Risk Factors Associated with Mortality among Mechanically Ventilated Patients with Coronavirus Disease 2019 Pneumonia: A Multicenter Cohort Study in Japan (J-RECOVER Study).

Objective Mortality analyses of patients with coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation in Japan are limited. The present study therefore determined the risk factors for mortality in patients with COVID-19 requiring invasive mechanical ventilation. Methods This retrospective cohort study used the dataset from the Japanese multicenter research of COVID-19 by assembling real-word data (J-RECOVER) study that was conducted between January 1 and September 31, 2020. Independent risk factors associated with in-hospital mortality were evaluated using a multivariate logistic regression analysis. Kaplan-Meier estimates of the survival were calculated for different age groups. A subgroup analysis was performed to assess differences in survival rates according to additional risk factors, including an older age and chronic pulmonary disease. Patients A total of 561 patients were eligible. The median age was 67 (interquartile range: 56-75) years old, 442 (78.8%) were men, and 151 (26.9%) died in the hospital. Results Age, chronic pulmonary disease, and renal disease were significantly associated with in-hospital mortality. Compared with patients 18-54 years old, the adjusted odds ratios of patients 55-64, 65-74, and 75-94 years old were 3.34 (95% CI, 1.34-8.31), 7.07 (95% CI, 3.05-16.40), and 18.43 (95% CI, 7.94-42.78), respectively. Conclusion Age, chronic pulmonary disease, and renal disease were independently associated with mortality in patients with COVID-19 requiring invasive mechanical ventilation, and age was the most decisive indicator of a poor prognosis. Our results may aid in formulating treatment strategies and allocating healthcare resources.

Reintubation in COVID-19 patients: a multicenter observational study in Japan (J-RECOVER study)

Background Reintubation is not an uncommon occurrence following extubation and discontinuation of mechanical ventilation. In COVID-19 patients, the proportion of reintubation may be higher than that of non-COVID-19 patients. Furthermore, COVID-19 patients may have a higher risk for developing laryngotracheal stenosis, along with a higher proportion of reintubation than in non-COVID-19 patients. Our understanding of the proportion of reintubation in COVID-19 patients is limited in Japan. Additionally, the reasons for reintubation have not been adequately examined in previous studies outside of Japan. Thus, the present study aimed to describe the proportion and causes of reintubation among COVID-19 patients in Japan. Methods This was a multicenter observational study that included 64 participating centers across Japan. This study included mechanically ventilated COVID-19 patients who were discharged between April 1, 2020 and September 30, 2020. The outcomes examined were the proportion and causes of reintubation. Results A total of 373 patients were eligible for inclusion in the current analysis. The median age of patients was 64 years and 80.4% were male. Reintubation was required for 35 patients (9.4%) and the most common causes for reintubation were respiratory failure (71.4%;n = 25) and laryngotracheal stenosis (8.6%;n = 3). Conclusions The proportion of reintubation among COVID-19 patients in Japan was relatively low. Respiratory failure was the most common cause for reintubation. Reintubation due to laryngotracheal stenosis accounted for only a small fraction of all reintubated COVID-19 patients in Japan.

Reintubation in COVID-19 patients: a multicenter observational study in Japan (J-RECOVER study).

BACKGROUND: Reintubation is not an uncommon occurrence following extubation and discontinuation of mechanical ventilation. In COVID-19 patients, the proportion of reintubation may be higher than that of non-COVID-19 patients. Furthermore, COVID-19 patients may have a higher risk for developing laryngotracheal stenosis, along with a higher proportion of reintubation than in non-COVID-19 patients. Our understanding of the proportion of reintubation in COVID-19 patients is limited in Japan. Additionally, the reasons for reintubation have not been adequately examined in previous studies outside of Japan. Thus, the present study aimed to describe the proportion and causes of reintubation among COVID-19 patients in Japan. METHODS: This was a multicenter observational study that included 64 participating centers across Japan. This study included mechanically ventilated COVID-19 patients who were discharged between April 1, 2020 and September 30, 2020. The outcomes examined were the proportion and causes of reintubation. RESULTS: A total of 373 patients were eligible for inclusion in the current analysis. The median age of patients was 64 years and 80.4% were male. Reintubation was required for 35 patients (9.4%) and the most common causes for reintubation were respiratory failure (71.4%; n = 25) and laryngotracheal stenosis (8.6%; n = 3). CONCLUSIONS: The proportion of reintubation among COVID-19 patients in Japan was relatively low. Respiratory failure was the most common cause for reintubation. Reintubation due to laryngotracheal stenosis accounted for only a small fraction of all reintubated COVID-19 patients in Japan.

