The Effects of a Comprehensive Rehabilitation Program Involving Traditional Chinese Medicine in Severe and Critical COVID-19 Patients: a Clinical Study (preprint)

Background: A year ago, a new type of coronavirus emerged. Once treated for severe and critical COVID-19 infections, patients are discharged from the hospital for further treatment and rehabilitation. The aim of this study was to  evaluate the efficacy and safety of a newly developed comprehensive rehabilitation program based on traditional Chinese medicine (TCM) in the rehabilitation of patients with severe and critical COVID-19.Methods: We recruited a total of 72 patients who had suffered from severe and critical COVID-19 infections and were undergoing rehabilitation in Chongqing, China. A comprehensive rehabilitation program was formulated according to the TCM syndromes of these patients. Specific treatments included oral TCM, Baduanjin, Moxibustion, Acupoint application, and foot baths. Prior to the initiation of treatment, and four weeks after the initiation of treatment, we carried out a range of assessments, including the TCM Syndrome curative effect score, the modified Medical Research Council (mMRC) dyspnea score, the St. George's Respiratory Questionnaire, the Short Form (SF)-36 Quality of Life Scale, and the 6-minute walking test. We also carried out CT scans, serology tests. Statistical analysis was also conducted to evaluate the efficacy and safety of TCM on severe and critical COVID-19 patients.Results: Analysis showed that there were significant differences (P < 0.05) when compared before and after four weeks of TCM treatment, in terms of the TCM syndrome curative effect score, mMRC dyspnea score, St. George's Respiratory Questionnaire score, SF-36 Quality of Life Scale score, and the 6-minute walking test. We also identified significant differences (P < 0.05) between these two timepoints, with regards to the neutrophil ratio, lymphoid cell ratio, lymphocytes, platelets, red blood cells, and hemoglobin. There were no significant differences when compared between the two timepoints with regards to white blood cells and neutrophils (P > 0.05). The efficacy of chest CT scans was 83.9%. Logistic regression showed that the CT scans of patients who did not take the TCM decoction did not improve significantly. The higher a patient’s score on the 6-minute walking test, the higher the probability of no significant improvement on the CT scan.Conclusions: A comprehensive rehabilitation program based on TCM improved a number of clinical parameters in patients suffering from severe and critical COVID-19 infections, including quality of life, clinical symptoms, exercise endurance, and respiratory function. TCM also enhanced lymphocytes, lymphocyte ratio, platelet, red blood cell (RBC) count, and hemoglobin content. TCM also appeared to contribute to the absorption of lung lesions.

Effects of Early Physical and Pulmonary Rehabilitation for Severely and Critically ill COVID-19 Patients: A Retrospective, Cohort, and Multicenter Study (preprint)

BackgroundEffects of early rehabilitation therapy in severe and critical COVID-19 patients remains to be elucidated. MethodsWe recruited 80 severely and critically ill COVID-19 patients in Chongqing from January 21 to March 15, 2020, who had received rehabilitation therapies or standard treatments within 72 h of intensive care unit (ICU) admission. We analyzed mortality rates, length of stay in the ICU and hospital, ventilator-free days, and adverse events during hospitalization. Respiratory function, independent functional status, muscle strength, exercise capacity and life quality were measured at hospital discharge and during a three-month follow-up. ResultsWe found no significant differences between the intervention and control groups in terms of ICU, hospital, and 28-day mortality rates, and lengths of stay in the ICU and hospital. Additionally, early rehabilitation enhanced the duration of ventilator-free days, with no increased adverse events and complications. Total lung capacity and carbon monoxide diffusion capacity, Barthel index, and functional independence measure for patients in the intervention group were all higher than those in the control group at hospital discharge and one month after discharge. Compared to the control group, patients in the intervention group had significantly higher Medical Research Council scores and greater walking distance capacities within 6 min at hospital discharge, as well as one month and three months after discharge. The St. George's Respiratory Questionnaire score was lower in the intervention group than in the control group at one month and three months after hospital discharge.ConclusionsEarly physical and pulmonary rehabilitation is safe and effective for severely and critically ill COVID-19 patients to promote their functional, physical, and psychological recovery.

A follow-up study of children infected with SARS-CoV-2 from Western China (preprint)

Background: To clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children. Methods: A total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in Western China were enrolled in this study and followed up until discharge and quarantine 14 days later. Results: Eleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD=7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test. Conclusions: Children with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.

Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). To date, no prophylactic vaccines or approved therapeutic agents are available for preventing and treating this highly transmittable disease. Here we report two monoclonal antibodies (mAbs) cloned from memory B cells of patients recently recovered from COVID-19, and both mAbs specifically bind to the spike (S) protein of SARS-CoV-2, block the binding of receptor binding domain (RBD) of SARS-CoV-2 to human angiotensin converting enzyme 2 (hACE2), and effectively neutralize S protein-pseudotyped virus infection. These human mAbs hold the promise for the prevention and treatment of the ongoing pandemic of COVID-19.

