Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

Association between SARS-CoV-2 anti-spike antibody titers and the development of post-COVID conditions: A retrospective observational study

Summary The symptoms that persist after an acute coronavirus disease 2019 (COVID-19) are referred to as post- COVID conditions. Although the cause of post-COVID conditions remains unclear, the host immune response to SARS-CoV-2 may be involved. Hence, we aimed to investigate the effect of serum antibody titers against SARS-CoV-2 on the development of post-COVID conditions. We conducted a retrospective observational study of COVID-19-recovered individuals who attended the clinic at the National Center for Global Health and Medicine between January 2020 and April 2021. Serum SARS-CoV-2 anti-spike antibody titers were measured and a questionnaire survey was used to collect information on the presence of post-COVID conditions and demographic characteristics of the participants. Participants were then divided into two groups: high peak antibody titer group [≥ 0.759 OD450 value], and low peak antibody titer group [< 0.759 OD450 value] and compared their frequency of post-COVID conditions. Of 526 individuals attending the clinic, 457 (86.9%) responded to the questionnaire. We analyzed the data of 227 (49.7%) participants with measurements of serum antibody titers during the peak period. The incidence of depressed mood was significantly higher in the group with higher antibody titers (odds ratio: 2.34, 95% CI: 1.17-4.67, p = 0.016). There was no significant difference in the frequency of the remaining symptoms between the two groups. Among post-COVID conditions, the depressed mood was more frequent in the group with high serum antibody titers which suggests a difference in pathogenesis between depressive mood and other post-COVID conditions that requires further investigation.

Exacerbations of Idiopathic Systemic Capillary Leak Syndrome following BNT162b2 mRNA COVID-19 Vaccine (Pfizer-BioNTech).

A Japanese man experienced three episodes of hypovolemic shock and was diagnosed with systemic capillary leak syndrome (SCLS). He developed SCLS exacerbation 2 days after receiving a second dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine, 1 year after the third episode. After fluid therapy and albumin administration, we initiated terbutaline and theophylline prophylaxis for SCLS. A literature review revealed that SCLS attacks often occur 1-2 days after the second COVID-19 vaccination. Patients with a history of SCLS should avoid COVID-19 vaccination and be carefully monitored for 1-2 days if they receive the vaccine.

The safety of plasma apheresis from donors recovering from COVID-19 infection in Japan.

PURPOSE: Since 2020, the novel coronavirus infection (COVID-19) has spread globally. A few studies have investigated the safety of COVID-19 convalescent plasma (CCP) apheresis from COVID-19. This study was the first retrospective observational study of CCP in Japan. METHODS: We recruit donors from April 2020 to November 2021 and plasmapheresis in our center (NCGM: national center for global health and medicine). We set the primary endpoint as the Donors Adverse Event (DAE) occurrence at the time of the CCP collection. Variable selection was used to explore the determinants of DAE. RESULTS: Mean and SD age was 50.5 (10.6) years old. Seventy-three (42.2 %) were female, and 87 (33.3 %) were multiple-times donors. Twelve (6.97 % by donors and 4.6 % in total collections) adverse events occurred. The DAEs were VVR (Vaso Vagal Reaction), paresthesia, hypotension, agitation, dizziness, malaise, and hearing impairment/paresthesia. Half of them were VVR during apheresis. DAE occurred only in first-time donors and more in severe illnesses such as using ventilation and ECMO. From the donor characteristics and variable selection, the risk factors are as follows: younger age, female, the severity of disease at the time of the disease, and lower SBP before initiation. Our DAE incidence did not differ from previous studies. DAEs were more likely to occur in CCP apheresis than in healthy donors. CONCLUSION: We confirm the safety of CCP apheresis in this study, although DAEs were more than healthy donors. More caution should be exercised in the plasma collection for future outbreaks of emerging infectious diseases.

Nasopharyngeal SARS-CoV-2 may not be dispersed by a high-flow nasal cannula.

