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BackgroundBetter understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.MethodsImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity 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. Multivariable logistic regression was performed.FindingsThe median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors 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%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.InterpretationIntegration 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.FundingNIH.

SARS-CoV-2 and its variants continue to infect hundreds of thousands every day despite the rollout of effective vaccines. Therefore, it is essential to understand the levels of protection that these vaccines provide in the face of emerging variants. Here, we report two demographically balanced cohorts of BNT162b2 vaccine recipients and COVID-19 patients, from which we evaluate neutralizing antibody titers against SARS-CoV-2 as well as the B.1.1.7 (alpha) and B.1.351 (beta) variants. We show that both B.1.1.7 and B.1.351 are less well neutralized by serum from vaccinated individuals, and that B.1.351, but not B.1.1.7, is less well neutralized by convalescent serum. We also find that the levels of variant-specific anti-spike antibodies are proportional to neutralizing activities. Together, our results demonstrate the escape of the emerging SARS-CoV-2 variants from neutralization by serum antibodies, which may lead to reduced protection from re-infection or increased risk of vaccine breakthrough., Here, the authors show that neutralization of human sera from both BNT162b2 vaccine recipients and from convalescent COVID-19 patients is less efficient against SARS- CoV-2 variants B.1.1.7 and B.1.351 and negatively associated with patient age.

Preventing human immunodeficiency virus (HIV) infection in newborns by vertical transmission remains an important unmet medical need in resource-poor areas where antiretroviral therapy (ART) is not available and mothers and infants cannot be treated prepartum or during the breastfeeding period. In the present study, the protective efficacy of the potent HIV-neutralizing antibodies PGT121 and VRC07-523, both produced in plants, were assessed in a multiple-SHIV (simian-human immunodeficiency virus)-challenge breastfeeding macaque model. Newborn macaques received either six weekly subcutaneous injections with PGT121 alone or as a cocktail of PGT121-LS plus VRC07-523-LS injected three times every 2 weeks. Viral challenge with SHIV(SF162P3) was twice weekly over 5.5 weeks using 11 exposures. Despite the transient presence of plasma viral RNA either immediately after the first challenge or as single-point blips, the antibodies prevented a productive infection in all babies with no sustained plasma viremia, compared to viral loads ranging from 10(3) to 5 × 10(8) virions/ml in four untreated controls. No virus was detected in peripheral blood mononuclear cells (PBMCs), and only 3 of 159 tissue samples were weakly positive in the treated babies. Newborn macaques proved to be immunocompetent, producing transient anti-Env antibodies and anti-drug antibody (ADA), which were maintained in the circulation after passive broadly neutralizing antibody clearance. ADA responses were directed to the IgG1 Fc CH2-CH3 domains, which has not been observed to date in adult monkeys passively treated with PGT121 or VRC01. In addition, high levels of VRC07-523 anti-idiotypic antibodies in the circulation of one newborn was concomitant with the rapid elimination of VRC07. Plant-expressed antibodies show promise as passive immunoprophylaxis in a breastfeeding model in newborns. IMPORTANCE Plant-produced human neutralizing antibody prophylaxis is highly effective in preventing infection in newborn monkeys during repeated oral exposure, modeling virus in breastmilk, and offers advantages in cost of production and safety. These findings raise the possibility that anti-Env antibodies may contribute to the control of viral replication in this newborn model and that the observed immune responsiveness may be driven by the long-lived presence of immune complexes.

Access to fast and reliable nucleic acid testing continues to play a key role in controlling the COVID-19 pandemic, especially in the context of increased vaccine break-through risks due to new variants. We report a rapid, low-cost (~ 2 USD), simple-to-use nucleic acid test kit for self-administered at-home testing without lab instrumentation. The entire sample-to-answer workflow takes

We compared the serum neutralizing antibody titers before and after two doses of the BNT162b2 COVID-19 vaccine in ten individuals who recovered from SARS-CoV-2 infection prior to vaccination to 20 individuals with no history of infection, against clinical isolates of B.1.1.7, B.1.351, P.1, and the original SARS-CoV-2 virus. Vaccination boosted pre-existing levels of anti-SARS-CoV-2 spike antibodies 10-fold in previously infected individuals, but not to levels significantly higher than those of uninfected vaccinees. However, neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees against every variant tested: 5.2-fold against B.1.1.7, 6.5-fold against B.1.351, 4.3-fold against P.1, and 3.4-fold against original SARS-CoV-2. Our study indicates that a first-generation COVID-19 vaccine provides broad protection from SARS-CoV-2variants in individuals with previous infection.

We tested human sera from large, demographically balanced cohorts of BNT162b2 vaccine recipients (n=51) and COVID-19 patients (n=44) for neutralizing antibodies against SARS-CoV-2 variants B.1.1.7 and B.1.351. Although the effect is more pronounced in the vaccine cohort, both B.1.1.7 and B.1.351 show significantly reduced levels of neutralization by vaccinated and convalescent sera. Age is negatively correlated with neutralization in vaccinee, and levels of variant-specific RBD antibodies are proportional to neutralizing activities.

Zika virus (ZIKV) emerged as a global public health threat throughout the Americas since 2014. Phylogenetically, the virus is composed of three main lineages, an African, Asian, and American lineage. The recent emergence and spread of ZIKV has raised questions regarding the breadth and potency of human primary ZIKV immune sera against antigenically diverse ZIKV. Although ZIKV is thought to compose a single antigenic serotype, in-depth evaluation of the antigenic relatedness of ZIKV across genetic variants has been limited to a relatively small series of early convalescent human immune sera (4–12 weeks) against a limited number (3) of genetic variants. Using virus neutralization assays, we characterize the potency and breadth of twelve primary ZIKV immune sera from adults infected 5 to 38 months previously against a panel of 11 ZIKV isolates from the African, Asian and American lineages. We assess the variability of neutralization potency of immune sera from these subjects and the variability of susceptibility to neutralization for each virus isolate. Overall, we found all sera neutralized all viruses at FRNT50 ranging from 1:271 to 1:4271, a 15.8-fold range, with only small differences between subject geometric mean titers (GMT) against all viruses and small differences between each ZIKV isolate and sensitivity to neutralization by all sera: when pooled, African strains were 1.3-fold more sensitive to neutralization by subject immune sera compared to pooled American strains. Finally, we subjected our data to analysis using antigenic cartography, finding that ZIKV are highly antigenically similar, with only a ~4-fold range across all antigenic distances between viruses, consistent with a single serotype., Author summary The recent emergence of Zika virus as an important human pathogen has raised questions about the durability and breadth of Zika virus immunity following natural infection in humans. While global epidemic patterns suggest that Zika infection elicits a protective immune response that is likely to offer long-term protection against repeat infection by other Zika viruses, only one study to date has formally examined the ability of human Zika immune sera to neutralize different Zika viruses. That study was limited because it evaluated human immune sera no more than 13 weeks after Zika virus infection and tested a relatively small number of Zika viruses. In this study, we examine twelve human Zika immune sera as far as 3 years after infection and test the sera against a total of eleven Zika virus isolates. Our results confirm the earlier study and epidemic patterns that suggest Zika virus exists in nature as a single serotype, and infection with one Zika virus can be expected to elicit protective immunity against repeat infection by any Zika virus for years to decades after the first infection.