To evaluate changes in neuropsychiatric symptoms among patients with multiple sclerosis (MS) following coronavirus disease of 2019 (COVID-19) infection using the National COVID Cohort Collaborative (N3C). The N3C represents the largest cohort of COVID-19 cases, through the unification of electronic health records from over 60 medical centers.

Out of 5,631,225 COVID-19 confirmed positive patients, we identified a cohort of patients with MS who were diagnosed with COVID-19. Conditions were searched using terms denoting common neuropsychiatric comorbid diagnoses, including anxiety, depression, pain, sleep disorders, fatigue, and cognitive disorders. We examined descriptively the percentages of patients who were newly diagnosed with each comorbid condition after COVID-19 infection. Additionally, we searched for various patient-reported outcome measures in the N3C dataset; only the Patient Health Questionnaire-9 (PHQ-9) had an adequate sample size in our cohort for analysis. To control for variability due to non-COVID-19 factors, we only included PHQ-9 scores that were reported one year before and after COVID-19 infection. A repeated-measures analysis of variance (ANOVA) was conducted to analyze the difference between PHQ-9 scores before and after COVID-19 diagnosis among MS patients.

In our final dataset, there were 40,690 patients who were diagnosed with MS and COVID-19. Among patients without pre-existing anxiety conditions, 9.18% were diagnosed with an anxiety disorder after COVID-19 infection. Among those who did not have a pre-existing cognitive disorder, 1.73% had such diagnoses after COVID-19 infection. Among those without previous depressive disorders, 8.89% were diagnosed with a depressive disorder after COVID-19 infection. Of those without fatigue conditions prior to COVID-19 in their medical records, 8.81% had documented fatigue in their records after contracting COVID-19. Of those without pain conditions in their medical records, 11.37% had documented pain in their records after COVID-19 infection. Finally, among patients without pre-existing sleep disorders, 8.71% were diagnosed with sleep disorders after COVID-19 infection. Regarding PHQ-9 scores, 50 patients had documented scores before their COVID-19 diagnosis and 50 after COVID-19 diagnosis (17 had scores for both before and after COVID-19 diagnosis). There was no significant difference in PHQ-9 scores before and after COVID-19 diagnosis (F(df) = 0.326, p = 0.572; meanbefore = 8.77, meanafter = 9.32).

Approximately 2-11% of MS patients developed new neuropsychiatric conditions after COVID-19 infection, with pain being the most common, followed by anxiety, fatigue, depression, and sleep disorders. Cognitive disorders were the least prevalent new onset neuropsychiatric sequelae of COVID-19 in this cohort. Additionally, there was a non-significant increase in severity of depressive symptoms, as indicated by a 1.36-point increase in PHQ-9 scores. These results suggest that patients with MS who have also been diagnosed with COVID-19 may be at risk for developing newly onset neuropsychiatric symptoms.