The National Early Warning Score on admission predicts severe disease and in-hospital mortality of the coronavirus disease 2019 Delta variant: A retrospective cohort study.

Background: Clinical risk scores are widely used in emergency medicine, and some studies have evaluated their use in patients with coronavirus disease 2019 (COVID-19). However, no studies have evaluated their use in patients with the COVID-19 Delta variant. We aimed to study the performance of four different clinical scores (National Early Warning Score [NEWS], quick Sequential Organ Failure Assessment [qSOFA], Confusion, Respiratory rate, Blood pressure, and Age ≥65 [CRB-65], and Kanagawa score) in predicting the risk of severe disease (defined as the need for intubation and in-hospital mortality) in patients with the COVID-19 Delta variant. Methods: This was a retrospective cohort study of patients hospitalized with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection between June 1 and December 31, 2021. The primary outcomes were the sensitivity and specificity of the aforementioned clinical risk scores at admission to predict severe disease. Areas under the receiver operating characteristic curves (AUROCs) were compared between the clinical risk scores and we identified new cut-off points for all four scores. Results: A total of 249 adult patients were included, of whom 18 developed severe disease. A NEWS ≥7 at admission predicted severe disease with 72.2% sensitivity and 86.2% specificity. The NEWS (AUROC 0.88) was superior to both the qSOFA (AUROC 0.74) and the CRB-65 (AUROC 0.67), and there was no significant difference between the NEWS and Kanagawa score (AUROC 0.86). Conclusion: The NEWS at hospital admission predicted the severity of the COVID-19 Delta variant with high accuracy.

Predicting the aggravation of coronavirus disease-19 pneumonia using chest computed tomography scans.

Presently, coronavirus disease-19 (COVID-19) is spreading worldwide without an effective treatment method. For COVID-19, which is often asymptomatic, it is essential to adopt a method that does not cause aggravation, as well as a method to prevent infection. Whether aggravation can be predicted by analyzing the extent of lung damage on chest computed tomography (CT) scans was examined. The extent of lung damage on pre-intubation chest CT scans of 277 patients with COVID-19 was assessed. It was observed that aggravation occurred when the CT scan showed extensive damage associated with ground-glass opacification and/or consolidation (p < 0.0001). The extent of lung damage was similar across the upper, middle, and lower fields. Furthermore, upon comparing the extent of lung damage based on the number of days after onset, a significant difference was found between the severe pneumonia group (SPG) with intubation or those who died and non-severe pneumonia group (NSPG) ≥3 days after onset, with aggravation observed when ≥14.5% of the lungs exhibited damage at 3-5 days (sensitivity: 88.2%, specificity: 72.4%) and when ≥20.1% of the lungs exhibited damage at 6-8 days (sensitivity: 88.2%, specificity: 69.4%). Patients with aggravation suddenly developed hypoxemia after 7 days from the onset; however, chest CT scans obtained in the paucisymptomatic phase without hypoxemia indicated that subsequent aggravation could be predicted based on the degree of lung damage. Furthermore, in subjects aged ≥65 years, a significant difference between the SPG and NSPG was observed in the extent of lung damage early beginning from 3 days after onset, and it was found that the degree of lung damage could serve as a predictor of aggravation. Therefore, to predict and improve prognosis through rapid and appropriate management, evaluating patients with factors indicating poor prognosis using chest CT is essential.

Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19.

BACKGROUND: The role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated. METHODS: We conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19. RESULTS: In this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively). CONCLUSION: Higher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.

Low SARS-CoV-2 antibody titers may be associated with poor clinical outcomes for patients with severe COVID-19.

