Cytomegalovirus Infection: Symptoms, Types, Causes and Treatment

Cytomegalovirus (CMV) is a common virus that quietly infects people all over the world. While most individuals never realize they’ve encountered it, CMV can cause significant health problems in certain groups, particularly newborns and people with weakened immune systems. Understanding the symptoms, types, causes, and treatment options for CMV is essential for everyone, especially those at higher risk. This article synthesizes the latest research to provide a comprehensive, approachable overview of CMV infection.

Symptoms of Cytomegalovirus Infection

Cytomegalovirus infection can manifest in many different ways, depending on an individual's age and immune status. Most people may not notice any symptoms, but for others—especially those with weakened immune systems or infants—the signs can be severe and long-lasting.

Main Symptom	Description	Affected Population	Sources
Malaise	General feeling of discomfort/fatigue	Immunocompetent adults	1
Fever	Elevated body temperature	All	1, 2
Sweats	Excessive sweating, often at night	Immunocompetent adults	1
Abnormal LFTs	Liver function test abnormalities	All	1, 8
Rash	Skin eruptions/irritation	Infants, immunocompromised	2
GI Symptoms	Nausea, fullness, vomiting, diarrhea	Immunocompromised, GI CMV	3, 5
CNS Symptoms	Seizures, developmental delay	Congenital CMV, infants	9
Ocular Disease	Retinitis, vision changes	Newborns, immunocompromised	6

Table 1: Key Symptoms

Symptom Variation by Population

CMV infection is often silent, but when symptoms emerge, they can mimic other illnesses:

• Immunocompetent Adults: Most develop few or no symptoms. When present, malaise, fever, and sweats are most common, sometimes accompanied by abnormal liver function tests. Notably, symptoms may last for weeks and can relapse in about 12% of cases 1.
• Immunocompromised Individuals: Symptoms are more severe and organ-specific, such as hepatitis, pneumonitis, or gastrointestinal symptoms like nausea, vomiting, and abdominal pain. CMV can also trigger severe diseases like retinitis, encephalitis, and myocarditis 2 3 4 5 6 8.
• Newborns and Infants: Congenital CMV can result in a range of issues, from mild symptoms to serious complications such as microcephaly, jaundice, seizures, and permanent hearing or vision loss 8 9.

Common and Organ-Specific Manifestations

Systemic Symptoms

• Fever, fatigue, and sweats are hallmarks of primary infection in healthy adults, though many cases go unnoticed 1 2.
• Swollen glands, sore throat, and mild hepatitis can resemble mononucleosis 10.

Gastrointestinal Tract

• In immunocompromised patients, CMV often causes GI diseases, leading to nausea, fullness, vomiting, diarrhea, and even ulcerations or bleeding. These symptoms can be persistent and require targeted treatment 3 5.

Liver Involvement

• Abnormalities in liver function tests are common, particularly in those with a symptomatic infection. Hepatitis and jaundice are more likely in severe or disseminated cases 1 8.

Central Nervous System

• Congenital infection can lead to developmental delays, hearing loss, microcephaly, and seizures. In rare cases, encephalitis occurs in immunosuppressed adults 8 9.

Ocular Disease

• CMV retinitis is especially common in AIDS patients and can lead to vision loss. Other CMV-related eye diseases include corneal endotheliitis and iridocyclitis, which may also affect immunocompetent individuals 6.

Other Manifestations

• Rash, myocarditis, pericarditis, aseptic meningitis, and hemolytic anemia have all been linked to CMV, especially in those with weakened immune defenses 8.

Types of Cytomegalovirus Infection

CMV infection is not a one-size-fits-all disease. It can present in various forms depending on how the virus is acquired and the host's immune response. Understanding these types is crucial for identifying risk and planning treatment.

Type	Description	Typical Population	Sources
Primary Infection	First-time infection with CMV	Children, adults	2 4 8 10
Latent Infection	Dormant virus after initial infection	Most infected people	2 4
Reactivation	Reactivation of latent virus, often under stress	Immunosuppressed	2 4 7
Congenital	Infection acquired in utero	Newborns	8 9 12
Perinatal/Neonatal	Infection acquired during or shortly after birth	Newborns	8
Tissue-Invasive	CMV infects organs (e.g., GI tract, eyes, lungs)	Immunocompromised	5 6 7

Table 2: Main Types of Cytomegalovirus Infection

Primary Infection

• Definition: Occurs the first time the body encounters CMV.
• Characteristics: Often asymptomatic, but can mimic mononucleosis with fever, fatigue, and lymphadenopathy. Primary infection in adults is rare after age 35 due to early-life exposure 8 10.
• Risks: Pregnant women are at risk of transmitting CMV to the fetus during primary infection 8 12.

Latent Infection and Reactivation

• Latent Stage: After initial infection, CMV remains dormant in body cells. The immune system usually keeps it in check 2 4.
• Reactivation: When the immune system is weakened—due to HIV/AIDS, organ transplantation, chemotherapy, or severe illness—CMV can reactivate, sometimes causing severe, even life-threatening disease 2 4 7.

Congenital and Perinatal CMV

• Congenital CMV: The virus crosses the placenta during pregnancy; can cause birth defects, hearing loss, and neurological disability. Outcomes range from asymptomatic to severe, lifelong sequelae 8 9 12.
• Perinatal/Neonatal CMV: Infection at or soon after birth, usually less severe than congenital infection 8.

Tissue-Invasive and Organ-Specific Disease

• In immunocompromised patients, CMV can invade organs such as the gastrointestinal tract, lungs, eyes, and brain. Each tissue-specific form has its own set of symptoms and treatment challenges 5 6 7.

