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Microbiology & Infectious Serology

CMV IgG (Cytomegalovirus — IgG antibodies)

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The cytomegalovirus IgG antibody test (CMV IgG) is a serological test used to determine whether a person has been exposed to cytomegalovirus at any point in their life—a past infection resulting in persistent humoral immunity, evidenced by the long-term presence of specific anti-CMV IgG antibodies in the serum. Cytomegalovirus is a ubiquitous herpesvirus (human herpesvirus type 5—HHV-5) characterized by its ability to establish lifelong latency in the body following primary infection, primarily in monocytes and myeloid cells, and to reactivate in the event of immunosuppression. Its seroprevalence is considerable: approximately 50–70% of Canadian adults are seropositive for CMV IgG, with significant variations based on geographic origin, socioeconomic status, and age (seroprevalence exceeding 80–90% in developing countries and disadvantaged communities). In the vast majority of immunocompetent individuals, primary CMV infection is asymptomatic or presents as a mild, self-limiting mononucleosis-like syndrome. The major clinical concern with CMV lies in three specific populations for whom infection—primary infection, reinfection, or reactivation—can have severe or fatal consequences: pregnant women (risk of fetal transmission with neurodevelopmental sequelae), immunocompromised individuals (solid organ or hematopoietic stem cell transplant recipients, HIV patients with low CD4 counts, patients on immunosuppressants), and newborns (congenital CMV—the leading infectious cause of sensorineural hearing loss and non-genetic mental retardation in developed countries). CMV IgG serology alone does not allow for determining the timing of infection or confirming an active infection—it must be interpreted in conjunction with anti-CMV IgM, the IgG avidity index, and quantitative CMV PCR depending on the clinical context.

What this test measures

  • CMV IgG: Immunoglobulin G antibodies specifically directed against cytomegalovirus proteins. They appear 2 to 4 weeks after primary infection, peak at 6 to 12 weeks, and then persist at stable, detectable levels for life. Their presence indicates past exposure to CMV (recent or old infection) and acquired humoral immunity. They alone do not distinguish between an old infection and a recent primary infection without measurement of avidity.
  • CMV IgM (often measured as a complement): immunoglobulin M antibodies appearing early during primary infection (as early as 1-2 weeks) and during reactivations; they usually persist for 3 to 6 months but can last up to 12 months or longer in some cases — their isolated presence therefore does not necessarily indicate a recent primary infection
  • CMV IgG Avidity Index: a measure of the binding strength (avidity) of anti-CMV IgG antibodies to their antigens — low avidity (< 30–40 %, depending on the laboratory) at the onset of infection, gradually increasing over 3 to 6 months to high avidity (> 60 %) in established infection; a key parameter for dating primary infection, particularly during pregnancy (high avidity in the first trimester = infection prior to pregnancy, therefore no risk of current primary infection)
  • Quantitative PCR for Cytomegalovirus (CMV viral load): Detection and quantification of CMV DNA in blood (plasma or leukocytes), urine, bronchoalveolar lavage fluid (BALF), cerebrospinal fluid (CSF), or stool, depending on the context. Essential for diagnosing active infection and monitoring treatment in immunocompromised individuals. Not part of the standard serological workup, but the reference test for at-risk situations.

