Human genetic basis of severe or critical illness in COVID-19

Abstract

Coronavirus Disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to considerable morbidity and mortality worldwide. The clinical manifestation of COVID-19 ranges from asymptomatic or mild infection to severe or critical illness, such as respiratory failure, multi-organ dysfunction or even death. Large-scale genetic association studies have indicated that genetic variations affecting SARS-CoV-2 receptors (angiotensin-converting enzymes, transmembrane serine protease-2) and immune components (Interferons, Interleukins, Toll-like receptors and Human leukocyte antigen) are critical host determinants related to the severity of COVID-19. Genetic background, such as 3p21.31 and 9q34.2 loci were also identified to influence outcomes of COVID-19. In this review, we aimed to summarize the current literature focusing on human genetic factors that may contribute to the observed diversified severity of COVID-19. Enhanced understanding of host genetic factors and viral interactions of SARS-CoV-2 could provide scientific bases for personalized preventive measures and precision medicine strategies.

Nonlinear interdependence of the results of measuring anti-SARS-CoV-2 IgG levels using Abbott and Euroimmun test systems

“…Seroconversion almost always occurs after confirmed COVID-19 even if the disease is mild [9] , [10] , [11] . The rate of formation and persistence of antibodies against SARS-CoV-2 depends on many factors: the severity of the disease and the time of blood sampling after the onset of COVID-19 symptoms [ 12 , 13 ], age [14] , cross-reactions due to previous diseases with coronaviruses of previous generations and vaccination with non-specific vaccines [15] and genetics component [ 16 , 17 ]. The antibodies blood level is affected by the functional of innant immunity as well as the balance between the links of adaptive immunity - cellular and humoral.…”

“…The antibodies blood level is affected by the functional of innant immunity as well as the balance between the links of adaptive immunity - cellular and humoral. The antibodies blood level depends on the intensity of cellular immunity [18] , the presence of OAS1 gene "Neanderthal" variants [19] and also different genetic variations of ACE2 receptors, TMPRSS2 gene, interferon receptor (IFNAR) complex, interferon-induced transmembrane proteins (IFITM), 2′-5′-Oligoadenylate synthase (OAS) family genes, Interleukin 6 и 1 (IL-6 и IL-1), toll-like receptors TLRs, Human Leukocyte Antigen (HLA) and some others [16] . Due to differences in individual manifestations of COVID-19 the intensity of humoral immunity in people infected with SARS-CoV-2 can vary by more than 1000 times [20] , [21] , [22] .…”

Cellular and Molecular Mechanisms of Pathogenic and Protective Immune Responses to SARS-CoV-2 and Implications of COVID-19 Vaccines

“…The initial assumption that SARS-CoV-2 infection was similar to a flu-like infection could not be substantiated after time over the course of the pandemic, as many COVID-19 patients developed severe forms of illnesses with features of acute respiratory distress syndrome (ARDS) [ 87 , 88 , 89 , 90 ]. It is assumed that when the initial interaction between PAMPs of SARS-CoV-2 and PPRs of the infected hosts is unable to block the progression of SARS-CoV-2 and its localization in the upper respiratory tract, then infection is established in the upper nasal area.…”

A comprehensive knowledgebase of known and predicted human genetic variants associated with COVID-19 susceptibility and severity

“…Consequently, the number of identified COVID-19-associated host genetic susceptibility variants has rapidly increased. However, current resources (along with review articles) include a relatively small set of variants [10][11][12] and are mostly derived from GWAS summary results 4 . COVID-19-associated variants have been identified by different methodologies, complicating the confidence assessment of these variants as pathogenic.…”

“…Consequently, the number of identified COVID-19-associated host genetic susceptibility variants has rapidly increased. However, current resources (along with review articles) include a relatively small set of variants 10-12 and are mostly derived from GWAS summary results 4 .…”