Background Steroid use for COVID-19 is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by SARS-CoV-2. This study aimed at evaluating at evaluating the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. Methods Parallel, double-blind, placebo-controlled, randomized, phase IIb clinical trial was performed with hospitalized patients aged ≥ 18 years with clinical, epidemiological and/or radiological suspected COVID-19, at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution), twice daily, for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. ClinicalTrials Identifier NCT04343729. Findings From April 18 to June 16, 2020, 647 patients were screened, 416 randomized, and 393 analyzed as mITT, MP in 194 and placebo in 199 individuals. SARS-CoV-2 infection was confirmed by RT-PCR in 81.3%. Mortality at day 28 was not different between groups. A subgroup analysis showed that patients over 60 years in the MP group had a lower mortality rate at day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until day 7. Conclusion The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population.

SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.

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Background: The use of corticosteroids may help control the cytokine storm occurring in acute respiratory failure due to the severe form of COVID-19. We evaluated the postacute effect of corticosteroids used during the acute phase, such as impairment in pulmonary function parameters, on day 120 (D120)-follow-up, in participants who survived over 28 days.Methods: This is a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial carried out between April 18 and October 9, 2020, conducted in hospitalized patients with clinical–radiological suspicion of COVID-19, aged 18 years or older, with SpO2 ≤ 94% on room air or requiring supplementary oxygen, or under invasive mechanical ventilation (IMV) in a referral center in Manaus, Western Brazilian Amazon. Intravenous methylprednisolone (MP) (0.5 mg/kg) was given two times daily for 5 days to these patients. The primary outcome used for this study was pulmonary function testing at day 120 follow-up visit.Results: Out of the total of surviving patients at day 28 (n = 246) from the Metcovid study, a total of 118 underwent satisfactory pulmonary function testing (62 in the placebo arm and 56 in the MP arm). The supportive treatment was similar between the placebo and MP groups (seven [11%] vs. four [7%]; P = 0.45). At hospital admission, IL-6 levels were higher in the MP group (P < 0.01). Also, the need for ICU (P = 0.06), need for IMV (P = 0.07), and creatine kinase (P = 0.05) on admission also tended to be higher in this group. In the univariate analysis, forced expiratory volume on 1st second of exhalation (FEV1) and forced vital capacity (FVC) at D120 follow-up were significantly higher in patients in the MP arm, being this last parameter also significantly higher in the multivariate analysis independently of IMV and IL-6 levels on admission.Conclusion: The use of steroids for at least 5 days in severe COVID-19 was associated with a higher FVC, which suggests that hospitalized COVID-19 patients might benefit from the use of MP in its use in the long-term, with less pulmonary restrictive functions, attributed to fibrosis.Trial Registration:ClinicalTrials.gov, Identifier: NCT04343729.

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