Specific COVID-19 risk behaviors and the preventive effect of personal protective equipment among healthcare workers in Japan

Summary As coronavirus disease 2019 (COVID-19) outbreaks in healthcare facilities are a serious public health concern, we performed a case-control study to investigate the risk of COVID-19 infection in healthcare workers. We collected data on participants' sociodemographic characteristics, contact behaviors, installation status of personal protective equipment, and polymerase chain reaction testing results. We also collected whole blood and assessed seropositivity using the electrochemiluminescence immunoassay and microneutralization assay. In total, 161 (8.5%) of 1,899 participants were seropositive between August 3 and November 13, 2020. Physical contact (adjusted odds ratio 2.4, 95% confidence interval 1.1-5.6) and aerosol-generating procedures (1.9, 1.1-3.2) were associated with seropositivity. Using goggles (0.2, 0.1-0.5) and N95 masks (0.3, 0.1-0.8) had a preventive effect. Seroprevalence was higher in the outbreak ward (18.6%) than in the COVID-19 dedicated ward (1.4%). Results showed certain specific risk behaviors of COVID-19;proper infection prevention practices reduced these risks.

Nationwide descriptive epidemiological study of patients with COVID-19 evacuated from Wuhan, China, to Japan from January to February 2020.

We investigated epidemiological findings regarding the route of coronavirus disease 2019 (COVID-19) and infection prevention and control (IPC) measures among returnees in the emergent evacuation from Wuhan, China to Japan under the COVID-19 outbreak in 2020. A total of 12 of 14 returnees (median age [range]: 49.5 years [29-65 years]; 9 men [75%]) were confirmed COVID-19. The proportions of returnees with COVID-19 were 12/566 (2.1%) in the 1-3 flights and 2/263 (0.8%) in the 4-5 flights. Six patients were asymptomatic on admission, while three patients developed symptoms thereafter. None reported a specific history of contact with animals, going to seafood markets, or visiting medical facilities. Two patients contacted with an individual confirmed or suspected to have COVID-19, respectively. Most patients resided in hotels in the center of Wuhan city, taking taxis and trains to work and supermarkets. Patients relatively adhered to IPC measures such as wearing a mask and hand hygiene. However, emphasis on IPC measures such as universal masking and more rigorous avoidance of exposure risk may have been necessary to prevent infection. In addition, forced social distancing due to lockdown might contribute to the lower infection rates in Flights 4 and 5, compared to Flights 1-3.

Non-serogroupable Neisseria meningitidis pneumonia in an immunocompetent patient with severe COVID-19 pneumonia: A case report.

Background: Non-serogroupable Neisseria meningitidis (N. meningitidis), the most common type of N. meningitidis in asymptomatic carriers, rarely causes infections. Most reported cases of infection are in patients with immunodeficiency, primarily complement deficiencies. Case presentation: A 54-year-old immunocompetent man was transferred to our hospital to treat severe coronavirus disease 2019 (COVID-19). The patient presented with cough producing a large amount of purulent sputum, which was considered an atypical presentation of COVID-19. Gram staining of the sputum revealed a large number of gram-negative diplococci phagocytosed by many neutrophils, and a diagnosis of bacterial pneumonia was established. The culture yielded non-serogroupable N. meningitidis, and the patient was diagnosed with non-serogroupable N. meningitidis pneumonia. Potential immunodeficiency was considered; however, testing including human immunodeficiency virus and complement factors showed no abnormalities. Conclusions: We report herein a rare case of non-serogroupable N. meningitidis pneumonia that occurred in an immunocompetent patient during the course of severe COVID-19. We consider impaired T cell function attributable to COVID-19 and dexamethasone administration may have triggered a transient immunosuppressive state and led to non-serogroupable N. meningitidis pneumonia.

Nosocomial outbreak of coronavirus disease in two general wards during the initial wave of the pandemic in 2020, Tokyo, Japan.

Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in China and subsequently spread worldwide. In Japan, many clusters occurred during the first wave in 2020. We describe the investigation of an early outbreak in a Tokyo hospital. Methods: A COVID-19 outbreak occurred in two wards of the hospital from April to early May 2020. Confirmed cases were individuals with laboratory-confirmed SARS-CoV-2 infection linked to Wards A and B, and contacts were patients or workers in Wards A or B 2 weeks before the index cases developed symptoms. All contacts were tested, and cases were interviewed to determine the likely route of infection and inform the development of countermeasures to curb transmission. Results: There were 518 contacts, comprising 472 health-care workers (HCWs) and 46 patients, of whom 517 were tested. SARS-CoV-2 infection was confirmed in 42 individuals (30 HCWs and 12 patients). The proportions of SARS-CoV-2 infections in HCWs were highest among surgeons, nurses, nursing assistants and medical assistants. Several HCWs in these groups reported being in close proximity to one another while not wearing medical masks. Among HCWs, infection was thought to be associated with the use of a small break room and conference room. Discussion: Nosocomial SARS-CoV-2 infections occurred in two wards of a Tokyo hospital, affecting HCWs and patients. Not wearing masks was considered a key risk factor for infection during this outbreak; masks are now a mandated countermeasure to prevent the spread of SARS-CoV-2 infection in hospital settings.

COVID-19-associated leukoencephalopathy in the absence of severe hypoxia with subsequent improvement: a case report.

BACKGROUND: Several cases of coronavirus disease 2019 (COVID-19)-associated leukoencephalopathy have been reported. Although most cases involve hypoxia, the pathophysiological mechanism and neurologic outcomes of COVID-19-associated leukoencephalopathy remain unclear. CASE PRESENTATION: We report a case of COVID-19-associated leukoencephalopathy without severe hypoxia in a 65-year-old woman diagnosed with pyelonephritis. After the initiation of intravenous ceftriaxone, her fever resolved, but she developed an altered state of consciousness with abnormal behavior and, subsequently, a relapse fever. She was diagnosed with COVID-19 pneumonia and was intubated. Lung-protective ventilation with deep sedation and neuromuscular blockade were used for treatment. After cessation of sedative administration, her mental status remained at a Glasgow Coma Scale score of 3. COVID-19 was assumed to have caused leukoencephalopathy due to the absence of severe hypoxia or other potential causes. She subsequently showed gradual neurologic improvement. Three months after the COVID-19 diagnosis, she regained alertness, with a Glasgow Coma Scale score of 15. CONCLUSION: Clinicians should consider leukoencephalopathy in the differential diagnosis of consciousness disorders in patients with severe COVID-19, even in the absence of severe hypoxia. Gradual neurologic improvement can be expected in such cases.

Effectiveness of remdesivir in hospitalized nonsevere patients with COVID-19 in Japan: A large observational study using the COVID-19 Registry Japan.

OBJECTIVES: To evaluate the effectiveness of remdesivir in the early stage of nonsevere COVID-19. Although several randomized controlled trials have compared the effectiveness of remdesivir with that of a placebo, there is limited evidence regarding its effect in the early stage of nonsevere COVID-19 cases. METHODS: We evaluated the effectiveness of remdesivir in the early stage of nonsevere COVID-19 using the COVID-19 Registry Japan, a nationwide registry of hospitalized patients with COVID-19 in Japan. Two regimens ("start remdesivir" therapy within 4 days from admission versus no remdesivir during hospitalization) among patients without the need for supplementary oxygen therapy were compared by a 3-step processing (cloning, censoring, and weighting) method. The primary outcome was a supplementary oxygen requirement during hospitalization. Secondary outcomes were 30-day in-hospital mortality and the risk of invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO). The data of 12,487 cases met our inclusion criteria. The "start remdesivir" regimen showed a lower risk of supplementary oxygen requirement (hazard ratio [HR]: 0.850, 95% confidence interval [CI]: 0.798-0.906, p value < 0.001). Both 30-day in-hospital mortality and risk of IMV/ECMO introduction were not significantly different between the 2 regimens (HRs: 1.04 and 0.983, 95% CI: 0.980-1.09 and 0.906-1.07, p values: 0.210 and 0.678, respectively). CONCLUSIONS: Remdesivir might reduce the risk of oxygen requirement during hospitalization in the early stage of COVID-19; however, it had no positive effect on the clinical outcome and reduction in IMV/ECMO requirement.