Causes of Cytomegalovirus Infection

CMV is a member of the herpesvirus family and spreads easily through close human contact. Its ability to remain dormant and reactivate makes it particularly challenging to control.

Cause	Transmission Route	At-Risk Groups	Sources
Body Fluids	Saliva, urine, blood, breast milk, semen	All	2 4 8
Congenital	Placental transfer during pregnancy	Fetuses, newborns	8 9 12
Blood Products	Transfusions, organ, stem cell transplant	Immunocompromised, infants	2 7 13
Reactivation	Immunosuppression triggers	Transplant, HIV/AIDS	2 4 7

Table 3: Main Causes and Transmission Routes

How CMV Spreads

• Close Contact: CMV is shed in many body fluids. Everyday contact with saliva or urine—especially from toddlers—makes it easy to pick up the virus 2 4 8.
• Sexual Transmission: Virus can be spread through semen and cervical secretions 2.
• Blood Transfusions and Organ Transplants: People who receive blood products or organs from infected donors are at risk, especially if their own immune response is weak 2 7 13.
• Congenital Transmission: If a woman contracts CMV during pregnancy, the virus can cross the placenta and infect the developing fetus, sometimes with devastating effects 8 9 12.

Factors That Increase Risk

• Young Children: High rates of infection in day-care and preschool environments due to frequent close contact 2 4.
• Immunocompromised Individuals: Transplant recipients, cancer patients, and people with HIV/AIDS are at greatest risk for severe disease, often due to reactivation of a previous infection 4 7 13.
• Pregnant Women: Risk is highest if primary infection occurs during pregnancy, leading to congenital disease 8 12.

Why CMV Is Hard to Eliminate

• Latency: Like all herpesviruses, CMV can remain dormant for years, hiding from the immune system until reactivated by stress, illness, or immunosuppression 2 4.
• Widespread Prevalence: Most adults have been infected by mid-adulthood. The virus is everywhere, making prevention difficult 8.

Treatment of Cytomegalovirus Infection

While most people with CMV don’t need treatment, those at risk of severe disease—such as immunocompromised patients and newborns—require careful management with antiviral drugs and supportive care.

Therapy	Use Case	Main Drugs/Intervention	Sources
Antivirals	Active/severe infection	Ganciclovir, Valganciclovir, Foscarnet, Cidofovir	11 14
Prophylaxis	Prevention in high-risk patients	Letermovir, Valacyclovir	13 15 12
Resistant CMV	Drug-resistant cases	Maribavir, Brincidofovir, T-cell therapy	13 14
In Utero Treatment	Pregnant women with symptomatic fetus	High-dose Valacyclovir	12
Supportive Care	General and mild cases	Symptom management	1 2 10

Table 4: Main Treatment Approaches

Antiviral Medications

• Ganciclovir and Valganciclovir: First-line therapies for severe or tissue-invasive CMV infection, especially in transplant recipients or those with AIDS. Used both for acute treatment and preemptive therapy 11 14.
• Foscarnet and Cidofovir: Alternatives for patients with ganciclovir-resistant CMV or those who can’t tolerate standard therapy 11 14.
• Letermovir: Recently approved for prophylaxis in stem cell transplant recipients. Demonstrated significant reduction in CMV reactivation and improved survival in high-risk patients 13 15.
• Valacyclovir: Used for prevention in pregnant women and transplant recipients; high-dose regimens showed effectiveness in reducing fetal complications 12.

Managing Drug Resistance

• Resistance Mechanisms: Mutations in viral genes can make CMV resistant to standard drugs, especially after prolonged exposure 14.
• Alternative Strategies: Dose escalation, combination therapy (e.g., ganciclovir plus foscarnet), or use of new agents like maribavir and brincidofovir. Cellular therapies, such as CMV-specific cytotoxic T-lymphocyte infusions, are experimental options for resistant cases 13 14.

Special Considerations

Congenital CMV

• Prenatal Intervention: High-dose valacyclovir during pregnancy can reduce the risk of fetal damage and improve outcomes in symptomatic fetuses, according to promising new research 12.
• Neonatal Care: Supportive measures and antiviral therapy (usually ganciclovir or valganciclovir) are used for infants with symptomatic congenital infection 8 12.

Transplant and Immunocompromised Patients

• Prevention: Prophylactic or preemptive antiviral therapy is standard of care, as reactivation is common and potentially fatal post-transplant 13 15.
• Monitoring: Regular CMV PCR testing guides the initiation and adjustment of therapy 13 14.

Immunocompetent Adults

• Symptom Relief: Most healthy adults recover without treatment; supportive care is sufficient 1 2 10.

Conclusion

Cytomegalovirus is a ubiquitous virus with a wide range of presentations, from silent infection to life-threatening disease in the vulnerable. Key points to remember:

• Most CMV infections are asymptomatic, but symptoms can range from mild fatigue and fever to severe organ-specific diseases, particularly in immunocompromised individuals and newborns.
• Types of CMV infection include primary, latent, reactivation, congenital, perinatal, and tissue-invasive forms.
• Transmission occurs through body fluids, congenital infection, blood products, and reactivation, with immunocompromised patients and fetuses at highest risk.
• Treatment relies on antiviral drugs (ganciclovir, valganciclovir, foscarnet, cidofovir), with newer agents and therapies available for resistant cases. Prevention and early intervention are crucial for high-risk groups.

By understanding CMV’s varied faces and the latest treatment strategies, patients and clinicians alike can better navigate the challenges of this common but sometimes dangerous virus.