We should pay more attention to sex differences to predict the risk of severe COVID-19: men have the same risk of worse prognosis as women more than 10 years older.

BackgroundPrioritization for COVID-19-related health policies usually considers age and certain other characteristics, but sex is rarely included despite the higher risk of severe disease in men. The aim of this study was to compare the impact of sex and age on the severity of COVID-19 by estimating the age difference in years for which the risk for men vs. women is the same.MethodsWe analyzed 23,414 Japanese COVID-19 in-patients aged 20-89 years (13,360 men and 10,054 women). We graded the severity of COVID-19 (0 to 5) according to the most intensive treatment required during hospitalization. The risk of grade 2/3/4/5 (non-invasive positive pressure ventilation / invasive mechanical ventilation / extracorporeal membrane oxygenation / death), grade 3/4/5, and separately grade 5 was analyzed using a multiple logistic regression model.ResultsThe risk of grades 2/3/4/5, 3/4/5 (primary outcome), and 5 for men relative to women was 2.76 [2.44-3.12], 2.78 [2.42-3.19], and 2.60 [2.23-3.03] (odds ratio [95% confidence interval] adjusted for age and date of admission), respectively. These risks for men were equivalent to those for women 14.1 [12.3-15.8], 11.2 [9.7-12.8], and 7.5 [6.3-8.7] years older, respectively.ConclusionsThe risks of worse COVID-19 prognosis (grades 3/4/5) in men were equivalent to those of women 11.2 years older. Reanalyzing data extracted from four previous studies also revealed a large impact of sex difference on the severity of COVID-19. We should pay more attention to sex differences to predict the risk of COVID-19 severity and to formulate public health policy accordingly.

Actual situation of handling Tokyo 2020 Games-related patients at a designated hospital during COVID-19 pandemic.

In preparation for the Tokyo 2020 Olympic and Paralympic Games, our hospital was responsible for accepting mainly media representatives, marketing partners, and other Games staff. Given that restricting our regular capacity to treat certain groups of patients could potentially result in social losses, to avoid this we made rigorous preparations for the entire hospital to accept Games-related patients. It was rational to set up a single 24-h contact point at the Emergency Department for making the decision on whether to accept the patient or not and for coordinating the patient's medical care. With respect to language support, International Health Care Center staffs were made available as interpreters on weekdays. Multilingual support was available all day via an application run on tablet devices. During a 67-day period, the hospital accepted 31 Games-related patients (mean age 43.4 years, male: female ratio 25:6). Eighteen patients were from Europe, 4 patients each were from North America and Asia, 2 each were from Central America, South America, and Africa, and 1 was from Oceania. The most common cause of visits was COVID-19, but none were severe cases. Other causes were diverse and included moderate and severe conditions. We summarized the challenges and experiences in handling Tokyo 2020 Games-related patients at a designated hospital during the COVID-19 pandemic.

Possible Autoimmune Encephalitis Associated with the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Successfully Treated with Steroids: A Case Report.

We encountered a 55-year-old woman with possible autoimmune encephalitis associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. She was not vaccinated against coronavirus disease 2019 (COVID-19). Consciousness disturbance, myoclonic-like movements and gait disturbance occurred 10 days after the COVID-19 symptom onset. Her neurological symptoms improved two days after methylprednisolone pulse therapy. Cerebrospinal fluid (CSF) was negative for SARS-CoV-2 reverse transcription-polymerase chain reaction, the CSF-to-serum albumin quotient was mildly elevated, and interleukin 6 and 8 levels were normal in serum but mildly elevated in CSF. Omicron variant infection may increase blood-brain barrier permeability and intrathecal inflammation, causing autoimmune encephalitis.

Poor prognosis of patients with severe COVID-19 admitted to an infectious disease intensive care unit during the pandemic caused by the Delta variant in Japan.

During the surge of coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) delta variant, our institution operated an intensive care unit (ICU) for patients with severe COVID-19. The study aim was to determine the survival rate and treatment outcomes of patients with severe COVID-19 treated in the ICU during the surge. A total of 23 consecutive patients with severe COVID-19 were admitted to the ICU between August 5 and October 6, 2021. Patients received multidrug therapy consisting of remdesivir, tocilizumab, heparin, and methylprednisolone. The patients were divided into two groups based on the ordinal scale (OS): a non-invasive oxygen therapy (OS-6) group, and an invasive oxygen therapy (OS-7) group. There were 13 (57%) and 10 (43%) patients in the OS-7 and OS-6 groups, respectively. All patients were unvaccinated. Sixteen patients (70%) were male. The median age was 53 years; the median body mass index (BMI) was 30.3 kg/m2; and the median P/F ratio on admission was 96. The 30-day survival rate was 69% and was significantly poorer in the OS-7 group (54%) than in the OS-6 group (89%; p = 0.05). The prevalence of obesity (p = 0.05) and the Sequential Organ Failure Assessment (SOFA) score on admission (p < 0.01) were significantly higher in the OS-7 group. Seven patients in the OS-7 group (54%) developed bacteremia. A low P/F ratio on admission was a significant unfavorable prognostic factor (hazard ratio: 10.9; p = 0.03). The survival rate was poor, especially in patients requiring invasive oxygen therapy. More measures are needed to improve the treatment outcomes of patients with severe COVID 19.

