Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102). METHODS: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). FINDINGS: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. INTERPRETATION: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. FUNDING: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).

Characteristics of cardiac injury complicating with acute kidney injury and mortality risk in coronavirus disease 2019 (COVID-19) patients

Objectives: This study aimed to identify the clinical features of cardiac injury complicating with acute kidney injury (AKI) and its risk for a fatal outcome in patients infected with coronavirus disease 2019 (COVID-19) pneumonia. Methods: Initial signs and symptoms and clinical laboratory, radiological, and treatment information were obtained from seven hospitals in China from January 23, 2020, to March 15, 2020. Results: Of 438 patients, 36 (8.22%) displayed isolated cardiac injury, 17 (3.88%) had isolated AKI, and 17 (3.88%) displayed cardiac injury complicating with AKI. Compared with patients without cardiac injury or AKI, patients with isolated cardiac injury, isolated AKI, and cardiac injury complicating with AKI were older (55, 65, 74 vs. 48 years, P < 0.0001) and critically severe. More patients displayed fatigue, dyspnea, and comorbidities in the group with cardiac injury complicating with AKI. Moreover, the indexes reflecting myocardial, renal, liver, and coagulation dysfunctions and infection-related factors were significantly different among the four groups. After adjustment for covariates, patients with cardiac injury complicating with AKI had a higher hazard ratio for mortality (6.64;95% confidence interval, 1.51–29.30). Conclusion: Cardiac injury complicating with kidney injury significantly increased the risk for in-hospital mortality in COVID-19 pneumonia patients. Therefore, early detection at admission and careful monitoring of myocardial and renal injury through biomarkers during hospitalization is recommended to reduce the harm to patients.

Mortality risk analysis for patients with severe coronavirus disease 2019 pneumonia

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is currently a global pandemic. Information about predicting mortality in severe COVID-19 remains unclear. METHODS: A total of 151 COVID-19 in-patients from January 23 to March 8, 2020, were divided into severe and critically severe groups and survival and mortality groups. Differences in the clinical and imaging data between the groups were analyzed. Factors associated with COVID-19 mortality were analyzed by logistic regression, and a mortality prediction model was developed. RESULTS: Many clinical and imaging indices were significantly different between groups, including age, epidemic history, medical history, duration of symptoms before admission, routine blood parameters, inflammatory-related factors, Na+, myocardial zymogram, liver and renal function, coagulation function, fraction of inspired oxygen and complications. The proportions of patients with imaging Stage III and a comprehensive computed tomography score were significantly increased in the mortality group. Factors in the prediction model included patient age, cardiac injury, acute kidney injury, and acute respiratory distress syndrome. The area under the receiver operating characteristic curve of the prediction model was 0.9593. CONCLUSIONS: The clinical and imaging data reflected the severity of COVID-19 pneumonia. The mortality prediction model might be a promising method to help clinicians quickly identify COVID-19 patients who are at high risk of death.

Clinical Value of COVID-19 Chest Radiography and High-Resolution CT Examination.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) pneumonia remains a matter of concern. Chest CT findings of COVID-19 pneumonia have been reported widely, while there is relatively rare research on chest X-ray (CXR). OBJECTIVE: The study was aimed to compare the CXR and chest CT findings of patients with confirmed COVID-19 infection and to explore their respective clinical values. METHODS: 28 inpatients with COVID-19 pneumonia who underwent both CXR and CT were included. The pulmonary manifestations of the lesions were recorded. Ground-glass opacity (GGO), consolidation, and fibrosis were quantified in CXR and chest CT separately. Consistency was analyzed using Fleiss' kappa and intraclass correlation coefficient. The stages of the disease in CXR and chest CT were evaluated. RESULTS: Approximately 67.9% (19/28) of subjects had abnormal findings on CXR. The common manifestations in CXR were ground-glass opacities (GGO) (100%, 19/19) and consolidation (68.4%, 13/19). 92.9% (26/28) of patients had abnormal manifestations on CT. The common manifestations in CT were GGO (88.5%, 23/26), consolidation (69.2%, 18/26), reticular opacity (69.2%, 18/26) and nodule (46.2%, 12/26). Among the abnormalities between CXR and CT, only consolidation was consistent (κ=0.510). GGO (ICC=0.501) and consolidation (ICC=0.431) scores were consistent in CXR and chest CT. The results of staging were the same in 14 cases, most of them were in stage I and stage II. While in other cases with inconsistent results, CT was more advanced in the disease stage than CXR, mainly stage III and stage IV. CONCLUSION: CXR is helpful to observe the change of the pulmonary lesions in patients with confirmed COVID-19 pneumonia. CT can be used for early diagnosis and staging of lesions.

