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Background People infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbidities. Neutralizing antibodies (nAbs) are thought to be a primary immune defense against the virus. Large, diverse, well-characterized cohorts of convalescent individuals provide standardized values to benchmark nAb responses to past SARS-CoV-2 infection and define potentially protective levels of immunity. Methods and findings This analysis comprises an observational cohort of 329 HIV-seronegative adults in the United States (n = 167) and Peru (n = 162) convalescing from SARS-CoV-2 infection from May through October 2020. The mean age was 48 years (range 18 to 86), 54% of the cohort overall was Hispanic, and 34% identified as White. nAb titers were measured in serum by SARS-CoV-2.D614G Spike-pseudotyped virus infection of 293T/ACE2 cells. Multiple linear regression was applied to define associations between nAb titers and demographic variables, disease severity and time from infection or disease onset, and comorbidities within and across US and Peruvian cohorts over time. nAb titers peaked 28 to 42 days post-diagnosis and were higher in participants with a history of severe Coronavirus Disease 2019 (COVID-19) (p 55 years, male sex assigned at birth, and, in some cases, body mass index were also independently associated with higher nAb titers, whereas hypertension was independently associated with lower nAb titers. nAb titers did not differ by race, underlying pulmonary disease or smoking. Two months post-enrollment, nAb ID50 (ID80) titers declined 3.5 (2.8)-fold overall. Study limitations in this observational, convalescent cohort include survivorship bias and missing early viral loads and acute immune responses to correlate with the convalescent responses we observed. Conclusions In summary, in our cohort, nAb titers after SARS-CoV-2 infection peaked approximately 1 month post-diagnosis and varied by age, sex assigned at birth, disease severity, and underlying comorbidities. Our data show great heterogeneity in nAb responses among people with recent COVID-19, highlighting the challenges of interpreting natural history studies and gauging responses to vaccines and therapeutics among people with recent infection. Our observations illuminate potential correlations of demographic and clinical characteristics with nAb responses, a key element for protection from COVID-19, thus informing development and implementation of preventative and therapeutic strategies globally. Trial registration ClinicalTrials.gov NCT04403880., Author(s): Shelly Karuna 1,*, Shuying Sue Li 1, Shannon Grant 1, Stephen R. Walsh 2, Ian Frank 3, Martin Casapia 4, Meg Trahey 1, Ollivier Hyrien 1, Leigh Fisher 1, [...]

Background Post-COVID conditions are characterised by persistent symptoms that negatively impact quality of life after SARS-CoV-2 diagnosis. While post-COVID risk factors and symptoms have been extensively described in localised regions, especially in the global north, post-COVID conditions remain poorly understood globally. The global, observational cohort study HVTN 405/HPTN 1901 characterises the convalescent course of SARS-CoV-2 infection among adults in North and South America and Africa. Methods We categorised the cohort by infection severity (asymptomatic, symptomatic, no oxygen requirement (NOR), non-invasive oxygen requirement (NIOR), invasive oxygen requirement (IOR)). We applied a regression model to assess correlations of demographics, co-morbidities, disease severity, and concomitant medications with COVID-19 symptom persistence and duration across global regions. Results We enrolled 759 participants from Botswana, Malawi, South Africa, Zambia, Zimbabwe, Peru, and the USA a median of 51 (interquartile range (IQR)=35-66) days post-diagnosis, from May 2020 to March 2021. 53.8% were female, 69.8% were 18-55 years old (median (md)=44 years old, IQR=33-58). Comorbidities included obesity (42.8%), hypertension (24%), diabetes (14%), human immunodeficiency virus (HIV) infection (11.6%) and lung disease (7.5%). 76.2% were symptomatic (NOR=47.4%; NIOR=22.9%; IOR=5.8%). Median COVID-19 duration among symptomatic participants was 20 days (IQR=11-35); 43.4% reported symptoms after COVID-19 resolution, 33.6% reported symptoms ≥30 days, 9.9% reported symptoms ≥60 days. Symptom duration correlated with disease severity (P<0.001, NIOR vs NOR; P=0.003, IOR vs NOR), lung disease (P=0.001), race (P<0.05, non-Hispanic Black vs White), and global region (P<0.001). Prolonged viral shedding correlated with persistent abdominal pain (odds ratio (OR) = 5.51, P < 0.05) and persistent diarrhoea (OR=6.64, P<0.01). Conclusions Post-COVID duration varied with infection severity, race, lung disease, and region. Better understanding post-COVID conditions, including regionally-diverse symptom profiles, may improve clinical assessment and management globally. [ABSTRACT FROM AUTHOR]

Background: The unprecedented scientific response to the SARS-Cov-2 pandemic in 2020 required the rapid development and activation of extensive clinical trial networks to study vaccines and therapeutics. The COVID-19 Prevention Network (CoVPN) coordinated hundreds of sites conducting phase 2 and 3 clinical trials of vaccines and antibody therapeutics. To facilitate these clinical trials, the CoVPN Volunteer Screening Registry (VSR) was created to collect volunteer information at scale, identify volunteers at risk of COVID-19 who met enrollment criteria, distribute candidates across clinical trial sites, and enable monitoring of volunteering and enrollment progress., Methods: We developed a secure database to support three primary web-based interfaces: a national volunteer questionnaire intake form, a clinical trial site portal, and an Administrative Portal. The Site Portal supported filters based on volunteer attributes, visual analytics, enrollment status tracking, geographic search, and clinical risk prediction. The Administrative Portal supported oversight and development with pre-specified reports aggregated by geography, trial, and trial site; charts of volunteer rates over time; volunteer risk score calculation; and dynamic, user-defined reports., Findings: Over 650,000 volunteers joined the VSR, and 1094 users were trained to utilize the system. The VSR played a key role in recruitment for the Moderna, Oxford-AstraZeneca, Janssen, and Novavax vaccine clinical trials, provided support to the Pfizer and Sanofi vaccine and prophylactic antibody clinical trials, and enhanced the diversity of trial participants. Clinical trial sites selected 166,729 volunteer records for follow-up screening, and of these 47·7% represented groups prioritized for increased enrollment. Despite the unprecedented urgency of its development, the system maintained 99·99% uptime., Interpretation: The success of the VSR demonstrates that information tools can be rapidly yet safely developed through a public-private partnership and integrated into a distributed and accelerated clinical trial setting. We further summarize the requirements, design, and development of the system, and discuss lessons learned for future pandemic preparedness., Competing Interests: Declaration of interests JK, NFA, KM, GBB, MT, and LR declare no conflicts; RL, SS, AK, DM, SM, and JH are employed by Oracle Corporation and hold stock options.