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Long-COVID symptoms worsened by stressful events

A recent study published in the Journal of Neurological Sciences reported that life stressors impact post-acute symptoms and long-term outcomes after hospitalization for coronavirus disease 2019 (COVID-19).

Post-acute sequelae of COVID-19 (PASC) have been observed in 25% to 69% of non-hospitalized patients and 33% to 90% of hospitalized patients. The variable prevalence could stem from differences in study design, symptoms, and assessment timing. Notwithstanding the numerous studies reporting the prevalence of post-COVID-19 sequelae, there is limited data on predictors of long-term quality of life and cognitive and functional outcomes.

Study: Life stressors significantly impact long-term outcomes and post-acute symptoms 12-months after COVID-19 hospitalization. Image Credit: / Shutterstock

About the study

In the present study, researchers prospectively examined the impact of demographics, hospital clinical variables, pre-COVID-19 comorbid conditions, and life stressors on six-month and one-year outcome metrics post-COVID-19 hospitalization. This observational study was conducted on patients hospitalized with COVID-19 from March 10 to May 20, 2022.

Follow-up interviews were conducted six months and one year after the initial COVID-19 diagnosis. Subjects were eligible if they were 18 years or older and hospitalized with a positive SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) test, with consent for the follow-up interview. Individuals were excluded if evaluated in the emergency room or outpatient setting.

Data on demographics, medical/neurologic history, new in-hospital neurologic or other complications, and medications used during acute COVID-19, were recorded. Disease severity was graded based on ventilation requirement and sequential organ failure assessment (SOFA) score. The modified Rankin scale (mRS) was used to assess subjects’ pre-COVID-19 baseline functional status. 

Longitudinal assessments were conducted via telephonic interviews. Contact was attempted at six and 12 months post-initial COVID-19 diagnosis. Functional and disability status was assessed using the mRS; cognitive outcomes were examined with the telephone Montreal Cognitive Assessment (t-MoCA).

The Barthel index was used for assessing activities of daily living (ADL), and the self-reported health metrics of depression, fatigue, sleep, and anxiety, were collected through the quality of life in neurologic disorders (NeuroQoL) short forms. PASC outcomes were defined as new/persistent symptoms occurring four weeks after COVID-19.


Follow-up interview attempts were made on 790 and 590 patients at six and 12 months, respectively. Of these, only 382 (48%) and 242 (41%) patients completed interviews at six and 12 months, respectively. Participants who completed only the six-month interview were older (median age: 69 years) than those completing the 12-month (65 years) interview.

No differences were found in sex, education level, race, pre-COVID-19 mRS scores, history of dementia/psychiatric disease, COVID-19 severity, and the rates of neurologic complications during hospitalization between patients who completed interviews at six months and 12 months. Headache, anxiety, cognitive abnormalities, depression, fatigue, and sleep disturbances were the common neurologic symptoms at 12 months.

About 90% of patients at six months and 87% at 12 months showed abnormalities on at least one assessed metric, with abnormalities on the mRS and t-MoCA being the most prevalent. A small but significant correlation was observed between post-acute COVID-19 symptoms and NeuroQoL anxiety scores ≥ 60. In addition, the authors noted an association of older age with poor mRS, t-MoCA scores, and Barthel Index at both time points and with NeuroQoL depression scores at one year.

The female sex was linked to elevated anxiety scores at one year and poor Barthel Index at six and 12 months. Neurologic complications such as hypoxic-ischemic brain injury and toxic metabolic encephalopathy strongly predicted poor Barthel Index and mRS at six and 12 months and worse fatigue and depression scores at one year. Poor SOFA scores and mechanical ventilation predicted a poor Barthel Index at six months.

The researchers did not find any consistent effect of COVID-19 medications on outcome metrics. However, more than 50% of participants reported having experienced a minimum of one life stressor in the month preceding the follow-up at 12 months. New personal illness, social isolation, financial insecurity, and illness/death of a close acquaintance were the most common life stressors.

The presence of stressors was strongly linked to post-acute COVID-19 symptoms and poor NeuroQoL scores. There was a significant association between food and financial insecurity, new disability/death of close contact, social isolation, and personal illness with worse NeuroQoL metrics. In contrast, new disability and personal illness were associated with Barthel Index and mRS.


In summary, the authors found independent associations of conventional predictors of poor outcomes, such as advanced age, poor pre-COVID-19 functional status, and disease severity, with worse t-MoCA, Barthel Index, and mRS scores and post-acute symptoms of COVID-19. In addition, they found that life stressors negatively impacted post-acute COVID-19 symptoms, depression, fatigue, sleep, and disability metrics. Taking life stressors into account, interventions aimed at alleviating life stress are associated with better cognitive, neuropsychiatric, and functional outcomes 12 months after hospitalization with COVID-19.



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