Inpatient Use of Metformin and Acarbose Is Associated with Reduced Mortality of COVID-19 Patients with Type 2 Diabetes Mellitus (preprint)

Type 2 diabetes mellitus (T2DM) is a strong risk factor for complications of coronavirus disease 2019 (COVID-19). The effect of T2DM medications on COVID-19 outcomes remains unclear. In a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 in Wuhan, we have previously found that metformin use prior to hospitalization is associated with reduced mortality. Here we continue to investigate the effects of inpatient use of T2DM medications, including metformin, acarbose, insulin, and sulfonylureas, on the mortality of COVID-19 patients with T2DM during hospitalization. We found that patients using metformin and acarbose, alone or both together, after admission were significantly more likely to survive than those who did not use either metformin or acarbose. Thus, our analyses suggest that inpatient use of metformin and acarbose together or alone during hospitalization should be studied in randomized trials.

Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis (preprint)

Background: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. Methods: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. Results: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). Conclusions: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

Engineered interferon alpha effectively improves clinical outcomes of COVID-19 patients (preprint)

Interferons are key to the antiviral host defense, yet the therapeutic value of interferon for coronavirus disease 2019 (COVID-19) is unknown. Recombinant super-compound interferon (rSIFN-co) is a new genetically engineered interferon, thus we conducted a multicenter, randomized controlled trial (ChiCTR2000029638) to evaluate the efficacy and safety of recombinant super-compound interferon versus traditional interferon alpha added to baseline antiviral agents (lopinavir–ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19. Participants received rSIFN-co (12 million international units [IU], twice daily) or interferon alpha (5 million IU, twice daily) nebulization added to baseline antiviral agents for no more than 28 days. The primary outcome was the time to clinical improvement. Secondary outcomes included the overall rate of clinical improvement assessed on day 28，the time to radiological improvement and virus nucleic acid negative conversion, and adverse events. 94 patients hospitalized with moderate-to-severe COVID-19 were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon alpha group). Individuals in the rSIFN-co group showed shorter time to clinical improvement (11.5 days vs 14.0 days; P = 0.019) as compared to those in the interferon alpha group. The overall rate of clinical improvement on day 28 was much higher in the rSIFN-co group than that in the interferon alpha group (93.5% vs 77.1%; difference, 16.4%; 95% confidence interval 3% to 30%). The time to radiological improvement and the time to virus nucleic acid negative conversion were also much shorter in the rSIFN-co group (8.0 days vs 10.0 days, P = 0.002; 7.0 days vs 10.0 days, P = 0.018, respectively). Adverse events were reported in 13 (28.3%) patients in the rSIFN-co group and 18 (37.5%) patients in the interferon alpha group. No patients died during the study. Our study showed that rSIFN-co added to antiviral agents was safe and more efficient than interferon alpha plus antiviral agents in the treatment of moderate-to-severe COVID-19. Future clinical study of rSIFN-co therapy alone or combined with other antiviral therapy is warranted.

Neutrophil surged for mortality of COVID-19: a correlational study (preprint)

Background: Multiorgan damage by SARS-CoV-2 results in alterations of many clinical measures associated with mortality of COVID-19. This research discussed the pioneering pathogenicity factors that lead to the extensive damage elusive. Objectives: A cohort of COVID-19 patients. Methods: : We conducted a correlational analysis of hospital outcomes with an independent cohort of COVID-19 patients and we also presented a death case to illustrate for time course of immune cell density. Results: : The results showed that dysregulated immune cell densities were correlated with hospitalization duration before death, not before discharge. High neutrophil densities allowed sorting out one third of total death cases while a density of less than 70% of the white blood cells allowed sorting out 70% of surviving cases. Conclusion: Collectively surged neutrophil was a top trigger for mortality in patients with COVID-19.

