failure; nevertheless, BNP has been shown with the highest predictive value, particularly related to pulmonary disorders. Plasma BNP has been reported to help differentiate cardiac from pulmonary etiologies of dyspnea in adults and neonates. Studies have shown that COVID-19 infection also increases serum levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) and BNP. This narrative review assesses aspects of ANP and BNP on their physiology, and predictive values as biomarkers. We present an overview of the NPs' synthesis, structure, storage, and release, as well as receptors and physiological roles. Following, considerations focus on ANP versus BNP, comparing their relevance in settings and diseases associated with respiratory dysfunctions. Finally, we compiled data from guidelines for using BNP as a biomarker in dyspneic patients with cardiac dysfunction, including its considerations in COVID-19.

The Cardiovascular Manifestations of COVID-19.

The Coronavirus 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus, has resulted in unprecedented morbidity and mortality worldwide. While COVID-19 typically presents as viral pneumonia, cardiovascular manifestations such as acute coronary syndromes, arterial and venous thrombosis, acutely decompensated heart failure (HF), and arrhythmia are frequently observed. Many of these complications are associated with poorer outcomes, including death. Herein we review the relationship between cardiovascular risk factors and outcomes among patients with COVID-19, cardiovascular manifestations of COVID-19, and cardiovascular complications associated with COVID-19 vaccination.

Risk of incident heart failure after COVID-19 recovery: a systematic review and meta-analysis.

Patients recovered from COVID-19 have an increased incidence of cardiovascular disease and heart structural changes. The aim of the present manuscript is to assess the risk of incident heart failure (HF) after COVID-19 infection. Data were obtained searching MEDLINE and Scopus for all studies published at any time up to September 1, 2022 reporting the risk of incident HF in COVID-19 recovered patients. The cumulative post-COVID-19 incidence and risk of incident HF were pooled using a random effects model and presented with the corresponding 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I2 statistic. Overall, 21,463,173 patients (mean age 54.5 years, 58.7% males) were analyzed. Among them, 1,628,424 had confirmed COVID-19 infection while the remaining 19,834,749 represented the controls. The mean length of follow-up was 9.2 months. A random effect model revealed a pooled incidence of post COVID-19 HF in 1.1% of cases (95% CI: 0.7-1.6, I2: 99.8%). Moreover, recovered COVID-19 patients showed an increased risk of incident HF (HR: 1.90, 95% CI: 1.54-3.24, p < 0.0001, I2 = 96.5%) in the same follow-up period. Meta-regression showed a direct relationship for the risk of incident HF using age (p = 0.001) and hypertension (HT) (p = 0.02) as moderators, while an inverse association was observed when the follow-up length was adopted as moderating variable (p = 0.01). COVID-19 survivors had an additional 90% risk of developing HF after COVID-19 infection in the long-term period. This risk was directly related with age and previous history of HT especially in the early post-acute phase of the infection.

Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort study.

BACKGROUND: In 2019, 600'000 people in Africa died of heart failure and heart diseases will increase on the continent. It is crucial to understand the regional etiologies and risk factors for heart failure and underlying heart diseases. However, echocardiography data from rural Africa are scarce and from Lesotho non-existent. This study aims to examine the occurrence, characteristics and etiology of heart failure and heart diseases using echocardiography data from a referral hospital in rural Lesotho. METHODS: We conducted a retrospective cohort study at Seboche Mission Hospital, the only referral hospital in Butha-Buthe district (Lesotho) with an echocardiography department. We included data from all individuals referred to the department between January 2020 and May 2021. From non-hospitalized patients echocardiographic diagnosis, sex and age were available, from hospitalized patients additional sociodemographic and clinical data could be extracted. RESULTS: In the study period, a total of 352 echocardiograms were conducted; 213 had abnormal findings (among them 3 children). The majority of adult participants (130/210; 64%) were female and most frequent heart diseases were hypertensive (62/210, 30%), valvular (39/210, 19%) and chronic pulmonary (37/210, 18%). Heart failure represented 11% of hospitalizations in the same period. Among the 126 hospitalized heart failure patients, the most common etiology was chronic pulmonary heart disease (32/126; 25%). Former mine workers and people with a history of tuberculosis were more likely to have a chronic pulmonary heart disease. CONCLUSIONS: The leading cause of heart disease in this setting is hypertension. However, in contrast to other African epidemiological studies, chronic pulmonary heart disease is unexpectedly common. There is an urgent need to improve awareness and knowledge about lung diseases, make diagnostic and therapeutic options available and increase prevention.

Left ventricular assist device implantation following multisystem inflammatory syndrome in children due to SARS-CoV-2.

Multisystem inflammatory syndrome in children (MIS-C) is rare, however, severe hyperinflammatory condition in children generally weeks after acute SARS-CoV-2 infection. A subset of MIS-C patients is presented with severe heart failure. We hereby report 8-year-old girl presenting acute severe left ventricular failure. Various medical treatments including inotropic agents and drugs related to SARS-CoV-2 infection and MIS-C were applied. However, venoarterial extracorporeal membrane oxygenation (ECMO) was needed to be performed. Due to unsuccessful attempts for ECMO weaning, left ventricular assist device was implanted to the patient with temporary right ventricular support from ECMO.

