Associations of COVID-19 Symptoms with Omicron Subvariants BA.2 and BA.5, Host Status, and Clinical Outcomes: A Registry-Based Observational Study in Sapporo, Japan (preprint)

Background: Previous SARS-CoV-2 infection and vaccination, coupled to rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We characterized clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. Methods: Individuals registered in Sapporo's web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Symptom frequencies, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. Results: For all omicron-infected individuals, cough was the most common symptom (62.7%), followed by sore throat (60.7%), nasal discharge (44.3%), and fever (38.8%). Omicron BA.5 infection was associated with a higher symptom burden than BA.2 in vaccinated and unvaccinated individuals. Omicron breakthrough-infected individuals with 3 or more vaccinations or previous infection were less likely to exhibit systemic symptoms, but more likely to exhibit upper respiratory symptoms. Infected elderly individuals had lower odds for all symptoms, but, when symptoms were manifest, systemic symptoms were associated with an increased risk, whereas upper respiratory symptoms with a decreased risk, of severe disease. Conclusion: Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a greater symptom burden than BA.2. Vaccination and prior infection mitigated systemic symptoms and improved outcomes, but increased upper respiratory tract symptom burden. Systemic, but not upper respiratory, symptoms in the elderly heralded severe disease.

Remdesivir in combination with immunomodulators improves respiratory status in COVID-19: A retrospective study (preprint)

Background: Although immunomodulators (tocilizumab or baricitinib) have been shown to improve outcomes in patients with coronavirus disease (COVID-19), the additive effect of remdesivir is unknown. We retrospectively tested the effect of remdesivir in combination with immunomodulators and standard treatments in COVID-19 patients.Methods: A retrospective, single-center study was conducted on patients with COVID-19 admitted to the Hokkaido University Hospital between April 2020 and September 2021, who were treated with either tocilizumab or baricitinib. The duration to achievement of oxygen-free in both groups was compared, and the effect of remdesivir use on respiratory status was examined through multivariate analysis. The severity of respiratory status in the two groups on day 14 and day 28 was compared. A sensitivity analysis using propensity score was also performed.Results: We enrolled 98 patients who received either tocilizumab or baricitinib. Of these, 72 patients used remdesivir (remdesivir group) and 26 did not (control group). Most cases were severe and treated with concomitant steroids. The remdesivir group had faster recovery of respiratory status compared to the control group (11 days vs. 26 days, P=0.033). Multivariate analysis showed that remdesivir use contributed to shorter time to being oxygen-free (hazard ratio [HR] = 2.33, 95 % confidence interval [CI] 1.17 – 4.46, P=0.016). Age, body mass index, diabetes mellitus, and time from onset to oxygen administration were independent prognostic factors. The remdesivir group achieved higher rate of oxygen free than the control group at days 14 and 28 after treatment (P=0.033, P=0.003, respectively). The degree of improvement from baseline severity was also higher in the remdesivir group (day 14; P=0.047, day 28; P=0.018). The survival time between two groups was not significantly different (HR = 0.55, 95 %CI 0.10 – 2.99, P=0.49). Similarly, the propensity score-matched patient groups showed the efficacy of remdesivir. Conclusions: Among patients with COVID-19 who used immunomodulator containing tocilizumab or baricitiib, remdesivir contributed to shorter respiratory recovery time and better respiratory status at days 14 and 28. Concomitant use of remdesivir may contribute to improved respiratory status in patients on immunomodulator and standard treatment.