Relationship between institutional intensive care volume prior to the COVID-19 pandemic and in-hospital death in ventilated patients with severe COVID-19.

We aimed to evaluate the association between ICU patient volume before the COVID-19 pandemic and the outcomes of ventilated COVID-19 patients. We analyzed ventilated patients with COVID-19 aged > 17 years and enrolled in the J-RECOVER study, a retrospective multicenter observational study conducted in Japan between January and September 2020. Based on the number of patients admitted to the ICU between January and December 2019, the top third institutions were defined as high-volume centers, the middle third ones as middle-volume centers, and the bottom third ones as low-volume centers. The primary outcome measure was in-hospital mortality. Multivariate logistic regression analysis for in-hospital mortality and ICU patient volume was performed after adjusting for multiple propensity scores. Among 461 patients, 158, 158, and 145 patients were admitted to low-volume (20 institutions), middle-volume (14 institutions), and high-volume (13 institutions) centers, respectively. Admission to middle- and high-volume centers was not significantly associated with in-hospital death compared with admission to low-volume centers (adjusted odds ratio, 1.11 [95% confidence interval (CI): 0.55-2.25] and adjusted odds ratio, 0.81 [95% CI: 0.31-1.94], respectively). In conclusion, institutional intensive care patient volume prior to the COVID-19 pandemic was not significantly associated with in-hospital death in ventilated COVID-19 patients.

Early intubation and decreased in-hospital mortality in patients with coronavirus disease 2019.

BACKGROUND: Some academic organizations recommended that physicians intubate patients with COVID-19 with a relatively lower threshold of oxygen usage particularly in the early phase of pandemic. We aimed to elucidate whether early intubation is associated with decreased in-hospital mortality among patients with novel coronavirus disease 2019 (COVID-19) who required intubation. METHODS: A multicenter, retrospective, observational study was conducted at 66 hospitals in Japan where patients with moderate-to-severe COVID-19 were treated between January and September 2020. Patients who were diagnosed as COVID-19 with a positive reverse-transcription polymerase chain reaction test and intubated during admission were included. Early intubation was defined as intubation conducted in the setting of ≤ 6 L/min of oxygen usage. In-hospital mortality was compared between patients with early and non-early intubation. Inverse probability weighting analyses with propensity scores were performed to adjust patient demographics, comorbidities, hemodynamic status on admission and time at intubation, medications before intubation, severity of COVID-19, and institution characteristics. Subgroup analyses were conducted on the basis of age, severity of hypoxemia at intubation, and days from admission to intubation. RESULTS: Among 412 patients eligible for the study, 110 underwent early intubation. In-hospital mortality was lower in patients with early intubation than those with non-early intubation (18 [16.4%] vs. 88 [29.1%]; odds ratio, 0.48 [95% confidence interval 0.27-0.84]; p = 0.009, and adjusted odds ratio, 0.28 [95% confidence interval 0.19-0.42]; p < 0.001). The beneficial effects of early intubation were observed regardless of age and severity of hypoxemia at time of intubation; however, early intubation was associated with lower in-hospital mortality only among patients who were intubated later than 2 days after admission. CONCLUSIONS: Early intubation in the setting of ≤ 6 L/min of oxygen usage was associated with decreased in-hospital mortality among patients with COVID-19 who required intubation. Trial Registration None.

Clinical epidemiology and outcomes of COVID-19 patients with extracorporeal membrane oxygenation support in Japan: a retrospective study.

Objective: To elucidate the clinical epidemiology and outcomes of patients with COVID-19 who received extracorporeal membrane oxygenation (ECMO) in the Osaka Prefecture, Japan. Methods: We conducted a retrospective study of COVID-19 patients who received ECMO. Among patients diagnosed with COVID-19 between January 29 and November 9, 2020, we targeted patients who received ECMO. The outcome was all-cause mortality. The baseline characteristics of the COVID-19 patients who received ECMO were summarized according to the outcome. A univariable logistic regression model was applied to evaluate the association of each factor (sex, age group, city of residence, presence of comorbidities, presence of close contact, use of dialysis, and wave) with all-cause mortality. Odds ratios (ORs) with 95% confidence intervals were calculated. Results: Among the 14,864 patients diagnosed with COVID-19 during the study period, 39 patients received ECMO. Fourteen patients (35.9%) died. All patients aged 30-39 years survived, whereas all patients aged ≥80 years died. Higher mortality was observed among patients in the higher age group, and the P value for trend was significant (P value for trend: 0.04). Conclusions: Of the 14,864 COVID-19 patients in Osaka Prefecture until November 2020, 39 underwent ECMO. Of these, 14 died.

