A novel anticoagulation treatment protocol using unfractionated heparin for coronavirus disease 2019 patients in Japan, 2022.

Hypercoagulability, which can be induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in the pathogenesis of coronavirus disease 2019 (COVID-19). Although anticoagulation therapy is expected to decrease the incidence of thrombosis and mortality in COVID-19 patients, the optimal use of anticoagulation therapy has not been established, especially using unfractionated heparin (UFH). Herein, we suggest a new anticoagulation treatment protocol for the use of UFH in Japanese COVID-19 patients. This protocol considers the safety regarding UFH usage, to lower major bleeding events, and reflects the latest evidence and the current situation regarding anticoagulation therapy in Japan.

Risk factors associated with asymptomatic hypoxemia among COVID-19 patients: a retrospective study using the nationwide Japanese registry, COVIREGI-JP.

Deaths of home-care patients with coronavirus disease (COVID-19) have become a social problem. One of their causes is hypoxemia without dyspnea which delays seeking medical attention. This was a retrospective study including patients registered in the COVID-19 Registry Japan, in which hospitalized patients with COVID-19 in 227 participating healthcare facilities were enrolled. The enrolled patients were divided into two groups: non-dyspneic patients with a peripheral capillary oxygen saturation (SpO2) ≤ 93% on admission (the hypoxemia without dyspnea group) and non-dyspneic patients with an SpO2> 93% (the control group). We conducted a multivariate logistic regression analysis to identify the factors associated with hypoxemia without dyspnea. 21544 patients were enrolled, 1035 (4.8%) patients were in the hypoxemia without dyspnea group, and 20509 (95.2%) patients were in the control group. The median respiratory rate (RR) of the hypoxemia without dyspnea group was higher than that of the control group (31/min vs. 18/min, p < 0.001). Age> 65, male, body mass index> 25, smoking, chronic obstructive pulmonary disease, other chronic lung disease, and diabetes mellitus were the independent factors associated with hypoxemia without dyspnea. Patients with those background should be closely monitored. RR is an important indicator of hypoxemia, even in the absence of dyspnea.

Evaluation of the efficacy of anticoagulation therapy in reducing mortality in a nationwide cohort of hospitalized patients with coronavirus disease in Japan.

OBJECTIVES: To determine whether anticoagulation therapy improves outcomes in patients with coronavirus disease 2019 (COVID-19) in Japan given their lower risk of thrombosis compared with Western cohorts. METHODS: The efficacy of anticoagulation therapy in hospitalized patients with COVID-19 was evaluated using a nationwide registry: the COVID-19 Registry Japan. The inverse probability of weight treatment method was used to adjust for baseline confounders in the anticoagulation and non-anticoagulation groups. RESULTS: Of the 1748 patients included, anticoagulants were used in 367 patients (treatment group). The patients in the anticoagulant group were older, predominantly male, and often presented with obesity, hyperlipidaemia, hypertension, diabetes and elevated D-dimer levels. Twenty-nine-day mortality was 7.6% in the whole cohort (treatment group, 11.2%; no treatment group, 6.6%), 6% in patients who were not treated with steroids (treatment group, 12.3%; no treatment group, 5.2%), and 11.2% in patients treated with steroids (treatment group, 10.5%; no treatment group, 11.8%). Mortality in the whole cohort was similar between the treatment and no treatment groups (P=0.99), and an insignificant decreasing trend in mortality was observed in patients treated with steroids (P=0.075). CONCLUSIONS: Anticoagulants may be beneficial in Asians, in whom comorbidities and risk of thrombosis may differ from other ethnic groups.

Fatty liver on computed tomography scan on admission is a risk factor for severe coronavirus disease.

OBJECTIVES: To alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission. METHODS: In this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19. RESULTS: Of 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19. CONCLUSION: Our study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients.

Safety of casirivimab/imdevimab administration in a SARS-CoV-2 positive maintenance dialysis patient in Japan.

Controlling excessive cytokine secretion is a crucial therapeutic strategy for managing coronavirus disease 2019 (COVID-19). Patients on dialysis are at a high risk of severe disease, given abnormal immune responses that can lead to prolonged inflammation. Moreover, patients undergoing dialysis have limited treatment options, as neither remdesivir nor baricitinib is available. The novel neutralizing monoclonal antibody cocktail REGEN-COV (formerly known as REGN-COV2; casirivimab/imdevimab), recently approved in Japan, is a promising drug for preventing severe diseases. However, there are few reports regarding its use in patients undergoing dialysis in Japan. Herein, we report the safe use of antibody cocktail therapy in patients with COVID-19 on hemodialysis receiving maintenance dialysis in Japan. Infusion reactions were not observed during administration. Due to the increasing number of patients with COVID-19 and the limited capacity of the healthcare system, antibody cocktail therapy needs to be enhanced. Antibody cocktail therapy for severe diseases can be safely administered to patients undergoing dialysis who do not require supplemental oxygen.

