The authors of a recent article examined findings from REACT-2, a study being carried out at Imperial College London, United Kingdom, and found that 37.5% of respondents who had contracted COVID-19 reported at least one persistent symptom.

Known as long COVID, this new multisystem disease comprises multiple symptoms following initial SARS-CoV-2 infection resolution. It includes ongoing symptomatic COVID-19 (from 4 to 12 weeks) and post–COVID-19 syndrome (12 weeks or more). Research in recent months has described the symptoms and clinical manifestations of this new disease, which can number more than 200.

To facilitate the guidance of a tailored rehabilitation intervention in the patient with long COVID, the Physical Therapy Department at the University of Málaga, Spain, developed an assessment for clinicians and researchers.

“The aim of our proposal is not to recommend, for example, whether one should exercise or not, but to investigate and determine which patients respond well to exercise and react well to the treatment,” explained Cristina Roldán-Jiménez, PhD. She is a physical therapist at the university and one of the authors of the assessment, which was published in the journal Medical Hypotheses.

This assessment proposal incorporates different types of questionnaires, functional tests, and stress tests. The purpose is to ensure that the treatment approach for long COVID is focused on the individual patient, seeing as it may depend on the etiology of the symptoms — something that objective tests can assess. “In this way, a classification can be made based on the impaired system, and the treatment can be guided accordingly,” declared Roldán-Jiménez.

Classifying Symptoms

Roldán-Jiménez, who is also a member of the Clinimetrics in Physical Therapy Group at the Biomedical Research Institute of Málaga (IBIMA TECH), stated that “fatigue is the most prevalent symptom in long COVID patients, affecting between 58% and 95.9% of them.” Another one of the most common clinical manifestations reported by patients is post-exertional malaise (PEM). “Recent clustering of long COVID patients has also shown the importance of respiratory symptoms, which predominate in up to 25% of them,” she noted.

Besides fatigue and respiratory symptoms, a cluster of symptoms and health status described in long COVID patients overlaps with those of other clinical populations, such as patients diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Long COVID symptoms had been classified by the system affected, such as cardiovascular, neurologic, pulmonary, gastrointestinal, or musculoskeletal.

A community study of over half a million people, the REACT-2 study clustered persistent symptoms, identifying the following two distinct groups: the “tiredness cluster,” with predominant fatigue that co-occurs with a cluster of less organ-specific symptoms, such as muscle aches, difficulty sleeping, and shortness of breath; and the “respiratory cluster,” with predominantly respiratory symptoms, such as shortness of breath and tight chest, as well as chest pain.

Fatigue-related symptoms, PEM, physical deconditioning, and response to exertion should be assessed in long COVID patients with predominant fatigue. “In contrast, the respiratory function by spirometry and the diffusion capacity should be objectively assessed in those patients with predominantly respiratory symptoms,” Roldán-Jiménez pointed out.

Assessment Proposal

For patients with predominant fatigue, the researchers propose an examination of fatigue-related symptoms. Some questionnaires have been developed to measure fatigue in post-viral syndromes. The DePaul Symptom Questionnaire (DSQ) is considered the gold standard to measure fatigue in patients with ME/CFS. It focuses on the following three factors: neuroendocrine, autonomic, and immune dysfunction; neurological/cognitive dysfunction; and PEM.

Although this questionnaire has not been validated in patients with long COVID, their response to the items may help clinicians determine symptoms contributing to fatigue in each patient.

The next stage would be to evaluate PEM, which is defined by the following characteristics:

• Marked, rapid physical or cognitive fatigability in response to exertion.

• Symptoms that worsen with exertion.

• Post-exertional exhaustion.

• Exhaustion is not relieved by rest.

• Substantial reduction in pre-illness activity level due to low threshold of physical and mental fatigability.

A 10-item questionnaire can be used to screen patients for PEM. A severity score of 2/4 (on a scale of 1 to 5) on two items indicates the presence of PEM. PEM can be comprehensively assessed by the DePaul Post-Exertional Malaise Questionnaire (DPEMQ). The DPEMQ consists of 53 questions, some of which assess the frequency and severity of symptoms on a Likert scale ranging from 0 to 4. “As patients may avoid exertion if they have experienced PEM, this questionnaire can complement physical tests,” Roldán-Jiménez noted.

The next component would be to evaluate for physical deconditioning. If a patient suffers from fatigue, it is necessary to assess whether it stems from a physical impairment. A battery of objective tests can be used to determine anaerobic capacity, aerobic capacity, and strength.

• Anaerobic capacity. The 30-second sit-to-stand test (30-STS) measures lower limb function and can imply peripheral muscular fatigue. During a short time (30 seconds), the patient is told to rise from a chair as fast as possible.

• Aerobic capacity. There is evidence that after COVID-19, patients present with a decrease in their aerobic capacity assessed by cardiopulmonary exercise testing (CPET). Other studies have found a reduced aerobic capacity due to physical deconditioning 3 months following hospital discharge.

• Hand grip strength. It is a reliable and valid procedure in healthy people and various clinical populations, and one of the most employed measures to assess muscle function. Therefore, this simple test can inform clinicians about the physical status of the patient.

“During the physical condition assessment, it should be considered that patients suffering from PEM may be adversely affected by some of these tests,” Roldán-Jiménez noted. Therefore, it is advisable to assess it on different days.

For patients with predominant respiratory symptoms, a different evaluation is proposed. The following two tests mainly assess respiratory function:

• Spirometry assesses outcomes such as forced vital capacity (FVC) or forced expiratory volume in the first second of the forceful exhalation (FEV1) and determines the respiratory pattern. After COVID-19 infection, 15% and 7% of patients present with a restrictive and obstructive pattern, respectively.

• The diffusion capacity of the lung is mainly assessed for carbon monoxide. The literature shows that 39% of patients present with an altered diffusion capacity after COVID-19 infection.

Clinical Implications

Following the proposed assessment, those patients who present with PEM and physical deconditioning may benefit from an energy conservation approach. Patients without PEM may tolerate physical exercise interventions, tailored to their baseline capacity and strength levels, to restore their physical function.

“There is still no extensive information about PEM in long COVID. However, qualitative research supports that, given the heterogeneity of the symptoms, recommendations for physical activity should be tailored to individuals’ clinical status and address both the physical and psychological impact of the condition,” noted Roldán-Jiménez.

By assessing the physical component of fatigue, PEM, and exercise response, clinicians may determine whether a patient is a good candidate for physical activity interventions. “If a patient presents with fatigue and, using an assessment, the clinician confirms that they have deconditioning, individualized progressive strengthening should be performed. But if, on the other hand, the test indicates that the patient has post-exertional malaise, a different approach has to be taken. And the same holds true with respect to respiratory conditions: There’s the symptom and the malaise that the patient displays, and then there’s confirming that this system is impaired,” Roldán-Jiménez indicated.

She then explained the situation. “Up until now, the impact of the pandemic has been measured in terms of hospitalizations and cumulative incidence. However, a huge number of people who had COVID-19 have sequelae. This is a big health crisis, yet hardly anyone’s talking about it.” In fact, experts already speak about long COVID being “one of the largest mass disabling events in modern history.”

“And there’s no specific treatment. Even when it comes to physical rehabilitation, it’s not clear what should be done. So, taking the experience gained in our research group and the information culled from scientific literature, we developed this assessment.” In conclusion, Roldán-Jiménez suggested that “future research should develop and validate measures to objectively assess the symptoms and functional status in long COVID patients.”

This article was translated from Univadis Spain.

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