Why did we conduct this study?
COVID-19-related neurological syndromes vary from self-reported mild symptoms such as headaches, myalgia, anosmia, and ageusia/dysgeusia to more severe clinical syndromes such as cerebrovascular disease, encephalopathy/delirium, inflammatory diagnoses (e.g., acute disseminated encephalomyelitis), and onset of new psychiatric diagnoses (e.g., psychosis).
Several studies have reported high rates of acute morbidity and mortality in patients with COVID-19-associated neurological and psychiatric complications compared to the general COVID-19 population. However, the post-acute impact of these complications on independence for activities of daily living (ADLs), return to employment, and the impact on mental health, are not well understood, particularly relative to having been hospitalised with COVID-19 more generally.
How did we do the study?
In this case-control study, we evaluated patient-centred functional outcomes after discharge from hospital in the form of impact on their ADLs, if these symptoms impacted their employment, and assessed this relative to mental health measures, intending to identify the proportions affected and risk factors associated with poor outcomes, so that early and appropriate rehabilitation and support could be provided to those affected in order to prevent longer-term morbidities.
Hospitalised adult patients (aged >16yrs) were recruited into the COVID Clinical Neuroscience Study (COVID-CNS) in the UK if they met the WHO criteria for definite or probable COVID-19. Cases were defined as those who developed a new neurological or psychiatric diagnosis in association with COVID-19 and were classified by specific diagnostic criteria as per established Clinical Case Definitions. Controls were defined as those without new neurological or psychiatric diagnoses, and control recruitment was targeted to match the cohort of cases for age, sex, premorbid Rockwood clinical frailty score, and epoch of the COVID-19 pandemic in the UK.
Participants were followed up after discharge at a median interval of 13-16 months for a structured assessment in a single face-to-face appointment to assess changes from pre-admission status with regards to function, occupational impact, and psychological symptoms using validated measures of anxiety and depression (Generalised anxiety disorder – 7 GAD-7, Patient health questionnaire – 9 PHQ-9), alongside patient-reported symptoms (drawn from Amyotrophic lateral sclerosis Functional rating scale - ALSFRS, Unified Parkinson’s disease rating scale - UPDRS scales) and employment.
A total of 651 patients, admitted to hospital between March 2020 and July 2022, were identified for follow-up who met the inclusion criteria, of whom 362 (55%) fulfilled the criteria for cases and 289 (45%) patients for controls.
What did we find?
A higher proportion of cases overall had moderate and fewer had severe WHO-grade COVID-19 on admission than controls. However, there was a greater proportion of cases requiring ventilation on admission than controls, suggesting a dichotomy of disease severity in the case group. Nevertheless, ultimately, cases were more likely than controls to require ventilation or critical care support during the admission.
A higher proportion of cases than controls had impairment in ADLs at follow-up at the median interval of 13-16 months . Cases were also more likely to report symptoms that impacted employment than controls and a higher percentage had become unemployed following discharge. There was no significant difference in the time from discharge to completing the follow-up assessment at a median interval of 13-16 months, or the proportion with an GAD-7 or PHQ-9 scores >5 between cases and controls overall.
Within specific diagnostic groups, the greatest proportion who had impairment in ADLs relative to controls were those who had had a neuropsychiatric or peripheral complication. The greatest proportions with symptoms impacting employment were those with neuropsychiatric, inflammatory, encephalopathy or peripheral complications. There was a significantly higher proportion of patients with PHQ-9 scores >5 at follow-up for those who had had encephalopathy or a neuropsychiatric complication. However, there were no significant differences in the proportions with GAD-7 scores >5 between any of the diagnostic groups of cases and controls.
On multivariate analysis with the risk factors among the cases, impairment of ADLs was associated with increased risk in females, those aged >50yrs, and known medical history of hypertension. Those cases who were receiving either statins or angiotensin inhibiting medication on admission had a lower risk of impairment in ADLs at follow-up.
What are the take home points?
In this large multi-centre case-control study, we identified that patients with neurological or psychiatric complications associated with COVID-19 were at higher risk than general hospitalised COVID-19 patients of having impairment in their activities of daily living and are more prone to have persisting symptoms affecting their employment even >12 months after discharge from hospital. Being female, aged more than 50 years old, and having hypertension was associated with a poor functional outcome, and being on angiotensin inhibitors or statins was associated with good functional outcomes. These findings have implications for the importance of identifying these patients for a multidisciplinary approach to rehabilitation and support to address the longer-term morbidities and also for future epidemic or pandemic infections.