Onset and prognosis of post-COVID-19 condition: A 2-Year observational study

In a recent study published in The Lancet Regional Health – Europe, researchers conducted a prospective cohort analysis over two years to systematically characterize the evolution and clinical presentation of post-coronavirus disease 2019 (COVID-19) condition (PCC), including the factors associated with PCC onset and recovery and the different subsyndromes that might be present.

Study: Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study. Image Credit: Dmitry Demidovich/Shutterstock.comStudy: Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study. Image Credit: Dmitry Demidovich/Shutterstock.com


Post-COVID-19 condition, also known as long coronavirus disease (long COVID) or post-acute sequelae of  COVID-19 (PASC), afflicts approximately 5% to 10% of the individuals who survive a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

It manifests in a wide range of symptoms consisting of debilitating fatigue, shortness of breath, post-exertional malaise, and other medical conditions that result in physical, psychological, and social impairments, cumulatively impacting the quality of life.

Due to the lack of understanding of the pathophysiology of PCC and the absence of validated diagnostic biomarkers or effective treatments, the clinical definitions currently used to manage the syndrome are imprecise.

Furthermore, whether PCC has a single basis or combines various unconnected subsyndromes with independent pathophysiologies remains unclear.

A recent large-scale cross-sectional study from the United States identified four clusters based on the major symptoms of alterations in smell and taste, post-exertional malaise, gastrointestinal symptoms and palpitations, and brain fog.

However, there continues to be considerable overlap of symptoms across these clusters, and their clinical implications in the long term remain unclear.

About the study

In the present study, the researchers examined a prospective cohort of individuals who had survived COVID-19 and had visited the largest monographic unit for long COVID in Spain.

This unit comprises a team of physicians, psychologists, and nurses and administers multidisciplinary care to more than 1,200 patients suffering from PCC.

The acute SARS-CoV-2 infection was confirmed based on polymerase chain reaction (PCR) test results of nasopharyngeal swabs, serology, lateral flow rapid tests, and clinical diagnoses of COVID-19.

The criteria stipulated by the World Health Organization (WHO), which defines PCC as the presence of uninterrupted or relapsing symptoms related to the SARS-CoV-2 infection for a minimum of three months after the onset of COVID-19, was used to diagnose PCC.

The impact of the COVID-19 vaccination on PCC symptoms in the short term was also explored. Baseline data included demographic information, any comorbidities present at the time of the SARS-CoV-2 infection, diagnostic tests used to determine COVID-19, hospitalization requirements, admission into the intensive care unit (ICU), and the need for mechanical ventilation. Information on any diagnostic imaging and treatments administered were also obtained. The follow-up visits were conducted three, six, 12, 18, and 24 months following the COVID-19 diagnosis.

The dominant SARS-CoV-2 variant in circulation during the infection period, inferred from the Global Initiative on Sharing Avian Influenza Data (GISAID) database, was used to determine the variant that infected each participant.

The participants were also categorized based on education levels. Structured questionnaires were used to interview the participants about persistent symptoms, whether the PCC symptoms were acute or gradual in onset, and whether the clinical course of the symptoms was relapsing and remitting or continuous.


The findings indicated that acute COVID-19 symptoms and other factors, such as socioeconomic factors and preexisting medical conditions, play an important role in developing PCC symptoms and the recovery process.

The presentation of symptoms such as headaches, fatigue, tachycardia, neurosensitive and neurocognitive problems, and dyspnea during the onset of COVID-19 were associated with the development of PCC.

Interestingly, the study reported that male subjects who had attained a tertiary level of education were not very likely to develop PCC after a SARS-CoV-2 infection.

Of the three clusters retrieved based on symptoms, those that belonged to cluster A, characterized by fatigue, were reported to have recovered from PCC symptoms during the follow-up visits.

Furthermore, subjects who required ICU admissions, had experienced alterations to their sense of taste or smell and appetite loss, or suffered from cardiovascular comorbidities were also considered likely to recover from PCC symptoms.

However, those presenting with impaired attention, muscle pain, tachycardia, or dyspnea were believed to have a much lower likelihood of recovery from PCC.


Overall, the results reported that while some symptom clusters indicate a higher likelihood of recovery from PCC, preexisting medical conditions, the severity of the initial COVID-19 symptoms and socioeconomic factors play a major role in the prognosis for PCC patients.

Persistent PCC symptoms are likely to be a substantial healthcare burden worldwide.

Journal reference:
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.


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