Infection with SARS-CoV-2, the virus that causes COVID-19, has raised concerns about its potential to lead to Non-Hodgkin’s Lymphoma (NHL). This concern is rooted in the known ability of other viruses to cause cancer and the profound effect SARS-CoV-2 has on the human immune system. Understanding this potential link requires examining the biology of this blood cancer and the virus’s interaction with immune cells.
Understanding Non-Hodgkin’s Lymphoma
Non-Hodgkin’s Lymphoma (NHL) is a diverse group of cancers originating in the lymphoid tissues, primarily the lymph nodes. These malignancies involve the uncontrolled growth of lymphocytes (white blood cells). NHL is classified based on the two main types of lymphocytes affected: B-cells and T-cells. The disease arises when genetic changes cause a single lymphocyte to multiply excessively and crowd out normal immune cells. NHL subtypes are broadly categorized as either indolent (slow-growing) or aggressive (rapid progression).
Viral Precedent for Lymphoma Development
The idea that a virus could be linked to lymphoma is well-established, providing a biological basis for concerns regarding SARS-CoV-2. Several viruses are recognized for their ability to cause or increase the risk of developing certain lymphomas by disrupting normal immune or cellular function.
Examples of Oncogenic Viruses
Epstein-Barr Virus (EBV) is associated with various lymphomas, including Burkitt lymphoma. EBV’s oncogenic potential comes from its ability to produce viral proteins, such as latent membrane protein 1 (LMP1), which activate cell growth pathways within infected B-cells, promoting survival and malignant transformation.
Human T-lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma by directly transforming T-cells through its viral proteins. In contrast, Human Immunodeficiency Virus (HIV) creates profound immunosuppression rather than directly causing lymphoma. This weakened immune surveillance allows other viruses, like EBV, to drive cancer development or permits pre-cancerous cells to proliferate unchecked.
How COVID-19 Affects Immune Regulation
SARS-CoV-2 infection causes significant immune dysregulation, creating a theoretical environment that could accelerate lymphomagenesis. This hyper-inflammatory state involves the uncontrolled release of pro-inflammatory signaling molecules, often called a “cytokine storm.”
Chronic inflammation, involving cytokines such as Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α), promotes cell survival and growth signals in lymphocytes. Persistent inflammation is a known cancer risk factor because it stresses cellular systems and increases the likelihood of genetic errors.
The virus also causes lymphopenia, a widespread depletion of T-cells and Natural Killer (NK) cells, especially in severe cases. Since T-cells identify and eliminate cancerous cells, this depletion impairs the body’s immune surveillance. Remaining T-cells often express markers of exhaustion, indicating they are functionally impaired. This combination of chronic inflammatory signaling and impaired T-cell surveillance provides a plausible biological pathway for lymphoid malignancies.
Scientific Findings on the COVID-19 and NHL Link
Current scientific evidence regarding a direct causal link between SARS-CoV-2 infection and the onset of NHL remains complex and evolving. The theoretical biological plausibility, rooted in immune dysregulation, has not translated into definitive epidemiological proof of increased incidence following infection. Long-term population studies are needed to assess the risk.
Ecological studies have found an association between areas with a higher historical incidence of NHL and a higher cumulative incidence of COVID-19 cases. This geographic correlation suggests shared susceptibility factors, such as genetic or environmental elements, making populations vulnerable to both diseases. It does not establish that the virus itself causes the cancer.
Clinical observations show a complicated picture, with case reports noting both new NHL diagnoses shortly after infection and, conversely, unexpected remission. One case described the complete remission of B-cell NHL following infection, suggesting massive immune activation can, in rare instances, trigger an anti-tumor response.
The current scientific consensus is that while SARS-CoV-2 immune disruption provides a theoretical mechanism for lymphomagenesis, there is no strong evidence that COVID-19 is a frequent and direct cause of NHL. Observed cases may relate to the acceleration of pre-existing, undiagnosed conditions due to immune stress or reflect delayed diagnosis during the pandemic. Continued surveillance is necessary to clarify long-term effects.