A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling.

Although vaccines have been developed, mutations of SARS-CoV-2, especially the dominant B.1.617.2 (delta) and B.1.529 (omicron) strains with more than 30 mutations on their spike protein, have caused a significant decline in prophylaxis, calling for the need for drug improvement. Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms. The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments, providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies. A total of 128 sequences were obtained after sequencing 196 memory B cells, and 42 sequences were left after merging extremely similar ones and discarding incomplete ones, followed by homology modeling of the antibody variable region. Thirteen candidate sequences were expressed, of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants. The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.

Characteristics of 12-Month Readmission for Hospitalized Patients with COPD: A Propensity Score Matched Analysis of Prospective Multicenter Study.

Purpose: Hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is considered as severe exacerbations. Readmission for severe exacerbations is a crucial event for COPD patients. However, factors associated with readmission for severe exacerbations are incomplete. The study aimed to investigate different characteristics between the severe and non-severe exacerbation groups. Patients and Methods: Patients hospitalized for severe AECOPD were included in multi-centers, and their exacerbations in next 12 months after discharge were recorded. According to exacerbations, patients were separated into the severe-exacerbation group and the non-severe exacerbation group. Propensity-score matching (PSM) and multivariable analyses were performed to compare the baseline characteristics of two groups. The Hosmer-Lemeshow test and receiver operating characteristic curve were applied to evaluate how well the model could identify clusters. Results: The cohort included 550 patients with severe AECOPD across 27 study centers in China, and 465 patients were finally analyzed. A total of 41.5% of patients underwent readmission for AECOPD within 1 year. There were no significant differences in baseline characteristics between groups after PSM. Severe exacerbations in the 12 months were related to some factors, eg, the duration of COPD (13 vs 8 years, P<0.001), the COPD Assessment Test (CAT) score (20 vs 17, P<0.001), the blood eosinophil percentage (1.5 vs 2.0, P<0.05), and their inhaler therapies. Patients readmitted with AECOPD had a longer time of diagnosis (≥9 years), more symptoms (CAT ≥10), and lower blood eosinophils (Eos <2%). A clinical model was derived to help identify patients at risk of readmission with severe exacerbations. Conclusion: These analyses confirmed the relevance of COPD at admission with future severe exacerbations. A lower blood eosinophils percentage appears to be related to readmission when combined with clinical history. Further studies are needed to evaluate whether this study can predict the risk of exacerbations.

Current status of prevention and treatment of respiratory diseases in primary care in China: a cross-sectional study.

BACKGROUND: China launched its new round of health care reform to develop primary care in 2009, establishing 954,390 primary care institutions that employed over 10 million staff by 2019. However, some studies have shown that the prevention and management of respiratory diseases is inadequate in these institutions. METHODS: We conducted a cross-sectional survey of grassroots institutions throughout China between September and December 2020 based on the standardized Prevention and Treatment System and Capacity Building Project of Respiratory Diseases in primary care settings. The operation of the respiratory department in primary health care institutions was evaluated in terms of facilities, drugs, personnel and management of chronic diseases by means of questionnaires. Descriptive analyses were performed to calculate percentages and frequencies of key parameters. RESULTS: A total of 144 primary health care institutions were surveyed, including 51 in the east, 82 in the west, 9 in the central and 2 in the northeast. Approximately 60% of institutions had spirometers and pulse oximeters. The majority had short-acting bronchodilators, theophylline, systemic corticosteroids, antibiotics, and traditional Chinese medicine. More than half had at least one respiratory physician and operator for spirometry. Half of the institutions carried out screening of chronic obstructive pulmonary disease within the jurisdiction. The institutions in the east were superior to those in the west regarding the equipment, common drugs, medical staff, and management of respiratory diseases. CONCLUSIONS: The study reveals that the overall operation of the respiratory department in primary care settings needs to be further strengthened. It is crucial to provide adequate essential equipment, medical professionals, and medicines for proper diagnosis and treatment of chronic respiratory diseases, as well as improving the management of diseases.

One-year follow-up study after patients with severe COVID-19 received human umbilical cord mesenchymal stem cells treatment.

