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1.
Topics in Antiviral Medicine ; 30(1 SUPPL):37-38, 2022.
Article in English | EMBASE | ID: covidwho-1880239

ABSTRACT

Background: Post-Acute Sequelae of SARS-CoV-2 (PASC) is characterized by persistent symptoms negatively impacting quality of life several weeks after SARS-CoV-2 diagnosis. Proposed risk factors include older age, female sex, comorbidities, and severe COVID-19, including hospitalization and oxygen requirement. Yet, associations of these factors with prolonged symptoms remain poorly understood globally. Methods: The global, observational cohort study HVTN 405/HPTN 1901 characterizes the clinical and immunologic course in the first year after SARS-CoV-2 infection among adults. The cohort was categorized by infection severity (asymptomatic;symptomatic with no oxygen requirement [NOR];non-invasive oxygen requirement [NIOR];or invasive oxygen requirement [IOR]). A regression model was applied to estimate geometric mean ratios (GMR) for duration and odds ratios (OR) for persistence of symptoms. Results: 759 participants from Peru (25.2%), USA (26.0%), Republic of South Africa (RSA, 37.7%), and non-RSA Sub-Saharan Africa (11.2%) were enrolled a median of 51 (IQR 35-66) days post-diagnosis, from May 2020 to Mar 2021. 53.8% were female, 69.8% were <55yo (median 44yo, IQR 33-58) and identified as non-Hispanic Black (42.7%), Hispanic (27.9%) or non-Hispanic White (15.8%). Comorbidities included obesity (42.8%), hypertension (24%), diabetes (14%), HIV infection (11.6%) and lung disease (7.5%). 76.2% were symptomatic (NOR 47.4%;NIOR 22.9%;and IOR 5.8%). Among symptomatic participants, median acute COVID-19 duration was 20 days (IQR 11-35);43.3% had ≥1 persistent symptom after COVID-19 resolution (39.8% NOR;49.1 % NIOR+IOR;p=0.037);16.8% reported ≥1 symptom >42 days (14.0% NOR;21.6% NIOR+IOR;p=0.025). Symptom duration was not associated with age or sex assigned at birth but was associated with disease severity (GMR 2.09;95%CI 1.5-2.91, p<0.001 for NIOR vs NOR;not significant for IOR vs NIOR), lung disease (GMR 2.43;95%CI 1.42-4.16, p=0.001), and global region (p<0.05, see Figure 1). Prolonged viral shedding was associated with persistent diarrhea (OR 6.59;95%CI 1.65-26.86;p=0.008). Conclusion: A recovery course consistent with PASC was significantly associated with infection severity, lung disease, and region. Regional differences in symptom profiles and duration may be influenced by viral diversity, genetic, or cultural factors and likely reflect disparities in healthcare access and interventions. Better understanding PASC associations may improve clinical assessment and management globally.

2.
Topics in Antiviral Medicine ; 29(1):87, 2021.
Article in English | EMBASE | ID: covidwho-1250335

ABSTRACT

Background: SARS-CoV-2 has claimed over a million lives and remains a global threat. Understanding immune responses to infection and developing validated laboratory assays to measure them is critical to the rapid development, assessment and implementation of effective interventions. Our development of a validated pseudovirus neutralization assay and characterization of neutralizing antibody (nAb) profiles in a diverse post-SARS-CoV-2 cohort can inform preventative and therapeutic efforts, including vaccine and monoclonal antibody development and deployment. Methods:This analysis comprises an observational cohort of n=330 adults in the US (n=168) and Peru (n=162), convalescing from SARS-CoV-2 infection and stratified by age, asymptomatic or symptomatic infection, and hospitalization. NAb titers are measured in serum by SARS-CoV-2.D614G Spike-pseudotyped virus infection of 293T/ACE2 cells. Multiple linear regression is applied to define associations between nAb titers and demographic variables, disease severity and duration, and co-morbidities within and across US and Peruvian cohorts over time. Results: The mean age is 48 years;49% were assigned female sex at birth, 51% male;54% are Latinx;50% identified as Other race, 34% White, 11% Black, 4%Asian. The mean days from SARS-CoV-2 diagnosis to enrollment was 52. NAb titers were higher in participants with a history of severe illness (p<0.001) and peaked 28-42 days post-diagnosis. ID50 (ID80) nAb titers >20 were detected at enrollment in 66% (46%) of asymptomatic, 86% (74%) of symptomatic and 95% (92%) of hospitalized individuals. Median ID50 (ID80) titers at enrollment among asymptomatic, symptomatic and hospitalized individuals were 107 (10), 482 (59) and 1,953 (366), respectively. Two months post-enrollment, median ID50 (ID80) titers among asymptomatic, symptomatic and hospitalized individuals declined to 30 (10), 130 (16) and 564 (103), respectively. Diabetes (p=0.011), age >55yo (p<0.001), male sex (p=0.003) and BMI ≥30 (p=0.021) were associated with higher ID80 titers. Hypertension was associated with lower ID50 titers (p=0.005). Conclusion: NAb titers after SARS-CoV-2 infection correlate with illness severity and underlying co-morbidities, and peak approximately one month postdiagnosis. Large, diverse, well-characterized cohorts of convalescent individuals facilitate development of standardized laboratory methods and reagents to measure immune responses and provide standardized values to benchmark SARS-CoV-2 vaccine-elicited responses.

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