Key Points
Question
What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?
Findings
In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.
Meaning
These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.
We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a repository of currently >14 million B and T cell receptor (BCR and TCR) sequences from the blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. Clonality and skewing of TCR repertoires were associated with interferon type I and III responses, early CD4 + and CD8 + T cell activation, and counterregulation by the co-receptors BTLA, Tim-3, PD-1, TIGIT, and CD73. Tfh, Th17-like, and nonconventional (but not classical antiviral) Th1 cell polarizations were induced. SARS-CoV-2-specific T cell responses were driven by TCR clusters shared between patients with a characteristic trajectory of clonotypes and traceability over the disease course. Our data provide fundamental insight into adaptive immunity to SARS-CoV-2 with the actively updated repository providing a resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.
Highlights d Low avidity and broad cross-reactivities of pre-existing SARS-CoV-2 memory T cells d Strong CCCoV-specific memory CD4 + T cell responses in all analyzed individuals d SARS-CoV-2-specific CD4 + T cells in COVID-19 patients lack cross-reactivity to CCCoVs d Low avidity and clonality of SARS-CoV-2-specific T cell responses in severe COVID-19
Coronavirus disease 2019 (COVID-19) displays high clinical variability but the parameters that determine disease severity are still unclear. Pre-existing T cell memory has been hypothesized as a protective mechanism but conclusive evidence is lacking. Here we demonstrate that all unexposed individuals harbor SARS-CoV-2-specific memory T cells with marginal cross-reactivity to common cold corona and other unrelated viruses. They display low functional avidity and broad protein target specificities and their frequencies correlate with the overall size of the CD4+ memory compartment reflecting the immunological age of an individual. COVID-19 patients have strongly increased SARS-CoV-2-specific inflammatory T cell responses that are correlated with severity. Strikingly however, patients with severe COVID-19 displayed lower TCR functional avidity and less clonal expansion. Our data suggest that a low avidity pre-existing T cell memory negatively impacts on the T cell response quality against neoantigens such as SARS-CoV-2, which may predispose to develop inappropriate immune reactions especially in the elderly. We propose the immunological age as an independent risk factor to develop severe COVID-19.
Background
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and hundreds of thousands of deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. Here, the humoral immune response of a cohort of 143 COVID-19 patients from the University Hospital Frankfurt/Main, Germany was characterized.
Methods
SARS-CoV-2-specific antibodies were detected by enzyme-linked immunosorbent assay (ELISA). SARS-CoV-2 and hCoV NL63 neutralization activity was analyzed with pseudotyped lentiviral vectors.
Results
COVID-19 severity increased with age and male patients encountered more serious symptoms than females. Disease severity correlated with the amount of SARS-CoV-2 specific IgG and IgA and the neutralization activity of the antibodies. The amount of SARS-CoV-2 specific IgG antibodies decreased with time after PCR conformation of the infection and antibodies directed against the nucleoprotein waned faster than spike directed antibodies. In contrast, for the common flu coronavirus NL63, COVID19 disease severity seemed to correlate with low NL63-neutralizing activities, suggesting the possibility of cross-reactive protection.
Conclusion
The results describe the humoral immune responses against SARS-CoV-2 and might aid the identification of correlates of protection needed for vaccine development.
Among HIV-infected patients, the rate of seroconversion after the first dose of an adjuvanted H1N1 influenza A vaccine was 68% and increased to 92% after a second doses.
Seroconversion after one dose of a split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine of HIV-infected patients was 69%. Studies to investigate whether a second dose of the vaccine will increase seroconversion rate are needed.
Seroconversion rates following influenza vaccination in patients with hematologic malignancies after hematopoietic stem cell transplantation (HSCT) are known to be lower compared to healthy adults. The aim of our diagnostic study was to determine the rate of seroconversion after 1 or 2 doses of a novel split virion, inactivated, AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HSCT recipients (ClinicalTrials.gov Identifier: NCT01017172). Blood samples were taken before and 21 days after a first dose and 21 days after a second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer of ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and ≥ 4-fold increase in AB titer 21 days after vaccination. Seventeen patients (14 allogeneic, 3 autologous HSCT) received 1 dose and 11 of these patients 2 doses of the vaccine. The rate of seroconversion was 41.2% (95% confidence interval [CI] 18.4-67.1) after the first and 81.8% (95% CI 48.2-97.7) after the second dose. Patients who failed to seroconvert after 1 dose of the vaccine were more likely to receive any immunosuppressive agent (P = .003), but time elapsed after or type of HSCT, age, sex, or chronic graft-versus-host disease was not different when compared to patients with seroconversion. In patients with hematologic malignancies after HSCT the rate of seroconversion after a first dose of an adjuvanted H1N1 influenza A vaccine was poor, but increased after a second dose.
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