Results Interpretation

Serological profile IgG IgM Interpretation and course of action
No CMV exposure (seronegative) Negative Negative Never infected with CMV — absence of acquired immunity; presents a risk of primary infection if exposed (contact with young children in daycare, unprotected sexual intercourse, transfusion or transplant from a CMV+ donor); important preventive measures in seronegative pregnant women; crucial importance for donor/recipient CMV matching in transplantation
Old infection (acquired immunity) Positive Negative Past infection with lasting immunity; CMV remains latent in the body for life; risk of reactivation in cases of immunosuppression; in seropositive pregnant women: risk of reinfection with a new strain or reactivation (risk of fetal transmission of 0.5–2 % vs. 30–40 % in primary infection); in transplant candidates: known CMV-positive status of the recipient — will guide post-transplant prophylaxis or preemptive strategy
Probable recent primary infection Positive Positive Combined IgG+ and IgM+ results — suggestive of a recent primary infection; supplement with measurement of the IgG avidity index: if low avidity (< 30–40 %) → primary infection within the last 3 months (high risk of fetal transmission during pregnancy); if high avidity (> 60 %) → past infection with persistent IgM (common and reassuring finding) or reactivation; quantitative CMV PCR if immunocompromised
Isolated IgM positive (IgG negative) Negative Positive Rare situation possibly corresponding to a very early primary infection before the appearance of IgG (serological window); false positive IgM due to cross-reaction (rheumatoid factor, EBV, other herpesviruses) - common; serological follow-up at 2-3 weeks to confirm the appearance of IgG; CMV PCR if suggestive symptoms
CMV reactivation in the immunocompromised Positive Variable Serology is not the reference test for diagnosing reactivation in immunocompromised patients—the antibody response may be absent or insufficient; diagnosis relies on quantitative CMV PCR in plasma; treatment thresholds are defined by transplant teams according to graft type and individual risk; weekly CMV PCR monitoring post-transplantation according to institutional protocols

Clinical indications for CMV IgG testing

  • Pre-nuptial or pre-conception check-up: determination of CMV serological status in women of childbearing age to identify seronegative women at risk of primary infection during pregnancy; information and preventive measures if seronegative (hand washing after contact with secretions of young children - main source of contamination for pregnant women, avoid sharing utensils and mouth-to-mouth kissing with young children).
  • Surveillance during pregnancy: CMV serology (IgG + IgM) is indicated if the pregnant woman presents with mononucleosis-like symptoms, if fetal anomalies suggestive of congenital CMV are detected on ultrasound (ventriculomegaly, bowel hyperechogenicity, intracranial calcifications, intrauterine growth restriction, microcephaly), or as part of a voluntary prenatal diagnostic approach. If seroconversion is confirmed: amniocentesis with CMV PCR on amniotic fluid after 21 weeks of amenorrhea to assess fetal transmission.
  • Pre-transplant assessment (solid organ and hematopoietic stem cells): systematic donor and recipient CMV serology — CMV D+/R− status (donor seropositive, recipient seronegative) is the situation with the highest risk of post-transplant CMV disease; it will guide prophylactic strategy (oral valganiclovir for 3–6 months post-transplantation) or preemptive strategy (weekly PCR surveillance with treatment if threshold is exceeded)
  • Immunodeficiency assessment (HIV, hematological disorders, chemotherapy): CMV status determination to evaluate reactivation risk; active CMV disease (retinitis, colitis, pneumopathy, encephalitis) occurs mainly when CD4 count is < 50 cells/mm³ in HIV; preventive treatment with valganciclovir in high-risk situations
  • Clinical presentation of CMV mononucleosis (heterophile-negative mononucleosis): prolonged fever, marked asthenia, mononucleosis syndrome (atypical lymphocytes on complete blood count) with a negative Monospot test - suspect CMV and EBV; CMV serology (IgG + IgM + avidity) and EBV; PCR if immunocompromised
  • Evaluation of prolonged unexplained fever: CMV can cause a persistent febrile syndrome even in the immunocompetent; this should be considered in the evaluation of prolonged fever without an identified source.

