COVID-19 severity and corticosteroid treatment have minimal effect on specific antibody production (preprint)

Background Dexamethasone is currently administered for Coronavirus disease 2019(COVID-19); however, there are concerns about its effect on specific antibodies’ production. The aim of this study was to evaluate whether specific antibodies were affected by COVID-19 severity and corticosteroid treatment.Methods Of 251 confirmed COVID-19 patients admitted to our hospital between January 26 and August 10, 2020, the early period of the pandemic, 75 patients with sera within 1 month of onset and 1month or longer were included in the research. A total of 253 serum samples from these patients were collected. The levels of specific antibodies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), immunoglobulin G (IgG) and M (IgM), were measured retrospectively. The results were compared separately of each COVID-19 severity, and with or without corticosteroid treatment.Results Among the 75 patients, 47, 18, and 10 had mild, moderate, and severe disease, respectively. The median age was 53.0 years and 22 (29%) were women. The most common comorbidities were hypertension and dyslipidemia. Corticosteroids were administered to 20 (27%) and 10 (53%), patients with moderate and severe disease, respectively. The positivity rates IgM increased first, and IgG was almost always positive after day 16, regardless of the severity of COVID-19. On days 6–10, both IgG and IgM positivity rates were higher in patients with moderate disease than in those with mild or severe disease. In patients with moderate disease, IgG positivity was similar over time, regardless of corticosteroid treatment.Conclusions In COVID-19 patients, specific IgG is positive and maintained for a long period of time, even after corticosteroid treatment. The effect of corticosteroid treatment in a COVID-19 epidemiological study using specific IgG antibodies was considered minor. COVID-19 patients were more likely to receive oxygen if IgM was positive 1 week after onset, but not mechanical ventilation. IgM measurement 1 week after onset may predict COVID-19 severity.

Observational study on Post COVID-19 condition using smart phones

Risk Factors Associated with Development and Persistence of Long COVID: A Cross-Sectional Study (preprint)

Background: Long coronavirus disease (COVID) has been a social concern. Though patient characteristics associated with the development of long COVID are partially known, those associated with its persistence have not been identified. Methods: We conducted a cross-sectional questionnaire survey of patients after COVID-19 recovery who visited the National Center for Global Health and Medicine between February 2020 and March 2021. Demographic and clinical data and data regarding the presence and duration of long COVID were obtained. We identified factors associated with the development and persistence of long COVID using multivariate logistic and linear regression analysis, respectively. Results: We analyzed 457 of 526 responses (response rate, 86.9%). The median age was 47 years, and 378 patients (84.4%) had mild disease in the acute phase. The number of patients with any symptoms after 6 and 12 months after onset or diagnosis were 120 (26.3%) and 40 (8.8%), respectively. Women were at risk for development of 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), and hair loss (OR: 3.00, 95% CI: 1.77-5.09) and for persistence of any symptoms (coefficient: 38.0, 95% CI: 13.3-62.8). Younger age and low body mass index were risk 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 risk factors for the development and persistence of long COVID. Many patients suffer from long-term residual symptoms, even in mild cases.

Risk factors associated with development and persistence of long COVID (preprint)

BackgroundLong COVID has been a social concern. Though patient characteristics associated with developing long COVID are partially known, those associated with persisting it have not been identified. MethodsWe conducted a cross-sectional questionnaire survey of patients after COVID-19 recovery who visited the National Center for Global Health and Medicine between February 2020 and March 2021. Demographic and clinical data, and the presence and duration of long COVID were obtained. We identified factors associated with development and persistence of long COVID using multivariate logistic and linear regression analysis, respectively. ResultsWe analyzed 457 of 526 responses (response rate, 86.9%). The median age was 47 years, and 378 patients (84.4%) had mild disease in acute phase. The number of patients with any symptoms after 6 and 12 months after onset or diagnosis were 120 (26.3%) and 40 (8.8%), respectively. Women were at risk for development of fatigue (OR 2.03, 95% 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), and hair loss (OR 3.00, 95% CI 1.77-5.09), and were at risk for persistence of any symptoms (coefficient 38.0, 95% CI 13.3-62.8). Younger age and low body mass index were risk 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). ConclusionWe identified risk factors for the persistence as well as development of long COVID. Many patients suffer from long-term residual symptoms, even in mild cases. SummaryOur cross-sectional questionnaire survey of patients recovering from COVID-19 revealed that women, young age, and low body mass index were risk factors for the development of multiple symptoms, and that even mild cases of COVID-19 suffered from long-term residual symptoms.

