Carlos Cordon-Cardo
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Researcher at Icahn School of Medicine at Mount Sinai
New York City (NYC) emerged as a coronavirus disease 2019 (COVID-19) epicenter in March 2020, but there is limited information regarding potentially unrecognized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections before the first reported case. We utilized a sample pooling strategy to screen for SARS-CoV-2 RNA in de-identified, respiratory pathogen-negative nasopharyngeal specimens from 3,040 patients across our NYC health system who were evaluated for respiratory symptoms or influenza-like illness during the first 10 weeks of 2020. We obtained complete SARS-CoV-2 genome sequences from samples collected between late February and early March. Additionally, we detected SARS-CoV-2 RNA in pooled specimens collected in the week ending 25 January 2020, indicating that SARS-CoV-2 caused sporadic infections in NYC a full month before the first officially documented case.
SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 19,860 individuals screened at Mount Sinai Health System in New York City. We also show that titers are stable for at least a period approximating three months, and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses and that these titers are stable for at least the near-term future.
Background Since December 2019, Coronavirus Disease 2019 (COVID-19) has become a global pandemic, causing mass morbidity and mortality. Prior studies in other respiratory infections suggest that convalescent plasma transfusion may offer benefit to some patients. Here, the outcomes of thirty-nine hospitalized patients with severe to life-threatening COVID-19 who received convalescent plasma transfusion were compared against a cohort of retrospectively matched controls. Methods Plasma recipients were selected based on supplemental oxygen needs at the time of enrollment and the time elapsed since the onset of symptoms. Recipients were transfused with convalescent plasma from donors with a SARS-CoV-2 (severe acute respiratory disease coronavirus 2) anti-spike antibody titer of [≥]1:320 dilution. Matched control patients were retrospectively identified within the electronic health record database. Supplemental oxygen requirements and survival were compared between plasma recipients and controls. Results Convalescent plasma recipients were more likely than control patients to remain the same or have improvements in their supplemental oxygen requirements by post-transfusion day 14, with an odds ratio of 0.86 (95% CI: 0.75~0.98; p=0.028). Plasma recipients also demonstrated improved survival, compared to control patients (log-rank test: p=0.039). In a covariates-adjusted Cox model, convalescent plasma transfusion improved survival for non-intubated patients (hazard ratio 0.19 (95% CI: 0.05 ~0.72); p=0.015), but not for intubated patients (1.24 (0.33~4.67); p=0.752). Conclusions Convalescent plasma transfusion is a potentially efficacious treatment option for patients hospitalized with COVID-19; however, these data suggest that non-intubated patients may benefit more than those requiring mechanical ventilation.
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The percentage of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can still be detected at considerable time post symptom resolution. Here we investigated both seroconversion and PCR-positivity in a large cohort of convalescent serum donors in New York City. Methods: Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via enzyme-linked immunosorbent assay for presence of anti SARS-CoV-2 spike antibodies. Results: All but three confirmed SARS-CoV-2 patients seroconverted to the SARS-CoV-2 spike while only 37.4% of suspected SARS-CoV-2 patients seroconverted. PCR-positivity was detected up to 28 days from symptom resolution. Conclusions: Here we show that the vast majority of confirmed COVID19 patients seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks post symptom resolution, but it is unclear if this signal represents infectious virus.
Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration's (FDA) guidelines for convalescent plasma recommends target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at low (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity increased with time post symptom onset (PSO), reaching a peak at 31-35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was ~93% (PRNT50) and ~54% (PRNT90). Sera with high SARS-CoV-2 antibody levels ([≥]960 ELISA titers) showed maximal activity, but not all high titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.