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Despite the considerable research efforts being made to learn more about COVID-19, little is known about the presence of SARS-CoV-2 genetic material in biological fluids other than respiratory droplets, blood, and feces 1,2. In particular, little is known about the presence of SARS-CoV-2 in the joints either post mortem3 or in vivo4. To the best of our knowledge, only Lopéz-Gonzalez et al.5 have published a description of acute arthritides occurring during hospitalisation due to COVID-19, and they did not find any SARS-CoV-2 genetic material in the patients' synovial fluid samples. The aim of this post mortem study was to assess the presence of SARS-CoV-2 RNA in the knee synovial fluid, synovial tissue, and bone tissue of COVID-19 patients in order to discover whether the joint is a possible route of transmission during orthopaedic surgical procedures, and clarify the possible role of SARS-CoV-2 as a directly arthritogenic virus. Post mortem synovial fluid, synovial tissue and bone tissue samples were collected from the knees of five patients who died of COVID-19 in our hospital between September and October 2020, and analysed for the presence of SARS-CoV-2 using a commercial real-time polymerase chain reaction (RT-PCR) panel. Quantitative RT-PCR was used to test post mortem nasopharyngeal swabs of all of the patients. No SARS-CoV-2 RNA was detected in any of the knee samples, despite the positivity of the throat swab. Our findings indicate that SARS-CoV-2 was not detected in knee synovial fluid, synovial membrane or bone. Therefore, our results suggest that all healthcare professionals performing surgical procedures on the joints of COVID-19 patients are exposed to a risk of contagion due to exposure to respiratory droplets, blood and body fluids, but not to direct exposure to joint- or bone-related tissues. Furthermore, given that some case reports of arthritis in COVID-19 patients 5-8 show that it is possible that COVID-19 patients display viral-mediated arthralgias and arthritis, the absence of the virus in the knee highlighted by our study suggests that it is unlikely that SARS-CoV-2 has a direct inflammatory action on the joint, but it could induce an inflammation-related reaction, manifesting as a reactive arthritis 9. [1]Cheng ZJ, Shan J. 2019 Novel coronavirus: where we are and what we know. Infection. 2020;(0123456789):1-9. doi:10.1007/s15010-020-01401-y [2]Chen Y, Chen L, Deng Q, et al. The Presence of SARS-CoV-2 RNA in Feces of COVID-19 Patients. J Med Virol. April 2020. doi:10.1002/jmv.25825 [3]Maiese A, Manetti AC, La Russa R, et al. Autopsy findings in COVID-19-related deaths: a literature review. Forensic Sci Med Pathol. 2020. doi:10.1007/s12024-020-00310-8 [4]Baldanti F, Novazzi F, Cassaniti I, Piralla A, Di A, Bruno R. Detection of the SARS-CoV-2 in different biologic specimens from positive patients with COVID-19, in Northern Italy. Authorea. 2020. doi:10.22541/au.159724509.93056098 [5]López-González M-C, Peral-Garrido ML, Calabuig I, et al. Case series of acute arthritis during COVID-19 admission. Ann Rheum Dis. 2020;0(0):annrheumdis-2020-217914. doi:10.1136/annrheumdis-2020-217914 [6]Parisi S, Borrelli R, Bianchi S, Fusaro E. Viral arthritis and COVID-19. Lancet Rheumatol. 2020;2(11):e655-e657. doi:10.1016/S2665-9913(20)30348-9 [7]Alivernini S, Cingolani A, Gessi M, et al. Comparative analysis of synovial inflammation after SARS-CoV-2 infection. Ann Rheum Dis. 2020;0(0):2-3. doi:10.1136/annrheumdis-2020-218315 [8]Talarico R, Stagnaro C, Ferro F, Carli L, Mosca M. Symmetric peripheral polyarthritis developed during SARS-CoV-2 infection. Lancet Rheumatol. 2020;2(9):e518-e519. doi:10.1016/S2665-9913(20)30216-2 [9]Di Carlo M, Tardella M, Salaffi F. Can SARS-CoV-2 induce reactive arthritis? Clin Exp Rheumatol. 2020;In press. We would like to thank the clinical staff of the Pathology Unit for their collaboration in performing the autopsies. None declared

Doc number: P19

Fabry disease is a rare X‐linked disorder, characterized by deficient activity of the lysosomal enzyme α‐galactosidase A. This leads to systemic accumulation of the glycosphingolipid globotriaosylceramide (Gb3) in all body tissues and organs, including the kidney. Renal manifestations are less evident in female heterozygotes than in male hemizygotes, according to the Lyon hypothesis. Accumulation of Gb3 occurs mainly in the epithelial cells of Henle's loop and distal tubule, inducing early impairment in renal concentrating ability; involvement of the proximal tubule induces Fanconi syndrome. All types of glomerular cells are involved, especially podocytes, and glomerular proteinuria may occur at a young age. The evolution of renal Fabry disease is characterized by progressive deterioration of renal function to end‐stage renal failure (ESRF). Ultrastructural study of kidney biopsies reveals typical bodies in the cytoplasm of all types of renal cells, characterized byconcentric lamellation of clear and dark layers with a periodicity of 35–50 Å.Management of progressive renal disease requires dietetic and therapeutic strategies, usually indicated in developing chronic renal failure, with dialysis and renal transplantation required for patients with ESRF. The recent development of enzyme replacement therapy, however, should make it possible to prevent or reverse the progressive renal dysfunction associated with Fabry disease.