Recently, immune response to coronavirus disease (COVID-19) has attracted attention where an association between higher antibody titer and worsening disease severity has been reported. However, our experiences with severe COVID-19 patients with low antibody titers led to hypothesizing that suppressed humoral immune response may be associated with poorer prognosis in severe COVID19. In this study, antibody titers in severe COVID19 patients were measured at 7, 10, 12, and 14 days after onset. Patients were divided into survivors and non-survivors. SARS-CoV-2 IgM in survivors and non-survivors were 0.06 AU and 0.02 AU (P = 0.048) at 10 days, 0.1 AU and 0.03 AU (P = 0.02) at 12 days, and 0.17 AU and 0.06 AU (P = 0.02) at 14 days. IgG in survivors and non-survivors were 0.01 AU and 0.01 AU (P = 0.04) at 7 days, 0.42 AU and 0.01 AU (P = 0.04) at 12 days, and 0.42 AU and 0.01 AU (P = 0.02) at 14 days. Multivariate analysis showed better survival among patients with IgM positivity at 12 days (P = 0.04), IgG positivity at 12 days (P = 0.04), IgM positivity at 14 days (P = 0.008), and IgG positivity at 14 days (P = 0.005). In severe COVID-19, low antibody titers on days 12 and 14 after onset were associated with poorer prognosis.

Efficacy of awake prone positioning for severe illness coronavirus disease 2019 patients: a propensity score‐adjusted cohort study

Aim Awake prone positioning (PP) in patients with coronavirus disease 2019 (COVID‐19) can improve oxygenation. However, evidence showing that it can prevent intubation is lacking. This study investigated the efficacy of awake PP in patients with COVID‐19 who received remdesivir, dexamethasone, and anticoagulant therapy. Methods This was a two‐center cohort study. Patients admitted to the severe COVID‐19 patient unit were included. The primary outcome was the intubation rate and secondary outcome was length of stay in the severe COVID‐19 unit. After propensity score adjustment, we undertook multivariable regression to calculate the estimates of outcomes between patients who received awake PP and those who did not. Results Overall, 108 patients were included (54 [50.0%] patients each who did and did not undergo awake PP), of whom 25 (23.2%) were intubated (with awake PP, 5 [9.3%] vs. without awake PP, 20 [37.0%];P < 0.01). The median length of stay in the severe COVID‐19 unit did not significantly differ (with awake PP, 5 days vs. without awake PP, 5.5 days;P = 0.68). After propensity score adjustment, those who received awake PP had a lower intubation rate than those who did not (odds ratio, 0.22;95% confidence interval, 0.06–0.85;P = 0.03). Length of stay in the severe COVID‐19 patient unit did not differ significantly (adjusted percentage difference, −24.4%;95% confidence interval, −56.3% to 30.8%;P = 0.32). Conclusion Awake PP could be correlated with intubation rate in patients with COVID‐19 who are receiving remdesivir, dexamethasone, and anticoagulant therapy. This study aimed to investigate the efficacy of awake prone positioning (PP) for patients with coronavirus disease 2019 (COVID‐19) using remdesivir, dexamethasone, and anticoagulation therapy. We undertook a two‐center propensity score‐adjusted cohort study in Japan from July 2020 to February 2021. We showed that awake PP could be correlated with intubation rate in patients with acute respiratory failure and COVID‐19.

Intensive care burden of COVID-19 in tertiary care hospitals during the first year of outbreak in Kawasaki City, Japan: A retrospective cohort study.

INTRODUCTION: This study aimed to describe the changes in the intensive care burden of coronavirus disease 2019 (COVID-19) during the first year of outbreak in Japan. METHODS: This retrospective cohort study included COVID-19 patients who received mechanical ventilation (MV) support in two designated hospitals for critical patients in Kawasaki City. We compared the lengths of MV and stay in the intensive care unit (ICU) or high care unit (HCU) according to the three epidemic waves. We calculated in-hospital mortality rates in patients with or without MV. RESULTS: The median age of the sample was 65.0 years, and 22.7% were women. There were 37, 29, and 62 patients in the first (W1), second (W2), and third waves (W3), respectively. Systemic steroids, remdesivir, and prone positioning were more frequent in W2 and W3. The median length of MV decreased from 18.0 days in W1 to 13.0 days in W3 (P = 0.019), and that of ICU/HCU stay decreased from 22.0 days in W1 to 15.5 days in W3 (P = 0.027). The peak daily number of patients receiving MV support was higher at 18 patients in W1, compared to 8 and 15 patients in W2 and W3, respectively. The mortality rate was 23.4%, which did not significantly change (P = 0.467). CONCLUSIONS: The lengths of MV and ICU/HCU stay per patient decreased over time. Despite an increase in the number of COVID-19 patients who received MV in W3, this study may indicate that the intensive care burden during the study period did not substantially increase.

