SARS-CoV-2 Viral Replication Persists in the Human Lung for Several Weeks after Symptom Onset.

Rationale: In the upper respiratory tract, replicating (culturable) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recoverable for ∼4-8 days after symptom onset, but there is a paucity of data about the frequency and duration of replicating virus in the lower respiratory tract (i.e., the human lung).Objectives: We undertook lung tissue sampling (needle biopsy) shortly after death in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patients served as a control group.Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, and immunohistochemistry.Measurements and Main Results: Thirty-eight percent (16 of 42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 wk) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (P < 0.05). Nasopharyngeal culture was negative in 23.1% (6 of 26) of decedents despite lung culture positivity. This hitherto undescribed biophenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary proinflammatory response but with concurrent viral culture positivity.Conclusions: Concurrent rather than sequential active viral replication continues to drive a heightened proinflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe coronavirus disease (COVID-19).

Skin infiltrating T-cell profile of drug reaction with eosinophilia and systemic symptoms (DRESS) reactions among HIV-infected patients.

Introduction: Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) is more common in persons living with HIV (PLHIV), and first-line anti-TB drugs (FLTDs) and cotrimoxazole are the commonest offending drugs. Limited data is available on the skin infiltrating T-cell profile among DRESS patients with systemic CD4 T-cell depletion associated with HIV. Materials and methods: HIV cases with validated DRESS phenotypes (possible, probable, or definite) and confirmed reactions to either one or multiple FLTDs and/or cotrimoxazole were chosen (n = 14). These cases were matched against controls of HIV-negative patients who developed DRESS (n = 5). Immunohistochemistry assays were carried out with the following antibodies: CD3, CD4, CD8, CD45RO and FoxP3. Positive cells were normalized to the number of CD3+ cells present. Results: Skin infiltrating T-cells were mainly found in the dermis. Dermal and epidermal CD4+ T-cells (and CD4+/CD8+ ratios) were lower in HIV-positive vs. negative DRESS; p < 0.001 and p = 0.004, respectively; without correlation to whole blood CD4 cell counts. In contrast, no difference in dermal CD4+FoxP3+ T-cells was found in HIV-positive vs. negative DRESS, median (IQR) CD4+FoxP3+ T-cells: [10 (0-30) cells/mm2 vs. 4 (3-8) cells/mm2, p = 0.325]. HIV-positive DRESS patients reacting to more than one drug had no difference in CD8+ T-cell infiltrates, but higher epidermal and dermal CD4+FoxP3+ T-cell infiltrates compared to single drug reactors. Conclusion: DRESS, irrespective of HIV status, was associated with an increased skin infiltration of CD8+ T-cells, while CD4+ T-cells were lower in HIV-positive DRESS compared to HIV-negative DRESS skin. While inter-individual variation was high, the frequency of dermal CD4+FoxP3+ T-cells was higher in HIV-positive DRESS cases reacting to more than one drug. Further research is warranted to understand the clinical impact of these changes.

A case of pericardial schistosomiasis and non-Hodgkin high grade B-cell lymphoma.

Chronic schistosomiasis affects either the genitourinary or gastrointestinal tract. Rarely, schistosomes cause ectopic disease, such as in the case of a South African woman from a non-endemic province, who presented with suspected pericardial tamponade because of tuberculosis. However, histology and polymerase chain reaction from pericardial biopsy confirmed Schistosoma haematobium. A finding of mediastinal non-Hodgkin lymphoma came to light when our patient's clinical condition unexpectedly deteriorated. Contribution: This case highlights an unusual manifestation of schistosomiasis.

Chronic rheumatic heart disease with recrudescence of acute rheumatic fever on histology: a case report.

Background: Rheumatic heart disease (RHD) is endemic in sub-Saharan Africa where it is the leading cause of cardiovascular mortality in the young. Rheumatic heart disease results from recurrent episodes of acute rheumatic fever (ARF), which are often difficult to diagnose clinically. Acute rheumatic fever may be diagnosed based on the revised Jones Criteria 2015 for the diagnosis of ARF. Histologically, acute rheumatic valvulitis manifests with active inflammation characterized by lymphocytic infiltration, Aschoff bodies, and Anitschkow cells. Chronic rheumatic valvulitis is associated with neovascularization, and/or dystrophic calcification. The combination of histological features of both ARF and chronic RHD is a rare finding. Case summary: Here we report on a case of a 59-year-old woman with mixed aortic and mitral valve disease of probable rheumatic aetiology (elevated C-reactive protein and prolonged PR interval) and with histological evidence of lymphocytic infiltration, Aschoff bodies, and fibrinoid necrosis admixed with features of chronic RHD. Discussion: Cases of chronic RHD admixed with ARF are very rare; however, they should be considered in regions with a high prevalence of RHDs.

Merkel cell carcinoma of the anorectum: a case report and review of the literature.

Merkel cell carcinoma is a highly aggressive neuroendocrine carcinoma that most commonly arises in sun-exposed skin. Established risk factors include advanced age, fair skin, chronic ultraviolet light exposure and immunosuppression. Merkel cell polyomavirus infection is implicated in a subset of cases. Primary extracutaneous Merkel cell carcinoma is exceedingly rare. We report a case of Merkel cell carcinoma of the anorectum in a 44-year-old woman of Indian descent with no apparent risk factors. She presented with rectal bleeding and worsening perineal discomfort. A polypoid tumor was identified in the anal canal. No cutaneous lesions were detected. Histopathology revealed a small round blue cell tumor with neuroendocrine features. Immunohistochemistry for CK20, synaptophysin, CD56, neurofilament and SATB2 were positive while CK7, CDX2 and TTF1 were negative. Polymerase chain reaction and immunohistochemistry were negative for Merkel cell polyomavirus. Merkel cell carcinoma should be considered in the differential diagnosis of a high grade neuroendocrine carcinoma at an unusual site such as the anorectum in this case. Correct diagnosis of Merkel cell carcinoma at an extracutaneous site is crucial because it should prompt careful evaluation for a skin primary and it may make the patient eligible for immune checkpoint inhibitor therapy.

Arteriovenous malformation after punch biopsy clinically mimicking a basal cell carcinoma: Case report and review of literature.

Arteriovenous malformations (AVM's) of the skin can be acquired post blunt or penetrating trauma. They may clinically mimic basal cell carcinomas and other lesions with overlying telangiectasia. Specific clinical, dermoscopic, and histological clues differentiate these conditions. AVM's may progress to destructive lesions and early surgical intervention is key.

Gene of the month: KIT.

Deranged pathway activation and KIT mutations occur in numerous solid and haematological malignancies, with gain-of-function mutations being the most common demonstrable abnormality. Through a complex series of interactions, activation of the KIT receptor tyrosine kinase leads to cell survival, evasion of apoptosis, angiogenesis, dysregulated cell cycle control and promotion of tumourigenesis. The KIT receptor tyrosine kinase is a well-studied therapeutic target in human malignancies. The KIT mutational status of a neoplasm plays an important role in predicting the response to targeted therapies. In this article we outline the structure, function and mutations of the KIT gene, its role in various neoplasms, therapeutic impacts and the role that these play in clinical patient outcome.