Accumulation of amino acids was studied in rice roots of 3-day-old seedlings subjected for 48 h to anaerobic conditions. Alanine and Gaba were the main amino acids accumulated under anoxia. Their synthesis was strongly inhibited by MSX and AZA, inhibitors of glutamine synthetase and glutamate synthase. These activities increased after 8 h of anaerobic treatment and, by immunoprecipitation of 35S-labeled proteins, it was shown that glutamine synthetase and ferredoxin-dependent glutamate synthase were synthesized during the treatment. These findings indicate that the glutamine synthetase/glutamate synthase cycle play an important role in anaerobic amino acid accumulation.

This observational cohort study of 4,160 AIDS patients hospitalised in a single institution in northern Italy between January 1985 and December 1999 was carried out in order to assess the natural history of cryptococcosis, the epidemiological trend of this opportunistic infection, the risk factors predictive of death at 10 weeks, the response to therapy, and autopsy findings. Cryptococcosis was diagnosed in 177 (4.2%) patients and was the AIDS-defining disease in 2.8% of cases. Its prevalence decreased significantly over time (from 6.4% in the period 1985-1989 to 5.7% in 1990-1993, 3.1% in 1994-1996, and 1.9% in 1997-1999, P <0.0001). Although neurologic disease was the most frequent clinical picture, a significant proportion of the patients (24.2%) presented with extraneural cryptococcosis. In a Cox multivariate analysis, high titres of cerebrospinal fluid antigen (>5000) and drug addiction were predictive of death at 10 weeks. A complete clinical and mycological response was achieved in 60.8% of the treated patients, with the highest response rate being observed in those treated with amphotericin plus flucytosine (66.6%). Cryptococcosis relapsed in 12.8% of patients on secondary prophylaxis. Autopsy findings demonstrated that cryptococcosis is a disseminated disease, but long-term antifungal treatment may be able to eradicate it in a subgroup of patients.

To correlate cerebral histopathological and immunohistochemical changes in the neuroclinical features of the AIDS dementia complex (ADC), autopsy results of 28 ADC patients were related, in a retrospective analysis, to scores on a standardised neurological examination performed at neurologic onset. From a histopathological point of view, the cases were classified as follows: 9 cases of HIV leucoencephalopathy (HIVL; diffuse myelin damage and rare microglial nodules), 7 cases of HIV encephalitis (HIVE; several microglial nodules and no myelin damage) and 12 cases of mixed HIVL and HIVE (HIVL-E). The groups differed significantly with respect to symptoms and CD4 count at neurologic onset, survival and neurological impairment. Immunohistochemically, the interstitial component (p24-positive cells scattered singly within the white matter) was significantly more prevalent in HIVL, and the micronodular component (p24-positive cells confined within microglial nodules) in HIVE. Neurological damage was worse in cases with a high prevalence of interstitial component or a low prevalence of micronodular component. HIVE, HIVL and HIVL-E are distinct clinical forms of ADC. Neurological impairment is related to white matter damage.

AIMS: To evaluate the histological changes seen in liver biopsies after interferon (IFN) treatment in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection. METHODS: Twenty four intravenous drug users with chronic hepatitis C were investigated histologically before beginning a 12 month course of IFN treatment and 18 months later. Twelve were HIV positive, without opportunistic or other viral infections (group A), and 12 were HIV negative (group B). RESULTS: According to alanine amino-transferase concentrations, four sustained responders and eight non-responders were found in group A; six sustained responders, five relapsers, and one non-responder were found in group B. HCV RNA became negative in one sustained responder of group A and in the six sustained responders of group B. When histological findings of biopsies performed before therapy and 18 months later were compared, no significant changes in the mean value of Knodell's index and subindices were found in group A, whereas in group B Knodell's index, piecemeal necrosis, and focal hepatocellular necrosis decreased significantly. CONCLUSIONS: In chronic hepatitis C, coinfection with HIV showed a tendency towards a lower response to IFN, although this did not reach statistical significance; however, none of the HIV positive patients developed cirrhosis during the follow up and this should be considered in clinical management of such patients.

Extracellular hyaline globules resulting from abnormal accumulation of matrix components have been described in several pathological conditions, including renal tumors. We studied 16 renal oncocytomas and observed these bodies in 11 of them. In these tumors, they showed a homogeneous texture as well as roundish, smooth contours, and were easily detected in hematoxylin-eosin sections in five cases. PAS staining greatly facilitated the identification of globules in the remaining six cases, where they were fewer in number. Immunohistochemically, they appeared to be composed primarily of basement membrane material, being strongly reactive to antibodies for type IV collagen, laminin, and heparan sulphate proteoglycan. In addition, a weak immunoreactivity for type I and type III collagen, and fibronectin was observed in some cases, whereas no globule stained for tenascin. We also analyzed 89 renal cell carcinomas, and found somewhat similar bodies in 10 of them. However, they were more scanty in the latter tumors, and displayed a more irregular configuration with granular or smudged contours. We conclude that, although the mere presence of extracellular hyaline globules does not justify a distinction between renal oncocytoma and renal cell carcinoma, the detection of a large number of well-demarcated, roundish extracellular bodies with smooth contours suggests renal oncocytoma.