Serum KL-6 levels predict clinical outcomes and are associated with MUC1 polymorphism in Japanese patients with COVID-19.

BACKGROUND: Krebs von den Lungen-6 (KL-6) is a known biomarker for diagnosis and monitoring of interstitial lung diseases. However, the role of serum KL-6 and the mucin 1 (MUC1) variant (rs4072037) in COVID-19 outcomes remains to be elucidated. We aimed to evaluate the relationships among serum KL-6 levels, critical outcomes and the MUC1 variant in Japanese patients with COVID-19. METHODS: This is a secondary analysis of a multicentre retrospective study using data from the Japan COVID-19 Task Force collected from February 2020 to November 2021, including 2226 patients with COVID-19 whose serum KL-6 levels were measured. An optimal serum KL-6 level cut-off to predict critical outcomes was determined and used for multivariable logistic regression analysis. Furthermore, the relationship among the allele dosage of the MUC1 variant, calculated from single nucleotide polymorphism typing data of genome-wide association studies using the imputation method, serum KL-6 levels and COVID-19 critical outcomes was evaluated. RESULTS: Serum KL-6 levels were significantly higher in patients with COVID-19 with critical outcomes (511±442 U/mL) than those without (279±204 U/mL) (p<0.001). Serum KL-6 levels ≥304 U/mL independently predicted critical outcomes (adjusted OR (aOR) 3.47, 95% CI 2.44 to 4.95). Moreover, multivariable logistic regression analysis with age and sex indicated that the MUC1 variant was independently associated with increased serum KL-6 levels (aOR 0.24, 95% CI 0.28 to 0.32) but not significantly associated with critical outcomes (aOR 1.11, 95% CI 0.80 to 1.54). CONCLUSION: Serum KL-6 levels predicted critical outcomes in Japanese patients with COVID-19 and were associated with the MUC1 variant. Therefore, serum KL-6 level is a potentially useful biomarker of critical COVID-19 outcomes.

Use of the neutrophil-to-lymphocyte ratio and an oxygen requirement to predict disease severity in patients with COVID-19

We investigated the association between complete blood count, including neutrophil-to-lymphocyte ratio (NLR) in combination with patient characteristics, and coronavirus disease (COVID-19) outcomes to identify the best prognostic indicator. We analyzed data of patients with confirmed COVID-19 from the nationwide database of the Japan COVID-19 Task Force between February 2020 and November 2021. A composite outcome was defined as the most severe condition, including noninvasive positive-pressure ventilation, high-flow nasal cannula, invasive mechanical ventilation, extracorporeal membrane oxygenation, or death. Of 2,425 patients in the analysis, 472 (19.5%) experienced a composite outcome. NLR was the best predictor of composite outcomes, with an area under the curve (AUC) of 0.81, and a sensitivity and specificity of 72.3% and 75.7%, respectively, using a cut-off value of 5.04. The combination of NLR and an oxygen requirement on admission had the highest AUC (0.88). This simple combination may help identify patients at risk of progression to severe disease.

COVID-19 infection risk assessment and management at the Tokyo 2020 Olympic and Paralympic Games: A scoping review.

The Tokyo 2020 Olympic and Paralympic Games was one of the largest international mass-gathering events held after the beginning of coronavirus disease 2019 (COVID-19) pandemic. In this scoping review, we extracted papers discussing COVID-19 risk assessment or management at the Tokyo 2020 Games to determine the nature of studies that were conducted. Among the 75 papers obtained from two search engines (PubMed and ScienceDirect) and four papers collected from hand-searches, 30 papers were extracted. Only eight papers performed both COVID-19 prior risk assessment and quantitative evaluation of effectiveness measures, highlighting the importance of rapid, solution-focused risk assessment. Furthermore, this review revealed that the findings regarding the spread of COVID-19 infection to citizens in the host country were inconsistent depending on the assessment methods and that assessments of the spread of infection outside the host country were lacking.

Characteristics and clinical effectiveness of COVID-19 vaccination in hospitalized patients in Omicron-dominated epidemic wave - a nationwide study in Japan.

