SARS-CoV-2 Induced Herpes Virus Reactivations and Related Implications in Oncohematology: When Lymphocytopenia Sets in and Immunosurveillance Drops Out

The severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), is a positive-sense single-stranded ribonucleic acid (RNA) virus contagious in humans and responsible for the ongoing coronavirus disease 2019 (COVID-19) [...].

The severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), is a positivesense single-stranded ribonucleic acid (RNA) virus contagious in humans and responsible for the ongoing coronavirus disease 2019 (COVID-19) [1].First identified in Wuhan, China, the World Health Organization declared the outbreak a pandemic on 11 March 2020 [2].To date, this disease has caused more than 6.9 million deaths [3].
SARS-CoV-2 mainly spreads via close contact and aerosols or respiratory droplets produced when speaking, breathing, exhaling, coughing, or sneezing [4].The virus enters human cells via the interaction between its spike protein and angiotensin-converting enzyme 2 (ACE2) receptors, ubiquitous throughout the body [5].
In 67-90% of the patients affected by severe COVID-19, lymphocytopenia occurs, a well-known marker of impaired cellular immunity; both killer T cells and helper T cells have been found to decrease in these circumstances [6].In addition, white pulp and lymphoid tissue depletion have been reported in the literature [7].Among the pathogenetic mechanisms to explain lymphopenia and lymphodepletion, there is a direct cytotoxic action of SARS-CoV-2 related to the ACE2-dependent or ACE2-independent entry into lymphocytes [6].
With the loss of immunosurveillance, latent pathogens in the body can be reactivated, as is the example of herpes viruses.They are a family of deoxyribonucleic acid (DNA) viruses, of which nine are known to primarily infect humans, and five cause extremely common diseases, such as orolabial and genital herpes due to human herpes virus 1 (HHV1) and human herpes virus 2 (HHV2), chickenpox and shingles from human herpes virus 3 (HHV3), and mononucleosis and mononucleosis-like syndrome from human herpes virus 4 (HHV4) and human herpes virus 5 (HHV5) [8].Over 90% of adults have been infected with at least one of these strains; depending on the virus, latent cells include neurons, monocytes, and B and T lymphocytes (Table 1).
The hypothesis that other DNA oncoviruses, such as human papillomavirus (HPV), may also take advantage of the immune system exhaustion induced by COVID-19 is under investigation [72], as known HPV can reactivate in the course of AIDS or graft-versus-host disease [73][74][75].From preliminary data in a lymphopenic setting, COVID-19 can lead to rapid progression of HPV-positive cervical intraepithelial neoplasia toward microinvasive carcinoma [76].Therefore, this further aspect should be deeply explored in the context of cervical cancer screening programs.

Table 1 .
Names, acronyms, synonyms, main diseases, latency cells, and transmission routes of the nine viruses belonging to the Herpesviridae family that infect humans.