Human mesenchymal stem cells treatment for severe COVID-19: 1-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The long-term consequences of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment for COVID-19 patients are yet to be reported. This study assessed the 1-year outcomes in patients with severe COVID-19, who were recruited in our previous UC-MSC clinical trial. METHODS: In this prospective, longitudinal, cohort study, 100 patients enrolled in our phase 2 trial were prospectively followed up at 3-month intervals for 1 year to evaluate the long-term safety and effectiveness of UC-MSC treatment. The primary endpoint was an altered proportion of whole-lung lesion volumes measured by high-resolution CT. Other imaging outcomes, 6 min walking distance (6-MWD), lung function, plasma biomarkers, and adverse events were also recorded and analyzed. This trial was registered with ClinicalTrials.gov (NCT04288102). FINDINGS: MSC administration improved in whole-lung lesion volume compared with the placebo with a difference of -10.8% (95% CI: -20.7%, -1.5%, p = 0.030) on day 10. MSC also reduced the proportion of solid component lesion volume compared with the placebo at each follow-up point. More interestingly, 17.9% (10/56) of patients in the MSC group had normal CT images at month 12, but none in the placebo group (p = 0.013). The incidence of symptoms was lower in the MSC group than in the placebo group at each follow-up time. Neutralizing antibodies were all positive, with a similar median inhibition rate (61.6% vs. 67.6%) in both groups at month 12. No difference in adverse events at the 1-year follow-up and tumor markers at month 12 were observed between the two groups. INTERPRETATION: UC-MSC administration achieves a long-term benefit in the recovery of lung lesions and symptoms in COVID-19 patients. FUNDING: The National Key R&D Program of China, the Innovation Groups of the National Natural Science Foundation of China, and the National Science and Technology Major Project.

Inspiratory and Expiratory Chest High-resolution CT: Small-airway Disease Evaluation in Patients with COVID-19.

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) has occurred worldwide. However, the small-airway disease in patients with COVID-19 has not been explored. AIM: This study aimed to explore the small-airway disease in patients with COVID-19 using inspiratory and expiratory chest high-resolution computed tomography (CT). METHODS: This multicenter study included 108 patients with COVID-19. The patients were classified into five stages (0-IV) based on the CT images. The clinical and imaging data were compared among CT images in different stages. Patients were divided into three groups according to the time interval from the initial CT scan, and the clinical and air trapping data were compared among these groups. The correlation between clinical parameters and CT scores was evaluated. RESULTS: The clinical data, including age, frequency of breath shortness and dyspnea, neutrophil percentage, lymphocyte count, PaO2, PaCO2, SaO2, and time interval between the onset of illness and initial CT, showed significant differences among CT images in different stages. A significant difference in the CT score of air trapping was observed between stage I and stage III. A low negative correlation was found between the CT score of air trapping and the time interval between the onset of symptoms and initial CT. No significant difference was noted in the frequency and CT score of air trapping among different groups. CONCLUSION: Some patients with COVID-19 developed small-airway disease. Air trapping was more distinguished in the early stage of the disease and persisted during the 2-month follow-up. Longer-term follow-up studies are needed to confirm the findings.

