More Than 200 Symptoms Across 10 Organ Systems Identified in Long COVID

Patients with long-term COVID have reported more than 200 symptoms across 10 organ systems*, in the largest international study of long-haulers to date, led by UCL scientists along with a patient-led research collaboration.

For the study, published in the Lancet’s EClinicalMedicine, patient researchers connected through the Body Politic online COVID-19 support group created a web-based survey to characterize the symptom profile and time course in patients with confirmed or suspected long-term COVID, along with the impact on daily life, work and return to health.

With responses from 3,762 eligible participants from 56 countries, the researchers identified a total of 203 symptoms in 10 organ systems; of these, 66 symptoms were followed for seven months. The most common symptoms were fatigue, post-exertional malaise (the worsening of symptoms after physical or mental exertion) and cognitive dysfunction, often referred to as brain fog.

From the diverse array of symptoms, others included: visual hallucinations, tremors, itchy skin, menstrual cycle changes, sexual dysfunction, palpitations, bladder control problems, shingles, memory loss, blurred vision, diarrhea, and tinnitus.

The research team, all of whom have had or continue to have long-term COVID, are now calling for a significant broadening of clinical guidelines for assessing long-term COVID, beyond currently recommended cardiovascular and respiratory function tests, including neuropsychiatric, neurological and activity intolerance symptoms.

In addition, as large numbers of tall hikers “suffer in silence,” the authors are calling for a national screening program, accessible to anyone who believes they have long-term COVID. Given the heterogeneous (diverse) composition of symptoms affecting multiple organ systems, it is only by identifying the cause that patients receive the right treatment.

Senior author Dr. Athena Akrami (neuroscientist at the Sainsbury Wellcome Center at UCL) explained the study: “While there has been much public discussion around long-term COVID, there are few systematic studies examining this population; therefore, relatively little is known about the range of symptoms and their progression over time, their severity and expected clinical course (lifespan), the impact on daily functioning and the expected return to basic health. With this unique approach, we went straight to ‘long haulers’ around the world to establish a foundation of evidence for medical research, improving care and advocacy for the long-term COVID population. This is the most comprehensive characterization of long-term COVID symptoms to date.”

The survey was open to people 18 years of age or older who had symptoms consistent with COVID-19, including those with and without a positive SARS-CoV-2 test. It consisted of 257 questions.

To characterize prolonged COVID symptoms over a longer duration, the analysis of study data was limited to respondents with illnesses lasting more than 28 days and whose symptoms occurred between December 2019 and May 2020, allowing analysis of symptoms from week one to month seven was possible. .

While the study didn’t estimate the prevalence of COVID in general, other studies estimate that one in seven people will have some symptoms 12 weeks after a positive test result (from the Office for National Statistics), or nearly 30% of people 12 weeks after. symptomatic disease (from the REACT study at Imperial College London).

Survey overview

In this long COVID cohort, the probability of symptoms lasting longer than 35 weeks (eight months) was 91.8%. Of the 3,762 respondents, 3,608 (96%) reported symptoms after 90 days, 2,454 (65%) had symptoms for at least 180 days (six months), and only 233 had recovered.

In those who recovered in less than 90 days, the average number of symptoms (11.4 of 66 symptoms measured over time) peaked at week two, and for those who did not recover within 90 days, it was the mean number of symptoms (17.2) peaked in month two. Respondents with symptoms longer than six months had an average of 13.8 symptoms at month seven. During their illness, participants experienced an average of 55.9 symptoms (out of the longer list of 203 measured in the study), across an average of 9.1 organ systems.

89.1% of the participants experienced a relapse, with exercise, physical or mental activity and stress as the main triggers. 45.2% reported that they needed a shorter work schedule compared to before the illness and 22.3% were not working at all at the time of the survey.

dr. Akrami said: “For the first time, this study sheds light on the vast spectrum of symptoms, particularly neurological, common and persistent in patients with long-term COVID.

“Memory and cognitive dysfunction, experienced by more than 85% of respondents, were the most pervasive and persistent neurological symptoms, equally common in all ages, and with a significant impact on work.

“Headaches, insomnia, dizziness, neuralgia, neuropsychiatric changes, tremors, sensitivity to sound and light, hallucinations (olfactory and others), tinnitus, and other sensorimotor symptoms were also all common, and may indicate greater neurological problems involving both central and the peripheral nervous system.

“Along with the well-documented respiratory and cardiovascular symptoms, there is now a clear need to broaden medical guidelines to assess a much wider range of symptoms when diagnosing long-term COVID. In addition, there are likely to be tens of thousands of long-term COVID patients suffering in silence, not sure if their symptoms are related to COVID-19. Building on the network of long-standing COVID clinics taking referrals from primary care physicians, we now believe a national program can be rolled out in communities that can screen, diagnose and treat all those suspected of having long-term COVID symptoms.”

The research team’s future work will focus on emerging topics in long-term COVID: mental health outcomes, diagnostic and antibody testing, symptom clustering, and socioeconomic impact of the disease.

Study restrictions

There are several limitations to this study. First, the retrospective nature of the study exposes the possibility of recall bias. Second, since the survey was distributed in online support groups, there is a sampling bias for tall COVID patients who joined support groups and were active participants of the groups at the time the survey was published. In addition, despite eight translations and inclusive outreach efforts, demographics were sharply skewed toward English-speaking (91.9%), white (85.3%) respondents.

Symptom Prevalence – Summary

Top three symptoms: fatigue 98.3%, post-exertional malaise (PEM) 89.0%, and brain fog and cognitive dysfunction in 85.1% (3,203) of respondents.

The top three most debilitating symptoms reported by patients were: fatigue (2,652 patients), difficulty breathing (2,242) and cognitive dysfunction (1,274).

Symptoms persist after six months

A total of 2,454 (65.2%) respondents had symptoms for at least six months. More than 50% had the following symptoms: fatigue (80%) post-exertional malaise (73.3%), cognitive dysfunction (58.4%), sensorimotor symptoms (55.7%), headache (53.6%) and memory problems (51%). In addition, between 30-50% of respondents experienced the following symptoms after six months: insomnia, palpitations, muscle aches, shortness of breath, dizziness and balance problems, sleep and language problems, joint pain, tachycardia and other sleep problems.

* 10 Organ systems: Systemic: fatigue, temperature, weakness, post-exertional malaise; Neuropsychiatric (subcategories): Cognitive functioning, memory, speech and language, neurological sensations, sleep, headache, emotion and mood, taste and smell, hallucinations; Cardiovascular: heart related, dermatological: skin related Gastrointestinal: gut/appetite related symptoms; Lung and Airways: Respiratory Related; Head, Ear, Eye, Nose, Throat (HEENT): both physical and sensory symptoms in HEET; Reproductive, genitourinary and endocrine: symptoms related to menstruation, thirst and urinary function, and low and high blood sugar; Immunological and Autoimmune: New and Increased Immune Responses; Musculoskeletal: tightness in the chest and pain and pain in the whole musculoskeletal system

Reference: July 15, 2021, ClinicalMedicine.
DOI: 10.1016/j.eclinm.2021.101019