Clinical Consideration for Mesenchymal Stem Cells in Treatment of COVID-19.

COVID-19, which has strongly affected the 21st century, is caused by severe acute respiratory syndrome (SARS)-CoV-2. The emergence of viral variants has rendered even vaccinated people prone to infection; thus, completely eradicating COVID-19 may be impossible. COVID-19 causes hyperinflammation, leading to organ damage and even death. SARS-CoV-2 infects not only the lungs, causing acute respiratory distress syndrome, but also the extrapulmonary organs. Not all patients with COVID-19 respond adequately to treatments with antiviral and anti-inflammatory drugs. Therefore, new treatments are urgently needed. Mesenchymal stem cells (MSCs) exhibit immunomodulatory activity and are used to safely and effectively treat various immune disorders. Evidence has indicated the efficacy of MSCs against COVID-19. However, the safety and efficacy of MSCs must be probed further. For this reason, we explored key clinical challenges associated with MSC therapy for COVID-19, such as sources, administration routes, cell dosage, treatment timepoint, and virus reactivation. We identified several challenges that must be addressed before MSCs can be clinically applied.

Effect of invasive mechanical ventilation on the diversity of the pulmonary microbiota.

Pulmonary microbial diversity may be influenced by biotic or abiotic conditions (e.g., disease, smoking, invasive mechanical ventilation (MV), etc.). Specially, invasive MV may trigger structural and physiological changes in both tissue and microbiota of lung, due to gastric and oral microaspiration, altered body posture, high O2 inhalation-induced O2 toxicity in hypoxemic patients, impaired airway clearance and ventilator-induced lung injury (VILI), which in turn reduce the diversity of the pulmonary microbiota and may ultimately lead to poor prognosis. Furthermore, changes in (local) O2 concentration can reduce the diversity of the pulmonary microbiota by affecting the local immune microenvironment of lung. In conclusion, systematic literature studies have found that invasive MV reduces pulmonary microbiota diversity, and future rational regulation of pulmonary microbiota diversity by existing or novel clinical tools (e.g., lung probiotics, drugs) may improve the prognosis of invasive MV treatment and lead to more effective treatment of lung diseases with precision.

Distinct immune responses in the early phase to natural SARS-CoV-2 infection or vaccination.

Immune responses elicited by viral infection or vaccination play key roles in the viral elimination and the prevention of reinfection, as well as the protection of healthy persons. As one of the most widely used Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there have been increasing concerns about the necessity of additional doses of inactivated vaccines, due to the waning immune response several months after vaccination. To further optimize inactivated SARS-CoV-2 vaccines, we compared immune responses to SARS-CoV-2 elicited by natural infection and immunization with inactivated vaccines in the early phase. We observed the lower antibody levels against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in the early phase of postvaccination with a slow increase, compared to the acute phase of SARS-CoV-2 natural infection. Specifically, IgA antibodies have the most significant differences. Moreover, we further analyzed cytokine expression between these two groups. A wide variety of cytokines presented high expression in the infected individuals, while a few cytokines were elicited by inactivated vaccines. The differences in antibody responses and cytokine levels between natural SARS-CoV-2 infection and vaccination with the inactivated vaccines may provide implications for the optimization of inactivated SARS-CoV-2 vaccines and the additional application of serological tests.

Immunomodulation of Mesenchymal Stem Cells in Acute Lung Injury: From Preclinical Animal Models to Treatment of Severe COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health challenge worldwide. Owing to the emergence of novel viral variants, the risks of reinfections and vaccine breakthrough infections has increased considerably despite a mass of vaccination. The formation of cytokine storm, which subsequently leads to acute respiratory distress syndrome, is the major cause of mortality in patients with COVID-19. Based on results of preclinical animal models and clinical trials of acute lung injury and acute respiratory distress syndrome, the immunomodulatory, tissue repair, and antiviral properties of MSCs highlight their potential to treat COVID-19. This review article summarizes the potential mechanisms and outcomes of MSC therapy in COVID-19, along with the pathogenesis of the SARS-CoV-2 infection. The properties of MSCs and lessons from preclinical animal models of acute lung injury are mentioned ahead. Important issues related to the use of MSCs in COVID-19 are discussed finally.

Reduced neutralization of SARS-CoV-2 B.1.617 variant by convalescent and vaccinated sera.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.

Symptomless multi-variable apnea prediction index assesses adverse outcomes in patients with Corona Virus Disease 2019.

PURPOSE: To explore the relationship between symptomless multi-Variable apnea prediction (sMVAP) index and adverse outcomes of patients with Corona Virus Disease 2019 (COVID-19). METHODS: According to the sMVAP quartiles, we divided all patients into four groups. The clinical electronic medical records, nursing records, laboratory findings, and radiological examinations for all patients with laboratory confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection were reviewed. Cox proportional hazard ratio (HR) models were used to determine the risk factors associated with in hospital death. RESULTS: A total of 97 patients were included in this study. The "Quartile 4" group 's ICU transfer rate was significantly higher than the "Quartile 1" group. Coronary heart disease, high d-dimer and sMVAP at admission were associated with increased odds of death. CONCLUSIONS: Using the sMVAP index for obstructive sleep apnea hypopnea syndrome (OSAHS) risk assessment, and then predicting the adverse outcomes of COVID-19 patients, is an effective method. Therefore, the use of sMVAP index for OSAHS screening for inpatients with COVID-19 should be vigorously promoted, and high-risk patients should be effectively managed.

Improved night shift schedule related to the mortality of critically ill patients with Corona Virus Disease 2019.

PURPOSE: To determine the relationship between the improved night shift schedule and the mortality of critically ill patients with Corona Virus Disease 2019 (COVID-19). METHODS: According to the time of the implementation of the new night shift schedule, we divided all patients into two groups: initial period group and recent period group. The clinical electronic medical records, nursing records, laboratory findings, and radiological examinations for all patients with laboratory confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection were reviewed. Cox proportional hazard ratio (HR) models were used to determine the risk factors associated with in hospital death. RESULTS: A total of 75 patients were included in this study. Initial period group includes 45 patients and recent period group includes 30 patients. The difference in mortality between the two groups was significant, 77.8% and 36.7%, respectively. Leukocytosis at admission and admitted to hospital before the new night shift schedule were associated with increased odds of death. CONCLUSIONS: Shift arrangement of medical staff are associated with the mortality of critically ill patients with COVID-19. The new night shift schedule might improve the continuity of treatment, thereby improving the overall quality of medical work and reducing the mortality of critically ill patients.