Defining long-term novel coronavirus using self-reported symptoms

In a recent article published in JAMA networkresearchers conducted a prospective observational cohort study to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) cases, otherwise known as long COVID, post-acute sequelae. developed symptom-based criteria for.

study: Development of a definition of acute sequelae of SARS-CoV-2 infection. Image credit: MeekoMedia/Shutterstock.com

Background

They proposed that PASC is a novel symptom caused by SARS-CoV-2 infection, and unlike previous reports, the researchers did not rely on predefined clinical symptoms. Researchers consider PASC to be a condition in which recurrence, persistence, or the presence of new symptoms >30 days after recovery from SARS-CoV-2 infection.

The effects of PASC are substantial in the short and long term. It impacts an individual’s health-related quality of life and economic income, while at the same time putting a strain on healthcare infrastructure.

Most of the published PASC studies focus on individual symptom frequencies to obtain inconsistent estimates of PASC prevalence due to the lack of comparison groups and their retrospective design.

Furthermore, the heterogeneity of PASC symptoms makes it difficult to define PASC precisely. It presents as a condition with diverse and often overlapping etiologies (eg, organ damage, gut microbiota abnormalities, immune dysregulation).

Understanding the mechanisms that govern PASC is of great public health importance as it may help devise preventive and therapeutic intervention strategies.

However, this requires data collection from large prospective cohort studies of SARS-CoV-2 infected and uninfected individuals specifically designed to characterize PASC. Additionally, this study should use appropriate analytical techniques and monitor persistent symptoms after recovery.

Changes in the incidence of PASC and its symptoms during the COVID-19 pandemic have been driven by the emergence of new SARS-CoV-2 strains, the introduction and subsequent availability of new treatments, relapses (breakthrough treatments), It is equally important to consider that it has changed for several reasons, such as the law). )Infection.

In the United States (US), the National Institutes of Health has launched the COVID Study to Enhance Recovery (RECOVER) to understand, prevent, and treat PASC.

About research

In this study, investigators analyzed data from the RECOVER adult cohort to diagnose PASC based on patient self-reported symptoms. They outlined and described several unique PASC subphenotypes that differentially impact health and well-being.

The authors expected PASC-based selection bias to be minimal and estimates to be more accurate among subcohorts enrolled 30 days after acute SARS-CoV-2 infection. RECOVER also collected self-reported symptoms of PASC using a standardized questionnaire developed in collaboration with patient representatives.

The team recruited all participants from 85 US locations and asked them to visit our offices and complete remote surveys.

Participant registration is in progress. However, this analysis considered 13,754 adult participants enrolled before 10 April 2023. These participants belonged to the acute and post-acute cohorts. That is, the registration date was within 30 days or more than 30 days from the index date (December 1). , 2021), respectively.

Also, study participants were required to complete the study visit after 6 months. Pre-enrolment SARS-CoV-2 infection was the primary exposure in this study, and the primary outcome was the presence of 44 symptoms, allowing the investigator to develop his definition of PASC based on the composite symptom score. It was helpful.

The research team reported overall symptoms and symptoms in three subcohorts: acute omicron, post-acute pleomicron, and post-acute omicron. They expected symptom frequency estimates within the acute Omicron subcohort to be more consistent with the corresponding population frequencies.

This analysis considered the frequency of symptom severity thresholds. ≥2.5%. Finally, we reported the frequency of symptoms by infection status and calculated the adjusted odds ratio (aOR) using weighted logistic regression.

The research team used the Least Absolute Shrinkage Selection Operator (LASSO) to distinguish between symptoms in infected and uninfected participants. We then assigned scores to each symbol based on the estimated coefficients.

In this way, each participant received a composite symptom score, and researchers used 10-fold cross-validation to select the optimal score threshold for PASC.

result

A total of 9,764 participants met study criteria, of which 8,646 were SARS-CoV-2 infected and 1,118 were uninfected. 37 out of 44 symptoms were frequent ≥2.5% all had aOR ≥1.5.

Symptoms such as PEM, fatigue, dizziness, brain fog, and gastrointestinal (GI) symptoms showed more than 15% difference in absolute frequency between infected and uninfected subjects.

However, the frequency of these symptoms (including severity thresholds) was comparable in infected participants. Without a severity threshold, the frequency of the corresponding symptoms observed is higher.

The distribution and demographics of comorbidities were similar in all three subcohorts, despite a higher proportion of unvaccinated individuals in the post-acute pre-Omicron subcohort. Symptoms were also most frequent in the post-acute pre-ommicron sub-cohort.

Strikingly, only 12 of 44 symptoms contributed to the PASC score. However, the authors noted a correlation between its elevated levels and gradual deterioration in health status and functioning, especially among participants infected in the pre-omicron era.

Also, the frequency of PASC was higher among recurrent infections who were first infected during the Omicron era.

Another observation is that long-term symptoms associated with SARS-CoV-2 infection span multiple organ systems, possibly due to persistent viral carriers, autoimmunity, or direct differential organ damage. It is believed that there is.

Conclusion

In this study, investigators developed a new framework for PASC diagnosis that incorporates the contribution of multiple self-reported symptoms. Updated algorithms may also take into account patient biological characteristics.

Taken together, the development of PASC biomarkers may provide a peek into the mechanistic basis of PASC and inform the selection of therapeutic interventions in future PASC clinical trials.