Characteristics and Outcomes of COVID-19 in Reproductive-Aged Pregnant and Nonpregnant Women in Osaka, Japan.

OBJECTIVE: To describe the clinical characteristics and outcomes of reproductive-aged female patients with coronavirus disease 2019 (COVID-19). METHODS: We conducted a retrospective study of female patients aged 10-49 years, diagnosed with COVID-19 in Osaka, Japan, between January and November 2020. We assessed their epidemiological and clinical characteristics according to their pregnancy status. RESULTS: A total of 4,156 patients were enrolled, of whom 29 (0.7%) were pregnant. Most patients exhibited mild symptoms, and 10.8% of the cases were asymptomatic. No moderate or severe cases were observed in pregnant women, whereas only 0.1% of the nonpregnant women had severe disease at diagnosis. No clusters were observed in the pregnant patients; however, most acquired the infection from a family member. Of the 29 pregnant women, 22 (75.9%) were hospitalized; whereas among the nonpregnant women, 579 (14.0%) were hospitalized (p < 0.001). No patients were admitted to the intensive care unit, and there were no deaths among women aged 10-49 years. CONCLUSIONS: Pregnant women accounted for 0.7% of the total cases of COVID-19 among women aged 10-49 years. Pregnant women were more likely to be hospitalized but generally had mild disease.

Shorter Incubation Period among Unvaccinated Delta Variant Coronavirus Disease 2019 Patients in Japan.

Few studies have assessed incubation periods of the severe acute respiratory syndrome coronavirus 2 Delta variant. This study aimed to elucidate the transmission dynamics, especially the incubation period, for the Delta variant compared with non-Delta strains. We studied unvaccinated coronavirus disease 2019 patients with definite single exposure date from August 2020 to September 2021 in Japan. The incubation periods were calculated and compared by Mann-Whitney U test for Delta (with L452R mutation) and non-Delta cases. We estimated mean and percentiles of incubation period by fitting parametric distribution to data in the Bayesian statistical framework. We enrolled 214 patients (121 Delta and 103 non-Delta cases) with one specific date of exposure to the virus. The mean incubation period was 3.7 days and 4.9 days for Delta and non-Delta cases, respectively (p-value = 0.000). When lognormal distributions were fitted, the estimated mean incubation periods were 3.7 (95% credible interval (CI) 3.4-4.0) and 5.0 (95% CI 4.5-5.6) days for Delta and non-Delta cases, respectively. The estimated 97.5th percentile of incubation period was 6.9 (95% CI 5.9-8.0) days and 10.4 (95% CI 8.6-12.7) days for Delta and non-Delta cases, respectively. Unvaccinated Delta variant cases had shorter incubation periods than non-Delta variant cases.

Factors associated with prolonged duration of viral clearance in non-severe SARS-CoV-2 patients in Osaka, Japan.

BACKGROUND: We investigated factors associated with prolonged viral clearance of SARS-CoV-2 among non-severe adult patients in Osaka, Japan. A total of 706 laboratory-confirmed COVID-19 patients were enrolled in this longitudinal observational study between 29 January 2020 and 31 May 2020, across 62 hospitals and three non-hospital recuperation facilities. METHODS: Logistic regression analysis was performed to investigate the factors associated with prolonged (29 days: upper 25% in duration) viral clearance of SARS-CoV-2. Linear regression analysis was conducted to assess these factors 14 days after symptom onset. RESULTS: The median duration of viral clearance was 22 days from symptom onset. After adjustment for sex, age, symptoms, comorbidity, and location of recuperation, comorbidities were associated with prolonged duration: (OR, 1.77 [95% CI, 1.11-2.82]) for one, (OR, 2.47 [95% CI, 1.32-4.61]) for two or more comorbidities. Viral clearance 14 days after symptom onset was 3 days longer for one comorbidity and 4 days longer for two or more comorbidities compared to clearance when there was no comorbidity. CONCLUSION: The presence of comorbidity was a robust factor associated with a longer duration of viral clearance, extending by 3 to 4 days compared to patients with no comorbidity.

