Researchers need to look beyond respiratory symptoms if they’re to solve the mysteries of this debilitating condition.
Long covid occurs in at least 10% of covid patients, affecting an estimated 65 million people worldwide; but research has been hampered by a failure to understand covid’s multi-system effects, according to a new study.
The finding was included in a paper published last Friday in Nature Reviews: Microbiology in which US-based researchers – led by respected US cardiologist Professor Eric Topol – analysed the current body of knowledge of long covid.
More than 200 symptoms have been identified, with impacts on multiple organ systems, according to the study. Since primary care patients can also present with multiple symptoms, management of their conditions can be challenging.
Similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field.
To date, problems gaining access to PCR and antibody testing, the failure to understand that covid affects multiple systems and the lack of post-viral knowledge have led to biases in long covid research and care.
“Most patients with covid from the first waves did not have laboratory-confirmed infection, with PCR tests being difficult to access unless individuals were hospitalised,” the paper says. “Only 1-3% of cases to March 2020 were likely detected, and the US Centre for Disease Control estimates that only 25% of cases in the USA were reported from February 2020 to September 2021.”
That percentage has likely decreased with the rise in use of at-home rapid tests, the researchers said.
“There is a broad misconception that everyone makes and retains SARS-CoV-2 antibodies, and many clinicians and researchers are unaware of the limited utility of antibody tests to determine prior infection,” the study said.
“Between 22% and 36% of people infected with SARS-CoV-2 do not seroconvert, and many others lose their antibodies over the first few months, with both non-seroconversion and seroreversion being more likely in women, children and individuals with mild infections.”
Also, early researchers often worked on the basis that covid had only respiratory sequelae. This narrative caused a delay in a more advanced understanding of the neurological, cardiovascular and other multisystem impacts of the condition.
“Many long covid clinics and providers still disproportionately focus on respiratory rehabilitation, which results in skewed electronic health record data,” the research found.
“Electronic health record data are also more comprehensive for those who were hospitalised with covid than for those who were in community care, leading to a bias towards the more traditional severe respiratory presentation and less focus on non-hospitalised patients, who tend to have neurological and/or ME/CFS-type presentations.”
Widespread lack of knowledge of viral-onset illnesses, especially ME/CFS and dysautonomia, as well as often imperfect coding, prevented clinicians from identifying these conditions. This has meant they are frequently absent from electronic health record data.
A comprehensive long covid research agenda that builds on existing knowledge of ME/CFS, dysautonomia and other viral-onset conditions is needed to address these biases, the researchers concluded.