OBJECTIVES: COVID-19 was severe in the Delta variant-dominated epidemic wave (fifth wave) in Japan. The clinical characteristics and effectiveness of COVID-19 vaccination are not fully understood in the Omicron variant-dominated wave (sixth and seventh waves), especially in hospitalized patients. We investigated the relationship between vaccination and disease severity in the Omicron-dominated wave and compared these variant-dominated waves. METHODS: The nationwide COVID-19 database (Japan COVID-19 Task Force) was used to compare clinical characteristics and critical outcomes in patients hospitalized with Delta (fifth, N = 735) vs Omicron-dominated waves (sixth, N = 495; seventh, N = 128). RESULTS: Patients in the sixth and seventh waves had a lower incidence of critical outcomes and respiratory outcomes, and a higher incidence of bacterial infection, although the mortality rate did not differ significantly between waves. In the sixth and seventh waves, 138 (27.9%) and 29 (22.7%) patients with COVID-19 were unvaccinated, respectively. Multivariable analysis adjusted with previously reported factors revealed that the proportion of (1) critical outcomes and (2) respiratory outcomes decreased in a frequency-dependent manner. Thus, (1) (the number of vaccinations): 1-2 times: adjusted odds ratio (aOR) 0.37 (95% confidence interval [CI]; 0.20-0.69); 3-4 times: aOR 0.25 (95% CI; 0.11-0.58); and (2) 1-2 times: aOR 0.43 (95% CI; 0.27-0.66); 3-4 times: aOR 0.36 (95% CI; 0.21-0.60). CONCLUSIONS: Patients hospitalized with COVID-19 with Omicron infections showed a lower incidence of critical outcomes than those with Delta infections, and COVID-19 vaccination may contribute to preventing respiratory failure.

Identification of SARS-CoV-2 variants in wastewater using targeted amplicon sequencing during a low COVID-19 prevalence period in Japan.

Wastewater-based epidemiology is expected to be able to identify SARS-CoV-2 variants at an early stage via next-generation sequencing. In the present study, we developed a highly sensitive amplicon sequencing method targeting the spike gene of SARS-CoV-2, which allows for sequencing viral genomes from wastewater containing a low amount of virus. Primers were designed to amplify a relatively long region (599 bp) around the receptor-binding domain in the SARS-CoV-2 spike gene, which could distinguish initial major variants of concern. To validate the methodology, we retrospectively analyzed wastewater samples collected from a septic tank installed in a COVID-19 quarantine facility between October and December 2020. The relative abundance of D614G mutant in SARS-CoV-2 genomes in the facility wastewater increased from 47.5 % to 83.1 % during the study period. The N501Y mutant, which is the characteristic mutation of the Alpha-like strain, was detected from wastewater collected on December 24, 2020, which agreed with the fact that a patient infected with the Alpha-like strain was quarantined in the facility on this date. We then analyzed archived municipal wastewater samples collected between November 2020 and January 2021 that contained low SARS-CoV-2 concentrations ranging from 0.23 to 0.43 copies/qPCR reaction (corresponding to 3.30 to 4.15 log10 copies/L). The targeted amplicon sequencing revealed that the Alpha-like variant with D614G and N501Y mutations was present in municipal wastewater collected on December 4, 2020 and later, suggesting that the variant had already spread in the community before its first clinical confirmation in Japan on December 25, 2020. These results demonstrate that targeted amplicon sequencing of wastewater samples is a powerful surveillance tool applicable to low COVID-19 prevalence periods and may contribute to the early detection of emerging variants.

COVID-19 infection risk assessment and management at the Tokyo 2020 Olympic and Paralympic Games: A scoping review

The Tokyo 2020 Olympic and Paralympic Games was one of the largest international mass-gathering events held after the beginning of coronavirus disease 2019 (COVID-19) pandemic. In this scoping review, we extracted papers discussing COVID-19 risk assessment or management at the Tokyo 2020 Games to determine the nature of studies that were conducted. Among the 75 papers obtained from two search engines (PubMed and ScienceDirect) and four papers collected from hand-searches, 30 papers were extracted. Only eight papers performed both COVID-19 prior risk assessment and quantitative evaluation of effectiveness measures, highlighting the importance of rapid, solution-focused risk assessment. Furthermore, this review revealed that the findings regarding the spread of COVID-19 infection to citizens in the host country were inconsistent depending on the assessment methods and that assessments of the spread of infection outside the host country were lacking.

Impact of accumulative smoking exposure and chronic obstructive pulmonary disease on COVID-19 outcomes: report based on findings from the Japan COVID-19 task force.