Potential Factors for Prediction of Disease Severity of COVID-19 Patients (preprint)

ObjectiveCoronavirus disease 2019 (COVID-19) is an escalating global epidemic caused by SARS-CoV-2, with a high mortality in critical patients. Effective indicators for predicting disease severity in SARS-CoV-2 infected patients are urgently needed. MethodsIn this study, 43 COVID-19 patients admitted in Chongqing Public Health Medical Center were involved. Demographic data, clinical features, and laboratory examinations were obtained through electronic medical records. Peripheral blood specimens were collected from COVID-19 patients and examined for lymphocyte subsets and cytokine profiles by flow cytometry. Potential contributing factors for prediction of disease severity were further analyzed. ResultsA total of 43 COVID-19 patients were included in this study, including 29 mild patients and 14 sever patients. Severe patients were significantly older (61.9{+/-}9.4 vs 44.4{+/-}15.9) and had higher incidence in co-infection with bacteria compared to mild group (85.7%vs27.6%). Significantly more severe patients had the clinical symptoms of anhelation (78.6%) and asthma (71.4%). For laboratory examination, 57.1% severe cases showed significant reduction in lymphocyte count. The levels of Interluekin-6 (IL6), IL10, erythrocyte sedimentation rate (ESR) and D-Dimer (D-D) were significantly higher in severe patients than mild patients, while the level of albumin (ALB) was remarkably lower in severe patients. Further analysis demonstrated that ESR, D-D, age, ALB and IL6 were the major contributing factors for distinguishing severe patients from mild patients. Moreover, ESR was identified as the most powerful factor to predict disease progression of COVID-19 patients. ConclusionAge and the levels of ESR, D-D, ALB and IL6 are closely related to the disease severity of COVID-19 patients. ESR can be used as a valuable indicator for distinguishing severe COVID-19 patients in early stage, so as to increase the survival of severe patients.

Epidemiological and clinical features of 2019-nCoV acute respiratory disease cases in Chongqing municipality, China: a retrospective, descriptive, multiple-center study (preprint)

BackgroundIn January 19, 2020, first case of 2019 novel coronavirus (2019-nCoV) pneumonia (COVID-19) was confirmed in Chongqing municipality, China. MethodsIn this retrospective, descriptive, multiple-center study, total of 267 patients with COVID-19 confirmed by real-time RT-PCR in Chongqing from Jan 19 to Feb 16, 2020 were recruited. Epidemiological, demographic, clinical, radiological characteristics, laboratory examinations, and treatment regimens were collected on admission. Clinical outcomes were followed up until Feb 16, 2020. Results267 laboratory-confirmed COVID-19 patients admitted to 3 designated-hospitals in Chongqing provincial municipality from January 19 to February 16, 2020 were enrolled and categorized on admission. 217 (81.27%) and 50 (18.73%) patients were categorized into non-severe and severe subgroups, respectively. The median age of patients was 48.0 years (IQR, 35.0-65.0), with 129 (48.3%) of the patients were more than 50 years of age. 149 (55.8%) patients were men. Severe patients were significantly older (median age, 71.5 years [IQR, 65.8-77.0] vs 43.0 years [IQR, 32.5-57.0]) and more likely to be male (110 [50.7%] vs 39 [78.0%]) and have coexisting disorders (15 [30.0%] vs 26 [12.0%]). 41 (15.4%) patients had a recent travel to Hubei province, and 139 (52.1%) patients had a history of contact with patients from Hubei. On admission, the most common symptoms of COVID-19 were fever 225(84.3%), fatigue (208 [77.9%]), dry cough (189 [70.8%]), myalgia or arthralgia (136 [50.9%]). Severe patients were more likely to present dyspnea (17 [34.0%] vs 26 [12.0%]) and confusion (10 [20.0%] vs 15 [6.9%]). Rales (32 [12.0%]) and wheezes (20 [7.5%]) are not common noted for COVID-19 patients, especially for the non-severe (11 [5.1%], 10 [4.6%]). 118 (44.2%). Most severe patients demonstrated more laboratory abnormalities. 231 (86.5%), 61 (22.8%) patients had lymphopenia, leukopenia and thrombocytopenia, respectively. CD4+T cell counts decrease was observed in 77.1 % of cases, especially in the severe patients (45, 100%). 53.1% patients had decreased CD+3 T cell counts, count of CD8+T cells was lower than the normal range in part of patients (34.4%). More severe patients had lower level of CD4+ T cells and CD+3 T cells (45 [100.0%] vs 29[56.9%], 31 [68.9%] vs 20 [39.2%]). Most patients had normal level of IL-2, IL-4, TNF- and INF-{gamma}, while high level of IL-6 and IL-17A was common in COVID-19 patients (47 [70.1%], 35 [52.2%]). Level of IL-6, IL-17A and TNF- was remarkably elevated in severe patients (32 [84.2%] vs 15 [51.7%], 25 [65.8%] vs 10 [34.5%], 17 [44.7%] vs 5 [17.2%]). All patients received antiviral therapy (267, 100%). A portion of severe patients (38, 76.0%) received systemic corticosteroid therapy. Invasive mechanical ventilation in prone position, non-invasive mechanical ventilation, high-flow nasal cannula oxygen therapy was adopted only in severe patients with respiratory failure (5[10.0%], 35[70.0%], 12[24.0%]). Traditional Chinese medicine was adopted to most of severe patients (43,86.0%). Conclusion:Our study firstly demonstrated the regional disparity of COVID-19 in Chongqing municipality and further thoroughly compared the differences between severe and non-severe patients. The 28-day mortality of COVID-19 patients from 3 designed hospitals of Chongqing is 1.5%, lower than that of Hubei province and mainland China including Hubei province. However, the 28-mortality of severe patients was relatively high, with much higher when complications occurred. Notably, the 28-mortality of critically severe patients complicated with severe ARDS is considerably as high as 44.4%. Therefore, early diagnosis and intensive care of critically severe COVID-19 cases, especially those combined with ARDS, will be considerably essential to reduce mortality.