Kinetics and durability of humoral responses to SARS-CoV-2 infection and vaccination (preprint)

We analyzed the kinetics and durability of the humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination using >8,000 longitudinal samples collected over a three-year period (April 2020 to April 2023) in the New York City metropolitan area. Upon primary immunization, participants with pre-existing immunity mounted higher antibody responses faster and achieved higher steady-state levels compared to naive individuals. Antibody durability was characterized by two phases: an initial rapid decay, followed by a phase of stabilization with very slow decay resulting in an individual spike binding antibody steady state. Booster vaccination equalized the differences in antibody levels between participants with and without hybrid immunity, but the antibody titers reached decreased with each successive antigen exposure. Break-through infections increased antibody titers to similar levels as an additional vaccine dose in naive individuals. Our study provides strong evidence for the fact that SARS-CoV-2 antibody responses are long lasting, with an initial waning phase followed by a stabilization phase.

The post-COVID-19 population has a high prevalence of crossreactive antibodies to spikes from all Orthocoronavirinae genera (preprint)

The Orthocoronaviridae subfamily is large comprising four highly divergent genera. Four seasonal coronaviruses were circulating in humans prior to the coronavirus disease 2019 (COVID-19) pandemic. Infection with these viruses induced antibody responses that are relatively narrow with little cross-reactivity to spike proteins of other coronaviruses. Here, we report that infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces broadly crossreactive binding antibodies to spikes from a wide range of coronaviruses including members of the sarbecovirus subgenus, betacoronaviruses including Middle Eastern respiratory syndrome coronavirus (MERS CoV), and extending to alpha-, gamma- and delta-coronavirus spikes. These data show that the coronavirus spike antibody landscape in humans has profoundly been changed and broadened as a result of the SARS-CoV-2 pandemic. While we do not understand the functionality of these crossreactive antibodies, they may lead to enhanced resistance of the population to infection with newly emerging coronaviruses with pandemic potential.

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: results from the IMPACC study (preprint)

Background: Better understanding of the association between characteristics of patients hospital-ized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1,164 patients from 20 hospitals across the United States. Disease severi-ty was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multi-variable logistic regression was performed. Findings: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsuper-vised clustering of ordinal score over time revealed distinct disease course trajectories. Risk fac-tors associated with prolonged hospitalization or death by day 28 included age [≥] 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) hav-ing at least one symptom consistent with PASC, most commonly dyspnea (56% among symp-tomatic patients). Female sex was the only associated risk factor for PASC. Interpretation: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. Funding: NIH

Introductions and early spread of SARS-CoV-2 in the New York City area (preprint)

New York City (NYC) has emerged as one of the epicenters of the current SARS-CoV2 pandemic. To identify the early events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus causing COVID19 in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV2 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. Moreover, we find evidence for community transmission of SARS-CoV2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.

A serological assay to detect SARS-CoV-2 seroconversion in humans (preprint)

SARS-Cov-2 (severe acute respiratory disease coronavirus 2), which causes Coronavirus Disease 2019 (COVID19) was first detected in China in late 2019 and has since then caused a global pandemic. While molecular assays to directly detect the viral genetic material are available for the diagnosis of acute infection, we currently lack serological assays suitable to specifically detect SARS-CoV-2 antibodies. Here we describe serological enzyme-linked immunosorbent assays (ELISA) that we developed using recombinant antigens derived from the spike protein of SARS-CoV-2. Using negative control samples representing pre-COVID 19 background immunity in the general adult population as well as samples from COVID19 patients, we demonstrate that these assays are sensitive and specific, allowing for screening and identification of COVID19 seroconverters using human plasma/serum as early as two days post COVID19 symptoms onset. Importantly, these assays do not require handling of infectious virus, can be adjusted to detect different antibody types and are amendable to scaling. Such serological assays are of critical importance to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of coronavirus SARS-Cov-2 antibody titers may, in the future, also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.