BACKGROUND: The novel coronavirus is still mutating, and the pandemic continues. Meanwhile, many COVID-19 survivors have residual postinfection clinical manifestations. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been shown to be effective in the early stages of COVID-19. OBJECTIVES: The aim of this study was to investigate long-term safety and efficacy of treatment in patients with severe COVID-19 patients who had received hUC-MSCs therapy. METHODS: Twenty-five discharged patients who had severe COVID-19 (including the standard treatment group and the standard treatment plus hUC-MSCs group) were enrolled in a 1-year follow-up. The assessment considered adverse effects (including effects on liver and kidney function, coagulation, ECG, tumor marker, and so on), pulmonary function, St George's Respiratory Questionnaire (SGRQ), postinfection sequelae and serum concentration of Krebs von den Lungen-6 (KL-6), malondialdehyde (MDA), H2S, carnitine, and N-6 long-chain polyunsaturated fatty acids (N-6 LC-PUFAs). MEASUREMENTS AND MAIN RESULTS: Pulmonary ventilation function had significantly improved at the 1-year follow-up in both the hUC-MSCs group and the control group compared with the 3-month follow-up (P < 0.01). Fatigue (60% [15/25]) remained the most common symptom at the 1-year follow-up. The rate of fatigue relief was significantly reduced in the hUC-MSCs group (25% [2/8]) compared to the control group (76.5% [13/17]) (P = 0.028). The level of KL-6 was significantly lower in the hUC-MSCs group (2585.5 ± 186.5 U/ml) than in the control group (3120.7 ± 158.3 U/ml) (P < 0.001). Compared with the control group, the hUC-MSCs group had a lower level of MDA (9.27 ± 0.54 vs. 9.91 ± 0.72 nmol/ml, P = 0.036). No obvious adverse effects were observed in the hUC-MSCs treatment group at 1 year after discharge. CONCLUSIONS: Intravenous transplantation of hUC-MSCs was a safe approach in the long term in the treatment of patients with severe COVID-19. In addition, hUC-MSCs had a positive effect on postinfection sequelae in COVID-19 survivors. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered 02 April 2020-Retrospectively registered, http://www.medresman.org.

Human Umbilical Cord Mesenchymal Stromal Cell Treatment of Severe COVID-19 Patients: A 3-Month Follow-Up Study Following Hospital Discharge.

Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 (COVID-19) patients. In this 3-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the health-related quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after 3 months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88% ± 8.46% and 59.45% ± 27.45% in the hUC-MSC and control groups (P < 0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95% ± 8.00% and 58.97% ± 19.16% in the hUC-MSC and control groups, respectively (P < 0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25 ± 3.69 vs. 31.9 ± 8.78, P < 0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P < 0.05). There were no significant differences in CT scores between the two groups (0.60 ± 0.88 vs. 1.00 ± 1.31, P = 0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating relative safety and preliminary efficacy of this treatment for patients with severe COVID-19.

Abnormal Coagulation Function of Patients With COVID-19 Is Significantly Related to Hypocalcemia and Severe Inflammation.

This study aimed to detect, analyze, and correlate the clinical characteristics, blood coagulation functions, blood calcium levels, and inflammatory factors in patients with mild and severe COVID-19 infections. The enrolled COVID-19 infected patients were from Wuhan Jin Yin-tan Hospital (17 cases, Wuhan, China), Suzhou Infectious Disease Hospital (87 cases, Suzhou, China), and Xuzhou Infectious Disease Hospital (14 cases, Xuzhou, China). After admission, basic information was collected; X-ray and chest CT images were obtained; and data from routine blood tests, liver and kidney function, myocardial enzymes, electrolytes, blood coagulation function, (erythrocyte sedimentation rate) ESR, C-reactive protein (CRP), IL-6, procalcitonin (PCT), calcitonin, and other laboratory tests were obtained. The patients were grouped according to the clinical classification method based on the pneumonia diagnosis and treatment plan for new coronavirus infection (trial version 7) in China. The measurements from mild (56 cases) and severe cases (51 cases) were compared and analyzed. Most COVID-19 patients presented with fever. Chest X-ray and CT images showed multiple patchy and ground glass opacities in the lungs of COVID 19 infected patients, especially in patients with severe cases. Compared with patients with mild infection, patients with severe infection were older (p = 0.023) and had a significant increase in AST and BUN. The levels of CK, LDH, CK-MB, proBNP, and Myo in patients with severe COVID-19 infection were also increased significantly compared to those in patients with mild cases. Patients with severe COVID-19 infections presented coagulation dysfunction and increased D-dimer and fibrin degradation product (FDP) levels. Severe COVID-19 patients had low serum calcium ion (Ca2+) concentrations and high calcitonin and PCT levels and exhibited serious systemic inflammation. Ca2+ in COVID-19 patients was significantly negatively correlated with PCT, calcitonin, D-dimer, PFDP, ESR, CRP and IL-6. D-dimer in COVID-19 patients was a significantly positively correlated with CRP and IL-6. In conclusion, patients with severe COVID-19 infection presented significant metabolic dysfunction and abnormal blood coagulation, a sharp increase in inflammatory factors and calcitonin and procalcitonin levels, and a significant decrease in Ca2+. Decreased Ca2+ and coagulation dysfunction in COVID-19 patients were significantly correlated with each other and with inflammatory factors.

