Efficacy and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.

MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I  2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I  2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.

COVID-19 and the effects on pulmonary function following infection: A retrospective analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been identified in over 110 million people with no studies comparing pre-infection pulmonary function to post-infection. This study's aim was to compare pre-infection and post-infection pulmonary function tests (PFT) in COVID-19 infected patients to better delineate between preexisting abnormalities and effects of the virus. METHODS: This was a retrospective multi-center cohort study. Patients were identified based on having COVID-19 and a pre- and post-infection PFT within one year of infection during the time period of March 1, 2020 to November 10, 2020. FINDINGS: There was a total of 80 patients, with an even split in gender; the majority were white (n = 70, 87·5%) and never smokers (n = 42, 52·5%). The majority had mild to moderate COVID-19 disease (n = 60, 75·1%) with 25 (31·2%) requiring hospitalization. There was no difference between the pre- and post-PFT data, specifically with the forced vital capacity (FVC) (p = 0·52), forced expiratory volume in 1 s (FEV1)(p = 0·96), FEV1/FVC(p = 0·66), total lung capacity (TLC) (p = 0·21), and diffusion capacity (DLCO)(p = 0·88). There was no difference in the PFT when analyzed by hospitalization and disease severity. After adjusting for potential confounders, interstitial lung disease (ILD) was independently associated with a decreased FEV1 (-2·6 [95% CI, -6·7 to - 1·6] vs. -10·3 [95% CI, -17·7 to -2·9]; p = 0·03) and an increasing age (p = 0·01) and cystic fibrosis (-1·1 [95% CI, -4·5 to- 2·4] vs. -36·5 [95% CI, -52·1 to -21·0]; p < 0·01) were associated with decreasing FVC when comparing pre and post infection PFT. Only increasing age was independently associated with a reduction in TLC (p = 0·01) and DLCO (p = 0·02) before and after infection. INTERPRETATION: This study showed that there is no difference in pulmonary function as measured by PFT before and after COVID-19 infection in non-critically ill classified patients. There could be a relationship with certain underlying lung diseases (interstitial lung disease and cystic fibrosis) and decreased lung function following infection. This information should aid clinicians in their interpretation of pulmonary function tests obtained following COVID-19 infection. FUNDING: No funding was obtained for this study.

Oxygen therapy via a noninvasive helmet: A COVID-19 novelty with potential post-pandemic uses.

COVID-19 has placed a significant strain upon healthcare resources at a global level and refractory hypoxemia is the leading cause of death among COVID-19 patients. The management of limited resources such as mechanical ventilators has remained a contentious issue both at an individual and institutional level since the beginning of the pandemic. As a result, the COVID-19 pandemic has presented challenges to critical care practitioners to find innovative ways to provide supplemental oxygen therapy to their patients. We present a single-center experience: a case series of five COVID-19 infected patients managed with a novel approach to provide supplemental oxygen and positive end-expiration pressure (PEEP) via the helmet. Three of the five patients responded to therapy, did not require intubation, and survived to discharge. The other two patients continued to deteriorate clinically, required endotracheal intubation, and subsequently expired during their hospitalization. We extrapolated our accumulated experience with non-invasive oxygen support by helmet in COVID-19 patients to a non-COVID-19 postoperative patient who underwent sinus surgery and developed hypoxemic respiratory failure also resulting in avoidance of endotracheal intubation. We conclude that oxygen therapy via a helmet is a safe, cost-effective technique to prevent intubation in carefully selected patients with infectious and non-infectious causes of hypoxic respiratory failure. Our positive experience with the system warrants further large-scale study and possible technique refinement.

Robotics in Simulated COVID-19 Patient Room for Health Care Worker Effector Tasks: Preliminary, Feasibility Experiments.

The coronavirus disease 2019 (COVID-19) pandemic has strained health care systems and personal protective equipment (PPE) supplies globally. We hypothesized that a collaborative robot system could perform health care worker effector tasks inside a simulated intensive care unit (ICU) patient room, which could theoretically reduce both PPE use and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures. We planned a prospective proof-of-concept feasibility and design pilot study to test 5 discrete medical tasks in a simulated ICU room of a COVID-19 patient using a collaborative robot: push a button on intravenous pole machine when alert occurs for downstream occlusion, adjust ventilator knob, push button on ICU monitor to silence false alerts, increase oxygen flow on wall-mounted flow meter to allow the patient to walk to the bathroom and back (dial-up and dial-down oxygen flow), and push wall-mounted nurse call button. Feasibility was defined as task completion robotically. A training period of 45 minutes to 1 hour was needed to program the system de novo for each task. In less than 30 days, the team completed 5 simple effector task experiments robotically. Selected collaborative robotic effector tasks appear feasible in a simulated ICU room of the COVID-19 patient. Theoretically, this robotic approach could reduce PPE use and staff SARS-CoV-2 exposure. It requires future validation and health care worker learning similar to other ICU device training.

Outcomes of COVID-19 With the Mayo Clinic Model of Care and Research.

OBJECTIVE: To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. METHODS: We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. RESULTS: A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19-directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. CONCLUSION: Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.

Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure.

The emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) at the end of 2019 in Hubei province China, is now the cause of a global pandemic present in over 150 countries. COVID-19 is a respiratory illness with most subjects presenting with fever, cough and shortness of breath. In a subset of patients, COVID-19 progresses to hypoxic respiratory failure and acute respiratory distress syndrome (ARDS), both of which are mediated by widespread inflammation and a dysregulated immune response. Mesenchymal stem cells (MSCs), multipotent stromal cells that mediate immunomodulation and regeneration, could be of potential benefit to a subset of COVID-19 subjects with acute respiratory failure. In this review, we discuss key features of the current COVID-19 outbreak, and the rationale for MSC-based therapy in this setting, as well as the limitations associated with this therapeutic approach.

Cell-based therapy to reduce mortality from COVID-19: Systematic review and meta-analysis of human studies on acute respiratory distress syndrome.

Severe cases of COVID-19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID-19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo-capillary barriers. The authors performed a systematic literature review and random-effects meta-analysis to determine the potential value of MSC therapy for treating COVID-19-infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO2 /FiO2 ratio, alveolo-capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.