Congenital Cytomegalovirus (CMV) — Specific Challenges

  • Epidemiology: Congenital CMV is the most common congenital infection in developed countries, affecting 0.5 to 1% of all live-born infants; in Canada, approximately 3,000 to 4,000 newborns are infected each year; 10–15% of infected newborns are symptomatic at birth (hepatosplenomegaly, microcephaly, petechiae, jaundice, chorioretinitis); 85–90% are asymptomatic, but 10–15% of these will develop late sequelae (sensorineural hearing loss, cognitive impairments)
  • Risk of fetal transmission: 30–40% % in cases of maternal primary infection during the first trimester (highest risk of severe complications); 1–2 % in cases of reactivation or reinfection in the presence of pre-existing immunity; maternal primary infection during the first trimester is the situation posing the highest risk
  • Neonatal diagnostics: CMV PCR on urine or saliva within the first 3 weeks of life (gold standard) — after this period, a positive PCR may reflect postnatal infection acquired through breast milk (benign) rather than congenital infection
  • Treatment: oral valganciclovir for 6 months in symptomatic newborns with central nervous system involvement — demonstrated reduction in auditory and neurodevelopmental sequelae at 2 years in the CASG 112 trial
  • Prevention: no vaccine currently available; strict hygiene measures for pregnant women who are seronegative: careful hand washing after diaper changes or contact with young children's nasal secretions, avoid sharing glasses, cutlery, toothbrushes with children under 3 years old, and avoid mouth-to-mouth kisses on their lips
ℹ️ In pregnant women, the simultaneous presence of anti-CMV IgG and IgM does not automatically equate to a recent primary infection—IgM can persist for several months after an old infection, and false positives are frequent. The IgG avidity index is the decisive test: high avidity in the first trimester of pregnancy reliably rules out a primary infection within the last 3 months and avoids unwarranted anxiety and unnecessary invasive investigations.

Reference values and units

  • CMV IgG: expressed in arbitrary units per milliliter (AU/mL) or as an index depending on the reagent used; positivity thresholds vary by analytical platform — usually negative if 1.0 AU/mL; refer to the reference values of the laboratory performing the analysis
  • CMV IgM: positive / negative / indeterminate according to signal/cut-off ratio; IgM are subject to false positives (rheumatoid factor, cross-reactions with other herpesviruses) — always interpret in clinical context
  • CMV IgG Avidity Index: low avidity < 30–40 % (depending on the laboratory) = probable recent infection (< 3 months); high avidity > 60 % = past infection; gray zone 30–60 % — interpretation based on context
  • PCR CMV (viral load): expressed in copies/mL or IU/mL (international units per milliliter); treatment thresholds in transplant recipients are defined by each transplant center according to the type of graft and individual risk; detectable PCR in the context of symptoms in an immunocompromised patient requires treatment without waiting for an arbitrary threshold
Situations requiring immediate medical attention

All transplanted or immunosuppressed patients (HIV with low CD4 count, intensive chemotherapy) presenting with fever, decreased visual acuity (flashes, floaters – suspect CMV retinitis), abdominal pain with bloody diarrhea (CMV colitis), or febrile dyspnea (CMV pneumonia) must be urgently evaluated with quantitative CMV PCR and infectious disease consultation. Pregnant women with prolonged fever or confirmed CMV seroconversion should be promptly referred for maternal-fetal medicine consultation to discuss fetal assessment (reference ultrasound, amniocentesis if indicated).

For the prescription of CMV serology as part of a prenuptial, preconception, prenatal, or pre-transplant assessment, Clinique Omicron offers consultations at our Quebec branches as well as via telemedicine. To book an appointment, visit cliniqueomicron.ca.

Consult at Clinique Omicron

Clinique Omicron physicians prescribe and interpret CMV serology (IgG, IgM, avidity) as part of pre-conception, prenatal, pre-transplant, and immunodeficiency evaluations. They refer patients to appropriate specialists (infectious disease specialist, maternal-fetal medicine specialist, hematologist, transplant nephrologist) based on results and clinical context. Consultations are available at our Quebec locations and via telemedicine throughout the province. To book an appointment, visit cliniqueomicron.ca.

The content of this page is provided for informational purposes only and does not substitute for the advice of a qualified healthcare professional. CMV serology interpretation should always be performed in a clinical context by a physician, particularly in pregnant women and immunocompromised patients.

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