Mass General to Participate in Nationwide NIH-Funded Study of Long COVID

During the first few months of the pandemic, patients began to report persistent symptoms after acute infection with the SARS-CoV-2 virus which were dubbed “long COVID” or “long-haul COVID”.  Individuals with long COVID, or what is now called post-acute sequelae of COVID (PASC), typically experience the persistence of certain symptoms after the acute symptoms of infection subside, or they may experience the new onset of symptoms 4-8 weeks after the acute infection.  These individuals present with a broad range of symptoms, including persistent respiratory difficulties, dizziness, cognitive impairment (what patients often call “brain fog”), sleep disturbance, depression, and anxiety.  While other post-viral syndromes have been described, our understanding of COVID post-viral symptoms is evolving. 

In an effort to better understand these persistent COVID symptoms, Zeina Chemali, MD, MPH, Medical Director of the McCance Center for Brain Health, and her colleagues have been studying individuals who survived COVID infection but continued to report significant symptoms.  The first report from this survivors study describes 100 patients (73% female, 74% White) with persistent symptoms. Most of the patients included in this cohort did not require hospitalization (73%); none of the hospitalized patients had severe illness.

The most commonly reported neuropsychiatric symptoms after COVID-19 infection were fatigue (67%), cognitive impairment or “brain fog” (61%), headache (58%), anxiety (33%), sleep disturbance (30%), and depression (21%).  Executive functioning complaints — problems with memory or attention/concentration — were reported by 81% of the participants.   The mean Montreal Cognitive Assessment (MoCA) score was 26.0 (SD=2.8).  (Scores on the MoCA range from zero to 30. A score of 26 and higher is considered normal.) 

Not so surprisingly, individuals with PASC appear to be a heterogeneous population.  In this examination of patients with persistent neuropsychiatric symptoms, this study identified four different subgroups of patients based on presentation and clinical findings.

• The first group reported predominant executive dysfunction (frontal-subcortical profile), presenting with attentional and naming difficulties, as well as confusion (“brain fog”), and, at the extreme end of the spectrum, mutism, apathy, and severe fatigue.
• A second group of patients presented with prominent memory difficulties.  These memory issues were also found to be related to frontal-subcortical circuitry dysfunction, but with memory encoding and retrieval as the main issues.
• In the third group, PASC appeared to worsen pre-existing disorders, such as migraine and other headache disorders, depression, anxiety, and sleep disorders.
• In a fourth group, PASC may have unmasked an unknown underlying disorder (e.g., neurodegenerative disorders, seizures, hypertension, and cardiac disease).

The findings are preliminary, and larger studies including a more diverse population are needed to better understand the neuropsychiatric sequelae of COVID-19 infection.  While it appears that some participants may have a pre-existing neuropsychiatric illness which is either worsened or unmasked by COVID infection, having a history of psychiatric illness did not significantly influence presenting complaints in this sample.

RECOVER: NIH-Funded Study of Long COVID

In order to better understand the long-term sequelae of COVID-19 infection, the National Institutes of Health (NIH) has launched the Researching COVID to Enhance Recovery (RECOVER) Initiative, with the goal of enrolling 40,000 adults and children with long COVID.  In the Boston area, a consortium of six sites, including Massachusetts General Hospital (MGH), will work together to recruit 909 participants over the next year to be part of the greater Boston COVID Recovery Cohort (BCRC) and will follow the participants over the next three years.  This research will help us to better understand and define the long-term consequences of COVID-19 infection and will lay the groundwork for developing interventions to prevent and treat these symptoms.  

The BCRC will recruit participants with PASC and is hoping to enroll not only hospitalized patients but also individuals who may have initially experienced milder illness.  The BCRC will also be inviting community and equity partners in the Boston area to join this initiative in order to engage and educate the Boston community on long-term symptoms of COVID-19 and to enroll a diverse cohort of participants from the Boston area. 

Gutierrez-Martinez L, Karten J, Kritzer MD, Josephy-Hernandez S, … Chemali Z.  Post-Acute Sequelae of SARS-CoV-2 Infection: A Descriptive Clinical Study. J Neuropsychiatry Clin Neurosci 2022 (in press).

Medical Grand Rounds: Post-Acute Sequelae of SARS Cov-2  (Zeina Chemali MD discusses long-term COVID19 symptoms in this VIDEO.)