Cytomegalovirus (CMV) is a latent infection virus that is widespread in the population.
CMV may reactivate under certain circumstances, and its hazardous nature has been proven,
especially in immunosuppressed patients. However, several studies have found that CMV
reactivation also exists in immunocompetent patients with a critical illness. Among those
patients, the incidence of CMV reactivation, which is more than 30%, is associated with
increased duration of hospital stay, and higher mortality.
Traditionally, critically ill patients have been considered immunocompetent but the
presence of sepsis and its immunomodulatory effects may lead to reactivation of dormant
viral infections. Sepsis due to its immunomodulatory effects may lead to reactivation of
CMV due to the release of pro-inflammatory cytokines such as TNF-alpha and IL-1beta which
has the ability to activate several transcription factors contributing in the CMV
reactivation. Clari et al showed that CMV infection in critically ill patients was
consistently associated with undetectable IFN-γ T cell responses within the first 2 days
of admission to the ICU, and that viral load was inversely related to IFN-γ T cell
responses. Similar results were also found by Venet et al that septic patients display
immune system paralysis, reduced Th1 cell function, increased IL-10 production
(anti-inflammatory), global lymphopenia affecting natural killer cells (NK)
quantitatively and qualitatively related to their interferon production.
Studies have documented significantly higher organ failure rates and mortality in
critically ill patients with CMV reactivation. Phillips Lachance et al performed a
systematic review to investigate the association between CMV reactivation and clinical
outcomes in immunocompetent critically ill patients. In this review, twenty-two studies
were included. CMV reactivation was associated with increased ICU mortality, overall
mortality, duration of mechanical ventilation, nosocomial infections, ICU length of stay.
CMV reactivation has also been studied in specific critically ill cohorts, exhibiting
there impact on mortality. David S Y Yong et al studied the effect of CMV reactivation on
mortality in immunocompetent acute respiratory distress syndrome (ARDS) patients. Of 399
ARDS patients, 68 % were CMV seropositive and reactivation occurred in 27 % of them which
was associated with overall increased ICU mortality. In another study among septic shock
cohort (329 patients), herpesvirus reactivations were documented in 68% patients without
prior immunodeficiency and concluded that reactivations could be independently associated
with mortality.
However, currently no study is currently available investigating the CMV reactivation and
it's kinetics during critical illness in non-immunosuppressed patients requiring
prolonged mechanical ventilation. In this planned observational study, the investigators
aimed to find out the prevalence of CMV reactivation, viral load and it's association
with the severity of illness in non-immunosuppressed ICU patients requiring prolong
mechanical ventilation.
All adult ICU patients requiring prolong mechanical ventilation will be considered for
inclusion and will be screened for the presence of Anti CMV IgG antibodies in blood. If
patient is IgG seropositive and meets inclusion/ exclusion criteria, then they will be
included in study and will be followed up for CMV reactivation during their ICU stay (on
weekly basis till maximum 28-days after the initiation of mechanical ventilation). In
patients who had CMV reactivation, viral load kinetics will be further followed up on
weekly basis for the next 3 weeks or ICU discharged (whichever comes first). Blood
samples will be collected in all; while tracheal aspirate sample will be collected in
whom who had an artificial airway.