Trends in survival during the pandemic in patients with critical COVID-19 receiving mechanical ventilation with or without ECMO: analysis of the Japanese national registry data.

BACKGROUND: The survival rate of patients with critical coronavirus disease-19 (COVID-19) over time is inconsistent in different settings. In Japan, a national database was organized to monitor and share the patient generation across the country in an immediate response to the COVID-19 pandemic. This study aimed to evaluate changes in survival over time and the prognostic factors in critical COVID-19 patients receiving mechanical ventilation with/without extracorporeal membrane oxygenation (ECMO) using the largest database in Japan. METHODS: This is a prospective observational cohort study of patients admitted to intensive care units in Japan with fatal COVID-19 pneumonia receiving mechanical ventilation and/or ECMO. We developed a prospective nationwide registry covering > 80% of intensive care units in Japan, and analyzed the association between patients' backgrounds, institutional ECMO experience, and timing of treatment initiation and prognosis between February 2020 and November 2021. Prognostic factors were evaluated by Kaplan-Meier analysis and Cox proportional hazards analysis. RESULTS: A total of 9418 patients were ventilated, of whom 1214 (13%) received ECMO. The overall survival rate for ventilated patients was 79%, 65% for those receiving ECMO. There have been five outbreaks in Japan to date. The survival rate of ventilated patients increased from 76% in the first outbreak to 84% in the fifth outbreak (p < 0.001). The survival rate of ECMO patients remained unchanged at 60-68% from the first to fifth outbreaks (p = 0.084). Age of ≥ 59 (hazard ratio [HR] 2.17; 95% confidence interval [CI] 1.76-2.68), ventilator days of ≥ 3 before starting ECMO (HR 1.91; 95% CI 1.57-2.32), and institutional ECMO experiences of ≥ 11 (HR 0.70; 95% CI 0.58-0.85) were independent prognostic factors for ECMO. CONCLUSIONS: During five COVID-19 outbreaks in Japan, the survival rate of ventilated patients tended to have gradually improved, and that of ECMO patients did not deteriorate. Older age, longer ventilator days before starting ECMO, and fewer institutional ECMO experiences may be independent prognostic factors for critical COVID-19 patients receiving ECMO.

Japanese rapid/living recommendations on drug management for COVID-19: updated guidelines (July 2022).

Background: Coronavirus disease (COVID-19), an infectious disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese Rapid/Living recommendations on drug management for COVID-19 using the experience of creating the J-SSCG. Methods: The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of recommendations. The first edition of this guideline was released on September 9, 2020, and this is the revised edition (version 5.0; released on July 15, 2022). Clinical questions (CQs) were set for the following 10 drugs: favipiravir (CQ1), remdesivir (CQ2), corticosteroids (CQ4), tocilizumab (CQ5), anticoagulants (CQ7), baricitinib (CQ8), casirivimab/imdevimab (CQ9-1), sotrovimab (CQ9-2), molnupiravir (CQ10), and nirmatrelvir/ritonavir (CQ11). Recommendations: Favipiravir is not suggested for all patients with COVID-19 (GRADE 2C). Remdesivir is suggested for patients with mild COVID-19 who do not require oxygen, and patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (both GRADE 2B). Corticosteroids are recommended for moderate and severe COVID-19 (GRADE 1B, 1A). However, their administration is not recommended for mild COVID-19 (GRADE 1B). Tocilizumab is suggested for moderate and severe COVID-19 (GRADE 2B, 2C). Anticoagulant administration is recommended for moderate and severe COVID-19 (Good Practice Statement). Baricitinib is suggested for moderate and severe COVID-19 (both GRADE 2C). Casirivimab/imdevimab and sotrovimab are recommended for mild COVID-19 (both GRADE 2C). Molnupiravir and nirmatrelvir/ritonavir are recommended for mild COVID-19 (both GRADE 2C). SARS-CoV-2 mutant strains emerge occasionally, and each time, the treatment policy at clinics is forced to change drastically. We ask health-care professionals in the field to refer to the recommendations in these guidelines and use these to keep up to date with COVID-19 epidemiological information.

COVID-19-Related Symptoms during the SARS-CoV-2 Omicron (B.1.1.529) Variant Surge in Japan.

