A Comparison of Clinical Presentations in Coronavirus Disease 2019 Caused by Different Omicron variants in Japan: A Retrospective Study.

Objective We evaluated the clinical differences in coronavirus disease 2019 (COVID-19) patients between the sixth wave with the Omicron BA.1/BA.2 dominant variant (from January to April 2022) and seventh wave with the Omicron BA.5 dominant variant (from July to August 2022). Methods This retrospective, single-center, observational study included COVID-19 patients admitted to our institution in the sixth wave (sixth-wave group) and the seventh wave (seventh-wave group). Inter-group comparisons of clinical presentations, the prognosis, and proportion of nosocomial infections were performed. Results A total of 190 patients were included (93 and 97 patients in the sixth- and seventh-wave groups, respectively). While there were no significant differences in severity, significantly more patients developed pneumonia caused by COVID-19 in the sixth-wave group than in the seventh-wave group. Although there was no marked difference in in-hospital deaths, more patients died from COVID-19 in the sixth-wave group than in the seventh-wave group. There were significantly more COVID-19 inpatients with nosocomial infections in the seventh-wave group than in the sixth-wave group. Pneumonia from COVID-19 was significantly more severe in the sixth-wave group than in the seventh-wave group. Conclusions COVID-19 patients in the seventh wave are at a lower risk of pneumonia than those in the sixth wave. However, even in the seventh wave, patients with underlying diseases have a risk of death because of the exacerbation of underlying diseases triggered by COVID-19.

Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia.

OBJECTIVES: To evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19. METHODS: We conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO2). RESULTS: There was no significant difference in the changes in the clinical progression scale between nafamostat with favipiravir and favipiravir alone groups (median, -0.444 vs -0.150, respectively; least-squares mean difference, -0.294; P = 0.364). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group. CONCLUSION: Although our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO2 were observed in the combination group.

Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2-induced lung exudative vasculitis and predicts COVID-19 severity.

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.

COVID-19 infection control education for medical students undergoing clinical clerkship: a mixed-method approach.

BACKGROUND: Coronavirus disease (COVID-19) has induced an urgent need to train medical students not only in infection prevention control but also in the treatment of infectious diseases, including COVID-19. This study evaluates the impact of simulated clinical practice with peer role-plays and a lecture on clinical education for COVID-19. METHODS: The sample for the study included 82 fourth- and fifth-year medical students undergoing clinical clerkship in respiratory medicine. They answered questionnaires and participated in semi-structured focus group interviews (FGIs) regarding the advantages of simulated clinical practice with peer role-plays and lectures on clinical education for COVID-19. RESULTS: A total of 75 students participated in the COVID-19 education program between January and November 2021. The responses to the questionnaire revealed that the satisfaction level of students with COVID-19 education was high. No significant change was found among students concerning fear of COVID-19 before and after the program. The degree of burden of handling information on COVID-19 reduced significantly, while the degree with respect to the use of personal protective equipment (PPE), including appropriate wearing and removing of PPE, and care of patients with confirmed COVID-19 while taking steps to prevent infection, exhibited a decreasing trend. Nine FGIs were conducted (n = 74). The advantages of simulated clinical practice were segregated into five categories (infection prevention control, educational methods, burden on healthcare providers, self-reflection, and fear of COVID-19); and that of the lecture were segregated into four categories (information literacy, knowledge of COVID-19, educational methods, and self-reflection). CONCLUSIONS: Simulated clinical practice with peer role-plays and the lecture pertaining to COVID-19 can prove to be efficient and safe methods for learning about COVID-19 infection and prevention control for medical students. They can reduce the burden of COVID-19 patients' care. Moreover, they can also provide an opportunity for self-reflection, realize the burden of medical care, and acquire relevant information.

Clinical Outcomes of Sotrovimab Treatment in 10 High-Risk Patients with Mild COVID-19: A Case Series.

