One in five never fully recover quality of life after COVID-like illness

Even without a positive COVID test, lasting symptoms can persist for months. A new study challenges assumptions about recovery and urges broader support for COVID-like illnesses.

Study: Association of SARS-CoV-2 With Health-related Quality of Life 1 Year After Illness Using Latent Transition Analysis. Image credit: Alina Troeva

In a recent study in the Open Forum Infectious Diseases journal, researchers conducted a 12-month-long longitudinal registry study of more than 1,450 patients reporting COVID-like symptoms (with approximately 25% COVID negative) to illustrate long COVID’s impacts on their health-related quality of life (HRQoL).

Background

‘Long COVID’ is an umbrella term that describes COVID-like health problems that develop or persist for weeks, months, or even years following initial infection symptoms. These conditions are often debilitating and result in significant HRQoL costs.

Estimates from prior research suggest that up to 36% of all COVID survivors experience some form of long COVID, highlighting its substantial public health burden and emphasizing the need for an improved understanding of its risk factors and recovery trajectories.

Unfortunately, long COVID is a relatively novel condition, with most of the existing literature focusing on symptom prevalence in clinically confirmed acute SARS-CoV-2 (COVID+) patients.  The impacts of long COVID on various areas of HRQoL, including social, cognitive, physical, and mental, remain unknown. HRQoL is a critical metric for monitoring patient recovery and guiding interventions, particularly in chronic conditions such as long COVID.

Furthermore, previous research has neglected SARS-CoV-2 negative (COVID-) patients, even those reporting chronic long COVID-like symptoms. This lack of between-group comparisons (COVID+ vs. COVID-) makes it unclear whether long-term deficits are unique to COVID-19 or reflect recovery patterns from undiagnosed respiratory illness.

In addition, COVID- individuals may include those with other respiratory illnesses, false-negative COVID-19 results, or unrelated pandemic-related stressors, which adds complexity to interpretation.

About the study

Study data were obtained from participants in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) cohort, a prospective, longitudinal study of patients reporting COVID-19-like symptoms. Researchers followed adults who reported COVID-like symptoms, such as fever, fatigue, muscle aches, loss of taste or smell, and persistent cough, at eight sites across the US.

Participants were either confirmed COVID+ or had similar symptoms but tested negative. By applying latent transition analysis (LTA), the team could track changes in HRQoL over a year and directly compare recovery patterns between these two groups.

The study was conducted between December 2020 and March 2023, with all included participants followed for 12 months. Participants were classified as COVID+ cases or COVID- controls based on US FDA-approved SARS-CoV-2 testing. In addition to sociodemographic and medical health records, participants were required to complete Patient-Reported Outcomes Measurement Information System (PROMIS) surveys (PROMIS-29, PROMIS SF-8a) at baseline (study enrolment) and every subsequent three months. The Hugo platform was used to collect and organize individual data.

PROMIS surveys recorded a broad view of participants’ HRQoL by assessing physical function and fatigue, mental well-being (including anxiety and depression), ability to participate socially, and cognitive abilities.

Using this information, the research applied LTA to group participants into different categories based on their overall quality of life: optimal, poor physical, poor mental, or poor overall HRQoL.

This approach allowed tracking how individuals’ well-being changed over a year. To better understand the differences within and between the COVID+ and COVID- groups, the researchers used multivariable regression models that considered participants’ backgrounds and baseline health, helping to ensure that the results reflected actual differences rather than underlying confounding factors.

Study findings

After excluding participants with incomplete data or dropouts from analyses, the final study sample comprised 1,096 COVID+ and 371 COVID- participants.

The study found that recovery patterns differed between groups. COVID+ patients generally experienced faster recovery in both physical and mental HRQoL compared to their COVID- counterparts. For example, by three months, 61% of COVID+ patients who started with poor physical HRQoL had improved to optimal HRQoL, compared to only 45% of COVID- participants.

Improvements in mental HRQoL were slower, with 50% of COVID+ patients with poor mental HRQoL recovering to optimal by nine months versus 30% among COVID- participants.

Overall, COVID+ participants were more likely to recover fully to the optimal HRQoL class than COVID- individuals, with a modest statistically significant difference.

Despite these recoveries, about 20% of participants in both groups remained in suboptimal HRQoL classes up to 12 months after their initial illness. This persistence was observed in COVID+ and COVID- patients, indicating that long-lasting health impacts may follow any COVID-like respiratory illness, not just confirmed cases.

The study also noted that among those with poor overall HRQoL, about half self-identified as having long COVID, highlighting some overlap but not a complete match between persistent HRQoL impairment and self-reported long COVID.

It is important to note that the COVID- group may have included people with other types of respiratory illness, false-negative COVID-19 results, or other factors, such as ongoing pandemic-related stress, which could also affect their HRQoL over time. The study authors caution that these complexities make direct group comparisons challenging and suggest the findings should be interpreted carefully.

Conclusions

The present study reveals that while COVID+ individuals demonstrate quicker physical and mental health recovery compared to COVID- peers,  approximately 20% of both cohorts experience persistent HRQoL impairment up to a year later, suggesting that long COVID incidence may extend to several COVID-like respiratory conditions.

The authors emphasize the importance of clinical monitoring and care for all individuals recovering from COVID-like illnesses, not only those with confirmed COVID-19, and recommend that healthcare systems prepare for prolonged rehabilitation needs across a broader patient population.

However, they also note that the comparison between COVID+ and COVID- groups is complicated by the mixed nature of the COVID- group and potential study limitations such as selection bias, generalizability, and possible misclassification of infection status. These factors should be considered when interpreting the study’s results.

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