Persistent psychopathology and neurocognitive impairment in COVID-19 survivors: Effect of inflammatory biomarkers at three-month follow-up

Abstract

COVID-19 outbreak is associated with mental health implications during viral infection and at short-term follow-up. Data on psychiatric and cognitive sequelae at medium-term follow-up are still lacking. During an ongoing prospective cohort study, the psychopathological and cognitive status of 226 COVID-19 pneumonia survivors (149 male, mean age 58) were prospectively evaluated one and three months after hospital discharge. Psychiatric clinical interview, self-report questionnaires, and neuropsychological profiling of verbal memory, working memory, psychomotor coordination, executive functions, attention and information processing, and verbal fluency were performed. Three months after discharge from the hospital, 35.8% still self-rated symptoms in the clinical range in at least one psychopathological dimension. We observed persistent depressive symptomatology, while PTSD, anxiety, and insomnia decreased during follow-up. Sex, previous psychiatric history, and the presence of depression at one month affected the depressive symptomatology at three months. Regardless of clinical physical severity, 78% of the sample showed poor performances in at least one cognitive domain, with executive functions and psychomotor coordination being impaired in 50% and 57% of the sample. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, predicted self-rated depressive symptomatology and cognitive impairment at three-months follow-up; and changes of SII predicted changes of depression during follow-up. Neurocognitive impairments associated with severity of depressive psychopathology, and processing speed, verbal memory and fluency, and psychomotor coordination were predicted by baseline SII. We hypothesize that COVID-19 could result in prolonged systemic inflammation that predisposes patients to persistent depression and associated neurocognitive dysfunction. The linkage between inflammation, depression, and neurocognition in patients with COVID-19 should be investigated in long-term longitudinal studies, to better personalize treatment options for COVID-19 survivors.

Interleukin-6 as potential mediator of long-term neuropsychiatric symptoms of COVID-19

“…However, SARS-CoV-2 does not seem to infect neurons directly, which leaves immunological alterations and inflammation following COVID-19 as a more promising explanation for these symptoms ( Nalbandian et al, 2021 ). This idea is supported by findings that baseline CRP and immune cell counts characteristic for systemic inflammation are associated with depressive symptoms following COVID-19 ( Mazza et al, 2021 , Mazza et al, 2020 ). This association also seems to be mitigated in patients who received the anti-IL-1β drug anakinra and the anti-IL-6 drug tocilizumab, which directly implicates the IL-6/IL-6R system ( Mazza et al, 2021 ).…”

Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19

“… 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 Overall, 7 studies were conducted in China 12 , 22 , 26 , 27 , 36 , 51 , 52 ; 6 each in the United Kingdom 9 , 15 , 21 , 28 , 32 , 37 and Spain…”

“…Thirty-three studies recruited only inpatients; 10 studies 11 , 13 , 29 , 34 , 35 , 40 , 41 , 45 , 47 , 48 included a combination of outpatients and inpatients, with the proportion of inpatients ranging from 23.0% to 80.0% ( Table 1 ), and 2 studies 24 , 33 included only outpatients. Three studies excluded patients who were unable or unwilling to receive a magnetic resonance imaging scan.…”

“…Data extracted included study and patient characteristics, selection criteria, length of follow-up, and outcome measurements ( Table 1 ). 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 We used 6 quality criteria based on the National Institutes of Health Quality Assessment Tool for Observational and Cohort Studies 53 to assess study design or features most likely to bias frequency estimates. Criteria comprised (1) prospective cohort (score range of 0-1, with 0 indicating no and 1 indicating yes), (2) representativeness (score range of 0-1, with 0 indicating sampling strategy unclear or nonconsecutive enrollees and 1 indicating patients were randomly selected or all eligible patients were included), (3) baseline severity of illness reported (score range of 0-1, with 0 indicating not reported and 1 indicating reported), (4) attrition (score range of 0-3, with 0 indicating not reported or attrition ≥30%, 1 indicating attrition of 20%-29%, 2 indicating attrition of 10%-19%, and 3 indicating attrition <10%), (5) repeated outcome measureme...…”

Immunological Interfaces: The COVID-19 Pandemic and Depression

“…Those who experience persistent symptoms for weeks or months after acute infection number in the thousands, and have created Facebook self-help groups, adopting the terminology "Long-Haul COVID" to describe their ongoing battle with health issues including worse cognition, low exercise tolerance, sleep problems, autonomic dysfunction as well as worsened mental health and autoimmunities (31)(32)(33). A recent study (34) more explicitly linked depressive psychopathology 3 months after hospitalization for COVID-19 pneumonia with elevated baseline scores on an index of immune activation and inflammation.…”