Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Dose, Infection, and Disease Outcomes for Coronavirus Disease 2019 (COVID-19): A Review.

The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dose, infection, and coronavirus disease 2019 (COVID-19) outcomes remains poorly understood. This review summarizes the existing literature regarding this issue, identifies gaps in current knowledge, and suggests opportunities for future research. In humans, host characteristics, including age, sex, comorbidities, smoking, and pregnancy, are associated with severe COVID-19. Similarly, in animals, host factors are strong determinants of disease severity, although most animal infection models manifest clinically with mild to moderate respiratory disease. The influence of variants of concern as it relates to infectious dose, consequence of overall pathogenicity, and disease outcome in dose-response remains unknown. Epidemiologic data suggest a dose-response relationship for infection contrasting with limited and inconsistent surrogate-based evidence between dose and disease severity. Recommendations include the design of future infection studies in animal models to investigate inoculating dose on outcomes and the use of better proxies for dose in human epidemiology studies.

Meningococcal vaccines and protein-energy undernutrition in children in the African meningitis belt.

BACKGROUND: Vaccines to prevent meningococcal meningitis in the African meningitis belt include PsACWY, a polysaccharide-only vaccine; and PsA-TT, a polysaccharide-protein conjugate vaccine. Protein-energy undernutrition, a condition where children do not receive enough macro- or micronutrients, is related to increased risk of infectious diseases and poor immune function. Reduced immune function could affect vaccine immunogenicity. We investigated connections between protein-energy undernutrition and vaccine immunogenicity and antibody waning to PsACWY and PsA-TT in children in the African meningitis belt. METHODS: This is a secondary analysis of data collected as part of four clinical trials testing the safety and efficacy of PsA-TT in children in Mali, Ghana, and Senegal. We identified whether anthropometric growth indices (low height-for-age, weight-for-height, or weight-for-age Z-score categories) were related to reduced vaccine-elicited antibody (measured with rabbit complement) from pre- to 1 month post-vaccination, in linear regression models. We also identified whether these growth indices were related to increased waning for vaccine-elicited antibody over time, in linear regression models. RESULTS: A total of 697 children were included in our analysis, of which 350 (50.2%) were female; the mean (SD) age was 1.0 (1.1) years, and 578 (83.0%) received PsA-TT. In linear regression models, no consistent statistical relationship was seen between pre-vaccination anthropometric Z-score categories and vaccine immunogenicity, or decline in antibody over time, for either vaccine, although children with low weight-for-height had a greater decline in antibody from 1 to 6 months post-vaccination. CONCLUSIONS: Our analysis did not find protein-energy undernutrition to be associated with immunogenicity or waning of PsACWY- or PsA-TT-elicited antibody in children living in the African meningitis belt. Future studies should consider measuring antibody titers at additional time points post-vaccination, and for longer periods of time, to determine if the rate of antibody waning over a period of several years is associated with protein-energy undernutrition.