We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.
Analysis of 772 complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from early in the Boston-area epidemic revealed numerous introductions of the virus, a small number of which led to most cases. The data revealed two superspreading events. One, in a skilled nursing facility, led to rapid transmission and significant mortality in this vulnerable population but little broader spread, whereas other introductions into the facility had little effect. The second, at an international business conference, produced sustained community transmission and was exported, resulting in extensive regional, national, and international spread. The two events also differed substantially in the genetic variation they generated, suggesting varying transmission dynamics in superspreading events. Our results show how genomic epidemiology can help to understand the link between individual clusters and wider community spread.
BACKGROUND
Characterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence.
METHODS
We measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic.
RESULTS
Between 14-28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63.
CONCLUSIONS
Among symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.
Background. Sensitive and specific SARS-CoV-2 serologic assays are needed to inform diagnostic, therapeutic, and public health decision-making. We evaluated three commercial serologic assays as stand-alone tests and as components of two-test algorithms.
Methods. Two nucleocapsid (Abbott IgG and Roche total antibody) and one spike-protein (DiaSorin IgG) antibody tests were included. We assessed sensitivity using 128 serum samples from symptomatic PCR-confirmed COVID-19-infected patients, and specificity using 1204 samples submitted for routine serologies prior to COVID-19's emergence, plus 64 pandemic-era samples from SARS-CoV-2 PCR-negative patients with respiratory symptoms. Assays were evaluated as stand-alone tests and as components of a two-test algorithm in which positive results obtained using one assay were verified using a second assay.
Results. The two nucleocapsid antibody tests were more sensitive than the spike-protein antibody test overall (70% and 70% versus 57%; P≤0.003), with pronounced differences observed using samples collected 7-14 days after symptom onset. All three assays were comparably sensitive (≥89%, P≥0.13) using samples collected >14 days after symptom onset. Specificity was higher using the nucleocapsid antibody tests (99.3% and 99.7%) compared with the spike protein antibody test (97.8%, P≤0.002). When any two assays were paired in a two-test algorithm, specificity was 99.9% (P<0.0001 to 0.25 compared with the individual assays), and positive predictive value (PPV) improved substantially with minimal effect on negative predictive value (NPV).
Conclusions. Two nucleocapsid antibody tests outperformed a spike protein antibody test. Pairing two different serologic tests in a two-test algorithm improves PPV compared with the individual assays alone, while maintaining NPV.
Candida auris is an emerging, often multidrug-resistant pathogen with important public health implications. Infections are associated with high mortality, and prevention of transmission requires stringent infection control measures, making C. auris a potential barrier to transplantation. We describe the first donor-derived C. auris transmission in a lung transplant recipient.
We enrolled seven individuals with recurrent symptoms or antigen test conversion following nirmatrelvir-ritonavir treatment. High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis. No known resistance-associated mutations were identified.
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