Poor prognosis in patients with prolonged post-COVID syndrome and predictors of its development

Objective. To assess the incidence of adverse events in patients with prolonged post-COVID syndrome and to determine the predictors of their development.

Materials and methods. A two-stage prospective clinical trial was conducted. The first stage was a cross-sectional screening study that identified, over a 3-year period, 305 patients who had had a new coronavirus infection (NCVI) 3 or more months earlier, based on the inclusion and exclusion criteria: 200 with prolonged post-COVID syndrome, 105 without symptoms of long-term COVID-19. The second phase was a prospective observational study, during which all deaths and hospitalizations of patients included into the study were recorded with retrospective evaluation of the data. At the end of the study, to determine the predictors of poor prognosis in patients with prolonged post-COVID syndrome, the patients in this group were divided into 2 subgroups (n=200) depending on the prognosis: the first subgroup included 85 patients with adverse events, and the second one contained 115 patients without adverse events during the observation period.

Results. The follow-up period of patients in the study lasted 24.6 [12.4; 47.7] months. Among 200 patients with prolonged post-COVID syndrome, 89 adverse clinical outcomes were detected in 85 (44.5 %) patients, in the group of patients without long-term symptoms of COVID-19, of 105 examined people, 22 adverse events in 22 (21.0 %) patients were revealed. Survival analysis showed no statistically significant differences in the incidence of fatal events between the groups. The frequency of hospitalizations, as well as the frequency of combined mortality and hospitalizations rate, were statistically significantly higher in the group of patients with post-COVID syndrome. It was determined that the development of prolonged post-COVID syndrome in patients who had NCVI increased the relative risk of the need for hospitalizations by 2.110 times, deaths and hospitalizations by 2.197 times. The predictive value of the development of a poor prognosis in patients with prolonged post-COVID syndrome was demonstrated by indicators reflecting the severe course of NCVI in the acute phase, the polysymptomatic presentation of long-term post-COVID syndrome, symptoms of anxiety, depression, cognitive impairments, the presence of a certain comorbid pathology and risk factors with no significant medical history before the verification of prolonged post-COVID syndrome, remodeling of the heart and arteries with high myocardial stress, non-specific inflammation, fibrosis and apoptosis.

Conclusions. In patients with prolonged post-COVID syndrome, a high incidence of adverse clinical outcomes is recorded, amounting to 44.5 %, associated with an increase in the need for hospitalizations and the frequency of deaths. Among the 124 parameters, 20 indicators reflecting various demographic, clinical and pathogenetic determinants demonstrated predictive significance of a poor prognosis in prolonged post-COVID syndrome.