Statistical Analysis of Mortality Rates of Coronavirus Disease 2019 (COVID-19) Patients in Japan Across the 4C Mortality Score Risk Groups, Age Groups, and Epidemiological Waves: A Report From the Nationwide COVID-19 Cohort.

Background: The mortality rates of coronavirus disease 2019 (COVID-19) have been changed across the epidemiological waves. The aim was to investigate the differences in mortality rates of COVID-19 patients in Japan across the 6 epidemiological waves stratified by age group and Coronavirus Clinical Characterisation Consortium (4C) mortality score risk group. Methods: A total of 56 986 COVID-19 patients in the COVID-19 Registry Japan from 2 March 2020 to 1 February 2022 were enrolled. These patients were categorized into 4 risk groups based on their 4C mortality score. Mortality rates of each risk group were calculated separately for different age groups: 18-64, 65-74, 75-89, and ≥90 years. In addition, mortality rates across the wave periods were calculated separately in 2 age groups: <75 and ≥75 years. All calculated mortality rates were compared with reported data from the United Kingdom (UK) during the early epidemic. Results: The mortality rates of patients in Japan were significantly lower than in the UK across the board, with the exception of patients aged ≥90 years at very high risk. The mortality rates of patients aged ≥75 years at very high risk in the fourth and fifth wave periods showed no significant differences from those in the UK, whereas those in the sixth wave period were significantly lower in all age groups and in all risk groups. Conclusions: The present analysis showed that COVID-19 patients had a lower mortality rate in the most recent sixth wave period, even among patients ≥75 years old at very high risk.

Severe coronavirus disease 2019 in a patient with TAFRO syndrome: A case report.

Background: TAFRO syndrome, a subtype of idiopathic multicentric Castleman disease, is an acute or subacute systemic inflammatory disease that causes fever, generalized oedema (pleural effusion or ascites), and thrombocytopenia and is associated with renal impairment, anaemia, and organomegaly (hepatosplenomegaly and lymph node enlargement). Coronavirus disease 2019 (COVID-19)-associated hyperinflammation is caused by dysregulation of proinflammatory cytokines. Cytokine storm syndrome is common to both COVID-19 and TAFRO syndrome.Case report.A 66-year-old man with TAFRO syndrome was admitted because of worsening renal function, right pleural effusion, and ascites. He was taking 20 mg prednisolone orally and 25 mg cyclosporin A orally twice daily. Despite administration of maximum oxygenation and remdesivir, the patient developed acute respiratory distress syndrome (ARDS) and was transferred to the intensive care unit. Results: Chest radiography showed bilateral lung infiltration. COVID-19 was confirmed with a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2. Chest and abdominal computed tomography showed massive ground-glass opacities in both lungs, slight right pleural effusion, hepatomegaly, splenomegaly, and ascites. Conclusion: To the best of our knowledge, this is the first report of COVID-19 in a patient with TAFRO syndrome. Despite receiving a moderate dose of a corticosteroid and a monoclonal antibody against the IL-6 receptor, our patient developed severe pneumonia, suggesting that strong immunomodulatory therapy in the antiviral phase of COVID-19 may promote viral growth and induce ARDS.

Multiple Secondary Healthcare-Associated Infections Due to Carbapenem-Resistant Organisms in a Critically Ill COVID-19 Patient on Extensively Prolonged Venovenous Extracorporeal Membrane Oxygenation Support-A Case Report.

Patients with severe Coronavirus disease 2019 (COVID-19) are at high risk for secondary infection with multidrug-resistant organisms (MDROs). Secondary infections contribute to a more severe clinical course and longer intensive care unit (ICU) stays in patients with COVID-19. A man in his 60s was admitted to the ICU at a university hospital for severe COVID-19 pneumonia requiring mechanical ventilation. His respiratory condition worsened further due to persistent bacteremia caused by imipenem-non-susceptible Klebsiella aerogenes and he required VV-ECMO. Subsequently, he developed a catheter-related bloodstream infection (CRBSI) due to Candida albicans, ventilator-associated pneumonia (VAP) due to multidrug-resistant Pseudomonas aeruginosa (MDRP), and a perianal abscess due to carbapenem-resistant K. aerogenes despite infection control procedures that maximized contact precautions and the absence of MDRO contamination in the patient's room environment. He was decannulated from VV-ECMO after a total of 72 days of ECMO support, and was eventually weaned off ventilator support and discharged from the ICU on day 138. This case highlights the challenges of preventing, diagnosing, and treating multidrug-resistant organisms and healthcare-associated infections (HAIs) in the critical care management of severe COVID-19. In addition to the stringent implementation of infection prevention measures, a high index of suspicion and a careful evaluation of HAIs are required in such patients.

Case Report: Successful Treatment of Five Critically Ill Coronavirus Disease 2019 Patients Using Combination Therapy With Etoposide and Corticosteroids.

Acute respiratory distress syndrome (ARDS) is the leading cause of mortality in hospitalized patients with coronavirus disease 2019 (COVID-19) because of limited effective therapies. During infection, the accumulation and activation of macrophages and monocytes in the lungs induce inflammatory mediators and contribute to tissue injury, leading to ARDS. However, therapeutic strategies that directly target activated macrophage and monocytes have not been reported. Combination treatment with etoposide (a cytotoxic agent) and a corticosteroid has been widely used for treating hemophagocytic lymphohistiocytosis characterized by the systemic activation of macrophages with overwhelming inflammation. Herein, we present five cases of COVID-19-associated ARDS treated with etoposide and corticosteroids. Three of the five patients were over 65 years of age and had various underlying diseases, including multiple myeloma. Four patients required invasive mechanical ventilation (MV), and one patient refused to be placed on MV due to underlying diseases. All patients were pre-treated with antiviral and/or other anti-inflammatory agents, but their condition deteriorated and hyperinflammation was noted. All five patients responded well to treatment and had an immediate response, as reflected by improvement in their respiratory condition and inflammatory marker levels and rapid resolution of fever after etoposide administration; however, some patients required a second dose of etoposide and longer course of steroids. All patients recovered, and there were no severe adverse events related to the drugs. Following successful treatment in these five patients, we plan to conduct a clinical trial to evaluate the efficacy and safety of combination therapy with etoposide and corticosteroid for treating COVID-19 patients in Japan.

Prolonged presence of SARS-CoV-2 in a COVID-19 case with rheumatoid arthritis taking iguratimod treated with ciclesonide.

We report a coronavirus disease 2019 (COVID-19) case with rheumatoid arthritis taking iguratimod. The patient who continued iguratimod therapy without dose reduction was treated with ciclesonide had an uneventful clinical course, but prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed after resolution of symptoms. The effects of disease-modifying antirheumatic drugs (DMARDs) and ciclesonide on clinical course and viral shedding remain unknown and warrant further investigation.