The exact profiles of the clinical symptoms related to the SARS-CoV-2 Omicron variant (B.1.1.529) remain largely uncertain. Therefore, this study aimed to clarify the clinical manifestations of infection with this variant. We enrolled individuals who were tested by quantitative nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) test at a large screening center in a city of Japan during the B.1.1.529 Omicron variant wave between January and May 2022, after contact with COVID-19 patients. Swab tests were planned to be performed approximately 4-5 days after contact. The presence of COVID-19-related symptoms was assessed at the swab test site. Among the 2,507 enrolled individuals, 943 (37.6%) were RT-PCR test-positive and 1,564 (62.4%) were test-negative. Among the 943 PCR test-positive participants, the prevalence of the symptoms was as follows: 47.3% with cough, 32.9% with sore throat, 18.4% with fatigability, 12.7% with fever of ≥ 37.5℃, 9.9% with dyspnea, 2.1% with dysosmia, and 1.4% with dysgeusia. The prevalence of cough, sore throat, dyspnea, and fatigability was higher among adults aged ≥ 18 years than among children and adolescents. The prevalence of dysosmia and dysgeusia remarkably decreased during the Omicron wave (1-3%) compared to during the pre-Omicron variant waves (15-25%). In summary, common COVID-19-related symptoms during the Omicron variant wave included cough and sore throat, followed by fatigability, fever, and dyspnea. The prevalence of most of these symptoms was higher in adults than in non-adults. The prevalence of dysosmia and dysgeusia remarkably decreased with the Omicron variant than with pre-Omicron variants.

Effectiveness of third vaccine dose for coronavirus disease 2019 during the Omicron variant pandemic: a prospective observational study in Japan.

The administration of a third booster dose of messenger ribonucleic acid (mRNA) vaccines against coronavirus disease 2019 (COVID-19) has progressed worldwide. Since January 2022, Japan has faced a nationwide outbreak caused by the Omicron variant, which occurred simultaneously with the progression of mass vaccination with the third booster dose. Therefore, this study evaluated the effectiveness of the third dose of vaccine by reverse transcription-polymerase chain reaction (RT-PCR) test using nasopharyngeal swab samples from adults aged ≥ 18 years tested after having close contact with COVID-19 cases between January and May 2022. Participants who completed only one dose were excluded from the study. Among the 928 enrolled participants, 139 had never been vaccinated, 609 had completed two doses, 180 had completed three doses before the swab test, and the overall RT-PCR test positivity rate in each group was 48.9%, 46.0%, and 32.2%, respectively. The vaccine effectiveness of the third dose to prevent infection after close contact was approximately 40% (95% confidence interval: 20-60%), which was the highest at 10-70 days after receiving the third dose. In conclusion, the effectiveness of the three-dose mRNA COVID-19 vaccine after close contact during the Omicron outbreak is approximately 40%.

Hour-1 bundle adherence was associated with reduction of in-hospital mortality among patients with sepsis in Japan.

BACKGROUND: The updated Surviving Sepsis Campaign guidelines recommend a 1-hour window for completion of a sepsis care bundle; however, the effectiveness of the hour-1 bundle has not been fully evaluated. The present study aimed to evaluate the impact of hour-1 bundle completion on clinical outcomes in sepsis patients. METHODS: This was a multicenter, prospective, observational study conducted in 17 intensive care units in tertiary hospitals in Japan. We included all adult patients who were diagnosed as having sepsis by Sepsis-3 and admitted to intensive care units from July 2019 to August 2020. Impacts of hour-1 bundle adherence and delay of adherence on risk-adjusted in-hospital mortality were estimated by multivariable logistic regression analyses. RESULTS: The final study cohort included 178 patients with sepsis. Among them, 89 received bundle-adherent care. Completion rates of each component (measure lactate level, obtain blood cultures, administer broad-spectrum antibiotics, administer crystalloid, apply vasopressors) within 1 hour were 98.9%, 86.2%, 51.1%, 94.9%, and 69.1%, respectively. Completion rate of all components within 1 hour was 50%. In-hospital mortality was 18.0% in the patients with and 30.3% in the patients without bundle-adherent care (p = 0.054). The adjusted odds ratio of non-bundle-adherent versus bundle-adherent care for in-hospital mortality was 2.32 (95% CI 1.09-4.95) using propensity scoring. Non-adherence to obtaining blood cultures and administering broad-spectrum antibiotics within 1 hour was related to in-hospital mortality (2.65 [95% CI 1.25-5.62] and 4.81 [95% CI 1.38-16.72], respectively). The adjusted odds ratio for 1-hour delay in achieving hour-1 bundle components for in-hospital mortality was 1.28 (95% CI 1.04-1.57) by logistic regression analysis. CONCLUSION: Completion of the hour-1 bundle was associated with lower in-hospital mortality. Obtaining blood cultures and administering antibiotics within 1 hour may have been the components most contributing to decreased in-hospital mortality.

