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BackgroundThere is an ongoing critical need to improve therapeutic strategies for COVID-19 pneumonia, particularly in the most severely affected patients. Adult mesenchymal stem cell (MSC) infusions have the potential to benefit critically ill patients with acute respiratory syndrome SARS-COV-2 infection, but clinical data supporting efficacy are lacking. MethodsWe conducted a case-control study of critically ill patients with laboratory-confirmed COVID-19, severe acute respiratory distress syndrome (ARDS). To evaluate clinical responsiveness in the most critically ill patient we examined outcomes in a sub-group of those requiring extracorporeal membrane oxygenation (ECMO) support. Patients (n=9) were administered with up to 3 infusions of intravenous (IV) MSCs and compared to a local ECMO control group (n=31). The primary outcome was safety, and the secondary outcomes were all-cause mortality (or rate of hospital discharge), cytokine levels, and viral clearance. FindingsMSC infusions (12 patients) were well tolerated and no side effects occurred. Of ECMO patients receiving MSC infusions, 2 out of 9 died (22.2%; 95%CI: 2.8%, 60.0%) compared with a mortality of 15 of 31 (48.4%; 95%CI: 30.2%, 66.9%; p = 0.25) in the ECMO control group. Isolated plasma exosomes containing the SARS-COV-2 Spike protein decreased after MSC infusions between day 14 or 21 after administration (p=0.003 and p=0.005, respectively) and was associated with a decrease in COVID-19 IgG Spike protein titer at same time points (p = 0.006 and p=0.007, respectively). Control ECMO patients receiving convalescent plasma did not clear COVID-19 IgG over the same time frame. InterpretationTogether these findings suggest that MSC IV infusion is well tolerated in patients with a broad range of severity including the most severe COVID-19 ARDS requiring ECMO. These data also raise the possibility that MSCs, in addition to exerting an immunomodulatory effect, contribute to viral clearance and strongly support the conduct of randomized placebo-controlled trial.
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ObjectiveEvaluate the prevalence and characteristics of olfactory or gustatory dysfunction in COVID-19 patients Study DesignMulticenter Case Series Setting5 tertiary care hospitals (3 in China, 1 in France, 1 in Germany) Subjects and Methods394 PCR confirmed COVID-19 positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and Visual Analogue Scale (VAS) were used to quantify olfactory and gustatory dysfunction respectively. All subjects at one hospital (Shanghai) without subjective olfactory complaints underwent objective testing. ResultsOf 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n=239), German (n=39) and French (n=116) cohorts were 32%, 69%, and 49% respectively. The median age of included subjects was 39 years old, 92/161 (57%) were male, and 10/161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10/90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. 43% (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. ConclusionsOlfactory and/or gustatory disorders may represent early or isolated symptoms of SARS-CoV-2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.
