The Cytomegalovirus (CMV) is a highly common virus belonging to the herpes family, and infection is typically asymptomatic in people with healthy immune systems. Once a person is infected, the virus establishes a latent, lifelong presence in the body. The presence of antibodies against CMV indicates past exposure, a state known as seropositivity. CMV negative blood, or seronegative blood, is simply blood donated by someone who has never been exposed to the virus, meaning their blood lacks these specific antibodies.
Understanding CMV Seronegativity
The rarity of CMV negative blood is relative, depending heavily on the population being examined. CMV seropositivity rates vary widely across different geographical regions, age groups, and socioeconomic factors. In the United States, the overall CMV seroprevalence in adults is estimated to be around 50% to 75%. This means roughly 25% to 50% of the US adult population is CMV negative and could potentially donate CMV negative blood.
However, in many developing nations, seroprevalence can exceed 90% due to higher rates of early childhood exposure. Even within the US, prevalence increases significantly with age and is generally higher among non-Hispanic Black and Mexican American populations compared to non-Hispanic White populations.
Because the majority of the total donor pool tests positive for the virus, CMV negative blood units represent a smaller fraction of the overall blood supply. Blood banks must actively identify and track these specific donors to ensure a supply is available for patients who require it.
Who Requires CMV Negative Blood and Why
The need for CMV negative blood is restricted to specific patient populations where a primary CMV infection could be life-threatening or cause severe developmental harm. This risk arises because the virus is transmitted through white blood cells (leukocytes) present in a blood transfusion. The body’s immune system usually controls this infection, but certain medical conditions prevent this control.
One vulnerable group is premature infants, especially very low-birth-weight neonates whose mothers are CMV negative. In these patients, a transfusion-transmitted CMV infection can lead to a severe sepsis-like syndrome, pneumonitis, liver issues, and potentially long-term neurodevelopmental complications or death. The infant’s immature immune system is unable to mount an effective defense against the virus.
Another high-risk group includes patients who are severely immunocompromised, such as recipients of solid organ or hematopoietic stem cell transplants. For these patients, a primary CMV infection can lead to widespread, tissue-invasive disease, including retinitis, hepatitis, and gastrointestinal inflammation. The highest risk is seen in CMV negative recipients who receive an organ from a CMV positive donor (D+/R- mismatch), but transfusion-transmitted CMV still poses a substantial danger.
CMV disease in these settings can cause graft rejection, increase morbidity and mortality, and make the patient more susceptible to other infections. Certain cancer patients undergoing intensive chemotherapy, which drastically reduces their white blood cell count, also require CMV negative blood. For these individuals, receiving blood free of the virus is a necessary safety measure.
Blood Safety Alternatives to CMV Negative Status
Due to the limited supply of CMV negative donors, blood centers rely on an alternative processing method called leukoreduction to mitigate the risk of transmission. Leukoreduction involves filtering the blood product to remove the majority of the white blood cells (leukocytes). This process is highly effective because CMV resides almost exclusively within these white blood cells, remaining largely absent in the plasma or red blood cells.
Modern prestorage leukoreduction techniques remove white blood cells to a very low, standardized level, making the blood product “CMV safe” for most high-risk patients. Since the virus is removed mechanically rather than relying on donor screening, leukoreduction allows blood from CMV positive donors to be used safely. This simplifies blood inventory management and ensures a more stable supply for hospitals.
Many large-scale studies and transfusion guidelines now consider leukoreduced blood products to be functionally equivalent to CMV negative blood for preventing transfusion-transmitted CMV infection. While some centers still mandate CMV negative blood for the most vulnerable patients, such as intrauterine transfusions or neonates, universal leukoreduction has become the primary strategy worldwide for reducing CMV transmission risk.