461. Classical Antigen Presenting Cell Activation Correlates with T Cell Immunity and COVID-19 Severity

Abstract Background The initial response of immune cells against respiratory viruses often determines the severity and duration of disease. The early trajectory of the immune response during infection with SARS-CoV-2 remains poorly understood. Dysregulation of innate immune factors that facilitate viral clearance and the adaptive response, such as type I interferons, have been implicated in severe COVID-19. However, collection of biological samples during the first seven days post-symptom onset has posed a logistical challenge, limiting our knowledge surrounding the immune responses that drive protection versus immunopathology. Methods From March 2020, Military Health System beneficiaries presenting with a positive SARS-CoV-2 test, a COVID-19 like illness, or a high-risk SARS-CoV-2 exposure at nine military medical treatment facilities across the United States were eligible for enrollment in our longitudinal cohort study, which included collection of respiratory sample, sera, plasma, and peripheral blood mononuclear cells (PBMCs). Twenty-five SARS-CoV-2 infected study participants provided samples with in the first seven days of symptom onset, fifteen of whom were hospitalized with COVID-19. We employed multiparameter spectral flow cytometry to comprehensively analyze the early trajectory of the innate and adaptive immune responses. Results We discovered that early activation of critical antigen presenting cell subsets was impaired upon comparing inpatients with outpatients, correlating with decreased antigen-experienced T cell responses. Specifically, we noted reduced expression of key costimulatory molecules, CD80 and CD86, on conventional dendritic cells that are required for viral antigen-specific T cell priming. Reduction in CD38, a marker of activation was also observed on inpatient dendritic cell subsets. Conclusion Reduced antigen presenting cell activation and expression of ligands that facilitate T cell engagement may impede the efficient clearance of SARS-CoV-2, coinciding with more severe disease in our cohort. Further analysis of the functional activation of early innate immune responses triggered by SARS-CoV-2 may unveil new immune biomarkers and therapeutic targets to predict and prevent severe disease associated with inadequate T cell immunity. Disclosures Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work))

The objective of this study was to compare the humoral response to infection in children vs. adults of a same family.
Methods. We performed a prospective cohort study at Sainte-Justine University Health Center in Montreal, Canada from July 2020 to March 2021. Children with a positive SARS-CoV-2 PCR were recruited from the COVID-19 clinic (index case), enrollment was offered to all household members. Serum IgG against SARS-CoV-2 native S1/S2 spike proteins was measured using the Diasorin (Liaison XL) assay, 4-6 months following a positive PCR. A mean antibody threshold of 15 Arbitrary unit per ml (AU/ml) was considered seropositive, with 94.4% positive agreement to plaque reduction neutralization tests (PRNT90) at a 1:40 ratio. Antibody titer was compared between children and adults.
Results. 111 participants (52 adults and 59 children) were recruited from 50 separate families. Characteristic of participants and their clinical symptoms are described in Table 1. Among all participants, 76.3% children were SARS-CoV-2 seropositive vs. 51.9% of adults (p=0.007). Median antibody titer was significantly higher in children vs. adults (82.8 AU,, vs 17.0 AU, [IQR: 6.8-77.8], p=0.006); findings were similar among SARS-CoV-2 PCR positive participants only. Overall, 13 participants were PCR positive but seronegative, 7 were PCR negative and seropositive, while 61 were both PCR positive and seropositive. Older participants and those with any comorbidity. Among the PCR positive group, the seropositive participants were younger (median age 31±17 vs 19±17 years, p=0.003) and more likely to have comorbidity (69% vs 29%, p=0.007).

Conclusion.
These results suggest that children have a stronger antibody response to SARS-CoV-2 infection than adults, and that older age and presence of comorbidity are associated with a less robust humoral response. Further work on the differences in response between children and adults may help elucidate mechanisms underlying the severity of disease Background. Previous studies have observed that multimorbidity, defined as two or more comorbidities, is associated with longer lengths of stay (LOS) and higher mortality in patients with COVID-19. In addition, inequality in social determinants of health (SDOH), dictated by economic stability, education access and quality, healthcare access and quality, neighborhoods and built environment, and social and community context have only added to disparities in morbidity and mortality associated with COVID-19. However, the relationship between SDOH and LOS in COVID-19 patients with multimorbidity is poorly characterized. Analyzing the effect SDOH have on LOS can help identify patients at high risk for prolonged hospitalization and allow prioritization of treatment and supportive measures to promote safe and expeditious discharge.
Methods. This study was a multicenter, retrospective analysis of adult patients with multimorbidity who were hospitalized with COVID-19. The primary outcome was to determine the LOS in these patients. The secondary outcome was to evaluate the role that SDOH play in LOS. Poisson regression analyses were performed to examine associations between individual SDOH and LOS.