OBJECTIVES: Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. METHODS: The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into <10 PY (n = 293), 10-30 PY (n = 497), and >30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV). RESULTS: The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY = 7.8%, 10-30 PY = 12.3%, >30 PY = 15.2%, COPD = 26.1%; P <0.001). A significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 years. CONCLUSION: Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.

Clinical significance of prediabetes, undiagnosed diabetes and diagnosed diabetes on critical outcomes in COVID-19: Integrative analysis from the Japan COVID-19 task force.

AIM: Diabetes mellitus (DM) is a known risk factor for severe coronavirus disease 2019 (COVID-19), but the clinical impact of undiagnosed diabetes and prediabetes in COVID-19 are unclear particularly in Japan. We clarify the difference in clinical characteristics, including age, sex, body mass index and co-morbidities, laboratory findings and critical outcomes, in a large Japanese COVID-19 cohort without diabetes, with prediabetes, undiagnosed diabetes and diagnosed diabetes, and to identify associated risk factors. MATERIALS AND METHODS: This multicentre, retrospective cohort study used the Japan COVID-19 Task Force database, which included data on 2430 hospitalized COVID-19 patients from over 70 hospitals from February 2020 to October 2021. The prevalence of prediabetes, undiagnosed diabetes and diagnosed diabetes were estimated based on HbA1c levels or a clinical diabetes history. Critical outcomes were defined as the use of high-flow oxygen, invasive positive-pressure ventilation or extracorporeal membrane oxygenation, or death during hospitalization. RESULTS: Prediabetes, undiagnosed diabetes and diagnosed diabetes were observed in 40.9%, 10.0% and 23.0%, respectively. Similar to diagnosed diabetes, prediabetes and undiagnosed diabetes were risk factors for critical COVID-19 outcomes (adjusted odds ratio [aOR] [95% CI]: 2.13 [1.31-3.48] and 4.00 [2.19-7.28], respectively). HbA1c was associated with COVID-19 severity in prediabetes patients (aOR [95% CI]: 11.2 [3.49-36.3]), but not other groups. CONCLUSIONS: We documented the clinical characteristics and outcomes of Japanese COVID-19 patients according to HbA1c levels or diabetes co-morbidity. As well as undiagnosed and diagnosed diabetes, physicians should be aware of prediabetes related to COVID-19 severity.

Sensitivity of rapid antigen tests for COVID-19 during the Omicron variant outbreak among players and staff members of the Japan Professional Football League and clubs: a retrospective observational study.

OBJECTIVES: Rapid antigen tests have been used to prevent the spread of the COVID-19; however, there have been concerns about their decreased sensitivity to the Omicron variant. In this study, we assessed the sensitivity and specificity of the rapid antigen test compared with the PCR test among the players and staff members of the Japan Professional Football League and clubs. Furthermore, we evaluated the relationship between the sensitivity and the duration from the onset of symptoms to testing or vaccine status. DESIGN: This was a retrospective observational study. METHODS: We used 656 results from both the rapid antigen and PCR tests for COVID-19 using samples collected on the same day from 12 January to 2 March 2022, during the Omicron variant outbreak in Japan. RESULTS: The sensitivity of the rapid antigen test compared with the PCR test was 0.63 (95% CI: 0.53 to 0.73) and the specificity was 0.998 (95% CI: 0.995 to 1.000). There were no significant associations between the sensitivity and the duration from the onset of symptoms to testing (including asymptomatic cases in the category) or vaccination status (p>0.05) with small effect sizes (Cramer's V or φ: ≤0.22). CONCLUSIONS: Even during the Omicron outbreak, the sensitivity of the rapid antigen tests did not depend on the duration from the onset of symptoms to testing.

Characteristics of hospitalized patients with COVID-19 during the first to fifth waves of infection: a report from the Japan COVID-19 Task Force.