Smoking, Comorbidities, and Severity of Disease in Hospitalized COVID-19 Patients in Japan (preprint)

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 17,702 COVID-19 inpatients aged 20-89 years (10,279 men and 7,423 women). We graded the severity of COVID-19 (grade 0 to 5) according to the most intensive treatment required during hospitalization. Associations of smoking status with severe grade 3/4/5 (invasive mechanical ventilation/extracorporeal membrane oxygenation/death) and separately with grade 5 (death) were analyzed using multiple logistic regression with grade 0 (no oxygen) as the control group. 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.Findings: Among men, former smoking significantly increased the risk of grade 3/4/5 and grade 5, with age-adjusted ORs (95% CI) of 1·50 (1·18-1·90) and 1·65 (1·23-2·21), respectively. An additional adjustment for comorbidities weakened these ORs to 1·29 (1·00-1·66) and 1.41 (1·01-1·95), respectively. 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.Interpretation: Smoking cessation should be recommended even if the observed relationship between current smoking and the severity of COVID-19 is null because current smoking increases the risks of future comorbidities due to different diseases that increase the risk of severe COVID-19.Funding Information: This research was funded by the Health and Labour Sciences Research grant (19HA1003, 20CA2031) and the National Center for Global Health and Medicine (20A-3002).Declaration of Interests: All authors report no conflict of interest.Ethics Approval Statement: This study was approved by the National Center for Global Health and Medicine (NCGM) ethics review (NCGM-G-003494-0).

Risk factors for severity on admission and the disease progression during hospitalization in a large cohort of COVID-19 patients in Japan (preprint)

Objectives: To investigate the risk factors contributing to severity on admission. Additionally, risk factors on worst severity and fatality were studied. Moreover, factors were compared based on three points: early severity, worst severity, and fatality. Design: A observational cohort study utilizing data entered in a Japan nationwide COVID-19 inpatient registry, COVIREGI-JP. Setting: As of August 31, 2020, 7,546 cases from 780 facilities have been registered. Participating facilities cover a wide range of hospitals where COVID-19 patients are admitted in Japan. Participants: Participants who had a positive test result on any applicable SARS-CoV-2 diagnostic tests, and were admitted to participating healthcare facilities. A total of 3,829 cases were identified from January 16 to May 31, 2020, of which 3,376 cases were included in this study. Primary and secondary outcoe measures: Primary outcome was severe or non-severe on admission, determined by the requirement of mechanical ventilation or oxygen therapy, SpO2, or respiratory rate. Secondary outcome was the worst severity during hospitalization, judged by the requirement of oxygen and/or IMV/ECMO. Results: Risk factors for severity on admission were older age, male, cardiovascular disease, chronic respiratory disease, diabetes, obesity, and hypertension. Cerebrovascular disease, liver disease, renal disease or dialysis, solid tumor, and hyperlipidemia did not influence severity on admission ; however it influenced worst severity. Fatality rates for obesity, hypertension, and hyperlipidemia were relatively lower. Conclusions: This study segregated the comorbidities driving severity and death. It is possible that risk factors for severity on admission, worst severity, and fatality are not consistent and may be propelled by different factors. Specifically, while hypertension, hyperlipidemia, and obesity had major effect on worst severity, their impact was mild on fatality in the Japanese population. Some studies contradict our results; therefore, detailed analyses, considering in-hospital treatments, are needed for validation. Trial registration: UMIN000039873. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045453

Evaluation of serum antibodies against SARS-CoV-2 in healthcare workers who participated in the operation of charter flights for the evacuation of Japanese residents from Hubei Province (preprint)

There are several recommendations for the use of personal protective equipment (PPE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the selection of appropriate PPE for the current situation remains controversial. We measured serum antibody titers for SARS-CoV-2 in 10 participants who were engaged in the operation of charter flights for the evacuation of Japanese residents from Hubei Province. All participants wore PPE in accordance with Centers for Disease Control and Prevention guidelines. A total of 17 samples were tested, and all were seronegative. Hence, we conclude that the current PPE recommendation is effective to protect healthcare workers from SARS-CoV-2 infection.

Effect of evacuation of Japanese residents from Wuhan, China, on preventing transmission of novel coronavirus infection: a modelling study (preprint)

Objective: In late January 2020, the Japanese government carried out three evacuations by aircraft from Wuhan, China, to avoid further cases of coronavirus disease 2019 (COVID-19) among Wuhan's Japanese residents. Evacuation by aircraft may be an effective countermeasure against outbreaks of infectious diseases, but evidence of its effect is scarce. This study estimated how many COVID-19 cases were prevented among the Japanese residents of Wuhan by the evacuation countermeasure. Results: Eleven imported COVID-19 cases were reported on Feb 1 from among the total 566 evacuees who returned to Japan. In the case of no evacuations being made, the cumulative number of COVID-19 cases among Wuhan's Japanese residents was estimated to reach 25 (95% CI [20,29]) on Feb 8 and 34 (95% CI [28,40]) on Feb 15. A 1-week delay in the evacuation might be led to 14 additional cases and a 2-week delay to 23 additional cases. Evacuation by aircraft can contribute substantially to reducing the number of infected cases in the initial stage of the outbreak.