Characterizing Long COVID: Deep Phenotype of a Complex Condition

Abstract

Importance: Since late 2019, the novel coronavirus SARS-CoV-2 has given rise to a global pandemic and introduced many health challenges with economic, social, and political consequences. In addition to a complex acute presentation that can affect multiple organ systems, there is mounting evidence of various persistent long-term sequelae. The worldwide scientific community is characterizing a diverse range of seemingly common long-term outcomes associated with SARS-CoV-2 infection, but the underlying assumptions in these studies vary widely making comparisons difficult. Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations of long COVID. Observations: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts of individuals three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to Human Phenotype Ontology (HPO) terms. Conclusions and Relevance: Patients and clinicians often use different terms to describe the same symptom or condition. Addressing the heterogeneous and inconsistent language used to describe the clinical manifestations of long COVID combined with the lack of standardized terminologies for long COVID will provide a necessary foundation for comparison and meta-analysis of different studies. Translating long COVID manifestations into computable HPO terms will improve the analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared or pooled more effectively. Furthermore, mapping lay terminology to HPO for long COVID manifestations will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, which may improve the stratification and thereby diagnosis and treatment of long COVID.

Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure

“…The phenomenon of “long COVID” is not fully understood, although various possible explanations have been proposed, including damage caused by immune response to infection as well as by the infection itself, in addition to negative consequences of the experience of lengthy illness and hospitalization. However, a lack of consistency among definitions used in different studies makes it difficult to develop precise definitions or identify specific symptoms associated with long-term effects of COVID-19 ( 108 , 109 ). Patient and family support groups for “long haulers” have been formed online, and patient-driven efforts to collect data about postacute COVID-19 provide valuable sources of information (e.g., reference 106 ).…”

Who has long-COVID? A big data approach

“…Post-COVID respiratory symptoms and associated treatments: These features are commonly reported for long-COVID patients. 7,9,22 A confounding factor that prioritizes these features may be that the long-COVID clinics at two of the three sites contributing long-COVID clinic patients are based in the pulmonary department. However, given that SARS-CoV-2 is a primary respiratory virus, it is not surprising that long-term respiratory symptoms were observed.…”

“…8 Evaluation and harmonization of patient-and clinically reported long-COVID features using the Human Phenotype Ontology (HPO) also revealed heterogeneous signs and symptoms, supporting the conclusion that a complex constellation of both patient-and clinically reported features is necessary to correctly classify and manage long-COVID patients. 9 The World Health Organization (WHO) recently published its own case definition of "post COVID-19 condition" (WHO's term) that includes twelve criteria, which similarly require a wide variety of patient-declared and clinical information. 10 In order to gain an understanding of the complexities of long-COVID, it will be necessary to recruit a large and diverse cohort of research participants.…”

Descriptive and Narrative Study of Long Covid Cases in General Practice and Diagnostic Value of Single Photon Emission Computed Tomography (SPECT scan)

“…The Long Covid is also very difficult to define 5 and a Delphi consensus, led by the WHO, was needed to reach a definition. 6 The vision of Long Covid in the international literature still has a strong selection bias. The articles that deal with it are very hospital-centric and talk more about the doctor’s view on Long Covid than the patient’s.…”