Kinetics of SARS-CoV-2 infection biomarkers in a household transmission study.

SARS-CoV-2 is the causative agent of COVID-19. Timely and accurate diagnostic testing is vital to contain the spread of infection, reduce delays in treatment and care, and inform patient management. Optimal specimen type (e.g. nasal swabs or saliva), timing of sampling, viral marker assayed (RNA or antigen), and correlation with viral infectivity and COVID-19 symptoms severity remain incompletely defined. We conducted a field study to evaluate SARS-CoV-2 viral marker kinetics starting from very early times after infection. We measured RNA and antigen levels in nasal swabs and saliva, virus outgrowth in cell culture from nasal swabs, and antibody levels in blood in a cohort of 30 households. Nine household contacts (HHC) became infected with SARS-CoV-2 during the study. Viral RNA was detected in saliva specimens approximately 1-2 days before nasal swabs in six HHC. Detection of RNA was more sensitive than of antigen, but antigen detection was better correlated with culture positivity, a proxy for contagiousness. Anti-nucleocapsid antibodies peaked one to three weeks post-infection. Viral RNA and antigen levels were higher in specimens yielding replication competent virus in cell culture. This study provides important data that can inform how to optimally interpret SARS-CoV-2 diagnostic test results.

Genetic Predisposition and the Variable Course of Infectious Diseases.

BACKGROUND: Contact with a pathogen is followed by variable courses of infectious disease, which are only partly explicable by classical risk factors. The susceptibility to infection is variable, as is the course of disease after infection. In this review, we discuss the extent to which this variation is due to genetic factors of the affected individual (the host). METHODS: Selective review of the literature on host genetics in infectious disease, with special attention to the pathogens SARSCoV- 2, influenza viruses, Mycobacterium tuberculosis, and human immunodeficiency virus (HIV). RESULTS: Genetic variants of the host contribute to the pathogenesis of infectious diseases. For example, in HIV infection, a relatively common variant leading to a loss of function of the HIV co-receptor CCR5 affects the course of the disease, as do variants in genes of the major histocompatibility complex (MHC) region. Rare monogenic variants of the interferon immune response system contribute to severe disease courses in COVID-19 and influenza (type I interferon in these two cases) and in tuberculosis (type II interferon). An estimated 1.8% of life-threatening courses of COVID-19 in men under age 60 are caused by a deficiency of toll-like receptor 7. The scientific understanding of host genetic factors has already been beneficial to the development of effective drugs. In a small number of cases, genetic information has also been used for individual therapeutic decision-making and for the identification of persons at elevated risk. CONCLUSION: A comprehensive understanding of host genetics can improve the care of patients with infectious diseases. Until the present, the clinical utility of host genetics has been limited to rare cases; in the future, polygenic risk scores summarizing the relevant genetic variants in each patient will enable a wider benefit. To make this possible, multicenter studies are needed that will systematically integrate clinical and genetic data.