Severity Clusters and Likelihood of Recovery from Post-Covid-19 Condition

ABSTRACT

Background: The Post-COVID-19 Condition (PCC) is a novel, long-lasting, poorly understood and highly disabling post-viral syndrome, which poses enormous healthcare, economic and socio-political challenges. Lack of validated biomarkers forces clinical management to be based on clinical definitions, which are imprecise. In the clinic, symptoms tend to present in clusters, which have yet to be properly defined. Also, it is unclear how often PCC resolves, and which factors influence PCC resolution. Method(s) To delineate PCC presentation clusters and explore factors related with PCC resolution, we performed a 2-year prospective cohort study in individuals who recovered from acute COVID-19 regardless of its acute and post-acute severity. All subjects were systematically followed in the outpatient post-COVID-19 clinic of a tertiary care hospital in Spain. PCC was defined as per the WHO 2021 definition. Persistent symptoms were those present >3 months after acute COVID-19, and lasting for >2 consecutive months. PCC recovery was the absence of PCC symptoms during >3 consecutive months. Symptom clusters were identified using Gower's distance matrices, dendograms, PCA and Silhouette techniques. Factors associated with PCC recovery were identified using a directed acyclic graph approach. Result(s) 548 subjects were included;341 (62%) had PCC. The latter were mostly females (69.8%) with mean age of 47.9 (SD 12.2) years. Only 38.1% required hospitalization and 9% required high-flow oxygen during acute COVID-19. Their most frequent comorbidities were allergy (31.4%), obesity (24.8%), dyslipidemia (24.0%) and hypertension (19.6%). At least 3 symptom clusters with additive symptoms were identified considering only symptoms present in >35% of subjects, Cluster A was enriched in fatigue and dyspnea;Cluster B had Cluster A symptoms plus headache, arthralgia and neurocognitive complains;Cluster C had Cluster B symptoms plus chest pain and tachycardia. PCC recovery was achieved by 26 (7.6%) individuals over 2 years. Male sex (RR 3.01;CI 1.4-6.3), ICU admission (RR 7.85;CI 2.6-23.2), metabolic comorbidity (RR 2.07;CI 1.1-4.1), and mild acute COVID-19 (RR 2.70;CI 1.1-4.6) increased the likelihood of PCC recovery. Conversely, subjects with muscle pain, impaired attention, dyspnea, and tachycardia were less likely to recover from PCC (RR 0.26;CI 0.13-0.52). Conclusion(s) At least 3 severity clusters can be identified in the PCC. Over the first 2 years, only a minority of subjects fully recover from PCC.