BACKGROUND Although sotrovimab reduces the risk of hospitalization or death due to COVID-19, there have been few reports of its use in clinical practice. Particularly, information on the effectiveness of sotrovimab against the omicron variant of the virus is limited. We present 10 cases of COVID-19 treated with sotrovimab at our unit between December 2021 and February 2022. CASE REPORT The age of the patients ranged from 32 to 81 years (median: 40 years). The comorbidities included lung cancer, cardiovascular disease, chronic kidney disease requiring hemodialysis, and AIDS. Two of the patients were also organ recipients. Oxygen saturation (SpO2) was above 97% in all patients. None of the patients presented with pneumonia on admission. However, blood test results showed that all patients had risk factors for severe COVID-19 outcomes. The interval from symptom onset to sotrovimab administration and resolution ranged from 2 to 5 days (median: 2 days) and 2 to 15 days (median: 5 days), respectively. Only 1 patient developed pneumonia and was treated with remdesivir after sotrovimab administration. However, this patient did not require oxygen therapy. Although no moderate to severe adverse events were observed, a mild adverse event was observed in 1 patient. CONCLUSIONS Sotrovimab could be safe and effective in preventing progression of COVID-19 in patients with a variety of underlying diseases and who are at high risk of severe disease outcomes.

Case of a Deep Neck Abscess During Treatment for COVID-19.

BACKGROUND COVID-19 is treated using antiviral and immunosuppressive drugs. Therefore, patients treated for COVID-19 may have an increased risk of secondary infection and a masked inflammatory response. We present a case of a deep neck abscess caused by pyogenic sternoclavicular arthritis during treatment for COVID-19. CASE REPORT A 55-year-old man with COVID-19 was admitted to the hospital with hypoxemia. He was then treated with remdesivir, tocilizumab, and dexamethasone and was placed in the prone position. When his condition stabilized, pain in the left shoulder appeared. There was no fever or elevation in inflammation markers, and he was administered analgesics. However, the pain worsened and redness of the left neck appeared. Plain computed tomography (CT) showed swelling of the left neck muscles. Because cellulitis was suspected, he was treated with antibiotics, but his symptoms did not improve. Three days after the plain CT, contrast-enhanced CT showed sternoclavicular arthritis, deep neck abscess, and mediastinal abscess. Therefore, an emergency incisional drainage was performed under general anesthesia. Wound cleaning and drainage were continued after surgery, and after drainage tubes were removed, the patient was discharged on postoperative day 17. CONCLUSIONS Cervical infections after COVID-19 treatment have been reported in a few cases. Particularly, deep neck abscesses require more attention since they could be fatal if not treated immediately. If a secondary infection is suspected in a patient treated with immunosuppressive drugs for COVID-19, a thorough physical examination should be performed to avoid misdiagnosis.

Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike.

Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely administered to human populations is not effective against BA.2, similar to BA.1, and that the antigenicity of BA.2 is notably different from that of BA.1. Cell culture experiments showed that the BA.2 spike confers higher replication efficacy in human nasal epithelial cells and is more efficient in mediating syncytia formation than the BA.1 spike. Furthermore, infection experiments using hamsters indicated that the BA.2 spike-bearing virus is more pathogenic than the BA.1 spike-bearing virus. Altogether, the results of our multiscale investigations suggest that the risk of BA.2 to global health is potentially higher than that of BA.1.

Possibility of deterioration of respiratory status when steroids precede antiviral drugs in patients with COVID-19 pneumonia: A retrospective study.