A mild-symptom COVID-19 patient showed consistently high pharyngeal viral loads in a period of ten days after hospitalization (preprint)

Background: The pandemics of coronavirus disease 2019 (COVID-19) threatens both human lives and health care system. COVID-19 patients may differ in their capability in spreading the causative virus, the severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2). Methods: In this study, oropharyngeal swabs specimens from 43 patients admitted to our hospital during the COVID-19 peak time in Wuhan, China were obtained to survey temporal profiles of the viral loads in their upper respiratory tract. An internal and an absolute mRNA control were included in the real-time RT-PCR analysis and RNA extraction step to remove the potential influence of experimental variations on the result interpretation. Results: We found about one third of the hospitalized COVID-19 patients were never tested as SARS-CoV-2 positive during the course of this study. One patient with mild symptoms displayed constant high levels of viral loads after hospitalization, which were orders of magnitude higher than all other positive patients. Conclusions: We propose that if pharyngeal viral loads in a patient could indicate its ability in spreading the virus to others, then identification and strict separation of the high viral load patients should provide an effective mean in restricting viral spreading and protect health care workers from infection.

Protocol for a retrospective cohort study for evaluating the early antibiotics use in non-severe COVID-19 patients (preprint)

The use of antibiotics is common in the treatment of COVID-19, but adequate evaluation is lacking. We aimed to evaluate the efficacy of antibiotic use in non-severe COVID-19 patients, particularly in patients admitted with low risk of bacterial infection. This is a multi-center retrospective cohort study. Patients are screened strictly according to the inclusion/exclusion criteria and are divided into two groups based on antibiotics exposure. The exposure is defined as the treatment of antibiotics prescribed within 48 hours after admission, with a course of treatment≥3 days; and patients in this group are classified as early antibiotic use group. Otherwise, patients are classified as the non early antibiotic use group. The primary end point of the study is progressing from non-severe type COVID-19 into severe type. This is the first protocol to put a focus on the transformation of the severity of the disease, based on a multi-center retrospective cohort design.

Evaluation of early antibiotics use in non-severe COVID-19 patients admitted with low risk of bacterial infection (preprint)

The use of antibiotics is common in the treatment of COVID-19, but adequate evaluation is lacking. This study aimed to evaluate the effect of early antibiotic use in non-severe COVID-19 patients admitted with low risk of bacterial infection. The multi-center retrospective cohort study included 1613 non-severe COVID-19 inpatients admitted with low risk of bacterial infection. During the follow-up of 30 days, the proportion of patients progressed into severe type COVID-19 in the early antibiotics use group was almost 1.5 times than that of the comparision group. In the mixed-effect model, the early use of antibiotics was associated with higher probability of developing severe type, staying in the hospital for over 15 days, and secondary infection. However, it was not significant association with mortality rate. Analysis with propensity score-matched cohort displayed similar results. It is suggested that antibiotic use should be avoided unless absolutely necessary in non-severe COVID-19 patients, particularly in the early stages.

Radiologic evaluation of discharge quality in patients with COVID-19 (preprint)

Background   Worldwide spread of the novel coronavirus disease 2019 (COVID-19) has made hundreds of thousands people sick and fortunately many of them have been treated and discharged. However, it remains unclear how well the discharged patients were recovering. Chest CT scan, with demonstrated high sensitivity to COVID-19, was used here to examine clinical manifestations in patients at discharge.Methods This study registered retrospectively single-center case series of 180 discharged patients, all confirmed with COVID-19 at Wuhan Red Cross Hospital in Wuhan, China. Epidemiological, demographic, clinical, laboratory and treatment data were collected. CT imaging features of absorption vs progressive stage were compared and analyzed.Results Five pulmonary lobes were affected in 54 (30%) of the 180 patients at the absorption stage, comparing to 66% of them at the progressive stage (P=1.45×10-11). Forty five (25%) patients had pleural effusion on admission and 13 of them still carried hydrothorax when discharged as per standard discharge criteria(P=4.48×10-6). Besides, compared with those at progressive stage, 97 (54%) discharged patients had interlobular thickening (P=6.95×10-3) and 43% of them still presented adjacent pleura thickening (P=5.58×10-5). The median total CT score of discharged patients at absorption stage was lower than progressive stage (3 vs 12.5 ). The median total CT score recovery rate was 67% (range, 0-100%) and 139 (77%) patients showed less than 90% improvement at discharge.Conclusions A majority (77%) of the discharged patients had not recovered completely. The current discharge criteria may need to include 90% or higher CT score-based recovery rate.Authors Jingwen Li, Xi Long, Fang Fang, and Xuefei Lv contributed equally to this work.Authors Zhicheng Lin and Nian Xiong are joint last coauthors.