A high-flow nasal cannula (HFNC) therapy plays a significant role in providing respiratory support to critically ill patients with coronavirus disease 2019 (COVID-19); however, the dispersion of the virus owing to aerosol generation is a matter of concern. This study aimed to evaluate if HFNC disperses the virus into the air. Among patients with COVID-19 admitted to private rooms with controlled negative pressure, we enrolled those admitted within 10 days of onset and requiring oxygenation through a conventional nasal cannula or HFNC therapy. Of the 17 patients enrolled, we obtained 22 samples (11 in the conventional nasal cannula group and 11 in the HFNC group). Viral RNA was detected in 20 nasopharyngeal swabs, and viable viruses were isolated from three nasopharyngeal swabs. Neither viral RNA nor viable virus was detected in the air sample at 0.5 m regardless of the oxygen-supplementation device. We detected viral RNA in two samples in the conventional nasal cannula group but not in the HFNC therapy group in gelatin filters located 3 m from the patient and the surface of the ventilation. This study directly demonstrated that despite viral RNA detection in the nasopharynx, viruses may not be dispersed by HFNC therapy. This warrants further research to determine if similar results can be obtained under different conditions.

Comorbidities as Risk Factors for Severe Disease in Hospitalized Elderly COVID-19 Patients by Different Age-Groups in Japan.

INTRODUCTION: Old age is an independent risk factor (RF) for severe COVID-19; evidence for clinico-epidemiological characteristics among elderly COVID-19 patients is scarce. We aimed to analyze clinical and epidemiological characteristics and comorbidities associated with COVID-19 inpatients in age-stratified populations of an elderly COVID-19 cohort. METHODS: We conducted a retrospective cohort study, using nationwide registry data of COVID-19 patients hospitalized before October 31, 2020 (major information entered in the registry as of December 28, 2020). Participants were divided by age according to the Japan Geriatrics Society and the Japan Gerontological Society: pre-old (65-74 years), old (75-89 years), and super-old (≥90 years). Multivariable logistic regression (MLR) analyses were conducted to identify stratified risk and relationships with comorbidities associated with worse outcomes in different age-groups of elderly patients. Demographics and supportive care were evaluated by category. RESULTS: Data of 4,701 patients from 444 hospitals were included. Most patients (79.3%) had at least one comorbidity; the proportion of patients with hypertension was high in all categories. The proportion of patients with dementia, cardiovascular disease, and cerebrovascular disease increased with age. The percentage of patients who underwent invasive mechanical ventilation/extracorporeal membrane oxygenation was lower in the super-old group. In total, 11.5% of patients died (5.3%, pre-old; 15.2%, old; and 22.4%, super-old). MLR showed that the risk of critical illness differed among age-groups. Male sex was a significant RF in all ages. Collagen disease, moderate to severe renal disorder, and dialysis were significant RFs in older patients, while hematological malignancies and metastatic tumors were more important RFs for severe disease in relatively younger patients. Most of the RFs for critical illnesses were associated with death. CONCLUSION: Differences in the epidemiological and clinical characteristics among the different age-groups were found.

Preserved SARS-CoV-2 neutralizing IgG activity of in-house manufactured COVID-19 convalescent plasma.

PURPOSE: In the current study, we aimed to evaluate the neutralizing IgG activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the coagulation factors of convalescent plasmas which we manufactured in-house without a fast-freezing technique. METHODS: We collected plasmas from eligible participants who had confirmed certain titers of neutralizing antibodies. The plasmas were frozen and stored in the ordinary biofreezer without a fast-freezing function. The purified-IgG neutralizing activity of 20 samples from 19 participants and the coagulation factors of 49 samples from 40 participants were evaluated before and after freezing. RESULTS: Purified-IgG maintained its neutralizing activities, with the median 50 % inhibitory concentration (IC50) of 10.11 mg/ml (IQR 6.53-18.19) before freezing and 8.90 m g/ml (IQR 6.92-28.27) after thawing (p = 0.956). On the contrary, fibrinogen and factor Ⅷ decreased significantly after freezing and thawing in our environment. No significant temperature deviation was observed during the storage period. CONCLUSION: Neutralizing IgG activity, which largely contributes to the antiviral activity of convalescent plasma, did not change through our in-house manufacturing, without fastfreezing and storage conditions for more than 200 days. Ordinary freezers without the fast-freezing function are suitable enough to manufacture and store convalescent plasmas. Hospitals or facilities without specified resources could easily collect and store convalescent plasmas in case of upcoming emerging or re-emerging infectious diseases on-demand with appropriate neutralizing antibody levels measurements.

