Background: The number of coronavirus disease 2019 (COVID-19) cases has rapidly increased all over the world. Specific information about immunity in non-survivors with COVID-19 is scarce. This study aimed to analyse the clinical characteristics and abnormal immunity of the confirmed COVID-19 non-survivors. Methods: In this single-centered, retrospective, observational study, we enrolled 125 patients with COVID-19 who were died between January 13 and March 4, 2020 in Renmin Hospital of Wuhan University. A total of 414 randomly recruited patients with confirmed COVID-19 who were discharged from the same hospital during the same period served as control. The demographic, clinical characteristics and laboratory findings at admission, and treatment used in these patients were collected. The immunity-related risk factors associated with in-hospital death were tested by logistic regression models and Receiver Operating Characteristic (ROC) curve.

We recently reported that inhibitors against human dihydroorotate dehydrogenase (DHODH) have broad-spectrum antiviral activities including their inhibitory efficacies on SARS-CoV-2 replication in infected cells. However, there are limited data from clinical studies to prove the application of DHODH inhibitors in Coronavirus disease 2019 (COVID-19) patients. In the present study, we evaluated Leflunomide, an approved DHODH inhibitor widely used as a modest immune regulator to treat autoimmune diseases, in treating COVID-19 disease with a small-scale of patients. Cases of 10 laboratory-confirmed COVID-19 patients of moderate type with obvious opacity in the lung were included. Five of the patients were treated with Leflunomide, and another five were treated as blank controls without a placebo. All the patients accepted standard supportive treatment for COVID-19. The patients given Leflunomide had a shorter viral shedding time (median of 5 days) than the controls (median of 11 days, P = 0.046). The patients given Leflunomide also showed a significant reduction in C-reactive protein levels, indicating that immunopathological inflammation was well controlled. No obvious adverse effects were observed in Leflunomide-treated patients, and they all discharged from the hospital faster than controls. This preliminary study on a small-scale compassionate use of Leflunomide provides clues for further understanding of Leflunomide as a potential antiviral drug against COVID-19.

Highlights A high rate of asymptomatic SARS-CoV-2 carriers was found in healthcare workers. Asymptomatic individuals had lower antibody levels in the acute phase. Asymptomatic IgG titration reduced during the early convalescent phase.

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25–0.90; p = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11–0.45; p < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19–induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.

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In this study, we investigated the acute exacerbation and outcomes of COPD patients during the outbreak of COVID-19 and evaluated the prevalence and mortality of COPD patients with confirmed COVID-19. Methods: A prospectively recruited cohort of 489 COPD patients was retrospectively followed-up for their conditions during the COVID-19 pandemic from December 2019 to March 2020 in Hubei, China. In addition, the features of 821 discharged patients with confirmed COVID-19 were retrospectively analyzed. Results: Of the 489 followed-up enrolled COPD patients, 2 cases were diagnosed as confirmed COVID-19, and 97 cases had exacerbations, 32 cases of which were hospitalized, and 14 cases died. Compared with the 6-month follow-up results collected 1 year ago, in 307 cases of this cohort, the rates of exacerbations and hospitalization of the 489 COPD patients during the last 4 months decreased, while the mortality rate increased significantly (2.86% vs 0.65%, p=0.023). Of the 821 patients with COVID-19, 37 cases (4.5%) had pre-existing COPD. Of 180 confirmed deaths, 19 cases (10.6%) were combined with COPD. Compared to COVID-19 deaths without COPD, COVID-19 deaths with COPD had higher rates of coronary artery disease and/ or cerebrovascular diseases. Old age, low BMI and low parameters of lung function were risk factors of all-cause mortality for COVID-19 patients with pre-existing COPD. Conclusion: Our findings imply that acute exacerbations and hospitalizations of COPD patients were infrequent during the COVID-19 pandemic. However, COVID-19 patients with pre-existing COPD had a higher risk of all-cause mortality.

Objective To evaluate the efficacy and safety of leflunomide, an approved dihydroorotate dehydrogenase inhibitor, to treat COVID-19 patients with prolonged post-symptomatic viral shedding. Methods We conducted a prospective, randomized, controlled, open-label trial involving hospitalized adult COVID-19 patients with prolonged PCR positivity. Patients were randomly assigned to receive either leflunomide (50 mg, q12h, three consecutive times, orally; then 20 mg, once daily for 8 days), in addition to nebulized interferon alpha 2a (IFN α-2a, 3 million IU each time, twice daily for 10 days), or nebulized IFN α-2a alone for 10 days. The primary end point was the duration of viral shedding. Results A total of 50 COVID-19 patients with prolonged PCR positivity were randomized into 2 groups; 26 were assigned to the leflunomide group, and 24 were assigned to the interferon alone group. Treatment with leflunomide was not associated with a difference from the interferon alone group in the duration of viral shedding (hazard ratio for negative RT-PCR, 0.70; 95% confidence interval, 0.391-1.256; P=0.186). In addition, the patients given leflunomide did not have a substantially shorter length of hospital stay than patients treated with interferon alone, with median (IQRs) durations of 29.0 (19.3-47.3) days and 33.0 (29.3-42.8) days, respectively, P=0.170. Two leflunomide recipients were unable to complete the full 10-day course of administration due to adverse events. Conclusions In COVID-19 patients with prolonged PCR positivity, no benefit in terms of the duration of viral shedding was observed with the combined treatment of leflunomide and IFN α-2a beyond IFN α-2a alone.

The cases of two patients (a husband and wife) with thrombocytopenia syndrome (SFTS) are reported herein. Both patients had a history of recent tick bite and displayed typical clinical SFTS symptoms including fever, thrombocytopenia, and leukopenia. The diagnosis was laboratory-confirmed by the provincial Center for Disease Control and Prevention (CDC). The husband died while the wife survived. SFTS virus was eventually identified in ticks collected from the couple.