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Disclosures: Aiyegbusi reports receiving funding from Gilead Sciences, Innovate UK, Janssen Pharmaceuticals, the NIHR Applied Research Centre, NIHR Birmingham Biomedical Research Centre and West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation. He also reports personal fees from Gilead Sciences Ltd, GlaxoSmithKline and Merck outside the study. Healio Primary Care could not confirm relevant financial disclosures at the time of publication. Please see the studies for all other authors’ relevant financial disclosures.
July 30, 2021
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International study identifies more than 200 long COVID symptoms

Disclosures: Aiyegbusi reports receiving funding from Gilead Sciences, Innovate UK, Janssen Pharmaceuticals, the NIHR Applied Research Centre, NIHR Birmingham Biomedical Research Centre and West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation. He also reports personal fees from Gilead Sciences Ltd, GlaxoSmithKline and Merck outside the study. Healio Primary Care could not confirm relevant financial disclosures at the time of publication. Please see the studies for all other authors’ relevant financial disclosures.
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Four papers offer new insight into long COVID symptoms, duration, onset and prevalence, with one paper documenting more than 200 symptoms of long COVID.

The findings were published shortly before President Joe Biden announced efforts to protect patients with long COVID from discrimination.

 The quote is: “There is now a clear need to widen medical guidelines to assess a far wider range of symptoms when diagnosing long COVID.” The source of the quote is Athena Akrami, PhD.

“We’re bringing agencies together to make sure Americans with long COVID, who have a disability, have access to the rights and resources that are due under the disability law, which includes accommodations and services in the workplace, in school and our health care system so they can live their lives in dignity and get the support they need as they continue to navigate these challenges,” Biden said on the 31st anniversary of the Americans with Disabilities Act.

Average patient experiences nearly 56 symptoms

In the first paper, researchers analyzed responses from 3,762 patients from 56 countries with either confirmed or suspected COVID-19 who completed an online survey that was conducted from Sept. 6, 2020, to Nov. 25, 2020.

The researchers wrote in EClinicalMedicine that their analysis yielded an estimated 203 symptoms lasting more than 28 days in 10 organ systems, 66 of which were traced over 7 months. More than 91% of patients needed at least 35 weeks to recover. On average, they reported experiencing 55.9 symptoms across 9.1 organ systems.

The most frequent symptoms after month 6 were fatigue (98.3%), post-exertional malaise (89%) and cognitive dysfunction (85.1%). These symptoms varied in their prevalence over time. Other symptoms included visual hallucinations, tremors, itchy skin, menstrual cycle changes, sexual dysfunction, heart palpitations, bladder control issues, shingles, memory loss, blurred vision, diarrhea and tinnitus, according to the researchers.

In addition, the researchers said that 96% of respondents indicated that their symptoms lasted more than 90 days, and 65% said their symptoms lasted for at least 180 days. About half of respondents (45.2%) needed a limited work schedule compared with their pre-COVID-19 schedule, and an additional 22.3% were not working at the time of the survey due to illness. The prevalence and trajectory of all symptoms were similar between those with confirmed and suspected COVID-19 except for loss of smell and taste.

“There is now a clear need to widen medical guidelines to assess a far wider range of symptoms when diagnosing long COVID,” co-author Athena Akrami, PhD, a neuroscientist at the Sainsbury Wellcome Centre at University College London, said in a press release.

Studies reveal trends in long COVID symptoms

The second study, published in the Journal of the Royal Society of Medicine, was an analysis of 27 articles on long COVID. Olalekan Lee Aiyegbusi MBChB, PhD, a research fellow at the Institute of Applied Health Research at the University of Birmingham in England, and colleagues identified two main symptom clusters associated with long COVID: fatigue, headache and upper respiratory complaints; and multisystem complaints such as ongoing fever and gastroenterological symptoms.

Like the first study, Aiyegbusi and colleagues also reported that fatigue — experienced by 47% of patients in their paper — was the most common long COVID symptom. Other common symptoms were dyspnea (32%), myalgia (25%), joint pain (20%), headache (18%), cough (18%), chest pain (15%), modified sense of smell (14%), modified sense of taste (7%) and diarrhea (6%).

