Project description:RNA was extracted from whole blood of subjects collected in Tempus tubes prior to COVID-19 mRNA booster vaccination. D01 and D21 correspond to samples collected at pre-dose 1 and pre-dose 2 respectively. RNA was also extracted from blood collected at indicated time points post-vaccination. DB1, DB2, DB4 and DB7 correspond to booster day 1 (pre-booster), booster day 2, booster day 4 and booster day 7 respectively. The case subject experienced cardiac complication following mRNA booster vaccination. We performed gene expression analysis of case versus controls over time.
Project description:BackgroundClinical trials of the BNT162b2 vaccine, revealed efficacy and safety. We report six cases of myocarditis, which occurred shortly after BNT162b2 vaccination.MethodsPatients were identified upon presentation to the emergency department with symptoms of chest pain/discomfort. In all study patients, we excluded past and current COVID-19. Routine clinical and laboratory investigations for common etiologies of myocarditis were performed. Laboratory tests also included troponin and C-reactive protein levels. The diagnosis of myocarditis was established after cardiac MRI.FindingsFive patients presented after the second and one after the first dose of the vaccine. All patients were males with a median age of 23 years. Myocarditis was diagnosed in all patients, there was no evidence of COVID-19 infection. Laboratory assays excluded concomitant infection; autoimmune disorder was considered unlikely. All patients responded to the BNT162b2 vaccine. The clinical course was mild in all six patients.InterpretationOur report of myocarditis after BNT162b2 vaccination may be possibly considered as an adverse reaction following immunization. We believe our information should be interpreted with caution and further surveillance is warranted.
Project description:Messenger RNA vaccines are the main COVID-19 vaccines authorized for use in the United States. Side effects are typically minor and transient. We report a case series of four subjects with an acute myocarditis-like illness following mRNA COVID-19 vaccination who were hospitalized at our hospital in Lubbock, Texas. Three patients were young men who presented with acute chest pain after the second dose of the mRNA-1273 vaccine. Another patient was a 53-year-old white woman who presented with acute left arm pain 3 days after the first dose of the mRNA-1273 vaccine. She was later found to have acute decompensated heart failure, and endomyocardial biopsy revealed eosinophilic injury-mediated myocarditis.
Project description:Cardiac microthrombi have been variably identified at autopsy of Covid-19 decedents. Little is known about the morphologic and molecular changes associated with cardiac microthrombi and whether predictive biomarkers exist. We sought to determine the prevalence, pathogenesis, and biomarker risk factors of Covid-19-associated cardiac microthrombi. In addition to histology and immunohistochemical analyses, we investigated right verticles from 8 Covid-19 decedents via single nuclei RNA sequencing for cell-type specific transcriptional differences between hearts with and without microthrombi, as well as between Covid-19 decedents and publicly available non-Covid-19 donor controls.
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection.MethodsStudy cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction.ResultsMale sex was more common in the COVID-19 group (P=0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (P=0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (P=0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (P=0.69, P=1.00, P=0.46, P=0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations.ConclusionsThis detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
Project description:AimsTo prospectively evaluate the incidence of myocardial injury after the administration of the fourth dose BNT162b2 mRNA vaccine (Pfizer-BioNTech) against COVID-19.Methods and resultsHealth care workers who received the BNT162b2 vaccine during the fourth dose campaign had blood samples collected for high-sensitivity cardiac troponin (hs-cTn) during vaccine administration and 2-4 days afterward. Vaccine-related myocardial injury was defined as hs-cTn elevation above the 99th percentile upper reference limit and >50% increase from baseline measurement. Participants with evidence of myocardial injury underwent assessment for possible myocarditis. Of 324 participants, 192 (59.2%) were female and the mean age was 51.8 ± 15.0 years. Twenty-one (6.5%) participants had prior COVID-19 infection, the mean number of prior vaccine doses was 2.9 ± 0.4, and the median time from the last dose was 147 (142-157) days. Reported vaccine-related adverse reactions included local pain at injection site in 57 (17.59%), fatigue in 39 (12.04%), myalgia in 32 (9.88%), sore throat in 21 (6.48%), headache in 18 (5.5%), fever ≥38°C in 16 (4.94%), chest pain in 12 (3.7%), palpitations in 7 (2.16%), and shortness of breath in one (0.3%) participant. Vaccine-related myocardial injury was demonstrated in two (0.62%) participants, one had mild symptoms and one was asymptomatic; both had a normal electrocardiogram and echocardiography.ConclusionIn a prospective investigation, an increase in serum troponin levels was documented among 0.62% of healthy health care workers receiving the fourth dose BNT162b2 vaccine. The two cases had mild or no symptoms and no clinical sequela.Clinical trial registrationClinicalTrials.gov Identifier: NCT05308680.
Project description:As of the end of 2020, coronavirus disease 2019 (COVID-19) remains a global healthcare challenge with alarming death tolls. In the absence of targeted therapies, supportive care continues to be the mainstay of treatment. The hallmark of severe COVID-19 is a thromboinflammatory storm driven by innate immune responses. This manifests clinically as acute respiratory distress syndrome, and in some patients, widespread thrombotic microangiopathy. Neutrophils and complement are key players in the innate immune system, and their role in perpetuating fatal severe COVID-19 continues to receive increasing attention. Here, we review the interplay between neutrophils, neutrophil extracellular traps, and complement in COVID-19 immunopathology, and highlight potential therapeutic strategies to combat these pathways.
Project description:Emerging reports raise concerns on the potential association between the COVID-19 vaccines and cardiac manifestations. We sought to evaluate cardiac complications associated with COVID-19 vaccination in a pooled analysis from our institution's cohort study and systematic review. Consecutive patients admitted in a tertiary hospital in Singapore between 1 January 2021 and 31 March 2021, with onset of cardiac manifestations within 14 days following COVID-19 vaccination were studied. Furthermore, a systematic review was performed, with PubMed, Embase, Research Square, MedRxiv, and LitCovid databases accessed from inception up to 29 June 2021. Relevant manuscripts reporting individual patient data on cardiac complications following COVID-19 vaccination were included. Thirty patients were included in the study cohort, with 29 diagnosed with acute myocardial infarction (AMI) and 1 with myocarditis. Five patients developed heart failure, two had cardiogenic shock, three intubated, and one had cardiovascular-related mortality. In the systematic review, 16 studies were included with 41 myocarditis and six AMI cases. In the pooled analysis of the study cohort and the systematic review, 35 patients had AMI and 42 had myocarditis. Majority were men, and myocarditis patients were younger than AMI patients. Myocarditis patients tended to present 72 hours post-vaccination, while AMI patients were older and typically presented 24 hours post-vaccination. Majority with AMI or myocarditis developed symptoms after the first and second vaccination dose respectively. This pooled analysis of patients presenting with cardiac manifestations following COVID-19 vaccination highlights the differences between myocarditis and AMI presentations in temporal association with the vaccination.