COVID-19 autopsy cases: detection of virus in endocrine tissues.

PURPOSE: The SARS-CoV-2 genome has been detected in a variety of human samples including blood, urine, semen, and faeces. However, evidence of virus presence in tissues other than lung are limited. METHODS: We investigated whether SARS-CoV-2 could be detected in 50 autoptic specimens of endocrine organs from 29 patients who died of COVID-19. RESULTS: The virus was detected in 25 specimens including ten abdominal subcutaneous adipose tissue samples (62%), six testes (67%), and nine thyroid (36%) samples. The analysis of multiple endocrine organ samples obtained from the same patients showed that, in virus-positive cases, the viral genome was consistently detected in all but two matched specimens. CONCLUSION: Our findings show that the virus spread into endocrine organs is a common event in severe cases. Further studies should assess the rate of the phenomenon in clinically mild cases. The potential long-term effects of COVID-19 on endocrine functions should be taken into consideration.

CD4+ Cell infiltration into subcutaneous adipose tissue is not indicative of productively infected cells during acute SHIV infection.

Limited longitudinal data exist on the effect of HIV on adipose tissue (AT). We found an increase in CD4+ cells and detectable SHIV-RNA in AT during acute SHIV infection. SHIV-RNA+ cells were rare, suggesting that AT is unlikely to be a major source of productively infected cells in SHIV infection.

The Molecular Signature of HIV-1-Associated Lipomatosis Reveals Differential Involvement of Brown and Beige/Brite Adipocyte Cell Lineages.

Highly active antiretroviral therapy has remarkably improved quality of life of HIV-1-infected patients. However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations. Among them, lipoatrophy of subcutaneous fat in certain anatomical areas and hypertrophy of visceral depots are the most common. Less frequently, lipomatous enlargements of subcutaneous fat at distinct anatomic areas occur. Lipomatous adipose tissue in the dorso-cervical area ("buffalo hump") has been associated with a partial white-to-brown phenotype transition and with increased cell proliferation, but, to date, lipomatous enlargements arising in other parts of the body have not been characterized. In order to establish the main molecular events associated with the appearance of lipomatosis in HIV-1 patients, we analyzed biopsies of lipomatous tissue from "buffalo hump" and from other anatomical areas in patients, in comparison with healthy subcutaneous adipose tissue, using a marker gene expression approach. Both buffalo-hump and non-buffalo-hump lipomatous adipose tissues exhibited similar patterns of non-compromised adipogenesis, unaltered inflammation, non-fibrotic phenotype and proliferative activity. Shorter telomere length, prelamin A accumulation and SA-ß-Gal induction, reminiscent of adipocyte senescence, were also common to both types of lipomatous tissues. Buffalo hump biopsies showed expression of marker genes of brown adipose tissue (e.g. UCP1) and, specifically, of "classical" brown adipocytes (e.g. ZIC1) but not of beige/brite adipocytes. No such brown fat-related gene expression occurred in lipomatous tissues at other anatomical sites. In conclusion, buffalo hump and other subcutaneous adipose tissue enlargements from HIV-1-infected patients share a similar lipomatous character. However, a distorted induction of white-to-"classical brown adipocyte" phenotype appears unique of dorso-cervical lipomatosis. Thus, the insults caused by HIV-1 viral infection and/or antiretroviral therapy leading to lipomatosis are acting in a location- and adipocyte lineage-dependent manner.

Changes in subcutaneous adipose tissue microRNA expression in HIV-infected patients.

OBJECTIVES: We evaluated the possibility that a pattern of abnormal microRNA (miRNA) expression could be fuelling the mechanisms causing HIV-associated lipodystrophy (HAL). METHODS: In this case-control study, samples of subcutaneous adipose tissue from eight consecutive HIV-infected patients on combination antiretroviral therapy with HAL (cases) were compared with those of eight HIV-negative subjects (controls). Human miRNA microarrays were used to probe the transcriptomes of the samples. Analysis of differentially expressed miRNAs was performed using DataAssist v2.0 software, applying a paired Student's t-test. RESULTS: Data showed that 21 miRNAs out of 754 were overexpressed in the patient group. Ten of these (i.e. miR-186, miR-199a-3p, miR-214, miR-374a, miR-487b, miR-532-5p, miR-628-5p, miR-874, miR-125-b-1* and miR-374b*) were up-regulated to a significant degree (fold change >2.5; P < 0.01). Eleven other miRNAs (i.e. miR-let-7d, miR-24, miR-30c, miR-125a-3p, miR-149, miR-191, miR-196-b, miR-218, miR-342-3p, miR-452 and miR-454*) were 2- to 2.5-fold more expressed in HIV+ samples than in controls. Levels of mRNA for lipin 1, the target of miR-218, were significantly lower in subcutaneous adipose tissue from HIV patients. CONCLUSIONS: In adipocytes of HIV-infected patients, the up-regulation of specific miRNAs could lead to an increased 'activation' that might contribute to the pathogenesis of HAL by increasing cell turnover and/or promotion of apoptosis.

