COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron.

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.

Breath-by-breath P0.1 measured on quasi-occlusion via Hamilton C6 may result in underestimation of respiratory drive and inspiratory effort.

We aimed to identify the threshold for P0.1 in a breath-by-breath manner measured by the Hamilton C6 on quasi-occlusion for high respiratory drive and inspiratory effort. In this prospective observational study, we analyzed the relationships between airway P0.1 on quasi-occlusion and esophageal pressure (esophageal P0.1 and esophageal pressure swing). We also conducted a linear regression analysis and derived the threshold of airway P0.1 on quasi-occlusion for high respiratory drive and inspiratory effort. We found that airway P0.1 measured on quasi-occlusion had a strong positive correlation with esophageal P0.1 measured on quasi-occlusion and esophageal pressure swing, respectively. Additionally, the P0.1 threshold for high respiratory drive and inspiratory effort were calculated at approximately 1.0 cmH2O from the regression equations. Our calculations suggest a lower threshold of airway P0.1 measured by the Hamilton C6 on quasi-occlusion than that which has been previously reported.

Prevalence of COVID-19 Mimics in the Emergency Department.

Objective Due to the lack of specific clinical manifestations and symptoms, it is difficult to distinguish COVID-19 from mimics. A common pitfall is to rush to make a diagnosis when encountering a patient with COVID-19-like symptoms. The present study describes a series of COVID-19 mimics using an outpatient database collected from a designated COVID-19 healthcare facility in Tokyo, Japan. Methods We established an emergency room (ER) tailored specifically for patients with suspected or confirmed COVID-19 called the "COVID-ER." In this single-center retrospective cohort study, we enrolled patients who visited the COVID-ER from February 1 to September 5, 2020. The outcomes included the prevalence of COVID-19, admission, potentially fatal diseases and final diagnosis. Results We identified 2,555 eligible patients. The median age was 38 (interquartile range, 26-57) years old. During the study period, the prevalence of COVID-19 was 17.9% (457/2,555). Non-COVID-19 diagnoses accounted for 82.1% of all cases. The common cold had the highest prevalence and accounted for 33.0% of all final diagnoses, followed by gastroenteritis (9.4%), urinary tract infections (3.8%), tonsillitis (2.9%), heat stroke (2.6%) and bacterial pneumonia (2.1%). The prevalence of potentially fatal diseases was 14.2% (298/2,098) among non-COVID-19 patients. Conclusion Several potentially fatal diseases remain masked among the wave of COVID-19 mimics. It is imperative that a thorough differential diagnostic panel be considered prior to the rendering of a COVID-19 diagnosis.

Abnormal pulmonary function and imaging studies in critical COVID-19 survivors at 100 days after the onset of symptoms.

BACKGROUND: The long-term repercussions of critical COVID-19 on pulmonary function and imaging studies remains unexplored. In this study, we investigated the pulmonary function and computed tomography (CT) findings of critical COVID-19 patients approximately 100 days after symptom onset. METHODS: We retrospectively extracted data on critical COVID-19 patients who received invasive mechanical ventilation during hospitalization from April to December 2020 and evaluated their pulmonary function, residual respiratory symptoms and radiographic abnormalities on CT. RESULTS: We extracted 17 patients whose median age was 63 (interquartile range [IQR], 59-67) years. The median lengths of hospitalization and mechanical ventilation were 23 (IQR, 18-38) and 9 (IQR, 6-13) days, respectively. At 100 days after symptom onset, the following pulmonary function abnormalities were noted in 8 (47%) patients: a diffusion capacity of the lung for carbon monoxide (%DLCO) of <80% for 6 patients (35%); a percent vital capacity (%VC) of <80% for 4 patients (24%); and a forced expiratory volume in one second/forced vital capacity (FEV1%) of <70% for 1 patient (6%) who also presented with %DLCO and %VC abnormalities. Twelve (71%) patients reported residual respiratory symptoms and 16 (94%) showed abnormalities on CT. CONCLUSIONS: Over 90% of the critical COVID-19 patients who underwent invasive mechanical ventilation continued presenting with abnormal imaging studies and 47% of the patients presented with abnormal pulmonary function 100 days after symptom onset. The extent of the residual CT findings might be associated with the degree of abnormal pulmonary function in critical COVID-19 survivors.

Prevalence of thromboembolic events and status of prophylactic anticoagulant therapy in hospitalized patients with COVID-19 in Japan.

INTRODUCTION: One of the most prominent and concerning complications associated with coronavirus disease 2019 (COVID-19) is venous and arterial thromboembolisms. The aim of the present study was to delineate the prevalence of thromboembolic events and the current status of prophylactic anticoagulation therapy in patients with COVID-19 in Japan. METHODS: Between February 1 and August 31, 2020, we performed a dual-center, retrospective cohort study based on data obtained from the medical charts of COVID-19 patients admitted to healthcare facilities in Japan. The primary outcome was any thromboembolic event including pulmonary embolism (PE), deep vein thrombosis (DVT), myocardial infarction, ischemic stroke and other systemic thromboemboli. RESULTS: During the study period, we extracted 628 consecutive patients admitted for COVID-19. Prophylactic anticoagulant therapy was administered in 63 (10%) patients of whom 20 (31.7%) were admitted to the intensive care unit (ICU). Thromboembolic events occurred in 18 (2.9%) patients (14.3% of patients in ICU and 2.2% of patients in the general wards). DVT were detected in 13 (2.1%) patients, PE in 11 (1.8%), and both DVT and PE in 6 (0.96%) patients. An increasing prevalence in thromboembolic events was noted with progressive clinical severity. Overall in-hospital mortality was 4.8%. CONCLUSIONS: Prophylactic anticoagulation therapy was administered in only 10% of all hospitalized COVID-19 patients. The prevalence of any thromboembolic events was 2.9% in COVID-19 patients with most events occurring in severe and critical patients. Therefore, prophylactic anticoagulation therapy may be warranted in severe and critical patients but in asymptomatic to moderate patients the practice remains controversial.