A Platform Trial of Optimal Treatment for Pneumonia including (Re-)Emerging Infections

Corticosteroids for hospitalized patients with mild to critically-ill COVID-19: a multicenter, retrospective, propensity score-matched study.

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

Why participation in an international clinical trial platform matters during a pandemic? Launching REMAP-CAP in Japan.

REMAP-CAP, a randomized, embedded, multifactorial adaptive platform trial for community-acquired pneumonia, is an international clinical trial that is rapidly expanding its scope and scale in response to the COVID-19 pandemic. Japan is now joining REMAP-CAP with endorsement from Japanese academic societies. Commitment to REMAP-CAP can significantly contribute to population health through timely identification of optimal COVID-19 therapeutics. Additionally, it will promote the establishment of a national and global network of clinical trials to tackle future pandemics of emerging and re-emerging infectious diseases, in collaboration with multiple stakeholders, including front-line healthcare workers, governmental agencies, regulatory authorities, and academic societies.

REMAP-CAP:Randomized,Embedded,Multifactorial Adaptive Platform trial for Community-Acquired Pneumonia Immune Modulation-2 Domain

Back to normal; serological testing for COVID-19 diagnosis unveils missed infections.

BACKGROUND: The gold standard for coronavirus disease (COVID-19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID-19 may offer advantages in detecting possibly overlooked infections by NAAT. METHODS: To evaluate seroconversion of NAAT-negative pneumonia patients, immunoglobulin M (IgM) and IgG targeting the spike protein of SARS-CoV-2 were semiquantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein. RESULTS: Eight suspected but unconfirmed COVID-19 pneumonia patients (median age, 39 years; range, 21-55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2-27 days). None of them had tested positive for SARS-CoV-2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS-CoV-2. The median period between onset and blood sampling was 26.5 days (7-51 days). CONCLUSION: Eight patients with COVID-19 pneumonia, initially tested negative for SARS-CoV-2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multitiered diagnostic algorithm for COVID-19.

Allocation of Mechanical Ventilators During a Pandemic: A Mixed-Methods Study of Perceptions Among Japanese Health Care Workers and the General Public.

BACKGROUND: In Japan, public dialogue on allocation of life-saving medical resources remains taboo, and discussion largely has been avoided. RESEARCH QUESTION: Do Japanese health care workers and the general public agree with principles of ventilator allocation developed internationally? STUDY DESIGN AND METHODS: A four-point Likert scale questionnaire was used to assess the extent of agreement or disagreement with internationally developed triage principles for rationing mechanical ventilators during pandemics. Questionnaires were distributed in person or online, and generalized linear models were used to analyze quantitative data. Free-text descriptions were analyzed qualitatively, both deductively and inductively, to compare respondent opinions with those described in previous US studies. RESULTS: Of 3,191 surveys distributed, 1,520 were returned. Allocation of resources to maximize survival from current illness ("save the most lives") was the most popular triage principle, with 95.8% of respondents in agreement. Allocation to ensure a minimum duration of benefit, as determined by predicted prognosis after illness ("ensure minimum duration of benefit"), and allocation to persons who have experienced fewer life stages ("life cycle") obtained agreement of 82.2% and 80.1%, respectively. Withdrawal and reallocation of mechanical ventilators to more appropriate patients was supported by 64.4% of respondents. Only 28.4% of respondents supported the principle of first-come, first-served access to ventilators. INTERPRETATION: Most respondents supported allocation principles developed internationally and disagreed with the idea of first-come, first-served allocation during resource shortages. The Japanese public seems largely to be prepared to discuss the ethical dilemmas and possible solutions regarding fair and transparent allocation of critical care resources as a necessary step in confronting present and future pandemics and disasters.

