Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18.

The ongoing global pandemic of COVID-19 disease, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly infect lung epithelial cells, and spread mainly through respiratory droplets. However, recent studies showed potential intestinal infection of SARS-CoV-2, implicated the possibility that the intestinal infection of SARS-CoV-2 may correlate with the dysbiosis of gut microbiota, as well as the severity of COVID-19 symptoms. Here, we investigated the alteration of the gut microbiota in COVID-19 patients, as well as analyzed the correlation between the altered microbes and the levels of intestinal inflammatory cytokine IL-18, which was reported to be elevated in the serum of in COVID-19 patients. Comparing with healthy controls or seasonal flu patients, the gut microbiota showed significantly reduced diversity, with increased opportunistic pathogens in COVID-19 patients. Also, IL-18 level was higher in the fecal samples of COVID-19 patients than in those of either healthy controls or seasonal flu patients. Moreover, the IL-18 levels were even higher in the fecal supernatants obtained from COVID-19 patients that tested positive for SARS-CoV-2 RNA than those that tested negative in fecal samples. These results indicate that changes in gut microbiota composition might contribute to SARS-CoV-2-induced production of inflammatory cytokines in the intestine and potentially also to the onset of a cytokine storm.

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

Long-term application of hydroxychloroquine could not prevent the infection of COVID-19.

INTRODUCTION: Current pandemic of the coronavirus induced disease 2019 (COVID-19) presents an urgent issue to the world due to lack of vaccine and medication. Hydroxychloroquine (HCQ) has generated a lot of controversies whether it is effective in prevention and treatment of COVID-19. Current report presents a 63-year-old woman who has taken HCQ for many years but still infected by COVID-19. CASE PRESENTATION: A patient with rheumatoid arthritis came to the clinic with fever and sore throat. The patient has been treated with 200 mg HCQ per day since 2016. Laboratory tests showed that the patient had lymphopenia, increased levels of high-sensitive C-reactive protein (hs-CRP) and serum Interleukin-6 (IL-6). Chest radiography showed that the patient had pneumonia. Throat swab test confirmed COVID-19 positive. On admission, she was treated with nebulized interferon alfa-2b, oral Lopinavir/Ritonavir, and ceftriaxone sodium for the COVID-19 in addition to HCQ. The patient stayed in hospital for 18 days, recovered from oxygen intake, and eventually discharged from hospital. Follow up investigation showed the patient developed antibody against COVID-19. CONCLUSIONS: Long-term application of HCQ could not prevent COVID-19 infection, but whether HCQ exerts benefit to alleviation of clinical symptoms and duration of hospital stays remains to be further investigated.

[Analysis of gastrointestinal symptoms in 80 patients with coronavirus disease 2019].

OBJECTIVE: To investigate the clinical characteristics of gastrointestinal symptoms in patients with coronavirus disease 2019 (COVID-19) during the whole disease process, and provide reference for etiological diagnosis and treatment. METHODS: The clinical data of patients with COVID-19 admitted in the Infectious Diseases Branch of the First Affiliated Hospital of University of Science and Technology of China from January 22nd, 2020 to March 8th, 2020 were analyzed retrospectively. According to whether there were gastrointestinal symptoms (poor appetite, nausea/vomiting and diarrhea), all patients were divided into gastrointestinal symptom group and asymptomatic group. The characteristics of gastrointestinal symptoms, such as poor appetite, nausea, vomiting and diarrhea were counted and analyzed, and the correlation between gastrointestinal symptoms and gender, age, basic diseases, disease severity, laboratory examination and drug treatment were analyzed. RESULTS: A total of 80 COVID-19 patients were involved, 43 cases (53.8%) presented with poor appetite, 17 cases (21.3%) had nausea and vomiting, and 33 cases (41.3%) had diarrhea. Among them, 5 cases, 1 case and 4 cases respectively preformed poor appetite, nausea/vomiting and diarrhea before admission, while the others experienced gastrointestinal symptoms within 48 hours after admission. Duration of poor appetite, nausea/vomiting and diarrhea (days) of all patients were 5.3±2.1, 2.2±1.0 and 1.4±0.9, respectively. The patients with poor appetite were older than those without symptoms (years old: 48.2±17.6 vs. 39.3±15.1), albumin (Alb) level and the lymphocytes ratio were lower than those in asymptomatic group [Alb (g/L): 39.8 (35.7, 45.1) vs. 46.1 (42.6, 49.4), lymphocytes ratio: 0.19 (0.09, 0.28) vs. 0.28 (0.17, 0.35)], while the neutrophil ratio, the levels of C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) were higher than those in asymptomatic group [the neutrophil ratio: 0.74 (0.61, 0.85) vs. 0.64 (0.52, 0.76), CRP (mg/L): 21.4 (3.9, 52.9) vs. 5.6 (2.4, 14.0), D-dimer (mg/L): 0.2 (0.2, 0.5) vs. 0.2 (0.1, 0.3), LDH (µmol×s-1×L-1): 4.49 (3.59, 5.19) vs. 3.12 (2.77, 4.90)]; at the same time, more traditional Chinese medicine was used in the patients with gastrointestinal symptoms [65.1% (28/43) vs. 40.5% (15/37), all P < 0.05]. In addition, 14 cases of 18 patients with cardiovascular diseases presented with poor appetite, 7 patients had nausea and vomiting symptoms. All of the 3 patients with chronic kidney disease presented with poor appetite, nausea and vomiting, and 2 of them had diarrhea. CONCLUSIONS: The gastrointestinal symptoms in patients with COVID-19 are common. Whether it is caused by the virus or related drugs, diet and mental conditions, clinicians should analyze the causes of these symptoms timely, and then provide a better treatment for patients with COVID-19.

Effective treatment of severe COVID-19 patients with tocilizumab.

After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People's Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.