ABSTRACT
BackgroundThe recent SARS-CoV-2 pandemic raises many scientific and clinical questions. One set of questions involves host genetic factors that may affect disease susceptibility and pathogenesis. New work is emerging related to SARS-CoV-2; previous work on other coronaviruses in humans or other host species may be relevant. ObjectivesTo review existing literature on host genetic factors and their association with infection and disease with coronaviruses in humans and in other host species. MethodsWe conducted a systematic review of literature on host genetic factors in humans associated with coronavirus outcomes. We also reviewed studies of host genetic factors associated with coronavirus outcomes in non-human species. We categorized articles, summarized themes related to animal studies, and extracted data from human studies for analyses. ResultsWe identified 1,187 articles of potential relevance. Forty-five studies examined human host genetic factors related to coronavirus, of which 35 involved analysis of specific genes or loci; aside from one meta-analysis on respiratory infections, all were candidate-driven studies, typically investigating small numbers of research subjects and loci. Multiple significant loci were identified, including 16 related to susceptibility to coronavirus (of which 7 identified protective alleles), and 16 related to outcomes or clinical variables (of which 3 identified protective alleles). The types of cases and controls used varied considerably; four studies used traditional replication/validation cohorts. Of the other studies, 28 involved both human and non-human host genetic factors related to coronavirus, and 174 involved study of non-human (animal) host genetic factors related to coronavirus. Key findingsWe have outlined key genes and loci from animal and human host genetic studies that may bear investigation in the nascent host genetic factor studies of COVID-19. Previous human studies have been limited by relatively low numbers of eligible participants and limited availability of advanced genomic methods. These limitations may be less important to studies of SARS-CoV-2.
ABSTRACT
The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research. Key QuestionsO_TEXTBOXKey Questions for SARS-CoV-2 O_LIWhat are the kinetics of immune responses to infection? C_LIO_LIDo people who have more severe disease mount stronger antibody responses after infection? C_LIO_LIHow do antibody responses vary between different types of antibodies or as measured by different assays? C_LIO_LIHow does the presence of antibodies impact the clinical course and severity of the disease? C_LIO_LIIs there cross-reactivity with different coronaviruses? C_LIO_LIDoes cross-reactivity lead to cross-protection? C_LIO_LIWill infection protect you from future infection? C_LIO_LIHow long will immunity last? C_LIO_LIWhat are correlates of protection? C_LI C_TEXTBOX
