[Analyze the application rules and effects of "Four Elements, One Peptide, and Two Transplantations" based on bundle treatment in coronavirus disease 2019].

OBJECTIVE: To explore the application rules and effects of "Four Elements, One Peptide, and Two Transplantations" in the bundle treatment of the patients with coronavirus disease 2019 (COVID-19), so as to provide a scientific evidence for effective treatment and prevention of severe type. METHODS: A retrospective comparative study method was used to analyze the clinical data of COVID-19 patients admitted to Wuxi Fifth People's Hospital from January 2020 to March 2022, including demographic information, underlying diseases, clinical classification, length of hospital stay, treatment cost, clinical symptoms, laboratory tests and other key indicators, and evaluate the application rules and effect of "Four Elements, One Peptide, and Two Transplantations" in the bundle treatment of the patients with COVID-19. RESULTS: The L-type new coronavirus strain was predominant in 2020, the Delta variant in 2021, and the Omicron variant in 2022. The proportion of mild cases was highest in 2022, with the highest proportion of > 65 years old patients developing severe and critical. Among the 150 patients, the proportion of interferon use (100.0%) was the highest in the bundle treatment regimen of "Four Elements, One Peptide, and Two Transplantation". The combined use of vitamin C, interferon and thymopeptide was highest in 2022. More than 75.0% of the age > 65 years old group had underlying diseases, which was also the age group with the highest proportion of "Four Elements, One Peptide, and Two transplantations". Compared with mild cases, the age, length of hospital stay, and hospitalization cost of patients with COVID-19 increased significantly with severity. Mild, ordinary, severe, and critically ill patients all had low lymphocyte counts, with 40.0% of severe patients having the lowest lymphocyte counts within 3 days of admission. The lymphocyte count of critically ill patients was reduced or continuously reduced after admission, and the use of the "Four Elements, One Peptide, and Two transplantations" method to regulate immunity can effectively save the lives of critically ill patients. Of all cases of COVID-19 infection, 51.3% were asymptomatic, followed by respiratory symptoms (48.7%) and lung lesions (38.0%). Patients with renal dysfunction received this bundle therapy was highest, followed abnormal coagulation and abnormal liver function. This bundle therapy promoted a significant increase in CD4+ T lymphocytes and B lymphocytes in various cases. After treatment, as the virus turns negative, the proportion of M1 type macrophages increased, and the proportion of regulatory T cell (Treg cells) that suppress immunity and the infection related C-C chemokine receptor type (CCR10+) Treg cells decreased. Mild adult cases showed a great change and declined rapidly. CONCLUSIONS: Advanced age with underlying diseases is a risk factor for severe disease of COVID-19, the "Four Elements, One Peptide, and Two transplantations" bundle fine treatment of COVID-19 can improve the proportion of lymphocyte composition and organ function, which can control the occurrence and development of severe diseases. In addition to the proportion of CD4+ T cells, the changes of the M1 macrophage, total Treg cell, and CCR10+ Treg cell proportions can be used to determine disease changes of adult patients.

Nebulization Therapy with Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes for COVID-19 Pneumonia.

BACKGROUND: Scientists have been facing numerous challenges in the development of an effective therapeutic strategy for the treatment of COVID-19 pneumonia. Several studies have suggested that improving patient immunity and reducing lung injury induced by SARS-CoV-2 may be effective for treating patients with COVID-19. METHODS: A pilot trial of nebulization therapy with exosomes of mesenchymal stem cells (MSCs) was performed on seven patients with COVID-19 pneumonia. Exosomes secreted from MSCs were collected and purified using multiple ultrafiltration steps. All patients were treated with nebulization of MSC-derived exosomes, and primary safety and efficacy outcomes were evaluated. RESULTS: Our clinical study demonstrated that nebulization of MSC-derived exosomes is a novel method that might be utilized in the treatment of COVID-19 pneumonia. Nebulization of MSC-derived exosomes did not induce acute allergic or secondary allergic reactions but did promote the absorption of pulmonary lesions and reduce the duration of hospitalization for mild cases of COVID-19 pneumonia. CONCLUSIONS: Nebulization of MSC-derived exosomes is a safe, effective, and simple method, and their application at the beginning of treatment may be more beneficial. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030261. Registered on 26 February 2020.

Application of Non-Invasive Ventilator in Treatment of Severe COVID-19 Patients.

BACKGROUND: Since December 2019, there has been a global outbreak of COVID-19. As of the end of July 2020, more than 600,000 deaths had been reported globally. The purpose of this paper is to further explore the application of non-invasive ventilation in severe COVID-19 patients. METHODS: A retrospective study was conducted to included 57 confirmed COVID-19 patients, among which 36 cases were severe. According to different oxygen inhalation methods, they were divided into non-invasive ventilator assisted ventilation group with 21 cases (group A) and 15 cases of nasal catheter oxygen inhalation group (group B). The data of respiration (RR), heart rate (HR), partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), and oxygenation index (OI) before the treatment of noninvasive ventilator assisted ventilation or nasal catheter oxygen treatment at 24, 48, and 72 hours of treatment of the 2 groups were collected and analyzed to determine whether the above indicators were statistically different in each time period. RESULTS: After 24 hours of treatment with noninvasive ventilator assisted ventilation in group A, RR gradually decreased, PaO2 and OI were significantly higher than before treatment, while after 24 hours of treatment, PaO2, RR, HR and other indexes in group B showed no significant improvement, and OI increased gradually after 48 hours of treatment, with statistically significant difference compared with that before treatment. CONCLUSIONS: Early adoption of non-invasive ventilation can effectively improve the hypoxic state of patients with severe COVID-19. The combination of underlying diseases will not prolong the use of non-invasive ventilation.

