In a recent study published in the journal Clinical & Experimental Allergy, a team of scientists conducted a systematic review to understand whether allergic diseases such as asthma and allergic rhinitis were risk factors for long coronavirus disease (long COVID).
Study: Allergic diseases as risk factors for Long-COVID symptoms: Systematic review of prospective cohort studies. Image Credit: p.ill.i / Shutterstock
Long COVID, also known as post-COVID syndrome or post-acute sequelae of COVID-19 (PASC), has rapidly become a significant health concern in the wake of the coronavirus disease 2019 (COVID-19) pandemic. It constitutes the persistence or recurrence of COVID-19 symptoms beyond 12 weeks after contracting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, where the symptoms cannot be explained by an alternate diagnosis. Long COVID often impacts multiple organ systems, with dyspnea and fatigue being the most common symptoms. In severe cases, symptoms associated with the cardiovascular, nervous, and gastrointestinal systems have also been observed.
Long COVID symptoms have been observed to persist for more than a year, and there have been no established links between the severity of the SARS-CoV-2 infection and the development of long COVID. The lack of clarity about the epidemiological basis of long COVID has impacted the development of effective treatment and rehabilitation strategies. Furthermore, while studies have identified comorbidities such as obesity, diabetes, and pre-existing pulmonary problems as potential risk factors for long COVID, there is a dearth of evidence on the role of allergic diseases such as allergic rhinitis and asthma in increasing the risk of long COVID.
About the study
In the present study, the scientists conducted a systematic review and comprehensive meta-analysis to examine the association between pre-existing allergic diseases and the increased risk of long COVID and determine the etiology of the disease. Studies published in German or English involving prospective cohorts of all ages that provided information on real-time polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections and pre-existing allergic conditions were evaluated. Only studies that had a follow-up period of a minimum of one year were included.
Long COVID was defined based on physician-diagnosed or self-reported symptoms that persisted or developed after an acute SARS-CoV-2 infection. Information on the study setting, study population, COVID-19 diagnoses, exposures consisting of allergies, assessments of exposures, outcomes consisting of long COVID symptoms and duration, and the methodologies for assessing long COVID symptoms were extracted from the studies for analysis.
Risk of bias was assessed for domains such as the recruitment and follow-up procedures, definitions and measurement of exposures, the validation of outcomes, analysis methods, and confounding. Additionally, for each examined outcome, the certainty of evidence was graded for risk of bias, indirectness, consistency, imprecision, and a few other domains. The meta-analysis was conducted for four subsets of study participants based on the presence of asthma in hospitalized individuals, asthma in the general population, allergies, and allergic rhinitis.
The results suggested that pre-existing asthma in hospitalized individuals and pre-existing rhinitis could increase the risk of long COVID. However, the association between pre-existing asthma in the general population or pre-existing allergies and an increased risk of long COVID was not apparent. The scientists believe that factors such as imprecision, indirectness, plausible confounding, and high risk of bias are major contributors to the low certainty of evidence.
The study also discussed some of the mechanistic considerations for examining the association between allergic diseases and an increased risk of long COVID. While studies have shown that allergic immune responses involving T-helper lymphocyte type 2 (Th-2) is thought to offer a certain degree of protection against SARS-CoV-2 infections, it could also increase the risk of long COVID. Understanding the contradicting roles of elevated eosinophil counts and Th-2 activity in COVID-19 and long COVID could help improve therapeutic strategies.
The activation of innate immune responses and the release of inflammatory cytokines in response to SARS-CoV-2 infection is also believed to exacerbate pre-existing allergic diseases or conditions. The review suggested that immunological dysregulation processes such as elevated interleukin-6 activity need to be examined as potential predictors of long COVID.
Overall, the findings indicated that there was a paucity of high-quality research on the involvement of pre-existing allergic diseases in exacerbating the risk of long COVID. This gap could be addressed by improving outcome assessment and exposure validations. The recent consensus on long COVID outcomes defines the Core Outcome Set as consisting of pain, fatigue, post-exertional malaise, changes in work or study, functioning and survival, cardiovascular, nervous, and respiratory system conditions, and mental health and cognitive outcomes.
The authors hope that the defined core outcomes and a clearer assessment of exposures involving distinctions between different allergic diseases will help improve our understanding of the factors that increase the risk of long COVID. Nonetheless, based on current evidence, they believe that allergic diseases such as rhinitis and asthma could increase the risk of long COVID.
- Wolff, D., Drewitz, K. P., Ulrich, A., Siegels, D., Deckert, S., Sprenger, A. A., Kuper, P. R., Schmitt, J., Munblit, D., & Apfelbacher, C. (2023). Allergic diseases as risk factors for Long-COVID symptoms: Systematic review of prospective cohort studies. Clinical & Experimental Allergy. https://doi.org/10.1111/cea.14391, https://onlinelibrary.wiley.com/doi/10.1111/cea.14391