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.

Liver resection in a patient with persistent positive PCR test for coronavirus disease 2019 (COVID-19): a case report.

BACKGROUND: The perioperative mortality rate is high in patients with coronavirus disease 2019 (COVID-19), and infection control measures for medical care providers must be considered. Therefore, the timing for surgery in patients recovering from COVID-19 is difficult. CASE PRESENTATION: A 65-year-old man was admitted to a hospital with a diagnosis of moderate COVID-19. He was transferred to our hospital because of risk factors, including heavy smoking history, type 2 diabetes mellitus, and obesity (BMI 34). Vital signs on admission were a temperature of 36.1 °C, oxygen saturation > 95% at rest, and 94% on exertion with 3 L/min of oxygen. Chest computed tomography (CT) showed bilateral ground-glass opacities, predominantly in the lower lungs. Contrast-enhanced abdominal CT incidentally revealed a liver tumor with a diameter of 80 mm adjacent to the middle hepatic vein, which was diagnosed as hepatocellular carcinoma (HCC). After being administered baricitinib, remdesivir, dexamethasone, and heparin, the patient's COVID-19 pneumonia improved, his oxygen demand resolved, and he was discharged on day 13. Furthermore, the patient was initially scheduled for hepatectomy 8 weeks after the onset of COVID-19 following a discussion with the infection control team. However, 8 weeks after the onset of illness, a polymerase chain reaction (PCR) test was performed on nasopharyngeal swab fluid, which was observed to be positive. The positive results persisted till 10 and 11 weeks after onset. Both Ct values were high (≥ 31) out of 45 cycles, with no subjective symptoms. Since we determined that he was no longer contagious, surgery was performed 12 weeks after the onset of COVID-19. Notably, medical staff wearing personal protective equipment performed extended anatomical resection of the liver segment 8 ventral area in a negative-pressure room. The patient had a good postoperative course, with no major complications, including respiratory complications, and was discharged on postoperative day 14. Finally, none of the staff members was infected with COVID-19. CONCLUSIONS: We reported a case regarding the timing of surgery on a patient with persistently positive PCR test results after COVID-19, along with a literature review.

SARS-CoV-2-Neutralizing Humoral IgA Response Occurs Earlier but Is Modest and Diminishes Faster than IgG Response.

Secretory immunoglobulin A (IgA) plays a crucial role in mucosal immunity for preventing the invasion of exogenous antigens; however, little is understood about the neutralizing activity of serum IgA. Here, to examine the role of IgA antibodies against COVID-19 illnesses, we determined the neutralizing activity of serum/plasma IgG and IgA purified from previously SARS-CoV-2-infected and COVID-19 mRNA vaccine-receiving individuals. We found that serum/plasma IgA possesses substantial but rather modest neutralizing activity against SARS-CoV-2 compared to IgG with no significant correlation with the disease severity. Neutralizing IgA and IgG antibodies achieved the greatest activity at approximately 25 and 35 days after symptom onset, respectively. However, neutralizing IgA activity quickly diminished to below the detection limit approximately 70 days after onset, while substantial IgG activity was observed until 200 days after onset. The total neutralizing activity in sera/plasmas of those with COVID-19 largely correlated with those in purified IgG and purified IgA and levels of anti-SARS-CoV-2-S1-binding IgG and anti-SARS-CoV-2-S1-binding IgA. In individuals who were previously infected with SARS-CoV-2 but had no detectable neutralizing IgA activity, a single dose of BNT162b2 or mRNA-1273 elicited potent serum/plasma-neutralizing IgA activity, but the second dose did not further strengthen the neutralization antibody response. The present data show that the systemic immune stimulation with natural infection and COVID-19 mRNA-vaccines elicits both SARS-CoV-2-specific neutralizing IgG and IgA responses in serum, but the IgA response is modest and diminishes faster than the IgG response. IMPORTANCE Secretory dimeric immunoglobulin A (IgA) plays an important role in preventing the invasion of foreign objects by its neutralizing activity on mucosal surfaces, while monomeric serum IgA is thought to relate to the phagocytic immune system activation. Here, we report that individuals with the novel coronavirus disease (COVID-19) developed both systemic neutralizing IgG (nIgG) and IgA (nIgA) active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the nIgA response was quick and reached the highest activity earlier than the nIgG response, nIgA activity was modest and diminished faster than nIgG activity. In individuals who recovered from COVID-19 but had no detectable nIgA activity, a single dose of COVID-19 mRNA vaccine elicited potent nIgA activity, but the second dose did not further strengthen the antibody response. Our study provides novel insights into the role and the kinetics of serum nIgA against the pathogen in both naturally infected and COVID-19 mRNA vaccine-receiving COVID-19-convalescent individuals.

