RESUMEN
To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5q35 (rs60200309-A at DOCK2) that was associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 x 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.
RESUMEN
BackgroundCoronavirus Disease 2019 (COVID-19) causes severe acute respiratory failure. Antibody-dependent enhancement (ADE) is known as the mechanism for severe forms of other coronavirus diseases. The clinical progression of COVID-19 before and after IgG antibody seroconversion was investigated. MethodsFifty-three patients with reverse transcriptase PCR (RT-PCT)-confirmed COVID-19 viral pneumonia with or without respiratory failure were retrospectively investigated. The timing of the first IgG antibody against SARS-CoV-2-positive date, as well as changes of C-reactive protein (CRP) as an inflammatory marker and blood lymphocyte numbers, was assessed using serial preserved blood samples. FindingsTen patients recovered without oxygen therapy (mild/moderate group), 32 patients had hypoxemia and recovered with antiviral drugs (severe/non-ICU group), and 11 patients had severe respiratory failure and were treated in the ICU (6 of them died; critical/ICU group). The first IgG-positive date (day 0) was observed from 5 to 18 days from the onset of disease. At day 0, a CRP peak was observed in the severe and critical groups, whereas there was no synchronized CRP peak on day 0 in the mild/moderate group. In the severe/non-ICU group, the blood lymphocyte number increased (P=0.0007) and CRP decreased (P=0.0007) after day 0, whereas CRP did not decrease and the blood lymphocyte number further decreased (P=0.0370) in the critical/ICU group. InterpretationThe respiratory failure due to COVID-19 viral pneumonia observed in week 2 may be related to an antibody-related mechanism rather than uncontrolled viral replication. In the critical form of COVID-19, inflammation was sustained after IgG seroconversion. Fundingnone