Prognostic Nomogram on Admission Predicting Progression for Patients with Nonsevere COVID-19

The present study aimed to establish a prognostic nomogram to stratify high-risk patients with Coronavirus Disease 2019 (COVID-19) who progressed from the nonsevere condition on admission to severe during hospitalization. This multicenter retrospective study included patients with nonsevere COVID-19 on admission from Jan 10, 2020 to Feb 7, 2020. In the training cohort, independent risk factors associated with disease progression were identified by univariate and multivariate analyses. The prognostic nomogram was established and then validated externally using C-index. The study included 351 patients (293 and 58 in the training and validation cohorts, respectively), with 27 (9.2%) and 5 (8.6%) patients progressed, respectively. In the training cohort, older age (OR 1.036, 95% CI 1.000-1.073), more lobes involved on chest CT (OR 1.841, 95% CI 1.117-3.035), comorbidity present (OR 2.478, 95% CI 1.020-6.018), and lower lymphocyte count (OR 0.081, 95% CI 0.019-0.349) were identified as independent risk factors. The prognostic nomogram was established in the training cohort with satisfied external prognostic performance (C-index 0.906, 95% CI 0.806-1.000). In conclusion, older age, comorbidity present, more lobes involved on chest CT, and lower lymphocyte count are independent risk factors associated with disease progression during hospitalization for patients with nonsevere COVID-19.

High-resolution Chest CT Features and Clinical Characteristics of Patients Infected with COVID-19 in Jiangsu, China.

BACKGROUND: A pneumonia associated with the coronavirus disease 2019 (COVID-19) recently emerged in China. It was recognized as a global health hazard. METHODS: 234 inpatients with COVID-19 were included. Detailed clinical data, chest HRCT basic performances and certain signs were recorded Ground-glass opacity (GGO), consolidation, fibrosis and air trapping were quantified. Both clinical types and CT stages were evaluated. RESULTS: Most patients (approximately 90%) were classified as common type and with epidemiologic history. Fever and cough were main symptoms. Chest CT showed abnormal attenuation in bilateral multiple lung lobes, distributed in the lower and/or periphery of the lungs (94.98%), with multiple shapes. GGO and vascular enhancement sign were most frequent seen, followed by interlobular septal thickening and air bronchus sign as well as consolidation, fibrosis and air trapping. There were significant differences in most of CT signs between different stage groups. The SpO2 and OI were decreased in stage IV, and the CT score of consolidation, fibrosis and air trapping was significantly lower in stage I (P<0.05). A weak relevance was between the fibrosis score and the value of PaO2 and SpO2 (P<0.05). CONCLUSIONS: Clinical performances of patients with COVID-19, mostly with epidemiologic history and typical symptoms, were critical valuable in the diagnosis of the COVID-19. While chest HRCT provided the distribution, shape, attenuation and extent of lung lesions, as well as some typical CT signs of COVID-19 pneumonia.

Clinical characteristics and changes of chest CT features in 307 patients with common COVID-19 pneumonia infected SARS-CoV-2: A multicenter study in Jiangsu, China

Objective The study was aimed to describe the clinical characteristics and evaluate the dynamic changes of chest CT features in the first three weeks in the common type fo COVID-19 pneumonia patients in Jiangsu Province. Methods 307 patients infected SARS-CoV-2 classified as common type were enrolled in the study. 628 chest CT scans were divided into three groups based on the time interval between symptoms and chest CT scan. The clinical characteristics were descriptively analyzed.The chest CT features were quantitatively evaluated. Mann-Whitney U test was used to test the differences in three groups and between men and women. Spearman rank correlation was used to test the association between the arterial blood gas(ABG) analysis results and chest CT scores. Results Fever (69.1%) and cough (62.8%) were common symptoms. 111(36.2%) patients were anorexia. GGO was the most common manifestation of COVID-19 pneumonia, which could be followed by consolidation and fibrosis. Lower lobe or subpleural region was the most common distribution form of lesion. More lung lobes were involved in the third week. Total chest CT scores in the second week were higher than the first week. Fibrosis Scores increased in the second and third week. Total CT score, GGO score and fibrosis score of male patients were significantly higher than female in the second week. Male patients had higher consolidation score and fibrosis score than female in the third week. Total CT score and GGO score had weak to moderate correlation with arterial blood gas indices. Conclusion Changes in chest CT were difficult to assess quantitatively in the first third weeks. Male patients recovered slower than female in the second week. Although CT score had correlations with arterial blood gas indices, long-term follow-up of pulmonary function test is needed to determine the recovery of lung.