A Mayo Clinic study explores long COVID and attempts at rehabilitation

As mentioned earlier in this issue of TreatmentUpdate, some people who have been diagnosed with acute SARS-CoV-2 infection can develop long-term symptoms, called long COVID, a month or more after symptoms of the acute infection have resolved.

The Mayo Clinic in Rochester, New York, has developed a COVID-19 Activity Rehabilitation Programme (CARP). This program is designed to evaluate and treat people who have long COVID.

Researchers with CARP produced a report on the first 100 people who entered the program from June through December 2020.

Participants were relatively young (45 years) and a majority were women (68%). Most participants (75%) had never been hospitalized for acute COVID-19.

Common symptoms of acute COVID-19 included the following:

  • fatigue
  • breathing problems
  • neurological issues
  • sleeping problems
  • mental health issues

About 34% of participants had difficulty with household chores because of fatigue and 67% had not returned to full-time work. Strikingly, many routine laboratory blood test results were within the normal range. Note that a different study of people with long COVID that used MRI scans of key organ systems has found signs of tissue injury.

Study details

CARP was developed from a program that doctors had created for interventions with earlier outbreaks of coronavirus-related diseases such as SARS (2003-2004) and MERS (2012 and later).

CARP has three main aims:

  1. to actively assess for associated conditions and detect problems arising from COVID-19 when people are recovering
  2. to help people improve their overall functioning and health, using physical and occupational therapy
  3. to facilitate a safe return to work

Participants received an extensive series of assessments, including laboratory analysis of blood samples, ultrasound and CT scans.

Here are some common pre-existing conditions found in the first 100 participants in the program:

  • history of depression or anxiety – 34%
  • asthma and other breathing issues – 23%
  • high blood pressure – 19%
  • chronic fatigue – 4%
  • diabetes – 3%


Here are common issues participants had upon entry to CARP:

  • fatigue – 80%
  • breathing problems – 59% (the most common was shortness of breath)
  • neurological problems – 59% (the most common was headache)

Participants also reported other issues, most commonly the following:

  • problems with memory and thinking clearly
  • problems with sleep
  • symptoms of anxiety and/or depression

About 84% of participants reported difficulty with the following:

  • household chores
  • driving a car
  • exercise
  • complex tasks at work

Prior to becoming infected with SARS-CoV-2, 91% of participants were employed. At the time they sought help with CARP, 63 people had returned to work. Of these 63, 46% did not need to limit their activity at work because of long COVID.


According to the CARP researchers, “interestingly, most tests were within normal limits.” Only two of 31 ultrasound scans of the heart found abnormalities. Tests of lung function found only a few people with abnormalities.

The autonomic nervous system

An exception was found in testing of the autonomic nervous system. The autonomic nervous system connects parts of the brain with many important organs and systems. Usually, the autonomic nervous system functions without most people being aware of it. This system affects functions such as heart rate, breathing, digestion, urination, and so on. In cases of dysautonomia, the autonomic nervous system does not function normally. Some symptoms of dysautonomia can include the following: dizziness upon sitting up or standing up as blood pressure temporarily falls, erectile dysfunction in men, and difficulty digesting food.

At the time of publication of the Mayo Clinic study, 15 participants had completed assessments of their autonomic nervous system reflexes. Doctors found that 12 of these 15 people had abnormalities. All 12 patients were referred to neurologists for further help.

Bear in mind

Most people in the present study were relatively young (45 years) and had not been hospitalized for COVID-19, yet they had long COVID.

Three times as many women as men sought help for long COVID. The researchers stated that they did not have enough data to explain why long COVID appeared to affect more women than men. However, they noted that a similar imbalance in gender has been found in people recovering from infection caused by a member of the herpes virus family, EBV (Epstein Barr Virus).

Many routine laboratory tests and even CT scans did not find serious abnormalities in people with long COVID. This suggests that routine tests are inadequate at helping doctors diagnose the underlying drivers of long COVID.

The Mayo Clinic researchers stated: “Patients reported that their cognitive and mood symptoms were often minimized or dismissed by healthcare providers, which is concerning since many [long COVID] symptoms are similar to prolonged [consequences] of traumatic brain injury for which prolonged or permanent inability to return to work has been recorded.”

The researchers also stated that their findings “provide impetus for a thorough assessment and consideration of all symptoms and their impact on financial capacity both at work and at home.”

Interventions – caution with exercise

CARP offered brain rehabilitation as well as physical and occupational therapy. Doctors cautiously introduced exercise into the lives of patients, as the CARP researchers stated that past research with SARS, MERS and chronic fatigue syndrome found that “excessive activity can result in prolonged worsening of symptoms and function.”

The researchers stated that psychosocial support “was heavily emphasized.” They offered such support because participants expressed feelings that the researchers described as “abandonment, guilt and frustration” during their first visit with the CARP team. Furthermore, the researchers found that more than 25% of participants “reported increased anxiety and depression symptoms compared to [their medical records before they were diagnosed with acute COVID-19].” Psychosocial support included referrals for counselling and mental health specialists.

Note that the present study was relatively small and participants entered the study via self-referral. Its findings may not be generalizable. However, its finding about more women getting long COVID is in alignment with some other studies. Also, the high level of autonomic nervous system disorders has been seen as part of an ongoing study by the U.S. National Institutes of Health.

Long COVID is not well understood and research in this area is in its infancy. It will take time to find answers to this often disabling and mysterious condition.

—Sean R. Hosein


  1. Vanichkachom G, Newcomb R, Cowl CT, et al. Post COVID-19 syndrome (long haul syndrome): Description of a multidisciplinary clinic at the Mayo Clinic and characteristics of the initial patient cohort. Mayo Clinic Proceedings. 2021; in press.
  2. Dennis A, Wamil M, Alberts J, et al. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study. BMJ Open. 2021 Mar 30;11(3):e048391.