Japanese rapid/living recommendations on drug management for COVID-19: updated guidelines (September 2021).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese rapid/living recommendations on drug management for COVID-19 using the experience of creating the J-SSCG. METHODS: The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of the recommendations. The first edition of this guideline was released on September 9, 2020, and this document is the revised edition (version 4.0; released on September 9, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ2), corticosteroids (CQ4), tocilizumab (CQ5), anticoagulants (CQ7), baricitinib (CQ8), and casirivimab/imdevimab (CQ9). Two CQs (hydroxychloroquine [CQ3] and ciclesonide [CQ6]) were retrieved in this updated version. RECOMMENDATIONS: Favipiravir is not suggested for all patients with COVID-19 (GRADE 2C). Remdesivir is suggested for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 2B). Corticosteroids are recommended for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 1B) and for patients with severe COVID-19 requiring mechanical ventilation/intensive care (GRADE 1A); however, their administration is not recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 1B). Tocilizumab is suggested for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 2B). Anticoagulant administration is recommended for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization and patients with severe COVID-19 requiring mechanical ventilation/intensive care (good practice statement). Baricitinib is suggested for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 2C). Casirivimab/imdevimab is recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 1B). We hope that these updated clinical practice guidelines will help medical professionals involved in the care of patients with COVID-19.

COVID-19 Transmission at Schools in Japan.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health concern in 2021. However, the risk of attending schools during the pandemic remains unevaluated. This study estimated the secondary transmission rate at schools using the results of a real-time reverse transcription-polymerase chain reaction (RT-PCR) screening test performed between July 2020 and April 2021, before starting the nationwide mass vaccination. A total of 1,924 students (20 RT-PCR-positive; 1.0%) from 52 schools or preschools were evaluated, together with 1,379 non-adults (95 RT-PCR-positive; 6.9%) exposed to SARS-CoV-2 in non-school environments. Assuming that the infectious index cases were asymptomatic and the transmission at schools followed a Bernoulli process, we estimated the probability of transmission after each contact at school as approximately 0.005 (0.5% per contact) with the current infection prevention measures at schools in Japan (i.e., hand hygiene, physical distancing, wearing masks, and effective ventilation). Furthermore, assuming that all children are capable of carrying the infection, then contact between an index case and 20-30 students per day at schools would yield the expected value for secondary cases of ≥ 1.0, during the 10 days of the infectious period. In conclusion, with the current infection prevention measures at schools in Japan, secondary transmission at schools would occur in approximately every 200 contacts. When considering this rate, compliance with the current infection prevention measures at schools and early detection and quarantine of the index cases would be effective in preventing the spread of COVID-19 at schools.

Discriminatory Value of Self-reported Olfactory Dysfunction in the Prediction of Coronavirus Disease 2019.

Objective Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), remains the world's largest public health concern in 2021. A history of close contact with infectious patients is a factor that predicts a positive SARS-CoV-2 test result. Meanwhile, the precise predictive value of symptoms suggestive of COVID-19 has not been fully elucidated. This study aimed to clarify the predictive and discriminatory value of each clinical symptom suggestive of COVID-19. Methods This study enrolled participants who were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction using a nasopharyngeal swab between November 2020 and January 2021. All enrolled patients were evaluated for data regarding the presence and closeness of contact with infectious patients and comprehensive clinical features (i.e., fever, cough, dyspnea, fatigue, dysosmia, and dysgeusia). Results Among the 1,744 tested participants, 144 tested positive for SARS-CoV-2. In the test-positive group, self-reported cough, fatigue, dysosmia, and dysgeusia were significant predictors of COVID-19, independent from a history of close contact. In particular, the presence of dysosmia was the strongest predictor of COVID-19 in both univariate and multivariate analyses. Among the 42 patients with self-reported dysosmia, 25 (59.5%) were SARS-CoV-2 test-positive. Self-reported dysosmia was reported by 25 (17.4%) of the 144 patients who tested positive for SARS-CoV-2, and 15 (60.0%) of the 25 COVID-19 patients with dysosmia had accompanying dysgeusia. Conclusion The presence of dysosmia was reported by 10-25% of patients with COVID-19, and is a significant predictor of COVID-19 infection, independent from a history of close contact.