A retrospective analysis from a single center for 60 COVID-19 patients with asymptomatic, mild to moderate, and severe conditions in Wuxi, China.

ABSTRACT: The aim of this study was to retrospectively analyze the clinical data of COVID-19 patients with different severity during February 2020 in Wuxi, China.The present retrospective study included a total of 60 cases who were diagnosed as COVID-19 patients and hospitalized in the Wuxi Fifth People's Hospital during February 2020 to March 2020. Among all patients 14 cases were asymptomatic, 25 cases were with mild stage, 13 cases were with moderate stage, and 8 cases were with severe stage. Basic clinical data as well as clinical characteristics, including temperature, respiratory rate, heart rate, blood gas analysis data, whole blood test data, and the prognosis condition, were collected and analyzed. Statistical analysis was conducted in different severity stage patients.Among the patients, the median temperature gradually increased from the asymptomatic to the severe patients and the median age increased from the mild to the severe patients with statistical difference. The hospitalization duration was the highest in severe patients. Higher heart rate, as well as lower oxygen partial pressure and oxygenation index were observed in severe patients than the other groups. Besides, higher CRP and globulin levels after admission were found in severe patients, and were gradually increased from the asymptomatic patients to the severe patients. On the contrary, the lymphocyte ratio and count was significant lower in severe patients. We also observed higher D-Dimer levels in the severe patients and the difference was statistical. Among all patients, 2 cases (3.33%) died and other patients were all cured after treatment.Statistical difference was mainly found mainly in age, hospitalization duration, temperature, CRP levels, O2 partial pressure and oxygenation index, globulin, lymphocyte ratio, and D-Dimer in patients with different severity. The higher CRP levels, lower O2 partial pressure and oxygenation index, higher globulin, lower lymphocyte ratio, and higher D-Dimer might be associated with the patients' severity.

Epidemiology and clinical re-positivity evaluation of SARS-CoV-2 cases in Wuxi

This study aimed to analyze the relationship between SARS-CoV-2 spreading and clinical classification to evaluate the transmission and pathogenicity characteristics of the local virus, and to understand the clinical characteristics of SARS-CoV-2 reactivation, on the basis of the clinical manifestations in Wuxi. We collected information on the SARS-CoV-2 positive cases admitted to The Fifth People's Hospital of Wuxi from January 23 to November 20, 2020. According to epidemiological and clinical characteristics, we analyzed the changes in the transmission and pathogenicity of the virus and the clinical manifestations of SARS-CoV-2 reactivation cases. The severe and critical COVID-19 cases appeared only before the second-generation, whereas the third-generation cases were all mild. The rate of severe illness in the second-generation (7.1%) was significantly lower than that in the first-generation (17.5%), and the overseas imported cases (n-generation cases) were asymptomatic and mild. The presence of antibodies (IgM and IgG) in partially asymptomatic and mild cases appeared to become negative. The clinical features of SARS-CoV-2 first-positive and reactivation cases showed that some cases (2/3) developed lung inflammation, but their blood clinical indicators were normal. The proportion of severe cases of SARS-CoV-2 infection in Wuxi has decreased gradually, and asymptomatic or mild cases may become a high-risk group of viral re-yang. Immunological indicators can help predict clinical re-positivity.

[Evaluation of the effects of immunotherapy and mesenchymal stem cells transplantation in the treatment of critically ill coronavirus disease 2019 patients].

