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.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).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.Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.
The severity of chest X-ray (CXR) findings is a prognostic factor in patients with coronavirus disease 2019 (COVID-19). We investigated the clinical and genetic characteristics and prognosis of patients with worsening CXR findings during early hospitalization. We retrospectively included 1656 consecutive Japanese patients with COVID-19 recruited through the Japan COVID-19 Task Force. Rapid deterioration of CXR findings was defined as increased pulmonary infiltrates in ≥ 50% of the lung fields within 48 h of admission. Rapid deterioration of CXR findings was an independent risk factor for death, most severe illness, tracheal intubation, and intensive care unit admission. The presence of consolidation on CXR, comorbid cardiovascular and chronic obstructive pulmonary diseases, high body temperature, and increased serum aspartate aminotransferase, potassium, and C-reactive protein levels were independent risk factors for rapid deterioration of CXR findings. Risk variant at the ABO locus (rs529565-C) was associated with rapid deterioration of CXR findings in all patients. This study revealed the clinical features, genetic features, and risk factors associated with rapid deterioration of CXR findings, a poor prognostic factor in patients with COVID-19.
ABSTRACT Background Chest computed tomography (CT) is a valuable tool for diagnosing and predicting the severity of coronavirus disease 2019 (COVID‐19) and assessing extrapulmonary organs. Reduced muscle mass and visceral fat accumulation are important features of a body composition phenotype in which obesity and muscle loss coexist, but their relationship with COVID‐19 outcomes remains unclear. In this study, we aimed to investigate the association between the erector spinae muscle (ESM) to epicardial adipose tissue (EAT) ratio (ESM/EAT) on chest CT and disease severity in patients with COVID‐19. Methods We analysed data from 1074 COVID‐19 patients enrolled in the Japan COVID‐19 Task Force database. The primary outcome was the rate of critical outcomes (requiring high‐flow oxygen therapy, invasive ventilator support or death). The incidence of critical outcomes was compared between patients with high and low ESM/EAT ratios. Results The low ESM/EAT group ( n = 353) had a higher incidence of critical outcomes (13.3% vs. 5.13%, p < 0.001) and mortality (2.55% vs. 0.69%, p = 0.019) than the high ESM/EAT group ( n = 721). In multivariable analysis, the low ESM/EAT ratio was associated with critical outcomes (adjusted odds ratio [aOR] 2.11, 95% confidence interval [CI] 1.22–3.66) independently of the known COVID‐19 severity factors including age, sex, body mass index (BMI), smoking history, lifestyle‐related comorbidities and pneumonia volume. Conclusion The low ESM/EAT ratio in COVID‐19 patients can be obtained on chest CT and used to predict critical outcomes after disease onset, demonstrating the importance of detailed body composition assessments in COVID‐19 practice.
Although SARS-CoV-2 RNAemia has been reported to strongly impact patients with severe COVID-19, the clinical characteristics of patients with COVID-19 harboring detectable intracellular SARS-CoV-2 RNA remain unknown.We included adult patients who had developed COVID-19 between February and September 2020. Total white blood cells derived from the buffy coat of peripheral whole blood were used to detect SARS-CoV-2 RNA using the Illumina COVIDSeq test. We compared the clinical characteristics between patients with and without detected viral RNA (detected and undetected groups).Among the 390 patients included, 17 harbored SARS-CoV-2 RNA in peripheral white blood cells. All 17 patients required oxygen support during the disease course and had higher intensive care unit admission (52.9% vs 28.9%, P = 0.035), mortality (17.7% vs 3.5%, P = 0.004), kidney dysfunction (severe, 23.5% vs 6.4%, P = 0.029), and corticosteroid treatment rates (76.5% vs 46.5%, P = 0.016) than those of patients in the undetected group.We propose that patients with circulating intracellular SARS-CoV-2 RNA in the peripheral blood exhibited the most severe disease course.
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.
To determine the effectiveness of baricitinib in patients with coronavirus disease 2019 (COVID-19), investigate whether baricitinib prevents the need for invasive mechanical ventilation and identify patient subgroups that would benefit from baricitinib.This observational matched-cohort study was conducted by the Japan COVID-19 Task Force, a nationwide multicenter consortium. Patients with COVID-19 aged ≥18 years were identified from 70 hospitals in Japan. Among patients with confirmed COVID-19 from February 2020 to September 2021, those receiving baricitinib were propensity-score matched with controls.Among 3309 patients, 144 propensity score-matched pairs were identified. Thirteen (9.0%) patients in the baricitinib group and 27 (18.8%) in the control group required invasive mechanical ventilation during the disease course (odds ratio, 0.43). Although the baricitinib group had more severe disease, there were no significant differences in the intensive care unit admission rates (odds ratio, 1.16) and mortality rates (odds ratio, 0.74) between groups. In subgroup analyses, baricitinib was associated with a significant reduction in the need for invasive mechanical ventilation in patients requiring oxygen support (odds ratio, 0.28), with rapid shadow spread on chest radiography (odds ratio, 0.11), or treated with remdesivir (odds ratio, 0.27), systemic corticosteroids (odds ratio, 0.31), or anticoagulants (odds ratio, 0.17).Baricitinib is effective at preventing the need for invasive mechanical ventilation in patients with COVID-19.
Objectives Severe acute respiratory syndrome coronavirus 2 significantly impacts Japan with a high number of infections and deaths reported. Long coronavirus disease (COVID) characterised by persistent symptoms after COVID-19 has gained recognition but varies across studies. This study aimed to investigate the differences in long COVID among patients hospitalised during Japan’s first three waves of the pandemic. Design Multicentre prospective cohort study. Setting 26 medical facilities across Japan between February 2020 and February 2021. Participants In total, 1066 hospitalised patients diagnosed with COVID-19 were included with 206, 301 and 559 patients in the first, second and third waves, respectively. Data were collected using electronic data capture and patient-reported outcome forms. Primary and secondary outcome measures Long COVID was assessed at 3, 6 and 12 months after COVID-19 diagnosis. Results Significant differences were observed between the waves in various baseline and clinical characteristics such as age, body mass index (BMI), comorbidities, the severity of COVID-19, complications and treatment during hospitalisation. Long COVID, particularly dyspnoea, was most prevalent in the first wave. Multivariate logistic regression analysis confirmed a significant positive association between the first wave and long COVID including dyspnoea after adjusting for age, sex, BMI, smoking status and COVID-19 severity. Conclusions Patients hospitalised during the first wave had a higher risk of experiencing long COVID, especially dyspnoea, than those hospitalised during the other waves. These findings underscore the need for continued monitoring and managing long COVID in COVID-19 survivors, particularly in those hospitalised during the first wave. Trial registration number UMIN000042299.