BACKGROUND: We aimed to elucidate differences in the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan, by COVID-19 waves, from conventional strains to the Delta variant. METHODS: We used secondary data from a database and performed a retrospective cohort study that included 3261 patients aged ≥ 18 years enrolled from 78 hospitals that participated in the Japan COVID-19 Task Force between February 2020 and September 2021. RESULTS: Patients hospitalized during the second (mean age, 53.2 years [standard deviation {SD}, ± 18.9]) and fifth (mean age, 50.7 years [SD ± 13.9]) COVID-19 waves had a lower mean age than those hospitalized during the other COVID-19 waves. Patients hospitalized during the first COVID-19 wave had a longer hospital stay (mean, 30.3 days [SD ± 21.5], p < 0.0001), and post-hospitalization complications, such as bacterial infections (21.3%, p < 0.0001), were also noticeable. In addition, there was an increase in the use of drugs such as remdesivir/baricitinib/tocilizumab/steroids during the latter COVID-19 waves. In the fifth COVID-19 wave, patients exhibited a greater number of presenting symptoms, and a higher percentage of patients required oxygen therapy at the time of admission. However, the percentage of patients requiring invasive mechanical ventilation was the highest in the first COVID-19 wave and the mortality rate was the highest in the third COVID-19 wave. CONCLUSIONS: We identified differences in clinical characteristics of hospitalized patients with COVID-19 in each COVID-19 wave up to the fifth COVID-19 wave in Japan. The fifth COVID-19 wave was associated with greater disease severity on admission, the third COVID-19 wave had the highest mortality rate, and the first COVID-19 wave had the highest percentage of patients requiring mechanical ventilation.

Impact of upper and lower respiratory symptoms on COVID-19 outcomes: a multicenter retrospective cohort study.

BACKGROUND: Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients. METHODS: This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death. RESULTS: Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.11-0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43-4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course. CONCLUSIONS: Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.

Cross-Border Transmissions of the Delta Substrain AY.29 During Tokyo Olympic and Paralympic Games.

Tokyo Olympic and Paralympic Games, postponed for the COVID-19 pandemic, were finally held in the summer of 2021. Just before the games, the Alpha variant was being replaced with the more contagious Delta variant. AY.4 substrain AY.29, which harbors two additional characteristic mutations of 5239C > T (NSP3 Y840Y) and 5514T > C (NSP3 V932A), emerged in Japan and became dominant in Tokyo by the time of the Olympic Games. Variants of SARS-CoV-2 genomes were performed to extract AY.29 Delta substrain samples with 5239C > T and 5514T > C. Phylogenetic analysis was performed to illustrate how AY.29 strains evolved and were introduced into countries abroad. Simultaneously, ancestral searches were performed for the overseas AY.29 samples to identify their origins in Japan using the maximum variant approach. As of January 10, 2022, 118 samples were identified in 20 countries. Phylogenetic analysis and ancestral searches identified 55 distinct introductions into those countries. The United States had 50 samples with 10 distinct introductions, and the United Kingdom had 13 distinct strains introduced in 18 samples. Other countries or regions with multiple introductions were Canada, Germany, South Korea, Hong Kong, Thailand, and the Philippines. Among the 20 countries, most European and North American countries have vaccination rates over 50% and sufficient genomic surveillances are conducted; transmissions seem contained. However, propagation to unvaccinated regions might have caused unfathomable damages. Since samples in those unvaccinated countries are also undersampled with a longer lead time for data sharing, it will take longer to grasp the whole picture. More rigorous departure screenings for the participants from the unvaccinated countries might have been necessary.

The detectability and removal efficiency of SARS-CoV-2 in a large-scale septic tank of a COVID-19 quarantine facility in Japan.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be present in sewage, and wastewater-based epidemiology has attracted much attention. However, the physical partitioning of SARS-CoV-2 in wastewater and the removal efficiency of treatment systems require further investigation. This study aimed to investigate the detectability and physical partitioning of SARS-CoV-2 in wastewater and assess its removal in a large-scale septic tank employing anaerobic, anoxic, and oxic processes in a sequential batch reactor, which was installed in a coronavirus disease 2019 (COVID-19) quarantine facility. The amount of SARS-CoV-2 RNA in wastewater was determined with polyethylene glycol (PEG) precipitation followed by quantitative polymerase chain reaction (qPCR), and the association of SARS-CoV-2 with wastewater solids was evaluated by the effect of filtration prior to PEG precipitation (pre-filtration). The amount of SARS-CoV-2 RNA detected from pre-filtered samples was substantially lower than that of samples without pre-filtration. These results suggest that most SARS-CoV-2 particles in wastewater are associated with the suspended solids excluded by pre-filtration. The removal efficiency of SARS-CoV-2 in the septic tank was evaluated based on the SARS-CoV-2 RNA concentrations in untreated and treated wastewater, which was determined by the detection method optimized in this study. Escherichia coli and pepper mild mottle virus (PMMoV) were also quantified to validate the wastewater treatment system's performance. The mean log10 reduction values of SARS-CoV-2, E. coli, and PMMoV were 2.47 (range, 2.25-2.68), 2.81 (range, 2.45-3.18), and 0.66 (range, 0.61-0.70), respectively, demonstrating that SARS-CoV-2 removal by the wastewater treatment system was comparable to or better than the removal of fecal indicators. These results suggest that SARS-CoV-2 can be readily removed by the septic tank. This is the first study to determine the removal efficiency of SARS-CoV-2 in a facility-level sequencing batch activated sludge system.

