How common is ME/CFS after COVID-19?
According to one published meta-analysis, the global prevalence of “post-acute sequelae of SARS-CoV-2,” defined by any symptom, is about 43% of patients overall following infection, and 49% at 120 days. Fatigue was the most commonly reported symptom, followed by memory problems. As of March 22, the World Health Organization estimated that there have been more than 470 million COVID-19 cases, which would give a figure of about 200 million people who are experiencing a wide range of long-COVID symptoms.
On the final day of the IACFSME conference, Luis Nacul, MD, of the University of British Columbia, Vancouver, presented several sets of data from his group and others aiming to determine the proportion of individuals who develop symptoms suggestive of ME/CFS following a COVID-19 infection.
Among a cohort of 88 adults hospitalized with confirmed SARS-CoV-2 infections during the first pandemic wave in 2020 and followed up in the respiratory clinic, rates of reported generalized fatigue were 67% at 3 months and 59.5% at 6 months. Substantial fatigue (that is, present most days and affecting activity levels) were reported by 16% at 3 months and 7% at 6 months. “This should represent in principle the maximum prevalence of cases who would meet the criteria for ME/CFS,” Dr. Nacul said.
Baseline age was indirectly associated with fatigue at 3 and 6 months, while the number of comorbidities a patient had was directly associated. Comorbidities also predicted severe fatigue at 3 months, but the numbers were too small for assessment at 6 months.
Studies involving nonhospitalized patients suggested lower rates. One meta-analysis showed 1-year rates of fatigue in 32% and cognitive impairment in 22%. Another showed very similar rates, reporting fatigue in 28% and memory/concentration difficulties in 18%-19%.
Dr. Nacul cautioned that these figures are likely overestimates since many of the study populations are taken from respiratory or long-COVID clinics. “The evidence on ‘post-COVID fatigue syndrome’ or ME/CFS following COVID is still evolving. There is a huge need for studies looking more closely at cases meeting well-defined ME/CFS criteria. This unfortunately hasn’t been done for most studies.”
Immune system dysfunction appears to underlie many cases
In a keynote address during the conference, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., pointed out that long COVID and ME/CFS are among many unexplained postacute infection syndromes associated with a long list of viral pathogens, including Ebola, the prior SARS viruses, Epstein-Barr virus, and Dengue, as well as nonviral pathogens such as Coxiella burnetii (Q fever syndrome) and Borrelia (posttreatment Lyme disease syndrome).
Dr. Iwasaki cited a recent Nature Medicine review article that she coauthored on this topic with an ME/CFS patient, noting: “We really need to understand why some people are failing to recover from these types of diseases.”
Emerging evidence supports four different hypotheses regarding pathogenesis: viral reservoir/viral pathogen-associated molecular pattern molecules, autoimmunity, dysbiosis/viral reactivation, and tissue damage
“Right now, it’s too early to exclude or make any conclusions about these. We need to have an open mind to dissect these various possibilities,” she said.
Two speakers reported findings of immune dysregulation in both ME/CFS and long COVID. Wakiro Sato, MD, PhD, of the National Center of Neurology and Psychiatry, Tokyo, reported that anti–G-protein coupled receptor antibodies were found in 33 (55%) of 60 patients with long COVID, and more than 40% had peripheral immune cell profile abnormalities. These findings were similar to those found in patients with ME/CFS, published by Sato’s team (Brain Behav Immun. 2021 Mar 29. doi: 10.1016/j.bbi.2021.03.023) and other researchers in Germany.
Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, presented data for an analysis of peripheral blood mononuclear cells from 26 donors with ME/CFS (8 with long COVID) and 24 healthy controls. In both patient groups, they found altered expression of inflammatory markers and decreases in CD8 T-cell number and function. The patients with long COVID showed evidence of sustained activation of both T-cell populations with increased CD38 and HLA-DR, associated with a compensatory increased frequency of activated CD4+CD8+ T cells.
“These results are consistent with immune dysregulation associated with overactivation and exhaustion of CD8 T cells, as observed in chronic viral infections and tumor environments,” Dr. Selin said.