Preventing thrombosis in a COVID-19 patient by combined therapy with nafamostat and heparin during extracorporeal membrane oxygenation.

Background: Preventing thrombosis in extracorporeal membrane oxygenation (ECMO) can be life-saving in cases of coronavirus disease (COVID-19); however, circuit thrombosis is a complication. This report describes a COVID-19 patient treated with nafamostat and heparin to prevent circuit thrombosis during ECMO support. Case presentation: A 63-year-old man was transferred to our hospital with respiratory failure due to COVID-19 pneumonia. He was provided venous-venous ECMO to maintain oxygenation. During ECMO support, occlusive circuit thrombosis developed despite systemic anticoagulation therapy with heparin. He was subsequently given combination therapy with nafamostat and heparin. Although the combination therapy could prevent circuit thrombosis, it was converted to heparin monotherapy because of hyperkalemia and hemothorax. After tracheostomy and a gradual improvement in oxygenation, ECMO was discontinued. He was transferred to another hospital for further rehabilitation. Conclusion: Combination therapy with nafamostat and heparin can prevent circuit thrombosis during ECMO. However, bleeding can still develop with this combination therapy during ECMO.

Personal protective equipment use by health-care workers in intensive care units during the COVID-19 pandemic in Japan: comparative analysis with the PPE-SAFE survey.

Aim: We investigated personal protective equipment (PPE) use and supply shortage, training, and adverse events among health-care workers (HCWs) in the intensive care unit (ICU) during the coronavirus disease (COVID-19) pandemic in Japan and compared the results with an international survey that used the same methodology. Methods: This Web-based survey was carried out from 14 April to 6 May, 2020, in Japan and included HCWs directly involved in ICU management of COVID-19 patients. A survey invitation was emailed using the Japanese Society of Intensive Care Medicine's mailing list. Results: We analyzed 460 valid responses from among 976 responses. The N95/FFP2 mask (77%) was the most frequently used, although half of our respondents reported reuse of single-use N95/FFP2 masks. The median duration (1 h) of uninterrupted PPE use per shift was less than that in the international study. The most common PPE-related adverse event was experiencing intense heat (75%). Logistic regression analysis revealed that being a nurse was independently associated with experiencing intense heat. Conclusion: Shortage of PPE and frequent mask reuse were prevalent during the COVID-19 pandemic in Japan. Intense heat is the most significant symptom, especially for nurses, even with short-duration PPE use. Strategies to protect HCWs from dehydration and intense heatstroke are needed.

The peripheral lymphocyte count as a predictor of severe COVID-19 and the effect of treatment with ciclesonide.

We investigated whether reduced lymphocyte count, could predict the development of severe COVID-19. We also examined whether ciclesonide could prevent the development of severe COVID-19 among patients with the predictors. This was a retrospective cohort study. Of the 30 included patients, 12, 14, and 4 were allocated to severe pneumonia, non-severe pneumonia, and non-pneumonia groups, respectively. The group of the low level of lymphocyte counts of the sixth day after onset was significantly intubated approximately three days later. The incidence of the severe pneumoniae requiring intubation are significantly lower in the patients treated with ciclesonide than without it (11.18 % vs 83.33 %, p = 0.0033). The lymphocyte count after ciclesonide treatment in the non-severe pneumonia group was significantly higher (p = 0. 0156) than before. The lymphocyte count could be used to identify patients that may develop severe COVID-19. Treatment with ciclesonide may prevent the development of severe COVID-19.