OBJECTIVE: To analyze the immunotherapy and clinical characteristics of coronavirus disease 2019 (COVID-19) patients, and focus on exploring the effects of immunotherapy and mesenchymal stem cells (MSC) transplantation in the critically ill patients' treatment. METHODS: Fity-five COVID-19 patients were admitted to the Fifth People's Hospital of Wuxi from January 23rd to March 31st, 2020 as the research object. The demographic characteristics of the cases and the methods of immunotherapy were analyzed, focusing on the immunized indicators, positivity of pathogens and clinical indicators of critically ill COVID-19 patient, and the effects of immunotherapy and stem cell transplantation were evaluated. RESULTS: Aged, male and people with comorbidities were the main risk factors in the development of severe and critical COVID-19. All of confirmed COVID-19 cases (n = 55) had been treated with interferon-α (IFN-α), of which 81.8% (n = 45, mild and ordinary) of the patients were recovered, 14.6% (n = 8) of the patients were converted to severe, 3.6% (n = 2) of the patients were converted to critical, and some severe patients were treated with gamma globulin and albumin as adjuvant treatment. Critically ill patients were not only treated with IFN-α, gamma globulin and albumin, but also treated with convalescent plasma and MSC transplantation. Due to pulmonary hemorrhage and persistently low blood oxygen saturation, terminal lung transplantation therapy was implemented. The total number of lymphocytes, CD4+, CD8+ T lymphocytes, natural killer (NK) cells and B cells in peripheral blood of the two critical COVID-19 patients were significantly reduced, and the functions of lung, liver, and kidney were severely damaged on admission, manifested as significant increase of the levels of blood C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN), etc. and decrease of blood oxygen saturation, and type I respiratory failure, and the noninvasive assisted ventilation was needed to improve. After adjuvant immunotherapy such as gamma globulin, the nucleic acid of 2019 novel coronavirus (2019-nCoV) turned into negative. The CRP of one critically ill patient was significantly lower than the value at admission (minimum of 21 mg/L). But the lung inflammation progressed rapidly, and the pathological results of the lung tissue from the lung transplantation showed hemorrhage and irreversible fibrosis. The ability to secrete immunoglobulin A (IgA) was significantly reduced. Liver function had been significantly improved and stabilized after treatment with convalescent plasma during the recovery period. MSC transplantation treatment reduced the BUN level by > 50% compared with the previous period, and the total number of lymphocytes in the patient increased by more than 2 times (rose from 0.23×109/L to 0.57×109/L), but the total amount of lymphocytes was still lower than the normal reference value (< 1.1×109/L). The lung inflammation lesions were obviously absorbed, and the vital signs were stable. CONCLUSIONS: In addition to IFN, gamma globulin, antiserum and MSC transplantation therapy can help clear the virus and reduce inflammation. Although MSC transplantation fail to completely change the immunecompromised state of critically ill patients, it controlled the progression of inflammation in the liver and kidneys.

Clinical characteristics and outcomes of 48 patients hospitalized for COVID-19 infection in Wuxi: A retrospective cohort study.

ABSTRACT: Since the first infected case of Coronavirus Disease 2019 (COVID-19) was reported in Wuhan, China in December 2019, the virus has spread swiftly, inflicting upon millions of people around the globe. The objective of the study is to investigate and analyze the clinical characteristics and outcomes of patients infected with COVID-19 in Wuxi, China.Cross-sectional study.The Fifth People's Hospital of Wuxi, China.A total of 48 COVID-19 patients were enrolled in the study from 23 January 2020 to 8 March 2020, and the clinical data of these subjects were collected.Epidemiological, clinical, laboratory, and radiologic characteristics, as well as treatment and outcome data, were collected and analyzed.Of these 48 patients with confirmed COVID-19, 3 were mild cases (6.3%), 44 were moderate cases (91.7%), 1 was severe case (2.1%). The median age of the subjects was 45 years (interquartile range [IQR], 24-59; range, 5-75 years). Twenty-five of the patients (52.1%) were male and 23 (47.9%) were female. Twenty-eight cases (58.3%) returned to Wuxi, Jiangsu Province. Thirty-four (70.8%) cases were infected due to clustering epidemic and 29 cases (85.3%) were attributable to family-clustering epidemic. No obvious clinical symptoms were observed in the cohort of patients, except for 3 mild cases. The most common symptoms include fever (41 [85.4%]), cough (28 [58.3%]), asthenia (13 [27.1%]), expectoration (11 [22.9%]), diarrhea (10 [20.8%]), and dyspnea (5 [10.4%]). Seventeen (35.4%) patients had lower lymphocyte values than baseline, 31 patients (64.6%) had higher d-dimers to exceed the normal range. The distribution of high-resolution computed tomography (HRCT)-positive lesions were as follows: left lung in 5 cases (10.4%), right lung in 9 cases (18.8%), and bilateral lungs in 31 cases (64.6%). In terms of density of lesions: 28 cases (58.3%) showed ground glass shadows in the lung, 7 cases (14.6%) showed solid density shadows, and 10 cases (20.8%) showed mixed density shadows. Extrapulmonary manifestations found that mediastinal lymph nodes were enlarged in 2 cases (4.2%) and that pleural effusion was present in 1 case (2.1%). All patients underwent treatment in quarantine. Forty-five (93.8%) patients received antiviral treatments, 22 (45.8%) patients received antibacterial treatments, 6 (12.5%) patients received glucocorticoid treatments, 2 (4.2%) patients received high flow oxygen inhalation treatments, and 6 (12.5%) patients received noninvasive ventilation treatments. As of 8 March 2020, all 48 patients included in this study were cured. The average time of hospitalization of the 48 patients was 18 ±â€Š6 (mean ±â€ŠSD) days, the average time of the lesion resorption was 11 ±â€Š4 days, and the average time taken to achieve negativity in the result of nucleic acid examination was (10 ±â€Š4) days.The epidemiological characteristics of 48 COVID-19 patients in Wuxi were mainly imported cases and clustered cases. The clinical manifestations of these patients were mainly fever and cough. Laboratory results showed that the lymphocytopenia and increased d-dimer are positively correlated with disease severity. Pulmonary imaging showed unilateral or bilateral ground glass infiltration. Most of the patients entered clinical recovery stage within 15 days after hospitalization.