Fat grafting as a vehicle for the delivery of recombinant adenoassociated viral vectors to achieve gene modification of muscle flaps.

BACKGROUND: The combination of gene therapy and plastic surgery may have the potential to improve the specificity that is needed to achieve clinically applicable treatment regimens. Our goal was to develop a method for gene modification that would yield sustainable production of gene products but would be less time consuming than existing protocols. METHODS: An adenoassociated virus was used to deliver gene products to pectoralis muscle flaps. Gene modification was accomplished via either direct injection or novel fat grafting techniques. RESULTS: The production of gene product was observable by both in vivo imaging and immunohistochemical staining. Gene products were not detected in tissues that were not in contact with the fat grafts that were incubated with the viral vector, indicating that the transduction stayed local to the flap. CONCLUSIONS: Using novel recombinant adenoassociated virus vectors, we have developed a method for gene delivery that is highly efficient and applicable to muscle flaps.

Human immunodeficiency virus atropy induces modification of subcutaneous adipose tissue architecture: in vivo visualization by high-resolution magnetic resonance imaging.

BACKGROUND: Human immunodeficiency virus (HIV) infection generally induces lipodystrophy. For targeted treatment a better understanding of its development is necessary. The utility of high-resolution magnetic resonance imaging (MRI) is explored. OBJECTIVES: The present study presents a way to visualize the adipose tissue architecture in vivo and to inspect modifications associated with the atrophy. METHODS: High-resolution MRI scans with surface coils were performed on the calf and at the lumbar region of three groups of patients: HIV patients with lipoatrophy, HIV patients without lipoatrophy and healthy volunteers. All patients underwent a clinical examination. In addition, dual energy X-ray absorptiometry (DEXA) measurements were taken. On the MRI scans adipose tissue thickness and adipose nodule size were measured. Results High-resolution MRI enabled identification of a clear disorganization of adipose tissue in patients with lipoatrophy. In addition, these patients presented a very small adipose tissue thickness on the calf and a very small nodule size. RESULTS: led to the hypothesis that adipose tissue disorganization appears before changes in DEXA measurements or clinically visible modifications. CONCLUSIONS: High-resolution MRI enabled visualization in vivo of precise changes in tissue organization due to HIV lipoatrophy. This imaging technique should be very informative for better monitoring of the atrophy.

Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is defined as a rare cytotoxic alpha/beta T-cell lymphoma characterized by primary involvement of subcutaneous tissue mimicking panniculitis and a predominant CD3+/CD4-/CD8+ phenotype in 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas. We presented a detailed study of SPTL, describing clinicopathologic, immunophenotypic, and molecular features of 22 cases in China. Strict diagnostic criteria according to the WHO-EORTC definition were applied to the diagnosis of all SPTL cases. Besides the common features described before, unusual CD4+/CD8- and CD4-/CD8- T-cell phenotypes were noted in 2 of our cases, respectively. CD30 was negative in all cases and CD56 was focally positive in 2 cases. Mortality in cases with angioinvasion (75%) was significantly higher than that in cases without angioinvasion (14.3%). Epstein-Barr virus (EBV) infection was detected in 1 immunocompetent patient by in situ hybridization. The frequency of rearranged TCRB, TCRG, and TCRD genes detected by BIOMED-2 multiplex polymerase chain reaction tubes was 80%, 67%, and 13%, respectively, with a total clonality detection rate of 100%. Clinical follow-up was available in 18 patients, ranging from 6 to 80 months. Most patients obtained complete or partial remission after therapy including one accompanied with EBV infection; 5 patients died: 3 of disease progression, 1 of severe infection, and 1 of complications caused by diabetes and hypertension. We conclude that SPTL as a cytotoxic lymphoma derived from alpha/beta T cell has a predominant CD4-/CD8+ phenotype, but unusual CD4+/CD8- and CD4-/CD8- phenotypes do exist. Owing to its indolent clinical course and relatively high survival rate, SPTL should be differentiated from cutaneous gamma/delta T-cell lymphoma. EBV is generally absent in SPTL but can rarely be detected especially in Asian population. Angioinvasion is a poor prognostic factor in SPTL.