Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19.
A 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.
From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old 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.
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.
NCT04343729.
Although high mortality has been reported in many COVID-19 studies, very limited postmortem information from complete autopsies is available. We report the findings in the adrenal glands in 28 ...autopsies with confirmed SARS-CoV-2 infection. Microscopic lesions were identified in the adrenal glands in 12/28 patients (46%). Seven cases showed necrosis, generally ischemic; four showed cortical lipid degeneration; two showed hemorrhage; and one unspecific focal adrenalitis. Vascular thrombosis in one patient and focal inflammation in association with other findings in three patients were observed. No case presented adrenal insufficiency. In conclusion, adrenal lesions are frequent in patients with severe COVID-19. The lesions are mild but could contribute to the lethal outcome.
We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite ...antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.
The diagnosis of long COVID is troublesome, even when functional limitations are present. Dynapenia is the loss of muscle strength and power production that is not caused by neurologic or muscular ...diseases, being mostly associated with changes in neurologic function and/or the intrinsic force-generating properties of skeletal muscle, which altogether, may partially explain the limitations seen in long COVID. This study aimed to identify the distribution and possible associations of dynapenia with functional assessments in patients with long COVID. A total of 113 patients with COVID-19 were evaluated by functional assessment 120 days post-acute severe disease. Body composition, respiratory muscle strength, spirometry, six-minute walk test (6MWT, meters), and hand-grip strength (HGS, Kilogram-force) were assessed. Dynapenia was defined as HGS < 30 Kgf (men), and < 20 Kgf (women). Twenty-five (22%) participants were dynapenic, presenting lower muscle mass (p < 0.001), worse forced expiratory volume in the first second (FEV
) (p = 0.0001), lower forced vital capacity (p < 0.001), and inspiratory (p = 0.007) and expiratory (p = 0.002) peek pressures, as well as worse 6MWT performance (p < 0.001). Dynapenia, independently of age, was associated with worse FEV
, maximal expiratory pressure (MEP), and 6MWT, (p < 0.001) outcomes. Patients with dynapenia had higher intensive care unit (ICU) admission rates (p = 0.01) and need for invasive mechanical ventilation (p = 0.007) during hospitalization. The HGS is a simple, reliable, and low-cost measurement that can be performed in outpatient clinics in low- and middle-income countries. Thus, HGS may be used as a proxy indicator of functional impairment in this population.
There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high ...concentration of the drug.
To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19.
This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon.
Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days).
Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4.
Out of a predefined sample size of 440 patients, 81 were enrolled (41 50.6% to high-dosage group and 40 49.4% to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 75.3%) were men. Older age (mean SD age, 54.7 13.7 years vs 47.4 13.3 years) and more heart disease (5 of 28 17.9% vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 18.9%) compared with the low-dosage group (4 of 36 11.1%). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%).
The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19.
ClinicalTrials.gov Identifier: NCT04323527.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect a broad range of human tissues by using the host receptor angiotensin-converting enzyme 2 (ACE2). Individuals with ...comorbidities associated with severe COVID-19 display higher levels of
ACE2
in the lungs compared to those without comorbidities, and conditions such as cell stress, elevated glucose levels and hypoxia may also increase the expression of
ACE2
. Here, we showed that patients with Barrett's esophagus (BE) have a higher expression of
ACE2
in BE tissues compared to normal squamous esophagus, and that the lower pH associated with BE may drive this increase in expression. Human primary monocytes cultured in reduced pH displayed increased
ACE2
expression and higher viral load upon SARS-CoV-2 infection. We also showed in two independent cohorts of 1,357 COVID-19 patients that previous use of proton pump inhibitors is associated with 2- to 3-fold higher risk of death compared to those not using the drugs. Our work suggests that pH has a great influence on SARS-CoV-2 Infection and COVID-19 severity.
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.
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 SpO
≤ 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.
Out of the total of surviving patients at day 28 (
= 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%;
= 0.45). At hospital admission, IL-6 levels were higher in the MP group (
< 0.01). Also, the need for ICU (
= 0.06), need for IMV (
= 0.07), and creatine kinase (
= 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.
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.
ClinicalTrials.gov, Identifier: NCT04343729.
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