Clinical clustering with prognostic implications in Japanese COVID-19 patients: report from Japan COVID-19 Task Force, a nation-wide consortium to investigate COVID-19 host genetics.

BACKGROUND: The clinical course of coronavirus disease (COVID-19) is diverse, and the usefulness of phenotyping in predicting the severity or prognosis of the disease has been demonstrated overseas. This study aimed to investigate clinically meaningful phenotypes in Japanese COVID-19 patients using cluster analysis. METHODS: From April 2020 to May 2021, data from inpatients aged ≥ 18 years diagnosed with COVID-19 and who agreed to participate in the study were collected. A total of 1322 Japanese patients were included. Hierarchical cluster analysis was performed using variables reported to be associated with COVID-19 severity or prognosis, namely, age, sex, obesity, smoking history, hypertension, diabetes mellitus, malignancy, chronic obstructive pulmonary disease, hyperuricemia, cardiovascular disease, chronic liver disease, and chronic kidney disease. RESULTS: Participants were divided into four clusters: Cluster 1, young healthy (n = 266, 20.1%); Cluster 2, middle-aged (n = 245, 18.5%); Cluster 3, middle-aged obese (n = 435, 32.9%); and Cluster 4, elderly (n = 376, 28.4%). In Clusters 3 and 4, sore throat, dysosmia, and dysgeusia tended to be less frequent, while shortness of breath was more frequent. Serum lactate dehydrogenase, ferritin, KL-6, D-dimer, and C-reactive protein levels tended to be higher in Clusters 3 and 4. Although Cluster 3 had a similar age as Cluster 2, it tended to have poorer outcomes. Both Clusters 3 and 4 tended to exhibit higher rates of oxygen supplementation, intensive care unit admission, and mechanical ventilation, but the mortality rate tended to be lower in Cluster 3. CONCLUSIONS: We have successfully performed the first phenotyping of COVID-19 patients in Japan, which is clinically useful in predicting important outcomes, despite the simplicity of the cluster analysis method that does not use complex variables.

Cross-Border Transmissions of the Delta Substrain AY.29 During Tokyo Olympic and Paralympic Games

Tokyo Olympic and Paralympic Games, postponed for the COVID-19 pandemic, were finally held in the summer of 2021. Just before the games, the Alpha variant was being replaced with the more contagious Delta variant. AY.4 substrain AY.29, which harbors two additional characteristic mutations of 5239C > T (NSP3 Y840Y) and 5514T > C (NSP3 V932A), emerged in Japan and became dominant in Tokyo by the time of the Olympic Games. Variants of SARS-CoV-2 genomes were performed to extract AY.29 Delta substrain samples with 5239C > T and 5514T > C. Phylogenetic analysis was performed to illustrate how AY.29 strains evolved and were introduced into countries abroad. Simultaneously, ancestral searches were performed for the overseas AY.29 samples to identify their origins in Japan using the maximum variant approach. As of January 10, 2022, 118 samples were identified in 20 countries. Phylogenetic analysis and ancestral searches identified 55 distinct introductions into those countries. The United States had 50 samples with 10 distinct introductions, and the United Kingdom had 13 distinct strains introduced in 18 samples. Other countries or regions with multiple introductions were Canada, Germany, South Korea, Hong Kong, Thailand, and the Philippines. Among the 20 countries, most European and North American countries have vaccination rates over 50% and sufficient genomic surveillances are conducted;transmissions seem contained. However, propagation to unvaccinated regions might have caused unfathomable damages. Since samples in those unvaccinated countries are also undersampled with a longer lead time for data sharing, it will take longer to grasp the whole picture. More rigorous departure screenings for the participants from the unvaccinated countries might have been necessary.

Development of a COVID-19 risk assessment model for participants at outdoor music festivals: evaluation of the validity and control measure effectiveness based on two actual events in Japan and Spain.

