key: cord-1004631-mmuyb8w5
authors: Leoni, E.; Cerati, M.; Finzi, G.; Lombardo, M.; Sessa, F.
title: COVID‐19 and HHV8 first spotted together: an affair under electron microscopy
date: 2021-02-05
journal: J Eur Acad Dermatol Venereol
DOI: 10.1111/jdv.17123
sha: e350331c9433cff1cd797edd92d621d1707f7cf7
doc_id: 1004631
cord_uid: mmuyb8w5

Despite the publication of articles about dermato-pathology of COVID-related skin lesions(1), only a few among these investigate patients with SARS-CoV-2 and other viral co-infections showing cutaneous manifestations. According to the growing attention dedicated by your journal to the topic of novel human coronavirus SARS-Cov-2, we decided to share the rather interesting case of a woman with previous history of Kaposi sarcoma without active skin lesions, who was recently hospitalized for COVID-19 infection.

cells displayed mild atypia and rare mitotic figures, and the underlying epidermis was atrophic with a basal hyperpigmentation (Fig. 1b,c) . As dermathopatologists, we performed an immunohistochemical analysis to further investigate the histological picture. The analysis results provided that all the spindle cells showed nuclear positivity for HHV8 (Clone 13B1) and cytoplasmatic reactivity for Podoplanin (Clone D2-40) (Fig. 1d,e) .

These findings confirm our suspect of Kaposi's sarcoma in plaque phase. Even though we could be satisfied with the diagnosis, we could not ignore the concurrent COVID-19 infection that seemed to correlate with skin rash development, so we decided to perform transmission electron microscope (TEM) analysis and with our surprise we observed not one, but two different viral families:

• Smaller nuclear viral particles (80 nm) consisting of central round black core surrounded by a brighter halo that we interpreted as HHV8 virus (Fig. 2a ,c orange arrow).

• Large cytoplasm vesicles containing spherical particles with crown-like spikes ranging from 80 to 100 nm in diameter that we identify as SARS-Cov-2 (Fig. 2b ,c blue arrow). Considering the well-known influence of the HIV virus on some form of Kaposi sarcoma, 2 we wonder, if there could be any similar relation between SARS-CoV-2 virus and HHV8. Finding both COVID-19 and HHV8 viruses in a patient's specimen observed under TEM 3 led us to speculate the mechanisms of coinfection of these pathogens. It also suggested a significant role of IL-6 in the process, which was already established during the trials using anti-IL-6 drugs in the hyperinflammatory phase of COVID-19 infection. 4 Moreover, we assume there is an interaction between the SARS-CoV-2 and the Kaposi sarcoma virus, where the first actor contributes to stimulate an hyperinflammatory status leading to proliferation of the HHV8 resulting in recurrence of Kaposi Sarcoma.

Lastly, we suggest the use of TEM to confirm the presence of the virus in skin specimens in laboratory environments, where specific antibodies versus SARS-CoV-2 are not available. (c) Figure 2 In these pictures, we can observe the HHV8 virus (a, orange arrow) and a macro vesicle containing numerous viral particles with the morphological features of corona virus particles (b, blu arrow). In figure c, instead, we can observe both viruses together.

Cutaneous manifestations of SARS-CoV-2 infection: a clinical update

Association of IL-6, IL-10 and CXCL10 serum concentrations with visceral Kaposi's sarcoma in people living with HIV/ AIDS

SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases

The role of interleukin 6 inhibitors in therapy of severe COVID-19

The patient has given written informed consent to the publication of her case details.