In addition, Aiygebusi and colleagues said that cognitive impairment (also known as brain fog), amnesia, sleep disorder, palpitations and sore throat were also common symptoms of long COVID. Less commonly reported symptoms were runny nose, sneezing, hoarseness and ear pain.

Patients with long COVID also frequently reported the disease affected their quality of life, mental health and employment.

“The presence of more than five symptoms in the first week of acute infection was significantly associated with the development of long COVID irrespective of age or gender,” Aiyegbusi and colleagues wrote.

In a press release, they said the trajectory of long COVID aligns with that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A previous analysis conducted 6 months after patients with SARS and MERS were discharged from the hospital showed that 25% experienced reduced lung function and exercise capacity.

A third paper published by Epic Health Research Network revealed similar trends in long COVID symptoms. Of 693,375 patients with COVID-19 who were included in the analysis, 9.4% experienced at least one long COVID symptom between 4 weeks to 6 months after their initial diagnosis.

The most common long COVID symptom in the Epic cohort was breathing difficulty, which occurred in 3.3% of the patients, followed by tiredness or fatigue (3%), chest pain (2.7%), palpitations (1%), brain fog (0.8%), myalgia (0.7%) and loss of smell or taste (0.3%). These symptoms were more prevalent in patients who were previously hospitalized for COVID‐19; according to the researchers, about two-thirds of long COVID diagnoses were in women.

Corneal nerve fiber loss

A fourth paper, this one in the British Journal of Ophthalmology, included 40 patients who had recovered from confirmed COVID‐19 infection and took a survey ascertaining whether they had long COVID.

The authors of the British Journal of Ophthalmology paper said that 55% of the patients had no clinical signs of pneumonia; 28% had clinical signs of pneumonia that did not necessitate oxygen therapy; 10% had been admitted to the hospital with pneumonia and received oxygen therapy; and 8% with pneumonia had been admitted to intensive care.

According to a press release, neurological symptoms were present at 4 weeks in 22 of the 40 patients, and at 12 weeks in 13 out of 29 patients. All 40 patients also underwent corneal confocal microscopy; these scans showed the patients with neurological symptoms 4 weeks after recovery from acute COVID‐19 had greater corneal nerve fiber damage and loss as well as higher numbers of dendritic cells when compared with corneal confocal microscopy scans of 30 people who never had COVID-19.

“Corneal confocal microscopy may have clinical utility as a rapid objective ophthalmic test to evaluate patients with long COVID,” the authors wrote.

References:

Aiyegbusi OL, et al. J R Soc Med. 2021;doi:10.1177/01410768211032850.

Bitigren G, et al. Br J Ophthalmol. 2021;doi:10.1136/bjophthalmol-2021-319450. Davis HE, et al. eClinicalMed. 2021;doi:10.1101/2020.12.24.20248802.

Davis HE, et al. eClinicalMed. 2021;doi:10.1101/2020.12.24.20248802.

Epic Health Research Network. Nearly 1 in 10 COVID patients seek treatment for long-term symptoms. https://ehrn.org/articles/nearly-1-in-10-covid-patients-seek-treatment-for-long-term-symptoms. Accessed July 28, 2021.

The BMJ. Nerve fibre loss and rise in key immune cells on eye surface may signal ‘long COVID’. https://www.bmj.com/company/newsroom/nerve-fibre-loss-and-rise-in-key-immune-cells-on-eye-surface-may-signal-long-covid/. Accessed July 28, 2021.

WhiteHouse.gov. Fact sheet. Biden-Harris Administration marks anniversary of Americans with Disabilities Act and announces resources to support Individuals with long COVID. https://www.whitehouse.gov/briefing-room/statements-releases/2021/07/26/fact-sheet-biden-harris-administration-marks-anniversary-of-americans-with-disabilities-act-and-announces-resources-to-support-individuals-with-long-covid/. Accessed July 28, 2021.

WhiteHouse.gov. Remarks by President Biden Celebrating the 31st anniversary of the Americans with Disabilities Act. https://www.whitehouse.gov/briefing-room/speeches-remarks/2021/07/26/remarks-by-president-biden-celebrating-the-31st-anniversary-of-the-americans-with-disabilities-act/. Accessed July 28, 2021.