In the largest international study of ‘chronic-haulers’ to date, led by UCL scientists in collaboration with a patient-led research collaborative, patients with long COVID reported more than 200 symptoms across 10 organ systems*.
Patient researchers connected through the Body Politic online COVID-19 support group devised a web-based survey to characterize the symptom profile and temporal course in patients with proven or suspected protracted COVID, as well as the impact on everyday life, work, and return to health, for the study, which was published in the Lancets EClinicalMedicine.
The researchers found a total of 203 symptoms in 10 organ systems using replies from 3,762 eligible volunteers from 56 nations; of these, 66 symptoms were monitored for seven months.
Fatigue, post-exertional malaise (the exacerbation of symptoms after physical or mental exertion), and cognitive impairment, also known as brain fog, were the most common symptoms.
Visual hallucinations, tremors, itchy skin, changes in the menstrual cycle, sexual dysfunction, heart palpitations, bladder control troubles, shingles, memory loss, blurred vision, diarrhea, and tinnitus were among the many complaints.
The researchers are now proposing for clinical guidelines on assessing extended COVID to be greatly widened beyond the already recommended cardiovascular and respiratory function testing to include neuropsychiatric, neurological, and exercise intolerance symptoms in addition to the currently recommended cardiovascular and respiratory function tests.
Furthermore, because a huge number of long transporters are “suffering in silence,” the authors propose a national screening program open to everyone who suspects they have long COVID.
Patients will only receive the proper treatment if the fundamental cause is identified, given the heterogeneous (different) make-up of symptoms that affect several organ systems.
“Although there has been a lot of public discussion concerning extended COVID, there are few systematic studies addressing this group; hence, relatively little is known about its range of symptoms, their progression over time, the severity, and projected clinical outcome (longevity),” said senior author Dr Athena Akrami (neuroscientist at the Sainsbury Wellcome Centre at UCL).
We used a novel approach by going straight to ‘long haulers’ all over the world in order to build a foundation of evidence for medical research, care enhancement, and advocacy for the long COVID population.
“This is the most thorough description of protracted COVID symptoms to date.” The poll was open to anybody aged 18 and up who exhibited symptoms compatible with COVID-19, including those who had a positive SARS-CoV-2 test and those who did not.
There were 257 questions in total.
In order to characterize long COVID symptoms through time, survey data was confined to respondents who had illnesses that lasted more than 28 days and whose symptoms began between December 2019 and May 2020, allowing examination of symptoms from week one to month seven.
While the study did not assess the general prevalence of protracted COVID, previous studies experience suggested that one in seven people have symptoms 12 weeks following a positive test result (Office for National Statistics), or nearly 30% of people 12 weeks after symptomatic disease (Imperial College London’s REACT study).
The risk of symptoms lasting longer than 35 weeks (eight months) was 91.8% in this extended COVID cohort.
Just 233 of the 3,762 responders had healed, with 3,608 (96%) reporting symptoms that lasted longer than 90 days, 2,454 (65%) experiencing symptoms for at least 180 days (six months), and 3,608 (96%) reporting symptoms that lasted longer than 90 days.
The average number of symptoms (11.4 out of 66 measured over time) peaked at week two in those who recovered in less than 90 days, whereas the average number of symptoms (17.2) peaked at month two in those who did not recover in 90 days.
In month seven, respondents who had symptoms for more than six months had an average of 13.8 symptoms.
Participants reported an average of 55.9 symptoms (out of a total of 203 in the study) across an average of 9.1 organ systems during their illness.
Exercise, physical or mental activity, and stress were the top triggers for 89.1% of people who relapsed.
In comparison to pre-illness, 45.2% required a restricted work schedule, and 22.3% were not working at all at the time of the study.
“For the first time, this study sheds light on the wide range of symptoms, particularly neurological symptoms, that are widespread and persistent in patients with protracted COVID,” Akrami added.
“Memory and cognitive dysfunction were the most pervasive and persistent neurologic symptoms, reported by over 85% of respondents, and were similarly common across all ages, with a significant impact on employment.”
“Headache, sleeplessness, vertigo, neuralgia, neuropsychiatric abnormalities, tremors, sensitivity to noise and light, hallucinations (olfactory and other), tinnitus, and other sensorimotor symptoms were all common, and may indicate greater neurological disorders involving both the central and peripheral nerve systems,” according to the study.
“In addition to the well-documented respiratory and cardiovascular symptoms, there is now a clear need to expand medical standards to consider a much broader spectrum of symptoms when diagnosing protracted COVID,” says the study.
Additionally, tens of thousands of long-term COVID sufferers are likely to be suffering in silence, unclear whether their symptoms are linked to COVID-19.
We now feel that a national program may be pushed out into communities to screen, diagnose, and treat all persons suspected of having long COVID symptoms, based on the network of long COVID clinics that accept GP referrals.” The research team’s future work will focus on developing areas in long COVID: mental health outcomes, diagnostic and antibody testing, symptom clustering, and socioeconomic imputation.
Study drawbacks This study has a number of limitations.
Secondly, the study’s retrospective design raises the likelihood of recollection bias.
Second, because the survey was distributed through online support groups, there is a sampling bias in favor of long-term COVID patients who joined support groups and were active members at the time the survey was published.
Nevertheless, despite eight translations and extensive outreach, the demographics were heavily biased towards English speakers (91.9%) and white responders (85.3%).
Fatigue was reported by 98.3% of respondents, followed by post-exertional malaise (PEM) by 89.0%, and brain fog and cognitive impairment by 85.1% (3,203).
Patients listed exhaustion (2,652 patients), respiratory troubles (2,242), and cognitive dysfunction (1,274) as the top three most debilitating symptoms.
Symptoms persist for at least six months A total of 2,454 (65.2%) respondents said that they had been suffering from symptoms for at least six months.
Fatigue (80%), post-exercise malaise (73.3%), cognitive impairment (58.4%), sensorimotor symptoms (55.7%), headaches (53.6%), and memory difficulties (51%) were all reported by more than half of the participants.
Furthermore, after six months of symptoms, 30%-50% of respondents reported enduring insomnia, heart palpitations, muscle aches, shortness of breath, dizziness and balance issues, sleep and language issues, joint pain, tachycardia, and other sleep issues.
* 10 Organ Systems: Systemic: weariness, fever, weakness, post-exercise malaise; Neuropsychiatric (sub-categories): Cognitive Functioning, Memory, Speech and Language, Neurological Sensations, Sleep, Headaches, Emotion and Mood, Taste and Smell, Hallucinations; Cardiovascular: heart-related symptoms; Dermatologic: skin-related symptoms; Gastrointestinal: bowel/appetite-related symptoms; Pulmonary and Respir
10.1016/j.eclinm.2021.101019 DOI: 10.1016/j.eclinm.2021.101019