Chronic post-COVID neuropsychiatric symptoms (PCNPS) persisting beyond one year from being infected during the Omicron wave

The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored. Our pre-registered hypotheses are 1. chronic PCNPS in patients infected with SARS-CoV-2 over a year ago during the Omicron wave showed a similar clustering pattern with symptoms in patients infected with pre-Omicron strain; 2. these chronic PCNPS are associated with a) clinical risk factors, such as, severity of the acute infection; b) socioeconomic status e.g., level of deprivation; and c) pre-infection vaccination status. We assessed 1205 subjects using app-based questionnaires and cognitive tasks. Partial network analysis on chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint-fatigue cluster and anxiety-depression symptoms cluster) and a minor headache-dizziness symptoms cluster, like our pre-Omicron cohort. Subjects with high number of symptoms (4 or more) can be further grouped into two distinct phenotypes: a cognitive complaint-fatigue predominant phenotype (CF) and another with symptoms across multiple clusters (AD-CF). Multiple logistic regression showed that both phenotypes are predicted by the level of deprivation before infection (adjusted p-value for CF and AD-CF = 0.025 and 0.0054 respectively). While the severity of acute COVID (adjusted p-value = 0.023) and the number of pre-existing medical conditions predict only the CF phenotypes (adjusted p-value = 0.003), past suicidal ideas predict the AD-CF phenotype (adjusted p-value < 0.001). Pre-infection vaccination status did not predict either phenotype. Our finding suggests that we should recognize the heterogeneity under the umbrella of chronic PCNPS, and a holistic bio-psycho-social approach is essential in understanding them.