Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness

Abstract

ImportanceLong-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use.ObjectiveTo compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection.Design, Setting, and ParticipantsThis cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form–Cognitive Function 8a scale, for which population-normed T scores were reported.ExposuresSARS-CoV-2 status (positive or negative test result) at enrollment.Main Outcomes and MeasuresMean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis.ResultsAmong 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19–positive group and 147 of 275 participants (53.5%) in the COVID-19–negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19–positive group vs the COVID-19–negative group only for social participation (β = 3.32; 95% CI, 1.84-4.80; P < .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19–positive group were concentrated among participants aged 18 to 34 years (eg, social participation: β = 3.90; 95% CI, 1.75-6.05; P < .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: β = 4.16; 95% CI, 2.12-6.20; P < .001).Conclusions and RelevanceIn this study, participants in both the COVID-19–positive and COVID-19–negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

Long-Term Symptoms Associated With SARS-CoV-2 Infection Among Blood Donors

“…A lower estimate of long-term symptoms came from a meta-analysis that estimated that 6.2% of nonhospitalized individuals who had symptomatic COVID-19 infection experienced 1 of 3 post–COVID-19 condition symptom clusters with a duration of 4 months . The actual prevalence of long-term symptoms after COVID-19 is unclear due to varying definitions, study designs, and the lack of an uninfected control group . Understanding the true burden of post–COVID-19 conditions is critical, and inclusion of a control group as a reference for baseline levels of symptoms should be prioritized.…”

Comparability of Control and Comparison Groups in Studies Assessing Long COVID

“…For example, a recent prospective observational study examined physical, mental, and social well-being outcomes between patients with COVID-19 and other upper respiratory infections. 8 This particular study included a control group, consisting of those with upper respiratory infections, which was more comparable than healthy people to those with COVID-19 infections. By doing this, researchers were better able to determine whether lingering symptoms were attributed to COVID-19 specifically or whether those symptoms can be attributed to any respiratory infections.…”

The definition of long COVID used in interventional studies

“…Because of this uncertainty, standardized definitions should be developed by reputable organizations with skills to critically evaluate study bias. Moreover, definitions should be based on studies that include control groups that are comparable to cases except for having had COVID 11 …”

“…Moreover, definitions should be based on studies that include control groups that are comparable to cases except for having had COVID. 11 The definition of long COVID should at a minimum specify a confirmed diagnosis of COVID-19, stipulate that symptoms had not been present prior to COVID-19 infection, and rule out pre-existing or concomitant conditions that could be causing symptoms thought to be due to long COVID. Moreover, because more severe infections of any type require longer recovery, the definition should also stipulate a duration of symptoms that is at least commensurate with the severity of initial COVID-19 infection.…”