Impact of long-COVID on health-related quality of life in Japanese COVID-19 patients.

BACKGROUND: The empirical basis for a quantitative assessment of the disease burden imposed by long-COVID is currently scant. We aimed to inform the disease burden caused by long-COVID in Japan. METHODS: We conducted a cross sectional self-report questionnaire survey. The questionnaire was mailed to 526 eligible patients, who were recovered from acute COVID-19 in April 2021. Answers were classified into two groups; participants who have no symptom and those who have any ongoing prolonged symptoms that lasted longer than four weeks at the time of the survey. We estimated the average treatment effect (ATE) of ongoing prolonged symptoms on EQ-VAS and EQ-5D-3L questionnaire using inverse probability weighting. In addition to symptom prolongation, we investigated whether other factors (including demography, lifestyle, and acute severity) were associated with low EQ-VAS and EQ-5D-3L values, by multivariable linear regression. RESULTS: 349 participants reported no symptoms and 108 reported any symptoms at the time of the survey. The participants who reported any symptoms showed a lower average value on the EQ-VAS (69.9 vs 82.8, respectively) and on the EQ-5D-3L (0.85 vs 0.96, respectively) than those reporting no symptoms considering the ATE of ongoing prolonged symptoms. The ATE of ongoing prolonged symptoms on EQ-VAS was - 12.9 [95% CI - 15.9 to - 9.8], and on the EQ-5D-3L it was - 0.11 [95% CI - 0.13 to - 0.09], implying prolonged symptoms have a negative impact on patients' EQ-VAS and EQ-5D-3L score. In multivariable linear regression, only having prolonged symptoms was associated with lower scores (- 11.7 [95% CI - 15.0 to - 8.5] for EQ-VAS and - 0.10 [95% CI - 0.13 to - 0.08] for EQ-5D-3L). CONCLUSIONS: Due to their long duration, long-COVID symptoms represent a substantial disease burden expressed in impact on health-related quality of life.

Long COVID: current status in Japan and knowledge about its molecular background.

Even after recovering from coronavirus disease 2019 (COVID-19), patients can experience prolonged complaints, referred to as "long COVID". Similar to reports in Caucasians, a follow-up study in Japan revealed that fatigue, dyspnea, cough, anosmia/dysgeusia, and dyssomnia are common symptoms. Although the precise mode of long COVID remains elusive, multiple etiologies such as direct organ damage by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), autoimmunity, prolonged inflammatory reactions, and psychiatric impairment seem to be involved. Notably, SARS-CoV-2 is neurotropic, and viral RNA and proteins are continuously detectable in multiple organs, including the brain. Viral proteins exert a number of different toxic effects on cells, suggesting that persistent infection is a key element for understanding long COVID. Here, we first reviewed the current status of long COVID in Japan, and then summarized literature that help us understand the molecular background of the symptoms. Finally, we discuss the feasibility of vaccination as a treatment for patients with long COVID.

Antibody responses after two doses of SARS-CoV-2 mRNA-1273 vaccine in an individual with history of COVID-19 re-infection.

