This study reports a very high HCMV seroprevalence in Seoul, South Korea, a developed country with a high socioeconomic status and well-organised public health system [20, 22]. As a result, our data may suggest high proportions of both seropositive donors and recipients (D+/R+), which is considered a usual intermediate risk for post-transplant HCMV infection and/or disease via the reactivation of a latent virus [9, 16, 23]. Our overall HCMV IgG seropositive rate is higher than the upper seroprevalence value (88%) of the 95% uncertainty interval in the worldwide general population, based on a recent meta-regression-based estimation . Seronegative individuals were extremely rare among those aged ≥ 31 years in the SOT recipients. In addition, HCMV seropositive rates and titres were generally proportional to age, except for teenagers. As HCMV may be horizontally transmitted by intimate contact, mainly by hand contact, the lowest seroprevalence observed in subjects between 11 to 15 years of age could be attributed to primary acquisition of HCMV at adolescence owing to improved hygiene [24, 25].
These analyses also revealed high HCMV IgG titres in the elderly population among SOT recipients and healthy subjects. A high HCMV IgG titre and persistent immune reactivation caused by an inflation in the population of long-lived, non-classical HCMV-specific effector memory CD8+ T lymphocytes have been associated with chronic inflammatory diseases, including atherosclerosis, stroke, and coronary artery disease [3, 4, 11, 26-28]. Therefore, the findings of high seropositivity and IgG titres in elderly individuals might suggest the need for further evaluation to prevent HCMV reactivation in a specific population, regardless of their immunocompromised status, as this approach could reduce the morbidity and mortality associated with inflammatory vascular diseases.
Despite the international distribution of HCMV, seropositivity rates around the world vary widely from 18% to 100%, according to geographical location, ethnicity, and specific subpopulation features [14, 29-32]. In a recent study by Li et al., stratification of serological profiles by age group revealed a very high IgG positive rate (97%) even among young individuals (0–14 years), in contrast to our data . A study conducted in the Netherlands, in 2006 to 2007, reported that non-western individuals (76.7%) had a considerably higher seroprevalence than native Dutch and western individuals (41.5%) . In general, the very high HCMV seroprevalence observed in South Korea is similar to that reported in the WHO Eastern Mediterranean region, rather than in the European region or the Americas [29, 31-33]. The different breastfeeding rates and HCMV IgM or IgG seropositive rates of women of reproductive age could contribute to the varied seroprevalence of HCMV between countries or regions, because mother-to-infant vertical transmission may have a major impact on global epidemiology of HCMV [33-35].
In a SOT setting reported in Hungary, living organ donors were found to have an HCMV seroprevalence of 85% . However, a detailed analysis of the pre-transplant HCMV IgG seropositivity rates and titres among SOT recipients according to age groups or transplant organs as well as in contrast to healthy subjects was not fully reported. In our study, SOT recipients had higher HCMV IgG seropositive rates and titres relative to healthy transplant donors. In addition, the healthy individuals were independently associated with significantly lower HCMV IgG seroprevalence in a logistic regression model. Patients who need SOT have higher HCMV seroprevalence and, therefore, exhibit a higher risk for post-transplant complications associated with HCMV than patients who do not need SOT. Therefore, pre-transplant anti-HCMV IgG assessments are clinically significant in predicting the development of post-transplant HCMV infection and/or disease [9, 16]. In addition, the HCMV serostatus can be clinically useful to stratify the risk groups for post-transplant HCMV reactivation and guide precise HCMV preventive strategies [9, 16].
It would be informative to reveal that patients who received SOT in the end stage organ disease state have higher HCMV IgG seropositive rates and titres compared to heathy individuals. This finding might be associated with asymptomatic intermittent HCMV replication and immune boosting against HCMV in chronic end stage medical diseases as well as polyclonal immune activation through pro-inflammatory cytokine release upon fulminant acute organ failure leading to SOT [37-40].
This retrospective study has several limitations. We were unable to perform further subgroup analyses according to various underlying morbidities and other immunosuppressive conditions, such as HSCT or haematologic malignancies with severe prolonged neutropenia. In addition, the study design did not allow the serial testing of anti-HCMV IgG titres in SOT recipients at the post-transplant period and subsequent evaluation of the dynamic change of HCMV IgG titres with recovery of transplanted organ function. Moreover, HCMV seroprevalence may differ according to study population, city, and region.
Despite these limitations, this study is the first, to our knowledge, to report a difference in the qualitative and quantitative anti-HCMV IgG findings between SOT recipients and healthy individuals according to serial age groups as well as transplanted organs in SOT recipients.