The Complex Intersection of SARS-CoV-2, Immunity, and Oncovirus Reactivation: A Comprehensive Exploration


The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, marked the beginning of a global health crisis.

This positive-sense single-stranded ribonucleic acid (RNA) virus swiftly gave rise to the ongoing coronavirus disease 2019 (COVID-19) pandemic, which the World Health Organization officially declared on March 11, 2020.

As of now, the world has grappled with over 6.9 million reported deaths due to COVID-19, a staggering toll that continues to evolve with each passing day.

The Mode of SARS-CoV-2 Transmission

SARS-CoV-2 primarily spreads through close contact and the inhalation of aerosols or respiratory droplets. These viral particles are generated when individuals speak, breathe, exhale, cough, or sneeze, making it highly contagious in various social settings. The virus enters human cells by binding to angiotensin-converting enzyme 2 (ACE2) receptors, which are found ubiquitously throughout the body, thus establishing a broad range of potential infection sites.

Immunological Implications of Severe COVID-19

One of the intriguing aspects of severe COVID-19 is the profound impact it has on the immune system. In 67-90% of patients affected by severe COVID-19, lymphocytopenia, or a decrease in lymphocyte count, occurs. Lymphocytes are crucial components of the immune system, including killer T cells and helper T cells. This depletion of lymphocytes is often associated with a loss of immunosurveillance, a condition that can have far-reaching consequences.

Lymphopenia and Lymphodepletion

Lymphopenia is a well-known marker of impaired cellular immunity and is frequently observed in severe COVID-19 cases. Research has shown that both ACE2-dependent and ACE2-independent mechanisms contribute to the direct cytotoxic action of SARS-CoV-2 on lymphocytes. This immune dysregulation can create an environment in which latent pathogens in the body can reactivate, leading to various complications.

The Herpesvirus Connection

One family of viruses that have gained attention in the context of COVID-19 is the herpesviruses. This family of DNA viruses includes nine strains known to primarily infect humans, with five causing common diseases such as orolabial and genital herpes (HHV1 and HHV2), chickenpox and shingles (HHV3), and mononucleosis (HHV4) and mononucleosis-like syndrome (HHV5). These viruses are adept at establishing latent infections in various cell types, including neurons, monocytes, and B and T lymphocytes.

Herpetic Reactivations in COVID-19

A growing body of literature has reported instances of herpetic reactivations during COVID-19. Surprisingly, these reactivations have also been observed following COVID-19 vaccination, including vaccines based on nucleoside-modified messenger RNAs (modRNAs) and adenoviral vectors. These findings have raised questions about the potential link between SARS-CoV-2 infection, vaccination, and the reactivation of herpesviruses.

Oncoviruses: Epstein-Barr Virus (EBV) and Kaposi’s Sarcoma-Associated Herpesvirus (HHV8)

Among the herpesviruses, Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (HHV8) are particularly notorious as oncoviruses. EBV is associated with a range of malignancies, including Burkitt’s lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma. HHV8 is responsible for Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. In rare cases of severe immunodeficiency, such as AIDS, these two viruses can synergistically contribute to the development of aggressive lymphomas.

Rare and Lethal Encounters

In exceptionally rare cases, the intersection of SARS-CoV-2 infection and herpetic reactivation can result in a lethal combination. This was exemplified by a 50-year-old female transplant recipient with type 1 diabetes mellitus, who developed EBV-positive HHV8-associated large B cell lymphoma with plasmablastic differentiation in the context of severe COVID-19.

Another case involved a 78-year-old male patient with SARS-CoV-2 infection who presented with EBV-positive diffuse large B cell lymphoma (DLBCL) involving multiple organs, including the lungs. These cases underscore the complexity of COVID-19’s impact on the immune system and its potential to unmask latent infections with dire consequences.

COVID-19 Vaccination and Oncovirus Associations

Similar associations have been reported following COVID-19 vaccination, both with modRNA and adenoviral vector-based vaccines. These findings have prompted calls for larger-scale surveys to explore the intricate relationship between vaccination, immune response, and the reactivation of oncoviruses like EBV and HHV8.

The Emerging HPV Connection

Beyond herpesviruses, the investigation into the potential reactivation of other oncoviruses, such as human papillomavirus (HPV), is underway. HPV reactivation has been observed in the context of AIDS and graft-versus-host disease. Preliminary data suggests that COVID-19 may accelerate the progression of HPV-positive cervical intraepithelial neoplasia to microinvasive carcinoma in lymphopenic individuals. This raises important questions about the role of COVID-19 in cervical cancer screening programs.


The ongoing COVID-19 pandemic continues to reveal the complex interplay between viral infections, the immune system, and the reactivation of latent pathogens. Herpesviruses, particularly EBV and HHV8, have been implicated in severe cases of COVID-19, adding an additional layer of complexity to the disease’s pathophysiology.

As we navigate the evolving landscape of COVID-19 and vaccination campaigns, further research is needed to elucidate the intricate connections between viral infections, immune dysregulation, and the resurgence of oncoviruses. These findings may inform strategies for managing the long-term health consequences of COVID-19 and guide future vaccination efforts.

reference link :


Please enter your comment!
Please enter your name here

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.