Effect of Past Chlamydophila pneumoniae Infection on the Short-Time Mortality of COVID-19: A Retrospective Cohort Study.

BACKGROUND: Although Chlamydophila pneumoniae (CP)is known to play a role in atherosclerosis and endothelial injury, its past infection on the mortality of coronavirus disease 2019 (COVID-19), which was also reported to be a vascular disease, remains unknown. METHODS: In this retrospective cohort study, we examined 78 COVID-19 patients and 32 bacterial pneumonia patients who visited a tertiary emergency center in Japan between April 1, 2021, and April 30, 2022. CP antibody levels, including IgM, IgG, and IgA, were measured. RESULTS: Among all patients, the CP IgA-positive rate was significantly associated with age (P = 0.002). Between the COVID-19 and non-COVID-19 groups, no difference in the positive rate for both CP IgG and IgA was observed (P = 1.00 and 0.51, respectively). The mean age and proportion of males were significantly higher in the IgA-positive group than in the IgA-negative group (60.7 vs. 75.5, P = 0.001; 61.5% vs. 85.0%, P = 0.019, respectively). Smoking and dead outcomes were significantly higher both in the IgA-positive group and IgG-positive group (smoking: 26.7% vs. 62.2, P = 0.003; 34.7% vs. 73.1%, P = 0.002, dead outcome: 6.5% vs. 29.8%, P = 0.020; 13.5% vs. 34.6%, P = 0.039, respectively). Although the log-rank test revealed higher 30-day mortality in the IgG-positive group compared to the IgG-negative group (P = 0.032), Cox regression analysis demonstrated no significant difference between the IgG-positive and negative groups (hazard ratio (HR) = 4.10, 95%CI = 0.94-18.0, P = 0.061). CONCLUSION: The effect of past CP infection on 30-day mortality in COVID-19 patients was not obvious.

Steroid Pulse Therapy as a Treatment for Patients With COVID-19 Pneumonia at an Intensive Care Unit: A Single-Center Retrospective Observational Study.

BACKGROUND: Evidence supporting the use of steroid pulse therapy in severely ill patients with coronavirus disease 2019 (COVID-19) pneumonia is lacking. Few studies have evaluated the efficacy of high-dose (1000 mg/day) methylprednisolone (mPSL), which is commonly used in Japan. AIM: This study aimed to compare the clinical outcomes with and without steroid pulse therapy (mPSL 1000 or 500 mg/day for three days) in patients with COVID-19 pneumonia, admitted to an intensive care unit (ICU). METHODS: Study design was retrospective observational study. The inclusion criterion was severe to critically ill adult patients with COVID-19 pneumonia requiring ICU admission. The exclusion criteria were as follows: patients (1) with a "Do not attempt to resuscitate" order; (2) with a "Do not intubate" order; or (3) admitted to the ICU owing to other infectious diseases were excluded. Treatment strategy was as follows: Patients were divided into two groups: steroid pulse therapy (Group P) and steroids without pulse therapy (Group NP). Group P received mPSL 1000 or 500 mg/day on ICU days 1-3, and Group NP received dexamethasone 6.6 mg or mPSL 1 or 2 mg/kg/day. The primary outcome was 28-day mortality. RESULTS: We enrolled 82 patients. Out of 70 who met the inclusion criteria, 48 and 22 were included in Groups P and NP, respectively. No difference in 28-day survival was observed between the Groups P and NP (log-rank P=0.11). After adjusting for covariates (age, sex, interleukin-6 level, and acute physiology and chronic health evaluation II score on ICU admission) using a multivariate Cox proportional hazard model, treatment with steroid pulse therapy significantly improved 28-day mortality (hazard ratio, 0.14; 95% confidence interval, 0.02-0.86; P=0.03). CONCLUSION: Steroid pulse therapy may improve the 28-day mortality in patients with COVID-19 pneumonia in the ICU.

Utility of dual-energy computed tomography in the association of COVID-19 pneumonia severity.