INTRODUCTION: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Although most patients with COVID-19 develop asymptomatic or mild disease, some patients develop severe disease. The effectiveness of various therapeutic agents, including antiviral drugs, steroids, and anti-inflammatories for COVID-19, have been being confirmed. The effect of administering steroids in early disease is unclear. This study therefore aimed to evaluate the effectiveness and risk of exacerbation of steroids administered preceding antiviral drugs in patients with COVID-19 pneumonia. METHODS: This retrospective, single-center, observational study included consecutive patients with COVID-19 between March 2020 and March 2021. Patients were divided into a steroids-first group and antiviral-drugs-first group. Mortality, duration of hospitalization, incidence rate and duration of intensive care unit (ICU) admission, intubation, and extracorporeal membrane oxygenation (ECMO) induction of the two groups were compared. RESULTS: A total of 258 patients were admitted during the study period. After excluding patients who received symptomatic treatment only, who were taking immunosuppressive drugs, or who were administered antiviral drugs only, 68 patients were included in the analysis, 16 in the steroids-first group and 52 in the antiviral-drugs-first group. The rate of intubation, ICU admission and ECMO induction were significantly higher in the steroids-first group than in the antiviral-drugs-first group (81.3% vs. 33.3, p<0.001, 75.0% vs. 29.4%, p = 0.001, and 31.3% vs. 7.8%, p = 0.017, respectively). Furthermore, patients who received steroids within ten days after starting antiviral drugs had significantly lower rates of ICU admission, intubation, and ECMO induction. (81.3% vs. 42.9% p = 0.011, 75.0% vs. 37.1% p = 0.012, and 31.3% vs. 8.6% p = 0.039, respectively). CONCLUSIONS: Administering steroids prior to antiviral drugs soon after symptom onset can aggravate disease severity. When administration of steroids is considered soon after symptom onset, it may be safer to initiate antiviral drugs first.

Alternative approaches for clinical clerkship during the COVID-19 pandemic: online simulated clinical practice for inpatients and outpatients-A mixed method.

BACKGROUND: The COVID-19 pandemic has created a need for educational materials and methods that can replace clinical clerkships (CCs) for online simulated clinical practice (online-sCP). This study evaluates the impact of using simulated electronic health records (sEHR) for inpatients, and electronic problem-based learning (e-PBL) and online virtual medical interviews (online-VMI) for outpatients, for an online-sCP using a learning management system (LMS) and online meeting system facilitated by a supervising physician. METHODS: The sEHR was reviewed by medical students and subsequently discussed with a supervising physician using an online meeting system. In the e-PBL, medical students reviewed the simulated patients and discussed on the LMS. For the online-VMI, a faculty member acted as an outpatient and a student acted as the doctor. Small groups of students discussed the clinical reasoning process using the online meeting system. A mixed-method design was implemented. Medical students self-assessed their clinical competence before and after the online-sCP. They answered questionnaires and participated in semi-structured focus group interviews (FGIs) regarding the advantages and disadvantages of the practice. RESULTS: Forty-three students completed the online-sCP during May and June 2020. All students indicated significant improvement in all aspects of self-evaluation of clinical performance after the online-sCP. Students using sEHR reported significant improvement in writing daily medical records and medical summaries. Students using e-PBL and online-VMI reported significant improvement in medical interviews and counseling. Students also indicated CCs as more useful for learning associated with medical interviews, physical examinations, and humanistic qualities like professionalism than the online-sCP. Eight FGIs were conducted (n = 42). The advantages of online-sCP were segregated into five categories (learning environment, efficiency, accessibility, self-paced learning, and interactivity); meanwhile, the disadvantages of online-sCP were classified into seven categories (clinical practice experience, learning environment, interactivity, motivation, memory retention, accessibility, and extraneous cognitive load). CONCLUSIONS: Online-sCP with sEHR, e-PBL, and online-VMI could be useful in learning some of the clinical skills acquired through CC. These methods can be implemented with limited preparation and resources.

Drug Fever Due to Favipiravir Administration for the Treatment of a COVID-19 Patient.

A 55-year-old Japanese man was hospitalized with the novel coronavirus disease 2019 (COVID-19). On the 14th day after the start of favipiravir administration, the patient developed a fever with a temperature of 38.1°C. His pulse rate also became elevated to 128 bpm, so relative bradycardia was not suspected. Since he was in good overall health and no concomitant symptoms and signs were apparent, we considered it to be drug fever due to favipiravir. After the completion of favipiravir treatment, the patient's temperature normalized within 24 hours. We herein report this case of drug fever caused by favipiravir.