Impacts of Natural Environmental Factors and Prevalence of Airway Symptoms on the Local Spread of COVID-19: A Time-Series Analysis in Regional COVID-19 Epidemics.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the world's largest public health concern in 2021. This study evaluated the associations of the prevalence of airway symptoms among the tested individuals and data regarding the natural environmental factors with the weekly number of newly diagnosed COVID-19 patients in Sendai City (Nt). For the derivatives of the screening test results, data from individuals with a contact history who underwent nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) testing between July 2020 and April 2021 (6,156 participants, including 550 test-positive patients) were used. The value of Nt correlated with the weekly RT-PCR test-positive rate after close contact, prevalence of cough symptoms in test-positive individuals or in test-negative individuals, lower air temperature, lower air humidity, and higher wind speed. The weekly test-positive rate correlated with lower air humidity and higher wind speed. In cross-correlation analyses, natural environmental factors correlated with the regional epidemic status on a scale of months, whereas the airway symptoms among non-COVID-19 population affected on a scale of weeks. When applying an autoregression model to the serial data of Nt, large-scale movements of people were suggested to be another factor to influence the local epidemics on a scale of days. In conclusion, the prevalence of cough symptoms in the local population, lower air humidity or higher wind speed, and large-scale movements of people in the locality would jointly influence the local epidemic status of COVID-19.

COVID-19 transmission in group living environments and households.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the world's largest public health concern. This study evaluated COVID-19 transmission risks in people in group living environments. A total of 4550 individuals with a history of recent contact with patients at different places (dormitory/home/outside the residences) and levels (close/lower-risk) were tested for SARS-CoV-2 viral RNA using a nasopharyngeal swab test between July 2020 and May 2021. The test-positive rate was highest in individuals who had contact in dormitories (27.5%), but the rates were largely different between dormitories with different infrastructural or lifestyle features and infection control measures among residents. With appropriate infection control measures, the secondary transmission risk in dormitories was adequately suppressed. The household transmission rate (12.6%) was as high as that of close contact outside the residences (11.3%) and accounted for > 60% of the current rate of COVID-19 transmission among non-adults. Household transmission rates synchronized to local epidemics with changed local capacity of quarantining infectious patients. In conclusion, a group living environment is a significant risk factor of secondary transmission. Appropriate infection control measures and quarantine of infectious residents will decrease the risk of secondary transmission in group living environments.

Predictors of SARS-CoV-2 Positivity Based on RT-PCR Swab Tests at a Drive-Through Outpatient Clinic for COVID-19 Screening in Japan.

In response to the COVID-19 pandemic caused by SARS-CoV-2 in 2020, we conducted drive-through nasopharyngeal swab testing for COVID-19 in Sendai city, Japan, since April 2020. All tested individuals were judged in advance by public health centers for the necessity of undergoing the test with possible contact history and/or symptoms suggestive of COVID-19. In this study, to identify the predictors of SARS-CoV-2 test positivity for more efficient and evidenced selection of suspected individuals, we enrolled 3,540 consecutive individuals, tested in the first 7 months of the testing program, with data regarding to the history of close contact with COVID-19 patients, including those involved in cluster outbreaks. This cohort included 284 foreign students (257 males and 27 females) from a vocational school involved in the largest cluster outbreak in the area. Close contact history was present in 952 (26.9%) of the participants. The reverse transcription-polymerase chain reaction (RT-PCR) test results showed that 164 participants (4.6%) were positive and 3,376 participants (95.4%) were negative for the SARS-CoV-2 nucleocapsid gene (N2). In the univariate and multivariate analyses, history of close contact with COVID-19 patients, higher age, cough symptoms, and non-native ethnicity were predictors for SARS-CoV-2 test positivity. However, the significance of age and foreign nationality disappeared or declined upon excluding the foreign students from the aforementioned largest cluster outbreak. In conclusion, a history of close contact with COVID-19 patients and the presence of cough symptoms are significant predictors of SARS-CoV-2 test positivity.