Aim: Coronavirus disease 2019 pneumonia differs from ordinary pneumonia in that it is associated with lesions that reduce pulmonary perfusion. Dual-energy computed tomography is well suited to elucidate the etiology of coronavirus disease 2019 pneumonia, because it highlights changes in organ blood flow. In this study, we investigated whether dual-energy computed tomography could be used to determine the severity of coronavirus disease 2019 pneumonia. Methods: Patients who were diagnosed with coronavirus disease 2019 pneumonia, admitted to our hospital, and underwent dual-energy computed tomography were included in this study. Dual-energy computed tomography findings, plane computed tomography findings, disease severity, laboratory data, and clinical features were compared between two groups: a critical group (18 patients) and a non-critical group (30 patients). Results: The dual-energy computed tomography results indicated that the percentage of flow loss was significantly higher in the critical group compared with the non-critical group (P < 0.001). Additionally, our data demonstrated that thrombotic risk was associated with differences in clinical characteristics (P = 0.018). Receiver operating characteristic analysis revealed that the percentage of flow loss, evaluated using dual-energy computed tomography, could predict severity in the critical group with 100% sensitivity and 77% specificity. However, there were no significant differences in the receiver operating characteristic values for dual-energy computed tomography and plane computed tomography. Conclusion: Dual-energy computed tomography can be used to associate the severity of coronavirus disease 2019 pneumonia with high accuracy. Further studies are needed to draw definitive conclusions.

Efficacy of different anticoagulant doses for patients with COVID-19: a systematic review and network meta-analysis.

PURPOSE: As no reported randomized control trials (RCTs) directly compare the three administration doses of anticoagulants (prophylactic dose, treatment dose, and no treatment), the most recommended dose to be administered to patients with coronavirus disease 2019 (COVID-19) remains unclear. The purpose of this study was to examine the effects of anticoagulant doses administered to patients with COVID-19, using a network meta-analysis (NMA) including high-quality studies. METHODS: All eligible trials from the Cochrane Central Register of Controlled Trials, MEDLINE, and Clinicaltrials.gov were included. We included RCTs and observational studies adjusted for covariates for patients aged ≥ 18 years and hospitalized due to objectively confirmed COVID-19. The main study outcome was mortality. RESULTS: In patients with moderate COVID-19, the prophylactic (relative risk (RR) 0.64 [95% confidence interval (CI) 0.52-0.80]) and treatment dose (RR 0.57 [95% CI 0.45-0.72] were associated with a lower risk of short-term mortality than that with no anticoagulant treatment. However, the prophylactic and treatment dose groups were not significantly different. The hierarchy for efficacy in reducing short-term mortality was treatment dose (P score 92.4) > prophylactic dose (57.6) > no treatment (0.0). In patients with severe COVID-19, due to the absence of trials with the no-treatment group, NMA could not be conducted. However, pairwise comparison did not show a significant difference between the prophylactic and treatment dose groups. CONCLUSIONS: Treatment and prophylactic doses of anticoagulants showed similar effects on mortality; however, the treatment dose is preferred over the prophylactic dose for patients with both moderate and severe COVID-19. TRIAL REGISTRATION NUMBER AND REGISTRATION DATES: PROSPERO (registration number: CRD42021245308, 05/21/2021).

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.

Chronic Pulmonary Aspergillosis During Convalescence From Severe COVID-19 Treated With Oral Itraconazole: A Report of Two Cases.

Invasive pulmonary aspergillosis (IPA) has been reported to occur secondary to coronavirus disease 2019 (COVID-19), and the condition has been termed COVID-19-associated pulmonary aspergillosis (CAPA). We diagnosed two severe COVID-19 cases with multiple cavitary lung lesions and chronic pulmonary aspergillosis (CPA) on days 58 and 48 of admission, respectively, with gradual improvement in the respiratory status. Both patients were positive for Aspergillus-precipitating antibodies (APAb). We chose oral itraconazole (ITCZ) for both patients because of its convenience in terms of long-term treatment. Cavitary lesions diminished after ITCZ administration. The risk factors for pulmonary aspergillosis in both patients were determined to be steroid pulse therapy, use of baricitinib, diabetes mellitus (DM), ICU admission, long hospital stay, and the use of broad-spectrum antibiotics. Pulmonary aspergillosis must be suspected in patients with severe COVID-19, even if they are asymptomatic, because not only IPA but also CPA can occur following COVID-19. Therefore, oral ITCZ may be a treatment option for CPA following COVID-19.

Methylprednisolone pulse therapy for critically ill patients with coronavirus disease 2019: A single-center retrospective observational study.

