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.

Physician Satisfaction With Telemedicine During the COVID-19 Pandemic: The Mayo Clinic Florida Experience.

OBJECTIVE: To evaluate physician perceptions and attitudes toward telemedicine use at a tertiary care academic institution in northeast Florida during the coronavirus disease 2019 pandemic. PATIENTS AND METHODS: An anonymous 38-question cross-sectional survey was developed using Qualtrics survey software (Qualtrics) and e-mailed to all staff physicians from all specialty disciplines at Mayo Clinic in Florida. The survey was open from August 17, 2020, through September 1, 2020. Collected data included general demographic characteristics and employment information, attitude and experience with telemedicine use before and during the coronavirus disease 2019 pandemic, perception of patients' experience, and the effect of telemedicine on burnout. RESULTS: The survey was distributed to 529 eligible physicians at our institution, with 103 physicians responding (20%). The distribution of specialties was 22% primary care specialties, 41% other internal medicine subspecialties, and 18% surgical specialties. Collectively, 63% found comparable quality of care when provided virtually (vs in-person) whereas 80% perceived telemedicine as cost-effective. A total of 76% of physicians felt that telemedicine increased flexibility and control over patient care activities, with 36% reporting improved work-life balance and 30% reporting improved burnout symptoms. Overall, 42% preferred using telemedicine over in-person visits when possible. CONCLUSION: Physicians generally had positive attitudes regarding the adoption of telemedicine and perceived that the quality of health care delivery as generally comparable to in-person care. Future studies are needed to explore attitudes regarding telemedicine after the pandemic and how this virtual technology may be further used to improve physicians' professional and personal well-being.

SARS-CoV-2 Infection in Multiple Sclerosis: Results of the Spanish Neurology Society Registry.

OBJECTIVE: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. METHODS: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. RESULTS: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. CONCLUSIONS: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease.

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population.

OBJECTIVE: Pivotal trial have shown that patients with multiple sclerosis (MS) receiving ocrelizumab had better outcomes. However, data on ocrelizumab in clinical practice are limited. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for multiple sclerosis (MS) in a real-world clinical setting. METHODS: We conducted a retrospective study including consecutive patients from nine public hospitals in south-eastern Spain who received ocrelizumab after it was approved. RESULTS: A total of 228 MS patients were included (144 with relapsing-remitting MS [RRMS], 25 secondary progressive MS [SPMS], and 59 primary progressive MS [PPMS]). Median follow-up period was 12 months (range, 1-32). No evidence of disease activity (NEDA) status at year 1 was achieved in 91.2% of the relapsing MS (RMS) population, while disability progression was detected in 37.5% of the PPMS patients (median follow-up period, 19 months). The most common adverse events reported were infusion-related reactions and infections, with the most common infections being urinary tract infections followed by upper respiratory infections and COVID-19. INTERPRETATION: The preliminary results in our real-world setting show that ocrelizumab presented excellent results in suppressing disease activity with a favorable and consistent safety profile.

Telemedicine Utilization in Neurosurgery During the COVID-19 Pandemic: A Glimpse Into the Future?

OBJECTIVE: To describe telemedicine utilization in neurosurgery at a single tertiary institution to provide outpatient care during the coronavirus disease 2019 (COVID-19) pandemic, with 315 telemedicine visits performed by the neurosurgery department. PATIENTS AND METHODS: In response to the COVID-19 pandemic national stay-at-home orders and postponed elective surgeries, we converted upcoming clinic visits into telemedicine visits and rescheduled other patients thought not to be markedly affected by surgical postponement. We reviewed the charts of all patients who had telehealth visits from April 1 through April 30, 2020, and collected demographic information, diagnosis, type of visit, and whether they received surgery; a satisfaction questionnaire was also administered. RESULTS: In March 2020, 94% (644 of 685) of the neurosurgery clinic visits were face-to-face, whereas in April 2020, 55% (315 of 573) of the visits were telemedicine (P<.001). In April, of the 315 telemedicine visits, 172 (55%) were phone consults and 143 (45%) video consults; 101 (32%) were new consults, 195 (62%) return visits, and 18 (6%) postoperative follow-up. New consults were more likely to be video with audio than return visits and postoperative follow-up (P<.001). Only 39 patients (12%) required surgery. Ninety-one percent of the questionnaire respondents were very likely to recommend telemedicine. CONCLUSION: Rapid implementation of telemedicine to evaluate neurosurgery patients became an effective tool for preoperative consultation, postoperative and follow-up visits during the COVID-19 pandemic, and decreased risks of exposure to severe acute respiratory syndrome coronavirus 2 to patients and health care staff. Future larger studies should investigate the cost-effectiveness of telemedicine used to triage surgical from nonsurgical patients, potential cost-savings from reducing travel burdens and lost work time, improved access, reduced wait times, and impact on patient satisfaction.

Addressing the Challenge of COVID-19: One Health Care Site's Leadership Response to the Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic created an extremely disruptive challenge for health care leaders that required a rapid, dynamic, and innovative response. The purpose of this manuscript is to share the leadership actions and decisions at Mayo Clinic in Florida during the first 6 months of the pandemic (February to July 2020). We note 4 strategies that contributed to an effective response: (1) leverage experience with disaster preparedness and mobilize regional and national networks; (2) use surge models to anticipate and to address supply chain issues as well as practical and financial effects of the pandemic; (3) adapt creatively to establish new safety and procedural protocols in various areas for various populations; and (4) communicate timely information effectively and be the common source of truth. Mayo Clinic in Florida was able to address the surges of patients with COVID-19, to provide ongoing tertiary care, and to restore function within the first 6 months with new, strengthened practices and protocols.

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.