Comparison of long-term outcome of patients with ST-segment elevation myocardial infarction between pre-COVID-19 and COVID-19 era.

AIMS: To compare major cardiovascular and cerebrovascular events (MACCE) rates between patients in the pre-COVID-19 era and COVID-19 era, and to assess the impact of the presence of COVID-19 (+) on long-term MACCE in ST-segment elevation myocardial infarction (STEMI) in Turkey. METHODS: Using the TURSER study (TURKISH ST-segment elevation myocardial infarction registry) data, the current study included 1748 STEMI patients from 15 centres in Turkey. Patients were stratified into COVID-19 era (March 11st-May 15st, 2020; n = 723) or pre-COVID-19 era (March 11st-May 15st, 2019; n = 1025) cohorts. Long-term MACCE rates were compared between groups. In addition, the effect of COVID-19 positivity on long-term outcomes was evaluated. The primary outcome was the occurrence of MACCE at long-term follow-up, and the secondary outcome was hospitalization with heart failure. RESULTS: The MACCE and hospitalization with heart failure rates between pre-COVID-19 era and COVID-19 era were 23% versus 22% (p = .841), and 12% versus 8% (p = .002), respectively. In the COVID-19 era, the rates of MACCE and hospitalization with heart failure COVID-19-positive versus COVID-19-negative patients were 40% versus 20%, (p < .001), and 43% versus 11% (p < .001), respectively. CONCLUSION: There was no difference between the pre-COVID-19 era and the COVID-19 era in terms of MACCE  in STEMI patients in Turkey. In the COVID-19 era, STEMI patients positive for COVID-19 had a higher rate of MACCE and heart failure hospitalization at the long-term follow-up.

Post-recovery COVID-19 and incident heart failure in the National COVID Cohort Collaborative (N3C) study.

Cardiac involvement has been noted in COVID-19 infection. However, the relationship between post-recovery COVID-19 and development of de novo heart failure has not been investigated in a large, nationally representative population. We examined post-recovery outcomes of 587,330 patients hospitalized in the United States (257,075 with COVID-19 and 330,255 without), using data from the National COVID Cohort Collaborative study. Patients hospitalized with COVID-19 were older (51 vs. 46 years), more often male (49% vs. 42%), and less often White (61% vs. 69%). Over a median follow up of 367 days, 10,979 incident heart failure events occurred. After adjustments, COVID-19 hospitalization was associated with a 45% higher hazard of incident heart failure (hazard ratio = 1.45; 95% confidence interval: 1.39-1.51), with more pronounced associations among patients who were younger (P-interaction = 0.003), White (P-interaction = 0.005), or who had established cardiovascular disease (P-interaction = 0.005). In conclusion, COVID-19 hospitalization is associated with increased risk of incident heart failure.

Heart failure caused by Takayasu's arteritis in the time of COVID-19: a case report.

The case of a 35-year-old female with heart failure is presented, where the symptoms overlap with the heterogeneous manifestations of coronavirus disease 2019 (COVID-19). Those similarities and a recent shift in priorities during the SARS-CoV-2 pandemic delayed the recognition of acute heart failure in this patient. During the differential diagnostic process, obliterative disease was discovered in the bilateral subclavian and right renal arteries, and the latter resulted in uncontrolled hypertension, which played a significant role in the development of heart failure. The aetiology of vascular alterations turned out to be Takayasu's arteritis. Diagnosing Takayasu's arteritis is typically not straightforward due to its nonspecific signs and symptoms. Therefore, it can be concluded from our case report that the rising incidence of COVID-19 and focus on ruling out infection can potentially defer alternative, but appropriate diagnostic tests, particularly for certain conditions like rare diseases. Early identification and intervention is especially important for treating acute heart failure, whereas delay increases the risk of severe complications and mortality.

Cardiac involvement in cancer patients under chemotherapy and diagnosed with COVID-19: case report and literature review.

Many cases of severe cardiac complications due to Coronavirus disease 2019 (COVID-19) were reported. Cancer and chemotherapy appear to be risk and prognostic factors for COVID-19. A 49-year-old Female, with a history of breast cancer treated by tumorectomy and anthracycline-based chemotherapy was admitted with acute respiratory distress syndrome (ARDS) confirmed as COVID-19. She also had elevated troponin I level (up to 43 g/L), and diffuse myocardial hypokinesia along with severe left ventricle dysfunction on echocardiography. Initial treatment included hydroxychloroquine, azithromycin, corticosteroids and mechanical ventilation. The evolution was marked by QT interval prolongation (QTc=523 ms) and occurrence of cardiogenic shock. The patient died of hemodynamic instability reluctant to resuscitation measures at the 2ndday of hospitalization. COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. Receiving chemotherapy especially anthracyclines may be a precipitating and prognostic factor of cardiac manifestations in COVID-19 cancer patients.

Covid-19 Infection During Pregnancy With Acute Heart Failure, Venous Thrombosis And Pneumonia.

