Frequent neurocognitive deficits after recovery from mild COVID-19

Abstract

Neuropsychiatric complications associated with coronavirus disease 2019 caused by the Coronavirus SARS-CoV-2 (COVID-19) are increasingly appreciated. While most studies have focussed on severely affected individuals during acute infection, it remains unclear whether mild COVID-19 results in neurocognitive deficits in young patients. Here, we established a screening approach to detect cognitive deficiencies in post-COVID-19 patients. In this cross-sectional study, we recruited 18 mostly young patients 20-105 days (median, 85 days) after recovery from mild to moderate disease who visited our outpatient clinic for post-COVID-19 care. Notably, 14 (78%) patients reported sustained mild cognitive deficits and performed worse in the Modified Telephone Interview for Cognitive Status screening test for mild cognitive impairment compared to 10 age-matched healthy controls. While short-term memory, attention and concentration were particularly affected by COVID-19, screening results did not correlate with hospitalization, treatment, viremia or acute inflammation. Additionally, Modified Telephone Interview for Cognitive Status scores did not correlate with depressed mood or fatigue. In two severely affected patients, we excluded structural or other inflammatory causes by magnetic resonance imaging, serum and cerebrospinal fluid analyses. Together, our results demonstrate that sustained sub-clinical cognitive impairments might be a common complication after recovery from COVID-19 in young adults, regardless of clinical course that were unmasked by our diagnostic approach.

Keywords: COVID-19; neurocognitive deficits; neurocognitive screenings; post-COVID-19.

Graphical Abstract

Figure 1

Cognitive deficiencies in post-COVID-19 patients. (A) Comparison of TICS-M total scores (P = 0.0002) between healthy individuals (n = 10) and post-COVID-19 patients (n = 18). Two-tailed Wilcoxon-test was used and mean with 95% confidence interval is shown. (B) Comparison of the different cognitive domains orientation (P = 0.9643), attention (P = 0.029), language and concentration (P = 0.009) and memory (P = 0.004) that were tested with the TICS-M. Two-tailed Wilcoxon-test was used and mean with 95% confidence interval is shown. (C, D) Linear regression analysis of TICS-M scores and Fatigue Assessment Scale (C; t = −1.3653, FDR-adjusted P = 0.3820, Estimate = –0.165) and Patient Health Questionnaire-9 Depression Scale (D; t = 0.8957, FDR-adjusted P = 0.3836, Estimate = 0.324) scores of post-COVID-patients. (E) Reported neuropsychiatric symptoms that sustained after recovery.

Figure 2

Cognitive deficits are independent from hospitalization and sickness duration. (A) Comparison of TICS-M total scores (P = 0.9644) between female (n = 10) and male (n = 8) post-COVID-19 patients. Two-tailed Wilcoxon-test was used. (B–E) Linear regression analysis of TICS-M scores and age in years (B; t = 1.0241, FDR-adjusted P = 0.6420, Estimate = 0.057), time to recovery from acute COVID-19 in days (C; t = −0.0576, FDR-adjusted P = 0.9548, Estimate = −0.003), duration of sickness in days (D; t = −0.0576, FDR-adjusted P = 0.9548, Estimate = 0.023) and duration of inpatient treatment in days (E; t = 0.8254, FDR-adjusted P = 0.7021, Estimate = 0.112) of post-COVID-patients. (F) Self-reported somatic symptoms that appeared at least once after recovery from COVID-19 and were reported from at least two patients. (G,H) Linear regression analysis of number of somatic and neurocognitive symptoms (G; t = 1.282, FDR-adjusted P = 0.2181, Estimate = 0.177) and number of somatic symptoms and TICS-M scores (H; t = 0.161, FDR-adjusted P = 0.874, Estimate = 0.068).

Figure 3

Cognitive deficits are independent from acute disease severity and viremia. (A) Comparison of TICS-M total scores (P = 0.9251) between post-COVID-19 patients who received supplementary oxygen during acute disease (n = 6) and patients who recovered without supplementary oxygen (n = 12). Two-tailed Wilcoxon-test was used. (B) Comparison of TICS-M total scores (P = 0.1589) between post-COVID-19 patients who received no treatment (n = 12), antibiotics (n = 2), remdesivir (n = 2) or tocilizumab (n = 1) during acute COVID-19. Two-tailed Wilcoxon-test was used. (C–H) Linear regression analysis of TICS-M scores and maximal anti-SARS-CoV2-IgG titre (C; t = 1.4352, FDR-adjusted P = 0.4626, Estimate = 0.014), cycle threshold values in SARS-CoV-2 PCR (D; t = 0.8422, FDR-adjusted P = 0.9358, Estimate = 0.064), CRP (E; t = −0.0811, FDR-adjusted P = 0.4363, Estimate = 0.021), ferritin (F; t = 0.1266, FDR-adjusted P = 0.4363, Estimate = 0.002), IL-6 (G; t = −0.1309, FDR-adjusted P = 0.4363, Estimate = 0.009), d-dimers (H; t = 0.8330, FDR-adjusted P = 0.4363, Estimate = 0.121) during acute COVID-19 infection.