Effectiveness of Favipiravir on Nonsevere, Early-Stage COVID-19 in Japan: A Large Observational Study Using the COVID-19 Registry Japan.

INTRODUCTION: Several randomized controlled trials have compared the effectiveness of favipiravir with that of placebo. However, evidence regarding its effect on nonsevere, early-stage coronavirus disease 2019 (COVID-19) remains insufficient. METHODS: We used the COVID-19 Registry Japan, a nationwide registry of inpatients with COVID-19, for evaluating the effectiveness of favipiravir on patients with nonsevere, early-stage COVID-19. Eligible patients, who did not need supplementary oxygen therapy at admission, were classified according to two regimens (starting favipiravir therapy within 4 days from admission vs. no favipiravir during hospitalization) and were then compared using a three-step method (cloning, censoring, and weighting). The primary outcome was supplementary oxygen requirement during hospitalization, and the secondary outcomes were the need for invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO) and overall mortality at 30 days. RESULTS: A total of 7654 cases were analyzed. The "start favipiravir" regimen did not show substantial differences in the primary outcome [hazard ratio 0.825, 95% confidence interval (CI) 0.657-1.04, p = 0.098] and both of the secondary outcomes [need for IMV/ECMO and overall 30-day mortality, hazard ratio 1.02 (95% CI 0.649-1.60) and 0.869 (95% CI 0.519-1.46), p = 0.929 and 0.594, respectively]. CONCLUSIONS: In this large cohort from a COVID-19 registry, favipiravir was not associated with a positive effect on the clinical outcome on patients with nonsevere, early-stage COVID-19, suggesting that it is not an essential drug for COVID-19 treatment.

Clinical characteristics of the first three waves of hospitalised patients with COVID-19 in Japan prior to the widespread use of vaccination: a nationwide observational study.

Background: Before widespread coronavirus disease (COVID-19) vaccinations, Japan experienced three COVID-19 epidemic waves. This study aimed to evaluate the characteristics of hospitalised COVID-19 patients and reveal temporal changes. Methods: This study included 33,554 hospitalised patients with COVID-19 from 553 healthcare facilities. Data were analysed by age group and epidemic wave (first wave, 01/01/2020-05/31/2020; second wave, 06/01/2020-10/31/2020; and third wave, 11/01/2020-03/31/2021). Findings: By age group, 3% (under 18), 22% (young), 34% (middle-aged), and 41% (older patients) were aged 0-17, 18-39, 40-64, and >65 years; while 16%, 35%, and 49% were in the first, second, and third wave, respectively. The patients' overall median age (58 years; interquartile range, 39-74) was lowest and highest during the second and third waves, respectively. The frequency of any comorbidity was lowest and highest during the second (44·5%) and third (63·6%) waves, respectively. The symptoms at admission and exposure history differed considerably with age. The overall case fatality rate (5%) was highest among older patients (11·4%). Case fatality rate was highest and lowest during the first (7·3%) and second (2·8%) waves, respectively. Medication use changed over time. Interpretation: Although the overall case fatality rate remained relatively low, it was more than twice as high among older patients. After adjusting for age and comorbidities, the risk of death was highest in the first wave. Funding: This work was supported by the Ministry of Health, Labour and Welfare "Research on Emerging and Re-emerging Infectious Diseases and Immunization" 19HA1003].

SARS-CoV-2 Omicron-neutralizing memory B cells are elicited by two doses of BNT162b2 mRNA vaccine.

