RESUMO
COVID-19 is genetically associated with numerous immune disorders, and young age at first intercourse (AFS) may lead to early activation of innate immunity. However, the genetic overlap between COVID-19 and AFS remains undetermined. Here we perform a large-scale cross-trait analysis to investigate their shared genetic etiology and causal relationship. An overall negative genetic correlation between the AFS and three COVID-19 traits was observed. We further identified 186, 221, and 213 shared genetic loci for AFS-COVID-19 infection, hospitalization, and severity, respectively. Among these shared loci, those closest to the genes CADM2, and ARPC1B showed the strongest signals. Our post-GWAS functional analysis revealed that the shared mapped genes were mainly involved in neural genesis and development within several brain structures. Finally, bidirectional Mendelian randomization (MR) results showed that earlier sexual debut may increase the risk of SARS-CoV-2 infection, hospitalization, and severity.
Assuntos
Traumatismos do Nervo Olfatório , Doenças do Sistema Imunitário , COVID-19RESUMO
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. Methods: A total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. Results: A total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. Conclusions Patients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.