The COVID-19 infection has spread rampantly, attaining pandemic status within three months of its first appearance. It has been classically associated with respiratory signs and symptoms. However, unusual presentations have also been reported in multiple literatures. We are reporting a case of acute heart failure in a pregnant patient diagnosed with Covid-19 infection. Her hospital course has been complicated by pneumonia and venous thrombosis during the postpartum period. Her laboratory investigations showed evidence of myocardial injury, acute heart failure, and COVID-19 infection in second PCR sample taken during postpartum period. Echocardiography exhibited features of severe left ventricle systolic dysfunction. She had successful delivery through caesarean-section, nevertheless, her postpartum period was complicated by pneumonia and right femoral venous thrombosis. CT scan of the chest and pulmonary arteries revealed infiltrations in the left lower lobe and right middle lobe, suggestive of consolidation, with no evidence of pulmonary embolism. Cardiac MRI displayed severe global LV and RV systolic dysfunction, but no evidence of myocardial infarction, myocardial infiltration, or abnormal myocardial delayed enhancement. Her condition improved and she was discharged on heart failure medications. During follow-up at the heart failure clinic, her symptoms continued to ameliorate, except the LV and RV systolic dysfunction which persisted. Multiple unusual presentations of Covid-19 infection have been reported in various literatures and screening of the COVID-19 infection should be practiced on regular basis especially among high-risk patients. Prompt identification of COVID-19 infection will lead to proper isolation and mitigation of infection spread among hospitalized patients and health care workers. Covid-19 PCR should be repeated in cases having clinical indication and negative first sample. A proper history and cardiac MRI can differentiate between different aetiologies of heart failure during pregnancy and peripartum COVID-19 infection. Adequate anticoagulation should be considered in COVID-19 patients due to the high risk of thromboembolism. Among patients with COVID-19 infection, CT chest helps demonstrate the extent of pulmonary involvement.

Impact of the COVID-19 Pandemic on Patients Without COVID-19 With Acute Myocardial Infarction and Heart Failure.

Background Excess mortality from cardiovascular disease during the COVID-19 pandemic has been reported. The mechanism is unclear but may include delay or deferral of care, or differential treatment during hospitalization because of strains on hospital capacity. Methods and Results We used emergency department and inpatient data from a 12-hospital health system to examine changes in volume, patient age and comorbidities, treatment (right- and left-heart catheterization), and outcomes for patients with acute myocardial infarction (AMI) and heart failure (HF) during the COVID-19 pandemic compared with pre-COVID-19 (2018 and 2019), controlling for seasonal variation. We analyzed 27 427 emergency department visits or hospitalizations. Patient volume decreased during COVID-19 for both HF and AMI, but age, race, sex, and medical comorbidities were similar before and during COVID-19 for both groups. Acuity increased for AMI as measured by the proportion of patients with ST-segment elevation. There were no differences in right-heart catheterization for patients with HF or in left heart catheterization for patients with AMI. In-hospital mortality increased for AMI during COVID-19 (odds ratio [OR], 1.46; 95% CI, 1.21-1.76), particularly among the ST-segment-elevation myocardial infarction subgroup (OR, 2.57; 95% CI, 2.24-2.96), but was unchanged for HF (OR, 1.02; 95% CI, 0.89-1.16). Conclusions Cardiovascular volume decreased during COVID-19. Despite similar patient age and comorbidities and in-hospital treatments during COVID-19, mortality increased for patients with AMI but not patients with HF. Given that AMI is a time-sensitive condition, delay or deferral of care rather than changes in hospital care delivery may have led to worse cardiovascular outcomes during COVID-19.

Implications of COVID-19 Vaccination on Hospital Encounters and Outcomes.

Adverse events, including cardiac involvement, after vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. We sought to evaluate trends of hospital encounters for vaccine recipients before and after vaccination. We analyzed patients who received the coronavirus disease 2019 (COVID-19) vaccine in the MedStar Health system (11 hospitals in Washington, District of Columbia and Maryland) from December 2020 through August 2021. We then compared hospital encounters (emergency department visits) of patients 60 days before a vaccine dose and 30 days after a vaccine dose, along with encounters related to the SARS-CoV-2 infection itself. The cohort included 5,217 patients who were vaccinated against COVID-19. Our analysis revealed a total of 6,751 emergency department visits, and we divided this total into 3 cohorts: fully vaccinated (n = 1,779), in vaccination window (n = 1,420), and before vaccination (n = 3,552). We found no significant association between vaccination and rate of presentation for acute coronary syndrome, pericarditis, myocarditis, heart failure, conduction abnormality, or noncardiac conditions. Further, encounters for complications related to SARS-CoV-2 infection decreased significantly from those before vaccination (5.4%) to those in vaccination window (4.2%) to those who were fully vaccinated (1.6%). These findings were consistent when all vaccinated encounters were combined into 1 cohort (fully vaccinated + in vaccination window). In conclusion, our analysis suggests that there is no significant association of COVID-19 vaccination with the rate of hospital encounters for cardiac disease, including acute coronary syndrome, pericarditis, myocarditis, congestive heart failure, and conduction abnormality. Further, administration of the vaccine resulted in a significant decrease in hospital encounters for SARS-CoV-2 infections and associated complications.