Multiple SARS-CoV-2 variants have mutations in the spike receptor binding domain (RBD) with potential to evade neutralizing antibody. In particular, the Beta and Omicron variants escape from antibody neutralizing activity in those who received two doses of BNT162b2 mRNA vaccine. Nonetheless, boosting with a third vaccine dose or by breakthrough infection improves the overall breadth of the neutralizing antibodies, but the mechanism remains unclear. Here, we longitudinally profiled the cellular composition of RBD-binding memory B cell subsets and their antibody binding and neutralizing activity against SARS-CoV-2 variants after the second dose of mRNA vaccine. Two doses of the mRNA vaccine elicited plasma neutralizing antibodies with a limited activity against Beta and Omicron but induced an expanded antibody breadth overtime, up to 4.9 months after vaccination. In contrast, more than one-third of RBD-binding IgG+ memory B cells with a resting phenotype initially bound the Beta and Omicron variants and steadily increased the B cell receptor breadth overtime. As a result, a fraction of the resting memory B cell subset secreted Beta and Omicron-neutralizing antibody when stimulated in vitro. The neutralizing breadth of the resting memory B cell subset helps us understand the prominent recall of Omicron-neutralizing antibodies after an additional booster or breakthrough infection in fully vaccinated individuals.

Critically ill patients with COVID-19 in Tokyo, Japan: A single-center case series.

INTRODUCTION: We reported, in our previous study, a patient with coronavirus disease 2019 (COVID-19) who was successfully treated with extracorporeal membrane oxygenation. Data on clinical courses and outcomes of critically ill patients with COVID-19 in Japan are limited in the literature. This study aimed to describe the clinical courses and outcomes of critically ill patients with COVID-19 in Tokyo, Japan. METHODS: This is a single-center case series study. Patients with COVID-19 treated with mechanical ventilation (MV) were reviewed retrospectively. Data on baseline characteristics, in-hospital treatment, and outcomes were collected. RESULTS: Between February 2, 2020, and June 30, 2020, 14 critically ill patients with COVID-19 were treated with MV. Most patients were male and had comorbidities, especially hypertension or diabetes; 35.7% were overweight and 21.4% were obese. The majority of the patients had dyspnea on admission. The median duration of MV was 10.5 days, and the 28-day mortality rate was 35.7%. In the four patients with COVID-19 who died, the cause of death was respiratory failure. CONCLUSIONS: As in previous reports from other countries, the mortality rate of patients with COVID-19 requiring intensive care remains high in Tokyo. Further study on the appropriate timing of MV initiation and specific treatments for critically ill patients with COVID-19 is needed.

SARS-CoV-2 Screening Test for Japanese Returnees From Wuhan, China, January 2020.

BACKGROUND: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) was found to be the causative microorganism of coronavirus disease 2019 (COVID-19), which started to spread in Wuhan, China. This study was to evaluate the effectiveness of questionnaire, symptoms-based screening, and polymerase chain reaction (PCR) screening of returnees from COVID-19-endemic areas on a chartered flight, to examine the proportion of infected persons and the proportion of asymptomatic persons among infected persons who returned from Wuhan. METHODS: A retrospective cohort study was done in 7 tertiary medical institutions in Japan. A total of 566 Japanese who returned from Wuhan participated in the study. RESULTS: Overall, 11 of the 566 passengers had a positive SARS-CoV-2 PCR result for pharyngeal swabs and 6 were asymptomatic. Only fever differed between SARS-CoV-2-positive and -negative individuals (P < .043). Six of the 11 PCR-positive individuals were asymptomatic; 4 remained positive on day 10, and 1 asymptomatic person tested positive up to day 27. Two of the 11 were negative on the first PCR test and positive on the second. CONCLUSIONS: Our results will be important insights on screening returnees from locked-down cities, as well as providing important data on the proportion of asymptomatic individuals infected with SARS-CoV-2. A 13-day observation period and a second round of PCR may be effective to screen patients, including asymptomatic infections.