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.
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.
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 outbreak of new coronavirus disease 2019 (COVID-19) reported for the first time in Wuhan, China in late December 2019 have rapidly spread to other countries and it was declared on January 30, ...2020 as a public health emergency of international concern (PHEIC) by the World Health Organization. Before the first COVID-19 cases were reported in Brazil, several measures have been implemented including the adjustment of legal framework to carry out isolation and quarantine. As the cases increased significantly, new measures, mainly to reduce mortality and severe cases, have also been implemented. Rapid and robust preparedness actions have been undertaken in Brazil while first cases have not yet been identified in Latin-American. The outcome of this early preparation should be analyzed in future studies.
The exact path leading to cognitive impairment that goes beyond malaria is unclear, but it appears to be the result of interactive factors. Time of exposure to disease and recurrences are potentially ...major determinant variables. Cognitive impairment is described mainly in children, rarely in adults. The disease in high endemic areas usually does not affect elderlies, because of acquired immunity over time. However, this population is relatively more frequently sick in lower endemic areas, such as in the Amazon. This study assessed the effect of Plasmodium vivax malaria on the executive and cognitive functions of elderlies, in the Brazilian Amazon. A cohort study was conducted to evaluate executive and cognitive functions one week (T0), two months (T2) and eight months (T8) after the malaria episode. Mini-Mental State Examination (MMSE), Beck Depression Inventory II (BDI-II), Clock Drawing Test (CDT), Wechsler adult intelligence scale (WAIS-III), and Wisconsin Card Sorting Test (WCST) were used to assess executive and cognitive functions. One hundred-forty elderlies were enrolled (70 with P. vivax malaria and 70 without malaria). P. vivax malaria was associated with impairment of the executive and cognitive functions in elderlies for up to 8 months after acute P. vivax malaria. Prior history of malaria, recurrences and higher parasitemia were independently associated with various surrogates of executive and cognitive impairment. With the increase in life expectancy, elderlies living in malaria endemic areas will deserve more attention from health authorities, to guarantee improvement of their quality of life in the tropics.
The severity, disabilities, and lethality caused by the coronavirus 2019 (COVID-19) disease have dumbfounded the entire world on an unprecedented scale. The multifactorial aspect of the infection has ...generated interest in understanding the clinical history of COVID-19, particularly the classification of severity and early prediction on prognosis. Metabolomics is a powerful tool for identifying metabolite signatures when profiling parasitic, metabolic, and microbial diseases. This study undertook a metabolomic approach to identify potential metabolic signatures to discriminate severe COVID-19 from non-severe COVID-19. The secondary aim was to determine whether the clinical and laboratory data from the severe and non-severe COVID-19 patients were compatible with the metabolomic findings. Metabolomic analysis of samples revealed that 43 metabolites from 9 classes indicated COVID-19 severity: 29 metabolites for non-severe and 14 metabolites for severe disease. The metabolites from porphyrin and purine pathways were significantly elevated in the severe disease group, suggesting that they could be potential prognostic biomarkers. Elevated levels of the cholesteryl ester CE (18:3) in non-severe patients matched the significantly different blood cholesterol components (total cholesterol and HDL, both
< 0.001) that were detected. Pathway analysis identified 8 metabolomic pathways associated with the 43 discriminating metabolites. Metabolomic pathway analysis revealed that COVID-19 affected glycerophospholipid and porphyrin metabolism but significantly affected the glycerophospholipid and linoleic acid metabolism pathways (
= 0.025 and
= 0.035, respectively). Our results indicate that these metabolomics-based markers could have prognostic and diagnostic potential when managing and understanding the evolution of COVID-19.
Glucose-6 phosphate dehydrogenase deficiency (G6PDd) was suggested as a risk factor for severe disease in patients with COVID-19. We evaluated clinical outcomes and glucose-6 phosphate dehydrogenase ...(G6PD) activity during and after illness in patients with COVID-19. This prospective cohort study included adult participants (≥ 18 years old) who had clinical and/or radiological COVID-19 findings or positive reverse transcription-polymerase chain reaction results. Epidemiological and clinical data were extracted from electronic medical records. Glucose-6 phosphate dehydrogenase activity was measured using SD Biosensor STANDARD G6PD® equipment on admission and 1 year after discharge. Samples were genotyped for the three most common single nucleotide polymorphisms for G6PDd in the Brazilian Amazon. Seven hundred fifty-three patients were included, of whom 123 (16.3%) were G6PD deficient. There was no difference between groups regarding the risks of hospitalization (P = 0.740) or invasive mechanical ventilation (P = 0.31), but the risk of death was greater in patients with normal G6PD levels (P = 0.022). Only 29 of 116 participants (25%) carried the African G6PDd genotype. Of 30 participants tested as G6PD deficient during disease, only 11 (36.7%) results agreed 1 year after discharge. In conclusion, this study does not demonstrate an association of G6PDd with severity of COVID-19. Limitations of the test for detecting enzyme levels during COVID-19 illness were demonstrated by genotyping and retesting after the disease period. Care must be taken when screening for G6PDd in patients with acute COVID-19.
Between April and July 2020, and, therefore, prior to the broad recommendation of corticosteroids for severe COVID-19, a total of 50 full autopsies were performed in Manaus. We confirmed two invasive ...cases of aspergillosis through histopathology and gene sequencing (4%) in our autopsy series. The confirmed invasive aspergillosis incidence seems much lower than expected based on the "probable and possible" definitions, and an individualized approach should be considered for each country scenario. Interestingly, a prolonged length of stay in the intensive care unit was not observed in any of the cases. Timely diagnosis and treatment of fungal infection can reduce mortality rates.
Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in the reduction of sexually transmitted HIV infections. The prolonged use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) ...co-formulation (TDF/FTC), however, may result in augmented risk of renal toxicity. We aimed to evaluate changes in the estimated Glomerular Filtration Rate (eGFR) in a real-world population setting of participants enrolled in PrEP Brazil, a 48-week prospective, open-label, demonstration study to assess the feasibility of daily oral TDF/FTC used by men who have sex with men and transgender women at high-risk of HIV infection, all over 18 years old.
Kidney function was assessed by serial measurement of serum creatinine and eGFR with the Modification of Diet in Renal Disease Study (MDRD) formula on weeks 4, 12, 24, 36 and 48. Adherence to PrEP was assessed by dosing TDF concentration in dried blood spots at weeks 4 and 48, measured by liquid chromatography-mass spectrometry or mass spectrometry.
Of 392 participants completing the 48-week follow-up protocol with TDF blood detectable levels and eGFR measures, 43.1% were young adults, of Caucasian ethnic background (57.9%), with BMI below 30 kg/m
, without arterial hypertension. At screening, median eGFR was 93.0 mL/min/1.73 m
. At week 4 follow-up, 90 (23% of the study population) participants presented reductions in eGFR greater than 10 mL/min/1.73 m
as compared to baseline eGFR, some as large as 59 mL/min/1.73 m
, but with no clinical outcomes (adverse events and renal adverse events) severe enough to demand TDF/FTC discontinuation. A negative relationship was observed between TDF blood levels and eGFR at weeks 4 (r = - 0.005; p < 0.01) and 48 (r = - 0.006; p < 0.01).
These results suggest that the renal function profile in individuals on TDF/FTC may be assessed on week 4 and then only annually, allowing a more flexible medical follow-up in primary care centers.
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