MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.

Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

Post-Mortem Diagnosis of Pediatric Dengue Using Minimally Invasive Autopsy during the COVID-19 Pandemic in Brazil.

We report the first pediatric disease in which the use of minimally invasive autopsy (MIA) confirmed severe dengue as the cause of death. During the COVID-19 pandemic, a previously healthy 10-year-old girl living in north-eastern Brazil presented fever, headache, diffuse abdominal pain, diarrhoea, and vomiting. On the fourth day, the clinical symptoms worsened and the patient died. An MIA was performed, and cores of brain, lungs, heart, liver, kidneys, and spleen were collected with 14G biopsy needles. Microscopic examination showed diffuse oedema and congestion, pulmonary intra-alveolar haemorrhage, small foci of midzonal necrosis in the liver, and tubular cell necrosis in the kidneys. Dengue virus RNA and NS1 antigen were detected in blood and cerebrospinal fluid samples. Clinical, pathological, and laboratory findings, in combination with the absence of other lesions and microorganisms, allowed concluding that the patient had died from complications of severe dengue.

Testicular pathology in fatal COVID-19: A descriptive autopsy study.

BACKGROUND: Multi-organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, going beyond the initially observed severe pneumonia. Evidence that the testis is also compromised is growing. OBJECTIVE: To describe the pathological findings in testes from fatal cases of COVID-19, including the detection of viral particles and antigens, and inflammatory cell subsets. MATERIALS AND METHODS: Postmortem testicular samples were obtained by percutaneous puncture from 11 deceased men and examined by reverse-transcription polymerase chain reaction (RT-PCR) for RNA detection and by light and electron microscopy (EM) for SARS-CoV-2. Immunohistochemistry (IHC) for the SARS-CoV-2 N-protein and lymphocytic and histiocytic markers was also performed. RESULTS: Eight patients had mild interstitial orchitis, composed mainly of CD68+ and TCD8+ cells. Fibrin thrombi were detected in five cases. All cases presented congestion, interstitial edema, thickening of the tubular basal membrane, decreased Leydig and Sertoli cells with reduced spermatogenesis, and strong expression of vascular cell adhesion molecule (VCAM) in vessels. IHC detected SARS-Cov-2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts in all cases. EM detected viral particles in the cytoplasm of fibroblasts, endothelium, Sertoli and Leydig cells, spermatids, and epithelial cells of the rete testis in four cases, while RT-PCR detected SARS-CoV-2 RNA in three cases. DISCUSSION AND CONCLUSION: The COVID-19-associated testicular lesion revealed a combination of orchitis, vascular changes, basal membrane thickening, Leydig and Sertoli cell scarcity, and reduced spermatogenesis associated with SARS-CoV-2 local infection that may impair hormonal function and fertility in men.

Radiological patterns of incidental epididymitis in mild-to-moderate COVID-19 patients revealed by colour Doppler ultrasound.

The testis is a potential target organ for SARS-CoV-2 infection. Our study intended to investigate any testicular involvement in mild-to-moderate COVID-19 men. We conduct a cross-sectional study in 18 to 55-year-old men hospitalised for confirmed COVID-19. A senior radiologist executed the ultrasound with multi-frequency linear probe in all participants, regardless of any scrotal complaints. Exclusion criteria involved any situation that could impair testicular function. Statistical analysis compared independent groups, classified by any pathological change. Categorical and numerical outcome hypotheses were tested by Fisher's Exact and Mann-Whitney tests, using the Excel for Mac, version 16.29 (p < .05). The sample size was 26 men (mean 33.7 ± 6.2 years; range: 21-42 years), all without scrotal complaints. No orchitis was seen. Eleven men (32.6 ± 5.8 years) had epididymitis (42.3%), bilateral in 19.2%. More than half of men with epididymitis displayed epididymal head augmentation > 1.2 cm (p = .002). Two distinct epididymitis' patterns were reported: (a) disseminated micro-abscesses (n = 6) and (b) inhomogeneous echogenicity with reactional hydrocele (n = 5). Both patterns revealed increased epididymal head, augmented Doppler flow and scrotal skin thickening. The use of colour Doppler ultrasound in mild-to-moderate COVID-19 men, even in the absence of testicular complaints, might be useful to diagnose epididymitis that could elicit fertility complications.

Pulmonary and systemic involvement in COVID-19 patients assessed with ultrasound-guided minimally invasive autopsy.

AIMS: Brazil ranks high in the number of coronavirus disease 19 (COVID-19) cases and the COVID-19 mortality rate. In this context, autopsies are important to confirm the disease, determine associated conditions, and study the pathophysiology of this novel disease. The aim of this study was to assess the systemic involvement of COVID-19. In order to follow biosafety recommendations, we used ultrasound-guided minimally invasive autopsy (MIA-US), and we present the results of 10 initial autopsies. METHODS AND RESULTS: We used MIA-US for tissue sampling of the lungs, liver, heart, kidneys, spleen, brain, skin, skeletal muscle and testis for histology, and reverse transcription polymerase chain reaction to detect severe acute respiratory syndrome coronavirus 2 RNA. All patients showed exudative/proliferative diffuse alveolar damage. There were intense pleomorphic cytopathic effects on the respiratory epithelium, including airway and alveolar cells. Fibrinous thrombi in alveolar arterioles were present in eight patients, and all patients showed a high density of alveolar megakaryocytes. Small thrombi were less frequently observed in the glomeruli, spleen, heart, dermis, testis, and liver sinusoids. The main systemic findings were associated with comorbidities, age, and sepsis, in addition to possible tissue damage due to the viral infection, such as myositis, dermatitis, myocarditis, and orchitis. CONCLUSIONS: MIA-US is safe and effective for the study of severe COVID-19. Our findings show that COVID-19 is a systemic disease causing major events in the lungs and with involvement of various organs and tissues. Pulmonary changes result from severe epithelial injury and microthrombotic vascular phenomena. These findings indicate that both epithelial and vascular injury should be addressed in therapeutic approaches.

SARS-CoV-2 and its relationship with the genitourinary tract: Implications for male reproductive health in the context of COVID-19 pandemic.

BACKGROUND: The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, named coronavirus disease 19 (COVID-19), is not the first well-known spillover of an animal originated virus to infect humans. However, one of the few to make such a fast jump in a powerful evolutionary shortcut. The incredible pattern of aggressiveness worldwide since the beginning of the outbreak is that up to 20% of those infected need hospitalization and 5% evolve to critical conditions, not limited to respiratory-related issues, but rather to systemic involvement. OBJECTIVE: This study aims to summarize the current knowledge about the effects of SARS-CoV-2 infection on the male genitourinary tract. MATERIALS AND METHODS: A narrative review was carried out to identify articles on the SARS-CoV-2 infection on the male genitourinary system. RESULTS: Considerations were made about the molecular characteristics of SARS-CoV-2 and immune response to coronavirus. We discussed the influence of the virus on the urinary system, potential mechanisms of COVID-19- related acute kidney injury (AKI), and the role of cytokine release syndrome on the renal pathophysiology of the disease. In the male reproductive tract, it was discussed the testis' vulnerability to SARS-CoV-2 invasion and the possible adverse effects on its function and the seminal findings of COVID-19. DISCUSSION AND CONCLUSION: During the COVID-19 pandemic, an international coordinated scientific effort must arise to understand the role of the urogenital system in the SARS-CoV-2 infection in the clinical setting.