ABSTRACT
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 5p35 (rs60200309-A at DOCK2) that was significantly 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.
Subject(s)
Obesity , COVID-19ABSTRACT
The COVID-19 pandemic is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins closely associated with the prognosis of COVID-19. We observed 27 proteins to be differentially expressed between the cohorts of severely ill COVID-19 patients with adverse and favorable prognosis. Ingenuity pathway analysis revealed that 15 out of the 27 proteins might be regulated by cytokine signalling relevant to interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF), and their differential expression was possibly implicated in the systemic inflammatory response and cardiovascular disorders. We further evaluated the practical prognosticators for the clinical prognosis of severe COVID-19 patients. Subsequent ELISA analyses further uncovered that CHI3L1 and IGFALS could be potent prognostic markers with a high sensitivity. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 patients and provide appropriate treatment based on their predicted prognosis.
Subject(s)
Necrosis , Cardiovascular Diseases , COVID-19ABSTRACT
ObjectiveSerological tests for COVID-19 have been instrumental in studying the epidemiology of the disease. However, the performance of the currently available tests is plagued by the problem of variability. We have developed a high-throughput serological test capable of simultaneously detecting total immunoglobulins (Ig) and immunoglobulin G (IgG) against two of the most immunologically relevant SARS-CoV-2 antigens, nucleocapsid protein (NP) and spike protein (SP) and report its performance in detecting COVID-19 in clinical samples. MethodsWe designed and prepared reagents for measuring NP-IgG, NP-Total Ig, SP-IgG, and SP-Total Ig (using N-terminally truncated NP ({Delta}N-NP) or receptor-binding domain (RBD) antigen) on the advanced chemiluminescence enzyme immunoassay system TOSOH AIA-CL. After determining the basal thresholds based on 17 sera obtained from confirmed COVID-19 patients and 600 negative sera. Subsequently, the clinical validity of the assay was evaluated using independent 202 positive samples and 1,000 negative samples from healthy donors. ResultsAll of the four test parameters showed 100% specificity individually (1,000/1,000; 95%CI, 99.63-100). The sensitivity of the assay increased proportionally to the elapsed time from symptoms onset, and all the tests achieved 100% sensitivity (153/153; 95%CI, 97.63-100) after 13 days from symptoms onset. NP-Total Ig was the earliest to attain maximal sensitivity among the other antibodies tested. ConclusionOur newly developed serological testing exhibited 100% sensitivity and specificity after 13 days from symptoms onset. Hence, it could be used as a reliable method for accurate detection of COVID-19 patients and to evaluate seroprevalence and possibly for surrogate assessment of herd immunity.
Subject(s)
COVID-19ABSTRACT
The COVID-19 is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we introduced an innovative approach utilizing data-independent acquisition (DIA) mass spectrometry to identify the serum proteins closely associated with the COVID-19 severity. We observed 23 proteins to be differentially expressed between the cohorts of critically ill COVID-19 patients with adverse and favorable prognosis. Myoglobin (MB), CHI3L1 and IGFALS were found to have a high sensitivity and specificity for their possible use as independent biomarkers to provide information on the disease prognosis. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 patients and provide appropriate treatment based on their predicted prognosis.Funding: This work was in part supported by grants from the Japan Agency for Medical Research and Development (JP19fk0108169 to YK and JP19fk0108110/JP20he0522001 to AR).Conflict of Interest: The authors declare no competing interests.Ethical Approval: This research plan and protocol was approved by the Clinical Ethics Committee of Yokohama City University Hospital (B2002000048). This study was also performed with the approval of the Clinical Ethics Committee in each of the medical facilities. Informed consent was obtained from all patients and/or their guardians before serum samples collection.