Comparative efficacy of tocilizumab and baricitinib in COVID-19 treatment: a retrospective cohort study (preprint)

Background: Although the biological agents tocilizumab and baricitinib have been shown to improve the outcomes of patients with COVID-19, a comparative evaluation has not been performed. The aim of our study was to evaluate the comparative effect of the use of tocilizumab and baricitinib on patient outcomes in COVID-19. Methods A retrospective, single-center study was conducted using the data of patients with COVID-19 admitted to Hokkaido University hospital between April 2020 and September 2021 and were treated with tocilizumab or baricitinib. The clinical characteristics of the patients who received each drug were compared. Univariate and multivariate logistic regression analyses were performed against the outcomes of all-cause mortality and the improvement in respiratory status. The development of secondary infection events was analyzed using the Kaplan–Meier method and the log-rank test. Results Among the 459 patients hospitalized with COVID-19 during the study, 64 received tocilizumab and 34 received baricitinib, and they were included in the study. Most patients were treated with concomitant steroids, and the severity of the disease at the time of initiation of biological agents was similar. The use of tocilizumab or baricitinib was not associated with all-cause mortality or the improvement in respiratory status within 28 days of drug administration. Age, chronic renal disease, and comorbid respiratory disease were independent prognostic factors for all-cause mortality, whereas anti-viral drug use and severity of COVID-19 at baseline were associated with the improvement in respiratory status. There was no significant difference in the infection-free survival rate between patients treated with tocilizumab and those with baricitinib. Conclusion There were no differences in efficacy and safety between tocilizumab and baricitinib in the treatment of COVID-19. Both these biological agents are expected to be equally safe and clinically effective.

Comparative efficacy of tocilizumab and baricitinib in COVID-19 treatment: a retrospective cohort study (preprint)

Summary Background Although biological agents, tocilizumab and baricitinib, have been shown to improve the outcomes of patients with COVID-19, a comparative evaluation has not been performed. Methods A retrospective, single-center study was conducted using the data of patients with COVID-19 admitted to the Hokkaido University hospital between April 2020 and September 2021, who were treated with tocilizumab or baricitinib. The clinical characteristics of patients who received each drug were compared. Univariate and multivariate logistic regression models were performed against the outcomes of all-cause mortality and the improvement in respiratory status. The development of secondary infection events was analyzed using the Kaplan–Meier analysis and the log-rank test. Results The use of tocilizumab or baricitinib was not associated with all-cause mortality and the improvement in respiratory status within 28 days of drug administration. Age, chronic renal disease, and comorbid respiratory disease were independent prognostic factors for all-cause mortality, while anti-viral drug use and severity of COVID-19 at baseline were associated with the improvement in respiratory status. There was no significant difference in the infection-free survival between patients treated with tocilizumab and those with baricitinib. Conclusion There were no differences in efficacy and safety between tocilizumab and baricitinib for the treatment of COVID-19.

Proposal of COVID-19 Clinical Risk Score for the management of suspected COVID-19 cases: a case control study (preprint)

BackgroundNo clinical scoring system has yet been established to estimate the likelihood of COVID-19 and to determine the suitability of diagnostic testing in suspected COVID-19 patients.MethodsThis was a single-center, retrospective, observational study of patients with suspected COVID-19 and confirmed COVID-19. Patient background, clinical course, laboratory and CT findings, and the presence of alternative diagnoses were evaluated. Clinical risk scores were developed based on clinical differences between patients with and those without COVID-19.ResultsAmong 110 patients suspected of COVID-19, 60.9% underwent PCR testing based on the judgment of physicians. Two patients were found to have COVID-19. The clinical characteristics of 108 non-COVID-19 patients were compared with those of 23 confirmed COVID-19 patients. Patients with COVID-19 were more likely to have a history of high-risk exposures and abnormal sense of taste and smell. Significantly higher rates of subnormal white blood cell count, lower eosinophil count, and lower procalcitonin level were observed in the COVID-19 group than in the non-COVID-19 group. When blood tests, CT findings, and the presence of alternative diagnoses were scored on an 11-point scale, i.e., “COVID-19 Clinical Risk Score”, the COVID-19 group scored significantly higher than the non-COVID-19 group, with more than four points in the COVID-19 group. All non-COVID cases that did not undergo PCR had a score of 4 or less.ConclusionsThe COVID-19 Clinical Risk Score enables risk classification of patients suspected of having COVID-19 and can help in decision-making in clinical practice, including appropriateness of diagnostic testing.