Clinical characteristics of moderate COVID-19 patients aggravation in Wuhan Stadium Cabin Hospital: A 571 cases of retrospective cohort study.

To report the clinical characteristics and potential risk factors of patients with coronavirus disease 2019 (COVID-19) in Wuhan Stadium Cabin Hospital in Hubei Province. A total of 571 patients of COVID-19 treated in the Wuhan Stadium Cabin Hospital were selected for analysis, univariable and multivariable logistic regression methods were used to explore the risk factors associated with disease aggravation. The main clinical symptoms of moderate COVID-19 were fever, cough and dyspnea, hypertension, diabetes, and coronary heart diseases were the main comorbidities both in transferred and stable patients. Twenty-six patients (4.55%) of mild and moderate patients had disease aggravation, and most of which occurred between 36 and 48 hours after admission. Multiple regression analysis showed increasing odds of disease aggravation associated with former smoker history, diabetes, dyspnea, consolidation, and interstitial abnormalities of computed tomography scanning, lymphopenia and elevated of C-reactive protein, the time points of transferred patients mainly between 36 and 48 hours (65.38%), and the average hospital stay for stable patients was 15 days.It could help clinicians to identify patients with poor prognosis at an early stage, and provide early warning role for timely intervention.

Carcinoembryonic Antigen: A Potential Biomarker to Evaluate the Severity and Prognosis of COVID-19.

Background and Objectives: Corona Virus Disease 2019 (COVID-19) has become a serious pandemic disease worldwide. Identification of biomarkers to predict severity and prognosis is urgently needed for early medical intervention due to high mortality of critical cases with COVID-19. This retrospective study aimed to indicate the values of carcinoembryonic antigen (CEA) in evaluating the severity and prognosis of COVID-19. Methods: We included 46 death cases from intensive care unit and 68 discharged cases from ordinary units with confirmed COVID-19 of Wuhan Jin Yin-tan Hospital from January 1 to March 22, 2020. Laboratory and radiologic data were analyzed retrospectively. All patients were followed up until April 10, 2020. Results: COVID-19 patients in the death group had significantly higher CEA levels (ng/ml) than discharged group (14.80 ± 14.20 vs. 3.80 ± 2.43, P < 0.001). The risk of COVID-19 death increased 1.317 times for each additional 1 ng/ml CEA level (OR = 1.317, 95% CI: 1.099-1.579). The standardized and weighted receiver operating characteristic curve (ROC) analysis adjusted to age, sex, and ferritin levels suggested that the area under the curve (AUC) of the serum CEA levels was 0.808 in discrimination between death cases and discharged cases with COVID-19 (P < 0.001). We found mortality of COVID-19 is associated with elevated CEA levels increased (HR = 1.023, 95% CI: 1.005-1.042), as well as age (HR = 1.050, 95% CI: 1.016-1.086) and ferritin levels (HR = 1.001, 95% CI: 1.001-1.002) by survival analysis of Cox regression model. Among discharged patients, CEA levels were significant lower in moderate cases compared to the severe and critical cases (P = 0.005; OR = 0.488, 95% CI: 0.294-0.808) from binary logistic regression analysis. The AUC of CEA levels was 0.79 in distinguishing moderate cases from discharged COVID-19 patients by standardized and weighted ROC analysis (P < 0.001). A positive correlation between CEA levels and CT scores existed in discharged patients (Correlation Coefficient: 0.687; P < 0.001). Conclusions: Elevated CEA levels increased the risk of death from COVID-19 and CEA levels were related to CT scores of the discharged patients positively.

Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells.

BACKGROUND: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. OBJECTIVES: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. METHODS: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. MEASUREMENTS AND MAIN RESULTS: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. CONCLUSIONS: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org.