Two Cases of Post-intubation Laryngotracheal Stenosis Occurring after Severe COVID-19.

We experienced two cases of post-intubation laryngotracheal stenosis (PILS) occurring in patients after acute coronavirus disease (COVID)-19 in a relatively narrow time period. The patients required mechanical ventilation for 9 days in one and 28 days in the other. In both cases, the patients were discharged but later developed symptoms of cough and dyspnea, which were later diagnosed as PILS. Persistent cough and dyspnea are common symptoms in both PILS and the recovery phase of severe COVID-19. For this reason, PILS should be considered in the differential diagnosis post-COVID-19 patients. In addition, the prevalence of PILS may be greater than that of other critical diseases in severe COVID-19 patients.

Prolonged euglycemic diabetic ketoacidosis triggered by a single dose of sodium-glucose cotransporter 2 inhibitor.

A 45-year-old woman was admitted for diabetic ketoacidosis (DKA). Aggressive rehydration and continuous intravenous insulin resulted in improved blood glucose levels; however, metabolic acidosis persisted. One day prior to admission, the patient took a single dose of a sodium-glucose cotransporter 2 (SGLT2) inhibitor and this likely contributed to the prolonged euglycemic DKA. A single dose of this drug remained effective for over 100 hours as evidenced by massive excretion of urine glucose continuing long after blood glucose normalisation. SGLT2 inhibitor use should be refrained in cases in which DKA has already occurred as they may result in increasing severity or prolonged DKA.

Retrospective analysis of survival in patients with leptomeningeal carcinomatosis from lung adenocarcinoma treated with erlotinib and gefitinib.

BACKGROUND: Leptomeningeal carcinomatosis is a relatively rare metastatic form of non-small cell lung cancer, which can impact prognosis. There is an increasing need for selecting suitable epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors among those currently included in standard care for EGFR mutation-positive patients. We compared the efficacy of gefitinib and erlotinib in survival of patients with leptomeningeal carcinomatosis. PATIENTS AND METHODS: The medical records of 269 patients who received tyrosine kinase inhibitors at a single center were retrospectively reviewed. Overall, 22 patients (8.2%) were treated with tyrosine kinase inhibitors for leptomeningeal carcinomatosis from non-small cell lung cancer with EGFR mutation between 2006 and 2016. Time to death from leptomeningeal carcinomatosis diagnosis was compared between the gefitinib and erlotinib groups. RESULTS: Gefitinib and erlotinib were administrated to 5 and 17 patients, respectively. Median progression-free survival was longer in the erlotinib group than in the gefitinib group (6.60 vs 2.12 months, P = 0.07). Overall survival was more than twice as long in the erlotinib arm compared with that in the gefitinib arm (7.20 vs 2.99 months, P = 0.32). Response in patients with exon 19 deletion was better than in those with exon 21 mutation (overall survival, 7.20 and 5.62 months, respectively, P = 0.12). CONCLUSIONS: Erlotinib seemed more effective than gefitinib in prolonging survival in leptomeningeal carcinomatosis from EGFR mutation-positive non-small cell lung cancer and may be particularly beneficial in patients with EGFR exon 19 mutations, warranting further studies.

Survival of patients with brain metastases from non-small cell lung cancer harboring EGFR mutations treated with epidermal growth factor receptor tyrosine kinase inhibitors.

Brain metastases (BM) is one of the most crucial distant metastases in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. There is no consensus about which EGFR tyrosine kinase inhibitor (TKI) is most effective against BM in such patients. Here, we compared prognoses of patients with EGFR-TKI naïve EGFR-positive BM treated with erlotinib or gefitinib after BM diagnosis. Of 269 patients with NSCLC treated with EGFR-TKIs at a single institution, we reviewed medical records of 205 patients with documented EGFR mutations. Eleven patients were administered erlotinib, and 52 patients were administered gefitinib as the first-line EGFR-TKI treatment after diagnosis. We used propensity score matching to balance patient backgrounds between groups, and the log-rank test to compare survival curves. Patients with BM at the induction of chemotherapy had a poorer prognosis than those without BM [median overall survival (OS) 18.5 vs. 28.0 months]. Meanwhile, there was no significant difference in OS between those with or without BM at the initiation of EGFR-TKI treatment (20.3 vs. 23.8 months). Median OS of patients treated with erlotinib was not significantly longer than that of patients treated with gefitinib (25.0 vs. 18.1 months). The presence of BM at the initiation of EGFR-TKI treatment had no apparent effect on survival. Erlotinib was deemed more effective than gefitinib in preventing intracranial lesions and prolonging survival; however, prospective studies are needed to confirm these results.