Controversy over claims about long COVID research

Scientists writing in an influential medical journal are questioning the state of long COVID research, saying it has created “widespread misunderstanding”.

The opinions have drawn criticism from others in the COVID-19 field, including accusations that some may be influenced by think tanks advocating against public health measures to control the virus.

An opinion piece in BMJ Evidence-Based Medicine has criticised the state of research on long COVID. The US authors believe that lack of control groups and “overly broad definitions” have created “undue concern and anxiety” about the condition.

The authors point out that many long COVID (also called post-acute sequelae of COVID or PASC) studies began at the height of the pandemic but didn’t follow the highest standard of medical rigour.

For instance the writers say, many studies lack control groups with people who didn’t test positive to SARS-CoV-2. They could also be prone to “sampling bias”. Particularly early in the pandemic, testing was limited in many parts of the world, meaning that those who received a positive test result were more likely to be severely ill with COVID-19.

The researchers call for clearer case definitions of long COVID, use of longitudinal studies to monitor the illness, and stronger use of control groups in studies.

“I agree with the first message of this paper, which is that we need well designed studies to provide a valid measure of the long-term effects of acute COVID-19 infection (Long COVID),” says Professor Michael Baker, a researcher at the University of Otago, New Zealand, who was not involved with the paper.

“Such studies need robust case definitions, adequate duration of follow-up, and suitable comparison groups. Now that the pandemic has been with us for more than three years, we should expect such high-quality studies.”

But Baker criticises another assertion made by the researchers.

“The second message of this paper appears to be that there is a negligible risk of long COVID, based on the selection of papers they have quoted. That message is concerning and does not fit with mainstream scientific evidence, nor the experience of the large population of people living with long COVID and the clinicians caring for them,” says Baker.

“Even if the risk of long COVID from a single infection is now relatively low with Omicron subvariants, and with vaccination fortunately pushing it down even further, it remains a serious problem that we need to manage.”

In one section of the paper, the researchers say that “the most well-designed studies provide reassuring estimates”, citing 2 studies that found low incidence of long COVID.

Baker says this section “severely damages [the paper]’s credibility”.

“The authors include just 2 studies to support that sweeping statement: one was in children, and in the other they reported and commented on the analysis of findings for people younger than 50 years.

“In doing this highly selective ‘mini meta-analysis’ they are contradicting the core message of their paper. This very biased treatment of the subject suggests that these authors have an underlying view of long COVID, rather than the evidence-informed perspective they are promoting.”

Dr Mona Jeffreys, an associate professor in epidemiology at Te Hernega Waka – Victoria University of Wellington, New Zealand, who also wasn’t involved in the research, says that “the paper is a careful assessment of the pitfalls of epidemiological studies”.

“However, the authors do not appear to have been informed by the Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome literature; they appear to prefer to focus on a set of pre-defined, persisting, single post-COVID symptoms, rather than considering long COVID as a term for a syndrome or collection of symptoms which can fluctuate in presence/absence as well as severity,” says Jeffreys.

The authors also include a list of “unintended consequences” of this poor long COVID research, including misdiagnoses and increased healthcare spending. Jeffreys says there is no evidence for these consequences, stating “these are not mentioned in the paper, and appear to be the authors’ impressions, rather than evidence-based statements.”

“This author group appears to have some undeclared conflicts of interest,” says Dr Amanda Kvalsvig, an associate professor in epidemiology at the University of Otago, who wasn’t involved in the study.

“For example, the lead author Høeg is linked with think tank groups that have been strongly advocating against public health measures throughout the COVID-19 pandemic. These links may explain the more optimistic view of this author group about long COVID risks.

“The authors have omitted to mention that alongside population surveys there is an extensive and active field of research to understand the impacts of this virus on the body. The science about longer-term effects of COVID-19 infection is now very much better understood than it was even a year ago.”