Autopsy findings of a patient with severe COVID-19 treated with long-term extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) therapy in patients with coronavirus disease 2019 (COVID-19) has a low frequency of use, and thus pathological findings in such patients are valuable. In this case report, a 62-year-old man with a history of hypertension presented with a runny nose. After an at-home COVID-19 positive test, he developed dyspnea and fever. Once admitted to our hospital, his oxygenation worsened, and ECMO was initiated. He died from respiratory failure 69 days after ECMO induction. Macroscopically, the lungs gained mass, were partially consolidated, and were airless. Histological analysis revealed diffuse bronchial epithelial metaplasia and adenoid metaplasia in the alveolar epithelium. Although the lung parenchyma was partially preserved, there was organizing and fibrosis that filled pulmonary alveolus due to COVID-19 and changes resulting from disuse and long-term ECMO.

Smoking and severe illness in hospitalized COVID-19 patients in Japan.

BACKGROUND: The aim of this study was to identify associations between smoking status and the severity of COVID-19, using a large-scale data registry of hospitalized COVID-19 patients in Japan (COVIREGI-JP), and to explore the reasons for the inconsistent results previously reported on this subject. METHODS: The analysis included 17 666 COVID-19 inpatients aged 20-89 years (10 250 men and 7416 women). We graded the severity of COVID-19 (grades 0 to 5) according to the most intensive treatment required during hospitalization. The smoking status of severe grades 3/4/5 (invasive mechanical ventilation/extracorporeal membrane oxygenation/death) and separately of grade 5 (death) were compared with that of grade 0 (no oxygen, reference group) using multiple logistic regression. Results were expressed as odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and other factors considering the potential intermediate effects of comorbidities. RESULTS: Among men, former smoking significantly increased the risk of grade 3/4/5 and grade 5, using grade 0 as a reference group, with age- and admission-date-adjusted ORs (95% CI) of 1.51 (1.18-1.93) and 1.65 (1.22-2.24), respectively. An additional adjustment for comorbidities weakened the ORs. Similar results were seen for women. Current smoking did not significantly increase the risk of grade 3/4/5 and grade 5 in either sex. CONCLUSIONS: The severity of COVID-19 was not associated with current or former smoking per se but with the comorbidities caused by smoking. Thus, smoking cessation is likely to be a key factor for preventing smoking-related disease and hence for reducing the risk of severe COVID-19.

Persistent intrathecal interleukin-8 production in a patient with SARS-CoV-2-related encephalopathy presenting aphasia: a case report.

BACKGROUND: Neurological manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized and include encephalopathy, although direct infection of the brain by SARS-CoV-2 remains controversial. We herein report the clinical course and cytokine profiles of a patient with severe SARS-CoV-2-related encephalopathy presenting aphasia. CASE PRESENTATION: An 81-year-old man developed acute consciousness disturbance and status epileptics several days after SARS-CoV-2 infection. Following treatment with remdesivir and dexamethasone, his consciousness and epileptic seizures improved; however, amnestic aphasia and agraphia remained. Two months after methylprednisolone pulse and intravenous immunoglobulin, his neurological deficits improved. We found increased levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1), but not IL-2 and IL-10 in the serum and cerebrospinal fluid (CSF), and the levels of serum IL-6 and MCP-1 were much higher than those in the CSF. The level of IL-8 in the CSF after immunotherapy was four times higher than that before immunotherapy. CONCLUSION: The cytokine profile of our patient was similar to that seen in severe SARS-CoV-2-related encephalopathy. We demonstrated (i) that the characteristic aphasia can occur as a focal neurological deficit associated with SARS-CoV-2-related encephalopathy, and (ii) that IL8-mediated central nervous system inflammation follows systemic inflammation in SARS-CoV-2-related encephalopathy and can persist and worsen even after immunotherapy. Monitoring IL-8 in CSF, and long-term corticosteroids may be required for treating SARS-CoV-2-related encephalopathy.

Direct hemoperfusion using a polymyxin B-immobilized polystyrene column for COVID-19.

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.

Corticosteroid therapy for severe COVID-19 pneumonia: optimal dose and duration of administration.

Severe COVID-19 is associated with a hyperinflammatory state, and corticosteroid therapy may be effective. We review the recent literature and discuss the appropriate dose and duration of corticosteroid therapy. Low-dose corticosteroid therapy is often used to treat COVID-19. However, several doses of methylprednisolone (or prednisolone) have been attempted, ranging from about 40 mg/day to 2 mg/kg/day. Doses may need to be adjusted depending on severity. Corticosteroid therapy is generally administered for a short period over several days. However, COVID-19-induced respiratory failure is often prolonged, so longer administration may be considered. Careful monitoring for complications due to corticosteroid therapy is vital.