Background COVID-19 is a multisystem disease that presents acute and persistent symptoms, the postacute sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARS-CoV-2, associated clotting or inflammatory processes during acute COVID-19. Various strategies are being chosen by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efficient in treating such a complex disease. Mesenchymal stromal cells (MSCs) are known for their immunomodulatory properties and regeneration ability; therefore, they are a promising tool for treating disorders involving immune dysregulation and extensive tissue damage, as is the case with COVID-19. This study aimed to assess the safety and explore the long-term efficacy of three intravenous doses of UC-MSCs (umbilical cord MSCs) as an adjunctive therapy in the recovery and postacute sequelae reduction caused by COVID-19. To our knowledge, this is one of the few reports that presents the longest follow-up after MSC treatment in COVID-19 patients. Methods This was a phase I/II, prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Seventeen patients diagnosed with COVID-19 who require intensive care surveillance and invasive mechanical ventilation—critically ill patients—were included. The patient infusion was three doses of 5 × 105 cells/kg UC-MSCs, with a dosing interval of 48 h (n = 11) or placebo (n = 6). The evaluations consisted of a clinical assessment, viral load, laboratory testing, including blood count, serologic, biochemical, cell subpopulation, cytokines and CT scan. Results The results revealed that in the UC-MSC group, there was a reduction in the levels of ferritin, IL-6 and MCP1-CCL2 on the fourteen day. In the second month, a decrease in the levels of reactive C-protein, D-dimer and neutrophils and an increase in the numbers of TCD3, TCD4 and NK lymphocytes were observed. A decrease in extension of lung damage was observed at the fourth month. The improvement in all these parameters was maintained until the end of patient follow-up. Conclusions UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients. Trial registration Brazilian Registry of Clinical Trials (ReBEC), UTN code-U1111-1254-9819. Registered 31 October 2020—Retrospectively registered, https://ensaiosclinicos.gov.br/rg/RBR-3fz9yr

Community respiratory viruses (CRVs) are commonly associated with seasonal infections. They have been associated with higher morbidity and mortality among children, elderly individuals, and immunosuppressed patients. In April 2009, the circulation of a new influenza A virus (FLUA H1N1v) was responsible for the first influenza pandemic of this century. We report the clinical and epidemiological profiles of inpatients infected with CRVs or with FLUA H1N1v at a tertiary care hospital in southern Brazil. In addition, we used these profiles to evaluate survivor and nonsurvivor patients infected with FLUA H1N1v. Multiplex reverse transcription-PCR (RT-PCR) and real time RT-PCR were used to detect viruses in inpatients with respiratory infections. Record data from all patients were reviewed. A total of 171 patients were examined over a period of 16 weeks. Of these, 39% were positive for FLUA H1N1v, 36% were positive for CRVs, and 25% were negative. For the FLUA H1N1v-and CRV-infected patients, epidemiological data regarding median age (30 and 1.5 years), myalgia (44% and 13%), need for mechanical ventilation (44% and 9%), and mortality (35% and 9%) were statistically different. In a multivariate analysis comparing survivor and nonsurvivor patients infected with influenza A virus H1N1, median age and creatine phosphokinase levels were significantly associated with a severe outcome. Seasonal respiratory infections are a continuing concern. Our results highlight the importance of studies on the prevalence and severity of these infections and that investments in programs of clinical and laboratory monitoring are essential to detect the appearance of new infective agents.

Microcirculation disturbances imply poor prognosis in septic shock. Microvascular reserve can be assessed by oximetry-derived Perfusion Index (PI) after vascular occlusion test (VOT). We investigated the relationship between PI during VOT, hyperlactatemia and mortality in septic shock and the role of adrenergic stimulus in these findings. The tests were performed in 106 patients within 24 h after admission. PI was evaluated before/after 03-min flow occlusion. Peaks of PI (ΔPI peak) and time-to-peak were evaluated. PI was also evaluated in hyperemic phases derived by mechanosensitive (ΔPI0-60) and metabolic mechanisms (ΔPI60-120). We compared nonsurvivors with survivors and patients with lowest and highest ΔPI peaks, divided by 50th-percentile. ΔPI peak was evaluated in presence/absence of hyperlactatemia. A correlation test between ΔPI peaks and noradrenaline doses and an assessment after doses increasing were also performed. The ΔPI peak values were higher in nonsurvivors [79% (47%-169%) vs 48% (25%-85%); p=0.003] although peaks were reached slower in nonsurvivors. ΔPI0-60 was similar between groups [-12% (-42%-28) vs 01% (-16%-23%); p = 0.211]. However, ΔPI60-120 was higher in nonsurvivors [49% (29%-84%) vs 31%(12%-65%); p = 0.035]. Additionally, the group with higher ΔPI peaks had higher mortality than those with lower peaks [HR 2.25 (95%-CI = 1.32-4.14); p = 0.003]. Mortality was extremely high in presence of hyperlactatemia. ΔPI peaks were positively correlated with noradrenaline doses and increased after increasing doses.In conclusion, high values of PI during VOT indicates higher mortality in septic shock and are associated to adrenergic stimulus. Additionally, the assessment of PI-VOT appears to improve the predictive value of arterial lactate.

Microcirculatory disorders have been consistently linked to the pathophysiology of sepsis. One of the major organs affected is the kidneys, resulting in sepsis-associated acute kidney injury (SA-AKI) that correlates considerably with mortality. However, the potential role of clinical assessment of peripheral perfusion as a possible tool for SA-AKI management has not been established. To address this gap, the purpose of this study was to investigate the prevalence of peripheral hypoperfusion in SA-AKI, its association with mortality, and fluid balance. This observational cohort study enrolled consecutive septic patients in the Intensive Care Unit. After fluid resuscitation, peripheral perfusion was evaluated using the capillary filling time (CRT) and peripheral perfusion index (PI) techniques. The AKI was defined based on both serum creatinine and urine output criteria. One hundred and forty-one patients were included, 28 (19%) in the non-SA-AKI group, and 113 (81%) in the SA-AKI group. The study revealed higher peripheral hypoperfusion rates in the SA-AKI group using the CRT (OR 3.6; 95% CI 1.35-9.55; p < 0.05). However, this result lost significance after multivariate adjustment. Perfusion abnormalities in the SA-AKI group diagnosed by both CRT (RR 1.96; 95% CI 1.25-3.08) and PI (RR 1.98; 95% CI 1.37-2.86) methods were associated to higher rates of 28-day mortality (p < 0.01). The PI's temporal analysis showed a high predictive value for death over the first 72 h (p < 0.01). A weak correlation between PI values and the fluid balance was found over the first 24 h (r =-0.20; p < 0.05). In conclusion, peripheral perfusion was not different intrinsically between patients with or without SA-AKI. The presence of peripheral hypoperfusion in the SA-AKI group has appeared to be a prognostic marker for mortality. This evaluation maintained its predictive value over the first 72 hours. The fluid balance possibly negatively influences peripheral perfusion in the SA-AKI.