Depression may be the strongest predictor of COVID-19-associated persistent brain fog, study finds

In a recent study published in Neurological Sciences, researchers assessed the prevalence of cognitive complaints (CC) in coronavirus disease 2019 (COVID-19) patients and explored the factors associated with brain fog after one year of COVID-19 diagnosis.

Study: Predictors of “brain fog” 1 year after COVID-19 disease. Image Credit: Mary Long/Shutterstock


Studies have frequently reported cognitive symptoms among long-COVID patients after ≤1 year of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with fatigue, anxiety, chest tightness, and myalgia. CC or brain fog includes attention difficulties, low thinking, and confusion.

Recent imaging studies have also reported functional alterations in the brains of individuals presenting with long-term symptoms of cognitive impairments post-SARS-CoV-2 infection. Persistent brain fog has been reported even after ≥1 year of SARS-CoV-2 infection; however, the mechanisms underlying brain fog and the association of brain fog with COVID-19 severity, long-term COVID-19 symptoms, and premorbid conditions need further investigation.

About the study

In the present study, researchers evaluated the prevalence of, and factors associated with CC among SARS-CoV-2-infected patients after one year of COVID-19 diagnosis.

The study comprised patients hospitalized due to COVID-19-associated pulmonary complications between 1 March and 31 May. The participants were evaluated after one year of hospital discharge and thorough neurological, psychological and clinical examinations were performed. Assessments included the impact of event scale-revised (IES-R), Montreal cognitive assessment (MoCA), Zung self-rating anxiety scale (SAS), fatigue severity scale (FSS), and the Zung self-rating depression scale (SDS).

The other assessments include the modified ranking scale (mRS), quick sequential organ failure assessment (qSOFA), low-flow oxygen requirements, non-invasive ventilation requirements, and total duration of oxygen therapy. Individuals were excluded from the analysis if they had cognitive impairments, depressive anamnestic syndrome, or premorbid conditions such as dementia.

Logistic regression modeling was used to evaluate potential factors related to brain fog after adjusting for several covariates such as sex, age, cumulative illness rating scale (CIRS) scores for premorbid conditions, level of education, and Brescia-COVID respiratory severity scale (BCRSS) scores.


Out of 246 patients, only 132 patients were considered for the final analysis. Two patients with cognitive impairments or premorbid dementia and three patients with the depressive anamnestic syndrome were excluded from the analysis. Only 22% (n=25) of participants reported brain fog after a year of SARS-CoV-2 infection. The average age of participants with CC was 68.5 years and most of them (72%, n=18) were males.

Participants with cognitive disorders showed lesser MoCA scores (23 versus 26) and greater IES-R scores (34 versus 26), SDS scores (41 versus 36), and FSS scores (34 versus 24), in comparison to non-CC participants. Of note, the SDS scores correlated significantly with brain fog after data adjustments for covariates and MoCA scores, indicating that depression was the best predictor of the development of cognitive impairments among long COVID patients, irrespective of their MoCA scores. The findings are fascinating, especially since patients with psychological disorders and premorbid cognitive decay were excluded from the analysis.

The team did not find a significant association between CC/brain fogging and the severity of SARS-CoV-2 infections, indicating that multiple factors may impact the long-term sequelae of COVID-19. Further research with prospective study designs and glial and neuronal marker assessment among post-COVID patients is required to improve understanding of the factors associated with cognitive decline or improvement post-acute phase of COVID-19.


Overall, the study findings showed that depression was the strongest predictor of persistent brain fog associated with COVID-19; however, longitudinal observational studies with larger sample sizes must be conducted to deepen understanding of the cognitive impairments among long COVID patients.

The authors believe that the present study is the first of its kind to highlight the positive correlation between brain fog or cognitive complaints and depression one-year post-COVID-19 recovery, irrespective of the severity of SARS-CoV-2 infections and the presence of comorbid conditions.

Further research is warranted for elucidating underlying mechanisms to guide the development of therapeutics and reduce the long-term neurological burden of COVID-19.

Journal reference:
  • Cristillo, V., Pilotto, A., Piccinelli, S.C. et al. (2022). Predictors of “brain fog” 1 year after COVID-19 disease. Neurological Sciences. doi:

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Anxiety, Brain, Brain Fog, Coronavirus, Coronavirus Disease COVID-19, covid-19, Dementia, Depression, Education, Fatigue, Hospital, Imaging, Oxygen, Oxygen Therapy, qSOFA, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Therapeutics

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Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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