We present a case of a 58-year-old Japanese man with a history of 2 previous COVID-19 infections, who received 2 doses of mRNA-1273 vaccine. We are not aware of any previous study regarding antibody tendency after 2 infections and 2 vaccinations. We evaluated his IgG titer of antispike protein and neutralizing activity from the first infection before and after 2 doses of vaccine. Both antispike IgG titer and neutralizing activity showed a tendency to decline almost 1 year after initial infection; they rapidly increased after the first vaccination, and they remained high after the second vaccination. Although this is a single case report, it seems to have generalizability because the findings are consistent with previous reports regarding single infections or 3 doses of vaccination. Our findings suggest that a single booster shot may provide sufficient protection and aid the understanding of immunologic responses of vaccination in patients with COVID-19 with history of re-infection.

Predictors of silent hypoxia in hospitalized patients with COVID-19 in Japan.

INTRODUCTION: Silent hypoxia (SH) is common in patients with coronavirus disease (COVID-19) in Japan and other countries. Early identification of SH is important as more treatment options for COVID-19 have become available. This study aimed to identify predictors of SH using a nationwide COVID-19 registry of hospitalized patients. METHODS: Adult patients who were admitted to hospital with COVID-19 between January 2020 and June 2021 and who were hypoxic on admission (SpO2: 70-93%), not transferred from another facility, and who did not have disturbance of consciousness, confusion, or dementia, were included. SH was defined as hypoxia in the absence of shortness of breath/dyspnea upon admission. Predictors of SH were identified using univariable and multivariable logistic regression. RESULTS: The study included 1904 patients, of whom 990 (52%) satisfied the criteria for SH. Compared to patients without SH, patients with SH were older, more likely to be female, and had a slightly higher SpO2 on admission. Compared to patients without SH, patients with SH had a lower prevalence of chronic lung disease (CLD) other than chronic obstructive pulmonary disease (COPD), asthma, and obesity. Multivariable analysis revealed that the independent predictors of SH were older age, a shorter interval from symptom onset to admission, higher SpO2, and an absence of CLD or COPD. CONCLUSIONS: The absence of underlying lung disease and older age were important predictors of SH. The results of this study, which is the largest such study reported to date in Japan, may help clarify the mechanism of SH.

A Multi-Center, Open-Label, Randomized Controlled Trial to Evaluate the Efficacy of Convalescent Plasma Therapy for Coronavirus Disease 2019: A Trial Protocol (COVIPLA-RCT).

BACKGROUND: Coronavirus disease 2019 is a global public health concern. As of December 2020, the therapeutic agents approved for coronavirus disease 2019 in Japan were limited to two drugs: remdesivir, an antiviral drug, granted a Special Approval for Emergency on 7 May 2020, and dexamethasone, which has an anti-inflammatory effect. The aim of this study is to evaluate the efficacy of convalescent plasma collected from donors who recovered from coronavirus disease 2019. METHODS: This is an open-label, randomized controlled trial comprising two groups: a convalescent plasma and a standard-of-care group. Plasma administered to patients with coronavirus disease 2019 randomized in the convalescent plasma group of this trial will be plasma that has been collected and stored in an associated study. Patients with a diagnosis of mild coronavirus disease 2019 will be included in this trial. The efficacy of convalescent plasma transfusion will be evaluated by comparing the convalescent plasma group to the standard-of-care group (without convalescent plasma transfusion) with respect to changes in the viral load and other measures. The primary endpoint will be time-weighted average changes in the SARS-CoV-2 virus load in nasopharyngeal swabs from day 0 to days 3 and 5. It is hypothesized that the intervention should result in a decrease in the viral load in the convalescent plasma group until day 5. This endpoint has been used as a change in viral load has and been used as an index of therapeutic effect in several previous studies. DISCUSSION: The proposed trial has the potential to prevent patients with mild COVID-19 from developing a more severe illness. Several RCTs of convalescent plasma therapy have already been conducted in countries outside of Japan, but no conclusion has been reached with respect to the efficacy of convalescent plasma therapy, which is likely in part because of the heterogeneity of the types of target patients, interventions, and endpoints among trials. Actually, previous clinical trials on plasma therapy have shown inconsistent efficacy and are sometimes ineffective in COVID-19 patients with severe disease, which is due to unmeasured neutralizing antibody titer in the COVID-19 convalescent plasma. To improve this issue, in this study, we measure neutralizing activity of convalescent plasma before administration and provide the plasma with high neutralizing activity to the subjects. It is hoped that this study will further evidence to support the role of convalescent plasma therapy in COVID-19.

