ABSTRACT
Coronavirus disease 2019 (COVID-19) was announced as an outbreak by the World Health Organization (WHO) in January 2020 and as a pandemic in March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to mild pneumonic disease. However, a minority of infected individuals develop severe respiratory symptoms. The objective of this study was to identify susceptible HLA alleles and clinical markers that can be used in risk prediction models for the early identification of severe COVID-19 among hospitalized COVID-19 patients. A total of 137 patients with mild COVID-19 (mCOVID-19) and 53 patients with severe COVID-19 (sCOVID-19) were recruited from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan for the period of February-August 2020. High-resolution sequencing-based typing for eight HLA genes was performed using next-generation sequencing. In the HLA association studies, HLA-A∗11:01:01:01 [Pc = 0.013, OR = 2.26 (1.27-3.91)] and HLA-C∗12:02:02:01∼HLAB∗ 52:01:01:02 [Pc = 0.020, OR = 2.25 (1.24-3.92)] were found to be significantly associated with the severity of COVID-19. After multivariate analysis controlling for other confounding factors and comorbidities, HLAA∗ 11:01:01:01 [P = 3.34E-03, OR = 3.41 (1.50-7.73)], age at diagnosis [P = 1.29E-02, OR= 1.04 (1.01-1.07)] and sex at birth [P = 8.88E-03, OR= 2.92 (1.31-6.54)] remained significant. The area under the curve of the risk prediction model utilizing HLA-A∗11:01:01:01, age at diagnosis, and sex at birth was 0.772, with sensitivity of 0.715 and specificity of 0.717. To the best of our knowledge, this is the first article which describes associations of HLA alleles with COVID-19 at the 4-field (highest) resolution level. Early identification of potential COVID-19 could help clinicians prioritize medical utility and significantly decrease mortality from COVID-19.
ABSTRACT
Despite the increase in COVID-19 cases globally, the number of cases in Japan has been relatively low, and an explosive surge in the prevalence has not occurred. In March 2020, the Ministry of Health, Labour and Welfare (MHLW) in Japan recommended the original criteria for polymerase chain reaction (PCR) testing, although there was a lack of evidence for appropriate targets for COVID-19 testing. This study aimed to evaluate the COVID-19 positive ratio and pre-screening criteria in Tokyo immediately after the insurance-covered SARS-CoV-2 PCR testing became available in Japan. We subjected 277 individuals with mild symptoms in metropolitan Tokyo (positive: 9.0%) from March 9 to 29, 2020, to SARS-CoV-2 PCR testing. The results revealed that 25 (9.0%) of them were PCR-positive. The sensitivity and specificity of the MHLW criteria were 100% and 10.7%, respectively. When the criteria excluded nonspecific symptoms, fatigue, and dyspnea, the sensitivity slightly decreased to 92%, and the specificity increased to 22.2%. The specificity was highest when the fever criterion was >= 37.5 degrees C for >= 4 days, and exposure/travel history, including age and underlying comorbidities, was considered. Our findings suggest that the MHLW criteria, including the symptoms and exposure/travel history, may be useful for COVID-19 pre-screening.
ABSTRACT
Background: Early detection of coronavirus disease (COVID-19) in patients likely to develop severe manifestations enables appropriate interventions, including rapid intensive care unit admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of COVID-19. Methods: Design A retrospective case series. Setting Single-center study, national center hospital designated for infectious disease. Patients Fifty-eight patients who tested positive for SARS-CoV-2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction (RT-PCR) were retrospectively studied. Measurements and main results Urinary β2-microglobulin (β2MG), liver-type fatty acid-binding protein (L-FABP) were serially measured. Serum interferon γ and monocyte chemotactic protein-1 were also evaluated. Results: The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (N = 12). Patients treated with oxygen were assigned to the moderate group (N = 13). Other patients were assigned to the mild group (N = 33). Urine tests revealed that low β2MG and L-FABP levels on admission were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, L-FABP tended to be persistently high. The resulting cutoff values were β2MG;Severe vs. Moderate+Mild: 2457 μg/dL (Specificity 76.9% and Sensitivity 90.0%, AUC 85.9%), L-FABP;Severe vs. Moderate+Mild: 22.0 μg/gCre (Specificity 84.6% and Sensitivity 90%, AUC 91.8%). Urinary β2MG and serum IFN-γ/MCP-1 showed a similar trend. Conclusions: Evaluating urinary biomarkers such as β2MG and L-FABP may allow determination of COVID-19 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.
ABSTRACT
We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.