Correlation of adverse effects and antibody responses following homologous and heterologous COVID19 prime-boost vaccinations.

BACKGROUND: Studies correlating reactogenicity and immunogenicity of COVID-19 vaccines are limited to BNT162b2, with inconsistent results. We investigated whether adverse reactions after other COVID-19 vaccines reliably predict humoral responses. METHODS: Adult volunteers were recruited for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines administered either 4 or 8 weeks apart. Adverse effects were routinely solicited and recorded by subjects in a standard diary card for up to 84 days post booster vaccination. Anti-SARS-CoV-2 IgG titers were measured pre- (visit 1), and post-booster dose at days 14 (visit 2) and 28 (visit 3). RESULTS: A total of 399 participants (75% women) with a median age of 41 (interquartile range, 33-48 IQR) years were included. Vaccine-induced antibody titers at days 14 and 28 were significantly higher among subjects who reported local erythema, swelling, pain, as well as systemic fever, chills, headache, myalgia, arthralgia, fatigue compared to those who did not experience local or systemic reactogenicity. Post-vaccination humoral responses did not correlate with the occurrence of skin rash and correlated weakly with gastrointestinal symptoms. A significant correlation between post-vaccination peak body temperature and anti-SARS-CoV-2 spike IgG at Day 14, independent of vaccine type and schedule, was found. CONCLUSION: Specific symptoms of reactogenicity such as post-vaccination injection site pain, swelling, erythema and fever, myalgia and fatigue are significantly predictive of the magnitude of the anti-SARS-CoV-2 antibody response.

Factors associated with viral rebound among COVID-19 patients receiving oral antivirals.

BACKGROUND: COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound. METHODS: We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units). RESULTS: A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P < 0.05). The overall proportion of viral rebound (n = 11) was 12.9%, which was more common among patients receiving NMV/r (10 [17.2%] vs. 1 [3.7%], P = 0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0-8.0) days after completion of antivirals. Initial lymphopenia (<0.8 × 109/L) was associated with viral rebound among overall population (adjusted odds ratio [aOR], 5.34; 95% confidence interval [CI], 1.33-21.71), and remained significant (aOR, 4.50; 95% CI, 1.05-19.25) even when patients receiving NMV/r were considered. CONCLUSION: Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant.

Temporal Dynamics of Anti-Type 1 Interferon Autoantibodies in Patients With Coronavirus Disease 2019.

Binding levels and neutralization activity of anti-type 1 interferon autoantibodies peaked during acute coronavirus disease 2019 and markedly decreased thereafter. Most patients maintained some ability to neutralize type 1 interferon into convalescence despite lower levels of binding immunoglobulin G. Identifying these autoantibodies in healthy individuals before the development of critical viral disease may be challenging.

Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19.

Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.