Severely Stressful Events Worsen Symptoms of Long COVID

Summary: Recent stressful experiences, such as the loss of a loved one or economic insecurity are strong predictors as to whether a person hospitalized for COVID-19 will experience symptoms of long COVID a year later.

Source: NYU Langone

The death of a loved one, financial or food insecurity, or a newly developed disability were some of the strongest predictors of whether a patient hospitalized for COVID-19 would experience symptoms of long COVID a year later, a new study finds.

Led by researchers from NYU Grossman School of Medicine, the study found that adult patients with such “major life stressors”—present in more than 50% of those followed—were at least twice as likely to struggle with depression, brain fog, fatigue, sleep problems, and other long-term COVID-19 symptoms, say the study authors.

Published online this week in the Journal of the Neurological Sciences (JNS), the analysis also confirmed the contribution of traditional factors to greater long COVID risk as shown by past studies—older age, disability level to start with, and a more severe initial case of COVID-19.

“Our study is unique in that it explores the impact of life stressors—along with demographic trends and neurological events—as predictors of long-term cognitive and functional disabilities that affected quality of life in a large population,” says lead study author Jennifer A. Frontera, MD, professor in the Department of Neurology at NYU Langone Health.

“Therapies that lessen the trauma of the most stress-inducing life events need to be a central part of treatment for long COVID, with more research needed to validate the best approaches.”

The research used standard telephone survey tools in the field—the modified Rankin Scale (mRS), the Barthel Index, the Montreal Cognitive Assessment (t-MoCA), and the NIH/PROMIS Neurological Quality Of Life (NeuroQoL) batteries—to measure level of daily function, clear thinking (cognition), anxiety, depression, fatigue and sleep quality.

The team attempted follow-up with each of 790 patients six months and a year after COVID-19 hospitalization within NYU Langone Health between March 10, 2020 and May 20, 2020.

Of these surviving patients, 451 (57%) completed 6-month and/or 12-month follow-up, and of them, 17% died between discharge and 12-month follow-up and 51% reported significant life stressors at 12-months.

In analyses that compared factors against each other for their contribution to worse outcomes, life stressors including financial insecurity, food insecurity, death of a close contact, and new disability were the strongest independent predictors of prolonged COVID-19 symptoms.

These same stressors also best predicted worse functional status, depression, fatigue, sleep scores, and reduced ability to participate in activities of daily living such as feeding, dressing, and bathing.

Gender was also a contributor, as past studies have found that women are more susceptible in general to—for instance—autoimmune diseases that could have an impact on outcomes. Additionally, undiagnosed mood disorders may have been unmasked by pandemic-related stressors.

Neurological long COVID may include more than one condition

A second study led by Frontera and colleagues, and published online September 29, 2022, in PLOS ONE, found that patients diagnosed as having long COVID neurological problems can be divided into three symptom groups.

Because there is no current biological definition of long COVID, many studies lump disparate symptoms into what is currently a blanket diagnosis, and without an assessment of clinical relevance, says Frontera. The resulting vagueness has made it “difficult to assess treatment strategies.”

This shows a person in a face mask
The study found that adult patients with such “major life stressors”—present in more than 50% of those followed—were at least twice as likely to struggle with depression, brain fog, fatigue, sleep problems, and other long-term COVID-19 symptoms, say the study authors. Image is in the public domain

For the PLOS ONE study, the research team collected data on symptoms, treatments received, and outcomes for 12 months after hospitalization with COVID-19, with treatment success measured again by standard metrics (modified Rankin Scale, Barthel Index, NIH NeuroQoL). The three newly identified disease groups were:

  • Cluster 1: Few symptoms (most commonly headache) in patients who received few therapeutic interventions
  • Cluster 2: Many symptoms, including anxiety and depression, in patients who received several treatments, including antidepressants to psychological therapy
  • Cluster 3: Primarily pulmonary symptoms such as shortness of breath. Many patients also complained of headache and cognitive symptoms, and mostly received physical therapy.

The most severely affected patients (symptom Cluster 2) had higher rates of disability, worse measures of anxiety, depression, fatigue and sleep disorders. The most severely affected patients had higher rates of disability, worse measures of anxiety, depression, fatigue and sleep disorders.

All patients whose treatment included psychiatric therapies reported symptom improvement, compared to 97% who received primarily physical or occupational therapy, and 83% who received few interventions.

The Brookings Institution estimated in August 2022 that roughly 16 million working-age Americans (aged 18 to 65) have long COVID, out of whom 2 to 4 million are out of work due to long COVID.