Increased Transmissibility of the SARS-CoV-2 Alpha Variant in a Japanese Population.

To assess the relative transmissibility of the SARS-CoV-2 Alpha variant compared to the pre-existing SARS-CoV-2 in Japan, we performed a cross-sectional study to determine the secondary attack rate of COVID-19 in household contacts before and after the Alpha variant became dominant in Osaka. We accessed 290 household contacts whose index cases were diagnosed between 1 and 20 December 2020 (the third epidemic group), at a time when Osaka was free of the Alpha variant. We also accessed 398 household contacts whose index cases were diagnosed between 20 April and 3 May 2021 (the fourth epidemic group), by which time the Alpha variant had become dominant. We identified 124 household contacts whose index case was determined positive for the Alpha variant (Alpha group) in this fourth group. The secondary attack rates in the fourth group (34.7%) and the Alpha group (38.7%) were significantly higher than that in the third group (19.3%, p < 0.001). Multivariable Poisson regression analysis with a robust error variance showed a significant excess risk in the fourth group (1.90, 95% CI = 1.47-2.48) and the Alpha group (2.34, 95% CI = 1.71-3.21). This finding indicates that the SARS-CoV-2 Alpha variant has an approximately 1.9-2.3-fold higher transmissibility than the pre-existing virus in the Japanese population.

Characteristics and outcomes of older patients with coronavirus disease 2019 in Japan.

AIM: The epidemiological characteristics, in-hospital treatments and outcomes of coronavirus disease 2019 among older patients have not been fully evaluated in Japan. METHODS: In this retrospective observational study carried out in Osaka Prefecture, Japan, we enrolled patients aged ≥60 years with laboratory-confirmed coronavirus disease 2019 from January to November 2020. The main outcome was mortality during the observation period, based on the Infectious Diseases Control Law. Cox regression analysis was used to evaluate the association between epidemiological factors and mortality among older patients with coronavirus disease 2019. RESULTS: Older patients accounted for 21.5% (3192/14 846) of the registered patients with coronavirus disease 2019. The number of patients according to age was as follows: 60-69 years, 1140 (35.7%); 70-79 years, 1058 (33.1%); 80-89 years, 749 (23.5%); and ≥90 years, 245 (7.7%). The proportion of deaths during the observation period was 8.5% (271/3192). The proportion of deaths increased with increasing age category (from 1.9% to 20.4%, P for trend <0.001). In multivariable Cox regression analysis, patients aged 70-79, 80-89 and ≥90 years had higher hazard ratios and 95% confidence intervals of death (2.62 [1.63-4.23], 5.99 [3.77-9.50] and 10.24 [6.03-17.40], respectively) than those aged 60-69 years. Factors such as male sex, presence of comorbidities, cluster cases in medical institutions and moderate/severe symptoms at diagnosis were also associated with mortality. CONCLUSIONS: This study shows the epidemiological characteristics of older patients with coronavirus disease 2019 in Osaka Prefecture, Japan. The proportion of deaths was 8.5% in total and increased with increasing age. Geriatr Gerontol Int 2021; 21: 629-635.

Characteristics and Survival of Intensive Care Unit Patients with Coronavirus Disease in Osaka, Japan: A Retrospective Observational Study.

The epidemiological and clinical characteristics, treatments, and outcomes of patients with coronavirus disease 2019 (COVID-19) who are admitted to the intensive care unit (ICU) have not been adequately evaluated in Japan. We analyzed the registry data of 205 patients with COVID-19 admitted to the ICU between February and November 2020, in Osaka Prefecture, Japan. A Cox proportional hazards model was used to assess the association between epidemiological factors and mortality among ICU patients. Of the 205 ICU patients, 161 (78.5%) were men and 149 (72.7%) were older than 60 years. A total of 117 patients (57.1%) had comorbidities. The most common symptoms at diagnosis were mild (n = 131, 63.9%). A total of 187 patients (91.2%) received mechanical ventilation, and 32 patients (15.6%) required extracorporeal membrane oxygenation. Patients were followed up for a median of 25 days after ICU admission. A total of 147 patients (71.7%) were alive at discharge, and 58 patients (28.3%) died. The hazard ratio for mortality among patients aged >80 years was 6.02 (95% confidence interval: 2.10-17.25) in the multivariable model, which was higher than that among those aged ≤59 years. These results are useful for recognizing the clinical course of this infection in ICU patients.