Factors associated with high antibody titer following coronavirus disease among 581 convalescent plasma donors: A single-center cross-sectional study in Japan.

INTRODUCTION: The ability to predict which patients with a history of coronavirus disease (COVID-19) will exhibit a high antibody titer is necessary for more efficient screening of potential convalescent plasma donors. We aimed to identify factors associated with a high immunoglobulin G (IgG) titer in Japanese convalescent plasma donors after COVID-19. METHODS: This cross-sectional study included volunteers undergoing screening for convalescent plasma donation after COVID-19. Serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein IgG antibodies were measured using a high-sensitivity chemiluminescence enzyme immunoassay. RESULTS: IgG antibodies were measured in 581 patients, 534 of whom had full information of selected independent variables. Multiple linear regression analysis revealed that increasing age (1.037 [1,025, 1.048]), days from symptom onset to sampling (0.997 [0.995, 0.998]), fever (1.664 [1.226, 2.259]), systemic corticosteroid use during SARS-CoV-2 infection (2.382 [1.576, 3.601]), and blood type AB (1.478 [1.032, 2.117]) predict antibody titer. CONCLUSION: Older participants, those who experienced fever during infection, those treated with systemic corticosteroids during infection, those from whom samples were obtained earlier after symptom onset, and those with blood type AB are the best candidates for convalescent plasma donation. Therefore, these factors should be incorporated into the screening criteria for convalescent plasma donation after SARS-CoV-2 infection.

Clinical and radiological findings of silent hypoxia among COVID-19 patients.

The aim of this study was to describe the clinical and radiological findings of COVID-19 patients with "silent hypoxia," who had no dyspnea on admission even though their oximetry saturation was less than 94%. This retrospective cohort study included all COVID-19 patients (n = 270) at a large tertiary care hospital between January 31 and August 31, 2020. Clinical and radiological characteristics of patients who met our criteria of "silent hypoxia", which included those who reported no dyspnea even though oximetry saturation was <94%, were extracted. Eight patients (3.0%) met the criteria for "silent hypoxia." The median age was 61 years (interquartile range [IQR]: 48.8-72.3), and five (62.5%) were men. All patients had consolidation on CT and showed a moderate to high COVID-19 CT severity score (median: 13.5, IQR: 10.8-15.3). The median FIO2 of the maximum oxygen required was 55 (IQR: 28-70)%. Two patients (25.0%) were intubated, and one patient (12.5%) underwent extracorporeal membrane oxygenation. Some COVID-19 patients with "silent hypoxia" may develop severe disease. Close and accurate monitoring of patients using arterial blood gas and pulse oximetry is necessary, regardless of their symptoms.

External validation and update of prediction models for unfavorable outcomes in hospitalized patients with COVID-19 in Japan.

INTRODUCTION: Most of the currently used prognostic models for COVID-19 are based on Western cohorts, but it is unknown whether any are applicable to patients with COVID-19 in Japan. METHODS: This retrospective cohort study included 160 patients with COVID-19 who were admitted to the National Center for Global Health and Medicine between January 26, 2020 and July 25, 2020. We searched PubMed for prognostic models for COVID-19. The predicted outcome was initiation of respiratory support or death. Performance of the candidate models was evaluated according to discrimination and calibration. We recalibrated the intercept of each model with our data. We also updated each model by adding ß2-microglobulin (ß2MG) to the model and recalculating the intercept and the coefficient of ß2MG. RESULTS: Mean patient age was 49.8 years, 68% were male, 88.7% were Japanese. The study outcomes occurred in 15 patients, including two deaths. Two-hundred sixty-nine papers were screened, and four candidate prognostic models were assessed. The model of Bartoletti et al. had the highest area under receiver operating characteristic curve (AUC) (0.88; 95% confidence interval 0.81-0.96). All four models overestimated the probability of occurrence of the outcome. None of the four models showed statistically significant improvement in AUCs by adding ß2MG. CONCLUSIONS: Our results suggest that the existing prediction models for COVID-19 overestimate the probability of occurrence of unfavorable outcomes in a Japanese cohort. When applying a prediction model to a different cohort, it is desirable to evaluate its performance according to the prevalent health situation in that region.

Hemoptysis and a Newly Formed Lung Bulla in a Case of Convalescent COVID-19 Pneumonia.

Coronavirus disease 2019 (COVID-19) is a novel infectious disease affecting the general population worldwide. A fever and cough are the common clinical presentations of COVID-19. In most of these patients, computed tomography (CT) shows bilateral peripheral ground-glass opacities. We herein report a case of hemoptysis and lung bulla in the convalescent phase of COVID-19. Based on the clinical observations, alveolar destruction was likely associated with hemoptysis and bulla formation. Therefore, we suggest the follow-up of COVID-19 patients whose clinical parameters indicate alveolar damage, even after their symptoms improve.