About this stress and COVID-19 research news

Author: Press Office
Source: NYU Langone
Contact: Press Office – NYU Langone
Image: The image is in the public domain

Original Research: Open access.
Life stressors significantly impact long-term outcomes and post-acute symptoms 12-months after COVID-19 hospitalization” by Jennifer A. Frontera et al. Journal of Neurological Sciences

Open access.
Post-acute sequelae of COVID-19 symptom phenotypes and therapeutic strategies: A prospective, observational study” by Jennifer A. Frontera et al. PLOS ONE


Abstract

Life stressors significantly impact long-term outcomes and post-acute symptoms 12-months after COVID-19 hospitalization

Background

Limited data exists evaluating predictors of long-term outcomes after hospitalization for COVID-19.

Methods

We conducted a prospective, longitudinal cohort study of patients hospitalized for COVID-19. The following outcomes were collected at 6 and 12-months post-diagnosis: disability using the modified Rankin Scale (mRS), activities of daily living assessed with the Barthel Index, cognition assessed with the telephone Montreal Cognitive Assessment (t-MoCA), Neuro-QoL batteries for anxiety, depression, fatigue and sleep, and post-acute symptoms of COVID-19. Predictors of these outcomes, including demographics, pre-COVID-19 comorbidities, index COVID-19 hospitalization metrics, and life stressors, were evaluated using multivariable logistic regression.

Results

Of 790 COVID-19 patients who survived hospitalization, 451(57%) completed 6-month (N = 383) and/or 12-month (N = 242) follow-up, and 77/451 (17%) died between discharge and 12-month follow-up. Significant life stressors were reported in 121/239 (51%) at 12-months. In multivariable analyses, life stressors including financial insecurity, food insecurity, death of a close contact and new disability were the strongest independent predictors of worse mRS, Barthel Index, depression, fatigue, and sleep scores, and prolonged symptoms, with adjusted odds ratios ranging from 2.5 to 20.8. Other predictors of poor outcome included older age (associated with worse mRS, Barthel, t-MoCA, depression scores), baseline disability (associated with worse mRS, fatigue, Barthel scores), female sex (associated with worse Barthel, anxiety scores) and index COVID-19 severity (associated with worse Barthel index, prolonged symptoms).

Conclusions

Life stressors contribute substantially to worse functional, cognitive and neuropsychiatric outcomes 12-months after COVID-19 hospitalization. Other predictors of poor outcome include older age, female sex, baseline disability and severity of index COVID-19.


Abstract

Post-acute sequelae of COVID-19 symptom phenotypes and therapeutic strategies: A prospective, observational study

Background

Post-acute sequelae of COVID-19 (PASC) includes a heterogeneous group of patients with variable symptomatology, who may respond to different therapeutic interventions. Identifying phenotypes of PASC and therapeutic strategies for different subgroups would be a major step forward in management.

Methods

In a prospective cohort study of patients hospitalized with COVID-19, 12-month symptoms and quantitative outcome metrics were collected. Unsupervised hierarchical cluster analyses were performed to identify patients with: (1) similar symptoms lasting ≥4 weeks after acute SARS-CoV-2 infection, and (2) similar therapeutic interventions. Logistic regression analyses were used to evaluate the association of these symptom and therapy clusters with quantitative 12-month outcome metrics (modified Rankin Scale, Barthel Index, NIH NeuroQoL).

Results

Among 242 patients, 122 (50%) reported ≥1 PASC symptom (median 3, IQR 1–5) lasting a median of 12-months (range 1–15) post-COVID diagnosis. Cluster analysis generated three symptom groups: Cluster1 had few symptoms (most commonly headache); Cluster2 had many symptoms including high levels of anxiety and depression; and Cluster3 primarily included shortness of breath, headache and cognitive symptoms. Cluster1 received few therapeutic interventions (OR 2.6, 95% CI 1.1–5.9), Cluster2 received several interventions, including antidepressants, anti-anxiety medications and psychological therapy (OR 15.7, 95% CI 4.1–59.7) and Cluster3 primarily received physical and occupational therapy (OR 3.1, 95%CI 1.3–7.1). The most severely affected patients (Symptom Cluster 2) had higher rates of disability (worse modified Rankin scores), worse NeuroQoL measures of anxiety, depression, fatigue and sleep disorder, and a higher number of stressors (all P<0.05). 100% of those who received a treatment strategy that included psychiatric therapies reported symptom improvement, compared to 97% who received primarily physical/occupational therapy, and 83% who received few interventions (P = 0.042).

Conclusions

We identified three clinically relevant PASC symptom-based phenotypes, which received different therapeutic interventions with varying response rates. These data may be helpful in tailoring individual treatment programs.

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