Characteristics and Outcomes of Pediatric COVID-19 Patients in Osaka, Japan.

The epidemiological information on characteristics, in-hospital treatments, and outcomes of the coronavirus disease 2019 (COVID-19) among pediatric patients has not been fully evaluated in Japan. This was a retrospective observational study conducted in the Osaka Prefecture, Japan, and we enrolled laboratory-confirmed COVID-19 patients aged ≤ 19 years old from January to November in 2020. Of 14,846 COVID-19 eligible patients, 1240 pediatric patients (8.4%) were registered during the study period; 329 were children aged 0-9 years (26.5%) and 911 were adolescents aged 10-19 years (73.5%). The majority of the patients exhibited mild symptoms at diagnosis (872, 70.3%), some were asymptomatic (296, 23.9%). Cluster infections occurred in child-care facilities (26, 7.9%) among children and in universities (27, 3.0%) and schools (18, 2.0%) among adolescents. The number of close-contact cases was 260 (69.0%) in children and 459 (50.4%) in adolescents. Sixty of the children (18.2%) and 90 of the adolescents (9.9%) were hospitalized. One patient received mechanical ventilation, and none underwent extracorporeal membrane oxygenation. One patient was admitted to the intensive care unit; there were no deaths. These results are useful for recognizing the clinical course from transmission route to outcomes of this infection in pediatric patients.

Characteristics of patients with novel coronavirus disease (COVID-19) during the first surge versus the second surge of infections in Osaka Prefecture, Japan.

In Japan, the differences in characteristics, severity, and mortality of novel coronavirus disease (COVID-19) patients between the first and second surges of infections have not been fully understood. This study is a retrospective cohort study of COVID-19 patients confirmed between February 1 and August 31, 2020 in Osaka Prefecture, Japan. Publicly available information on patients was collected from the website of Osaka Prefecture. Patients were divided into two groups according to the date of the positive laboratory test result: the first surge (February 1 to May 22) and the second surge (May 23 to August 31). Patients' characteristics were compared between the two groups. A multivariable Cox proportional-hazards model was applied to compare severity and mortality between the two groups, where sex, age group at the onset date, city of residence, and days to test positive were adjusted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. A total of 8,541 patients included 1,780 and 6,761 patients in the first and second surges, respectively. Age at the onset date was younger in the second surge (p < 0.001), and median of days from the onset date to the positive test date shortened from 7 to 6 days (p < 0.001). The multivariable Cox proportional-hazards model revealed that both severity and mortality were lower in the second surge than in the first surge (severity: HR: 0.51 [0.39-0.67]; mortality: HR: 0.37 [0.25-0.56]). In conclusion, severity and mortality were lower in the second surge than in the first surge among COVID-19 patients in Osaka Prefecture, Japan.

The characteristics and clinical course of patients with COVID-19 who received invasive mechanical ventilation in Osaka, Japan.

OBJECTIVE: To describe the detailed clinical course of patients with coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. METHODS: We conducted a case series of patients with COVID-19 who received invasive mechanical ventilation in Osaka, Japan, between January 29 and May 28, 2020. We describe the patient characteristics and clinical course from onset. Additionally, we fitted logistic regression models to investigate the associations between patient characteristics and the 30-day mortality rate. RESULTS: A total of 125 patients who received invasive mechanical ventilation (median age [interquartile range], 68 [57-73] years; male, 77.6%) were enrolled. Overall, the 30-day mortality was 24.0%, and the median (interquartile range) length of ICU stay and length of invasive mechanical ventilation use were 16 (12-29) days and 13 (9-26) days, respectively. From clinical onset, 121 patients (96.8%) were intubated within 14 days. In multivariable logistic regression analysis, age of 65 years or older (odds ratio, 3.56; 95% confidence interval, 1.21-10.49; P = 0.02) and male sex (odds ratio, 3.75; 95% confidence interval, 1.00-11.24, P = 0.04) were significantly associated with a higher 30-day mortality rate. CONCLUSIONS: In this case series of patients with COVID-19 who received invasive mechanical ventilation in Japan, the 30-day mortality rate was 24.0%, and age 65 years or older and male sex were associated with higher 30-day mortality rate.