People with acute respiratory illness during the pandemic suffered similar levels of poor well-being in the months afterward whether they tested positive for SARS-CoV-2 or not, a registry study showed.

In a cohort of people who all had initial symptoms suggestive of COVID-19, those who had moderate to severe scores at 3 months on the pain, mood, and other quality-of-life measures on the Patient-Reported Outcomes Measurement Information System (PROMIS) scale were actually less likely to have tested positive for the coronavirus as to have had other causes of illness (39.6% vs 53.5%, P<0.001).

“The presence and persistence of poor mental health among nearly 1 in 4 participants (21.9% of the COVID-19-positive group and 27.3% of the COVID-19-negative group) may reflect a more general pandemic exposure, which participants in both groups experienced,” Lauren Wisk, PhD, of the University of California, Los Angeles and colleagues reported in a paper published in JAMA Network Open.

The similarly bad self-reported well-being may be “in part because being seriously sick during a pandemic is incredibly stressful and the pandemic limits your availability of resources to manage your illness (access to healthcare, access to friends and family, etc.),” Wisk told MedPage Today.

The SARS-CoV-2 positive group included both those who were recovered and participants who might have had long COVID, the researchers noted. “Therefore, all results should be interpreted to reflect a more general burden of SARS-CoV-2 infection and the COVID-19 pandemic in addition to any specific burdens associated with long COVID.”

Wisk also cautioned against interpreting the study data as evidence that long COVID is an overstated diagnosis. Rather, she told MedPage Today: “I think the takeaway is that long COVID exists — just as other lingering negative effects after other illnesses — but that some of what we are classifying as long COVID may be due to the viral infection and some may be due to the broader pandemic impacts.”

The researchers did consider the possibility of false-negative tests blurring the findings, Wisk told MedPage Today in an email. “We asked participants if they subsequently tested positive, and only two reported that they had.” But because not everyone retests, potential misclassification was a limitation of the study, her group acknowledged.

The study findings also emphasized the importance of concurrent control groups in studying COVID-19 sequelae, the researchers wrote.

Study Critique

David Putrino, PT, PhD, director of rehabilitation innovation at Icahn School of Medicine at Mount Sinai in New York City, expressed concern in a phone interview with MedPage Today that the researchers framed their findings in a way that will do harm to patients.

“Tests are frequently negative. By the time you get the test, the antibodies fade or there are those 20% that do not seroconvert,” Putrino said, noting that guidance from the CDC and the World Health Organization indicates that testing is imperfect “and a diagnosis does not need to include a positive test.”

“This paper should really be a call to understand that a whole bunch of folks now have long COVID, who also have a negative test on their medical record, which is going to make it harder for them to access short- and long-term disability if their condition progresses,” he said.

Self-report would “only capture the tip of the iceberg — what patients can consciously feel,” added Colin D. Furness, MISt, PhD, MPH, of the University of Toronto, in an email to MedPage Today. “Much of what is long COVID isn’t perceptible. Vascular damage is painless but can lead to strokes several months later. Brain tissue loss can lead to significant loss in cognitive performance on tests without the person being aware of deficits. Diabetes may take quite a while to diagnose, as would infertility.”

All that can be concluded, he argued, “is that all kinds of illnesses can have lingering unpleasant effects, particularly if there are comorbidities.”

Study Details

The study included 1,000 adults enrolled in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) from Dec. 11, 2020, to Sept. 10, 2021, who had acute symptoms suggestive of SARS-CoV-2 infection at the time of testing. There were 722 who had any molecular or antigen-based assay test approved or authorized by the FDA that tested positive for SARS-CoV-2, and 278 who tested negative within the 42 days leading up to enrollment.

Of the participants, two-thirds were women; 15.3% were Hispanic, 70% were white, and 13.4% were Black or African American.

Participants completed the 29-item PROMIS survey and the PROMIS Short Form-Cognitive Function 8a at baseline and at 3-months follow-up. The primary outcome was the mean PROMIS score for the study group and controls.

While scores in both groups were similar overall, when comparing 3 month follow-up to mean baseline PROMIS scores, participants in the test-negative group had less of a mean difference (indicating less improvement) than test-positive participants at 3 months for:

• Physical function (3.1 vs 6.1 points, P<0.001)
• Fatigue (-3.5 vs -5.3, P=0.01)
• Social participation (2.8 vs 6.1, P<0.001)

Researchers highlighted that participants who tested positive had greater overall changes in their social participation at 3 months compared to test-negative participants, noting that “these improvements were concentrated among those who were younger and those who received testing in an ambulatory setting.”

At baseline, those in the COVID-19 positive group versus negative group, respectively, reported significantly lower mean scores for anxiety, depression, pain interference, and pain intensity. But mean differences in scores in the two groups from baseline to 3 months were not significant for cognitive function, anxiety, depression, fatigue, sleep disturbance, pain interference, and pain intensity.

There were no significant or clinically meaningful differences in the groups if they got their COVID-19 test in the emergency department or hospital; but for those who received their COVID-19 test in an ambulatory setting, improvements were significantly better for PROMIS results from baseline to 3 months for social participation and cognitive function.

The researchers noted that, “future evaluations of post-COVID-19 sequelae should assess key well-being domains, including social participation, in addition to discrete symptoms, to fully capture the patient experience of long-term decrements in health and well-being. Information on social participation may specifically help to identify COVID-19 experiences for which more intense intervention and/or treatment may be required to return patients to their previous activities of daily living” and “these broader pandemic societal impacts therefore call for increased attention to mental health services irrespective of SARS-CoV-2 infection status.”

Further, the researchers said, “these findings suggest that many COVID-19-positive individuals are able to achieve well-being scores that approach the U.S. average but do not imply that all patients with COVID-19 achieve well-being after illness.”

Limitations

Researchers said this study was limited by the low diversity of the registry population and potential selection bias due to limited access to a verifiable COVID-19 test and internet-enabled devices to administer study components. Furthermore, the higher-risk population with more severe illness might have been less willing to participate. In addition, people with cognitive impairment may have been less likely to enroll in the study.

The study was also limited by lack of information on the acute conditions that caused illness in the test-negative population (for example, bacterial pneumonia, respiratory syncytial virus, or streptococcal pharyngitis).

“Finding an appropriate comparison group for COVID-19-positive participants is difficult,” they noted, and “comparison with this COVID-19-negative group may underestimate the decrement in well-being compared with the general population who do not experience illness.”

Study data was also limited to COVID-19 variants circulating in September 2021.

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