We developed an environmental exposure model to estimate the coronavirus disease 2019 (COVID-19) risk among participants at outdoor music festivals and validated the model using two real events-one in Japan (Event 1) and one in Spain (Event 2). Furthermore, we considered a hypothetical situation in which Event 1 was held but enhanced measures were implemented to evaluate the extent to which the risk could be reduced by additional infection control measures, such as negative antigen tests on the day of the event, wearing of masks, disinfection of environmental surfaces, and vaccination. Among 7,392 participants, the total number of already- and newly-infected individuals who participated in Event 1 according to the new model was 47.0 (95% uncertainty interval: 12.5-185.5), which is in good agreement with the reported value (45). The risk of infection at Event 2 (1.98 × 10-2; 95% uncertainty interval: 0.55 × 10-2-6.39 × 10-2), calculated by the model in this study, was also similar to the estimated value in the previous epidemiological study (1.25 × 10-2). These results for the two events in different countries highlighted the validity of the model. Among the additional control measures in the hypothetical Event 1, vaccination, mask-wearing, and disinfection of surfaces were determined to be effective. Based on the combination of all measures, a 94% risk reduction could be achieved. In addition to setting a benchmark for an acceptable number of newly-infected individuals at the time of an event, the application of this model will enable us to determine whether it is necessary to implement additional measures, limit the number of participants, or refrain from holding an event.

U-shaped association between abnormal serum uric acid levels and COVID-19 severity: reports from the Japan COVID-19 Task Force.

OBJECTIVES: This study aimed to identify the relationship between abnormal serum uric acid levels or a history of hyperuricemia and COVID-19 severity in the Japanese population. METHODS: We included 1523 patients enrolled in the Japan COVID-19 Task Force cohort between February 2020 and May 2021. We compared the clinical characteristics, including co-morbidities, laboratory findings, and outcomes, particularly invasive mechanical ventilation (IMV), among patients with and without abnormal uric acid levels or a history of hyperuricemia. RESULTS: Patients with high serum uric acid levels were older and had higher body weight and body mass index than those without. In addition, the multiple logistic regression analysis revealed a significant association between high serum uric acid levels or a history of hyperuricemia and an increased risk of IMV (odds ratio [OR] = 1.77; P = 0.03/OR = 1.56; P = 0.04). Moreover, patients with low uric acid levels on admission were also associated significantly with the requirement of IMV (OR = 5.09; P <0.0001). CONCLUSION: Abnormal serum uric acid levels or a history of hyperuricemia were significantly associated with COVID-19 severity in the Japanese cohort.

Effects of mild obesity on outcomes in Japanese patients with COVID-19: a nationwide consortium to investigate COVID-19 host genetics.

BACKGROUND: Obesity is reported to be a risk factor for severe disease in patients with coronavirus disease 2019 (COVID-19). However, there are no specific reports on the risk of severe disease according to body mass index (BMI) in Japan. Thus, this study aimed to investigate the effect of obesity stratified by BMI on the severity of COVID-19 in the general Japanese population. METHODS: From February 2020 to May 2021, 1 837 patients aged ≥18 years were enrolled in the Japan COVID-19 Task Force. Patients with known BMI and disease severity were analyzed. Severity was defined as critical if the patient was treated in the intensive care unit, required invasive mechanical ventilation, or died. RESULTS: Class 1 obesity (25.0 ≤ BMI < 30.0 kg/m2), class 2 obesity (30.0 ≤ BMI < 35.0 kg/m2), and class 3 or 4 obesity (BMI ≥ 35 kg/m2) were present in 29%, 8%, and 3% of the cases, respectively. Multiple logistic regression analysis with known risk factors for critical illness indicated that class 2 obesity was an independent risk factor for oxygenation (adjusted odds ratio, 4.75) and critical cases (adjusted odds ratio, 1.81). Class 1 obesity and class 3 or 4 obesity were independent risk factors for oxygen administration (adjusted odds ratios 2.01 and 3.12, respectively), but not for critical cases. However, no differences in the mortality rates were observed between the BMI classes (P = 0.5104). CONCLUSION: Obesity is a risk factor for respiratory failure in Japanese patients with COVID-19, regardless of the degree of obesity. However, it may not cause severe COVID-19 in a dose-response relationship with BMI. COVID-19 patients with mild obesity may benefit from aggressive intensive care.