Aim: This study compared the clinical outcomes of critically ill patients with coronavirus disease (COVID-19) pneumonia treated with high-dose methylprednisolone and other steroids. Methods: This retrospective observational study included critically ill COVID-19 pneumonia adult patients with tracheal intubation treated between April 1, 2020, and September 15, 2021. Of the 46 patients who met the inclusion criteria, 36 received steroid pulse therapy (Group P) and 10 received steroids without pulse therapy (Group NP). Subgroup analyses in Group P by methylprednisolone dose of 1000 or 500 mg for 3 days during intensive care unit stay were carried out. The primary and secondary outcomes were 28-day mortality and steroid-associated complications, respectively. Results: In the Kaplan-Meier curve analysis, there was no difference in the 28-day survival between P and NP groups (log-rank P = 0.046). Univariate Cox proportional hazard model also showed that Group P had a decreased 28-day mortality (hazard ratio 0.30; [95% confidence interval, 0.20-0.44]; P < 0.01). After adjusting for covariates (age, sex, remdesivir, baricitinib, and favipiravir), using the multivariate Cox proportional hazards model, Group P had improved 28-day mortality (0.50 [0.30-0.85], P = 0.01). Conclusion: Steroid pulse therapy might improve the 28-day and in-hospital mortality in critically ill patients with COVID-19 pneumonia.

Methylprednisolone pulse therapy for critically ill patients with coronavirus disease 2019: A single‐center retrospective observational study

Aim This study compared the clinical outcomes of critically ill patients with coronavirus disease (COVID‐19) pneumonia treated with high‐dose methylprednisolone and other steroids. Methods This retrospective observational study included critically ill COVID‐19 pneumonia adult patients with tracheal intubation treated between April 1, 2020, and September 15, 2021. Of the 46 patients who met the inclusion criteria, 36 received steroid pulse therapy (Group P) and 10 received steroids without pulse therapy (Group NP). Subgroup analyses in Group P by methylprednisolone dose of 1000 or 500 mg for 3 days during intensive care unit stay were carried out. The primary and secondary outcomes were 28‐day mortality and steroid‐associated complications, respectively. Results In the Kaplan–Meier curve analysis, there was no difference in the 28‐day survival between P and NP groups (log–rank P = 0.046). Univariate Cox proportional hazard model also showed that Group P had a decreased 28‐day mortality (hazard ratio 0.30;[95% confidence interval, 0.20–0.44];P < 0.01). After adjusting for covariates (age, sex, remdesivir, baricitinib, and favipiravir), using the multivariate Cox proportional hazards model, Group P had improved 28‐day mortality (0.50 [0.30–0.85], P = 0.01). Conclusion Steroid pulse therapy might improve the 28‐day and in‐hospital mortality in critically ill patients with COVID‐19 pneumonia. In the Kaplan–Meier curve analysis, there was no difference in 28‐day survival between the P and NP groups (log rank P = 0.046). However, in univariate analysis using Cox proportional hazard model, steroids pulse therapy decreased the risk of death in critically‐ill patients with COVID‐19 pneumonia (hazard ratio [HR]: 0.30, 95% confidence interval [CI];0.20‐0.44, P 0.01).

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.

DUAL-energy computed tomography findings in a case of COVID-19.

BACKGROUND: COVID-19 pneumonia has lesions with a decreased blood flow. Dual-energy computed tomography is suitable to elucidate the pathogenesis of COVID-19 pneumonia because it highlights the blood flow changes in organs. We report the dual-energy computed tomography findings of a successfully treated case of COVID-19 pneumonia. CASE PRESENTATION: An obese 49-year-old man with COVID-19 pneumonia was transferred from another hospital on day 11 after onset of illness. Although he was hypoxemic (PaO2/FiO2 = 100), tracheal intubation was not performed after anticipating difficulty in weaning from mechanical ventilation. Prone position therapy and nasal high flow therapy were administered, and the patient was discharged after his condition improved. Dual-energy computed tomography was performed three times during hospitalization, and it revealed improvement in the blood flow defect, unlike plain computed tomography that did not show much improvement. CONCLUSION: Dual-energy computed tomography can assess perfusion in COVID-19 pneumonia in real time and may be able to predict its severity.

Japanese rapid/living recommendations on drug management for COVID-19.

The coronavirus disease (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-SSCGs. 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 9 September, 2020, and this document is the revised edition (version 3.1) (released 30 March, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ2), hydroxychloroquine (CQ3), corticosteroids (CQ4), tocilizumab (CQ5), ciclesonide (CQ6), and anticoagulants (CQ7). Favipiravir is recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 2C); remdesivir for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Hydroxychloroquine is not recommended for all COVID-19 patients (GRADE 1B). Corticosteroids are recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 1B) and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 1A); however, their use is not recommended for mild COVID-19 patients not requiring supplemental oxygen (GRADE 1B). Tocilizumab is recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Anticoagulant therapy is recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 2C). We hope that these clinical practice guidelines will aid medical professionals involved in the care of COVID-19 patients.