Factors associated with development and persistence of post-COVID conditions: A cross-sectional study.

INTRODUCTION: The post-COVID condition has become a social concern. Although the patient characteristics associated with the development of this condition are partially known, those associated with its persistence have not been identified. METHODS: We conducted a cross-sectional questionnaire-based survey among patients who had recovered from COVID-19 and visited the National Center for Global Health and Medicine between February 2021 and March 2021. Demographic and clinical data, and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the development and persistence of post-COVID conditions using multivariate logistic and linear regression analyses, respectively. RESULTS: We analyzed 457 of 526 responses (response rate, 86.9%). The median patient age was 47 years. Of these, 378 patients (84.4%) had mild disease in the acute phase. The number of patients with symptoms at 6 and 12 months after onset or diagnosis was 120 (26.3%) and 40 (8.8%), respectively. Women were at risk of developing fatigue (odds ratio [OR]: 2.03, 95% confidence interval [CI]: 1.31-3.14), dysosmia (OR: 1.91, 95%CI: 1.24-2.93), dysgeusia (OR: 1.56, 95%CI: 1.02-2.39), hair loss (OR: 3.00, 95%CI: 1.77-5.09), and persistence of any symptoms (coefficient: 38.0, 95%CI: 13.3-62.8). Younger age and low body mass index were factors for developing dysosmia (OR: 0.96, 95%CI: 0.94-0.98 and OR: 0.94, 95%CI: 0.89-0.99, respectively) and dysgeusia (OR: 0.98, 95%CI: 0.96-1.00 and OR: 0.93, 95%CI: 0.88-0.98, respectively). CONCLUSION: We identified factors involved in the development and persistence of post-COVID conditions. Many patients, even those with mild conditions, experience long-term residual symptoms.

Factors Associated With Prolonged Psychological Distress Among Nurses and Physicians Engaged in COVID-19 Patient Care in Singapore and Japan.

This study explores the factors contributing to the prolonged psychological distress of frontline nurses and physicians caring for COVID-19 patients in hospitals in Singapore and Japan. A cross-sectional survey between September and December 2020 yielded 1,644 responses (23.8%), from 62 nurses and 64 physicians in Singapore and 1,280 nurses and 238 physicians in Japan. Multivariate logistic regression analysis revealed that significant risk factors for prolonged psychological distress included being a frontline nurse [adjusted odds ratio (aOR) = 2.40, 95% confidence interval (CI): 1.24-4.66], having an underlying medical condition (aOR = 1.74, 95% CI: 1.22-2.46), experiencing prejudice because they undertook COVID-19 patient care (aOR = 3.05, 95% CI: 2.23-4.18), having trouble dealing with panicked or uncooperative patients (aOR = 2.36, 95% CI: 1.71-3.25), and experiencing an outbreak of COVID-19 in the hospital (aOR = 2.05, 95% CI: 1.38-3.04). Factors inversely associated with psychological distress included age (OR = 0.98, 95% CI: 0.97-1.00), number of beds in the hospital (aOR = 0.73, 95% CI: 0.57-0.94), clinical practice of carefully putting on and taking off personal protective equipment in daily COVID-19 patient care (aOR = 0.52, 95% CI: 0.37-0.73), and knowledge on COVID-19 (aOR = 0.82, 95% CI: 0.72-0.94). These results could help us identify vulnerable healthcare providers who need urgent mental care during the COVID-19 pandemic. Measures that may reduce psychological strain include adequate supply of medical resources, education on precautionary measures, and communication strategies to combat discrimination against frontline healthcare providers.

Successful use of casirivimab/imdevimab anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19.

Management of COVID-19 patients with humoral immunodeficiency is challenging. We describe a woman with COVID-19 with multiple relapses due to anti-CD20 monoclonal antibody treatment. She was successfully treated with casirivimab/imdevimab and confirmed to have neutralizing antibodies. This case suggests that monoclonal antibodies have therapeutic and prophylactic value in patients with humoral immunodeficiency.