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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 1,164 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 RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe did a systematic search of the PubMed database from January 1st, 2020 until April 24th, 2022 using the search terms: "hospitalized" AND "SARS-CoV-2" OR "COVID-19" AND "Pro-spective" AND "Antibody" OR "PCR" OR "long term follow up" and applying the following filters: "Multicenter Study" AND "Observational Study". No language restrictions were applied. While clinical, laboratory, and radiographic features associated with severe COVID-19 in hospitalized adults have been described, description of the kinetics of SARS-CoV-2 specific assays available to clinicians (e.g. PCR and binding antibody) and their integration with other variables is scarce for both short and long term follow up. The current literature is comprised of several studies with small sample size, cross-sectional design with laboratory data typically only recorded at a single point in time (e.g., on admission), limited clinical characteristics, variable duration of follow up, single-center setting, retrospective analyses, kinetics of either PCR or antibody testing but not both, and outcomes such as death or, mechanical ventilation that do not allow delineation of variations in clinical course. Added value of this studyIn our large longitudinal multicenter cohort, the description of outcome severity, was not limited to survival versus death, but encompassed a clinical trajectory approach leveraging longitudinal data based on time in hospital, disease severity by ordinal scale based on degree of respiratory illness, and presence or absence of limitations at discharge. Fatal COVID-19 cases had the lowest ratio of antibody to viral load levels over time as compared to non-fatal cases. Integration of PCR cycle threshold and antibody values with demographics, baseline comorbidities, and laboratory/radiographic findings identified additional risk factors for outcome severity over the first 28 days. However, female sex was the only variable associated with persistence of symptoms over time. Persistence of symptoms was not associated with clinical trajectory over the first 28 days, nor with antibody/viral loads from the acute phase. Implications of all the available evidenceThe described calculated ratio (binding IgG/PCR Ct value) is unique compared to other studies, reflecting host pathogen interactions and representing an accessible approach for patient risk stratification. Integration of SARS-CoV-2 viral load and binding antibody kinetics with other laboratory as well as clinical characteristics in hospitalized COVID-19 patients can identify patients likely to have the most severe short-term outcomes, but is not predictive of symptom persistence at one year post-discharge.
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BackgroundThe influence of pre-existing humoral immunity, inter-individual demographic factors, and vaccine-associated reactogenicity on immunogenicity following COVID vaccination remains poorly understood. MethodsTen-fold cross-validated least absolute shrinkage and selection operator (LASSO) and linear mixed effects models were used to evaluate symptoms experienced during natural infection and following SARS-CoV-2 mRNA vaccination along with demographics as predictors for antibody (AB) responses in COVID+ participants in a longitudinal cohort study. ResultsIn previously infected individuals, AB were more durable and robust following vaccination when compared to natural infection alone. Higher AB were associated with experiencing dyspnea during natural infection, as was the total number of symptoms reported during the COVID-19 disease course. Both local and systemic symptoms following 1st and 2nd dose of SARS-CoV-2 mRNA vaccines were predictive of higher AB after vaccination, as were the demographic factors of age and Hispanic ethnicity. Lastly, there was a significant temporal relationship between AB and days since infection or vaccination. ConclusionVaccination in COVID+ individuals ensures a more robust immune response. Experiencing systemic and local symptoms post-vaccine is suggestive of higher AB, which may confer greater protection. Age and Hispanic ethnicity are predictive of higher AB.
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The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in November of 2021 in South Africa and Botswana as well as in a sample of a traveler from South Africa in Hong Kong.1,2 Since then, B.1.1.529 has been detected in many countries globally. This variant seems to be more infectious than B.1.617.2 (Delta), has already caused super spreader events3 and has outcompeted Delta within weeks in several countries and metropolitan areas. B.1.1.529 hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness.2,4-6 Here, we investigated the neutralizing and binding activity of sera from convalescent, mRNA double vaccinated, mRNA boosted as well as convalescent double vaccinated and convalescent boosted individuals against wild type, B.1.351 and B.1.1.529 SARS-CoV-2 isolates. Neutralizing activity of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529 while neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at strongly reduced levels. Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated but was mostly retained in vaccinated individuals.
