Defining Post-COVID Symptoms (Post-Acute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification

Background : Single studies support the presence of several post-COVID-19 symptoms; however, no meta-analysis differentiating hospitalized and non-hospitalized patients has been published to date. This meta-analysis analyzes the prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized patients recovered from COVID-19 . Methods : MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were searched up to March 15, 2021. Peer-reviewed studies or preprints reporting data on post-COVID-19 symptoms collected by personal, telephonic or electronic interview were included. Methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. We used a random-effects models for meta-analytical pooled prevalence of each post-COVID-19 symptom, and I² statistics for heterogeneity. Data synthesis was categorized at 30days, 60days, and ≥90 days after . Results : From 15,577 studies identified, 29 peer-reviewed studies and 4 preprints met inclusion criteria. The sample included 15,244 hospitalized and 9,011 non-hospitalized patients. The methodological quality of most studies was fair. The results showed that 63.2%, 71.9% and 45.9% of the sample exhibited ≥one post-COVID-19 symptom at 30, 60, or ≥90days after onset/hospitalization. Fatigue and dyspnea were the most prevalent symptoms with a pooled prevalence ranging from 35% to 60% depending on the follow-up. Other post-COVID-19 symptoms included cough (20-25%), anosmia (10-20%), ageusia (15-20%) or joint pain (15-20%). Time trend analysis revealed a decreased prevalence 30days after with an increase after 60days . Conclusion : This meta-analysis shows that post-COVID-19 symptoms are present in more than 60% of patients infected by SARS-CoV‑2. Fatigue and dyspnea were the most prevalent post-COVID-19 symptoms, particularly 60 and ≥90 days after.

Post-COVID syndrome is increasingly recognized as a new clinical entity in the context of SARS-CoV-2 infection. Symptoms persisting for more than three weeks after the diagnosis of COVID-19 characterize the post-COVID syndrome. Its incidence ranges from 10% to 35%, however, rates as high as 85% have been reported among patients with a history of hospitalization. Currently, there is no consensus on the classification of post-COVID syndrome. We reviewed the published information on post-COVID syndrome, putting emphasis on its pathogenesis. The pathogenesis of post-COVID syndrome is multi-factorial and more than one mechanism may be implicated in several clinical manifestations. Prolonged inflammation has a key role in its pathogenesis and may account for some neurological complications, cognitive dysfunction, and several other symptoms. A multisystem inflammatory syndrome in adults (MIS-A) of all ages has been also described recently, similarly to multisystem inflammatory syndrome in children (MIS-C). The post-infectious inflammatory pathogenetic mechanism of MIS-A is supported by the fact that its diagnosis is established through serology in up to one third of cases. Other pathogenetic mechanisms that are implicated in post-COVID syndrome include immune-mediated vascular dysfunction, thromboembolism, and nervous system dysfunction. Although the current data are indicating that the overwhelming majority of patients with post-COVID syndrome have a good prognosis, registries to actively follow them are needed in order to define the full clinical spectrum and its long-term outcome. A consensus-based classification of post-COVID syndrome is essential to guide clinical, diagnostic, and therapeutic management. Further research is also imperative to elucidate the pathogenesis of post-COVID syndrome.

This multicenter study presents prevalence data and associated risk factors of post-COVID-19 cough one year after hospital discharge in COVID-19 survivors. Individuals recovered from COVID-19 at three public hospitals in Madrid (Spain) were scheduled for a telephonic interview. They were systematically asked about the presence of respiratory symptoms, e.g., fatigue, dyspnea, chest pain, and cough after hospital discharge. Clinical and hospitalization data were collected from hospital records. Overall, 1,950 patients (47% women, mean age:61, SD:16 years) were assessed at 11.2 months (SD 0.5) after hospital discharge. Just 367 (18.8%) were completely free of any respiratory post-COVID -19 symptom. The prevalence of long-term cough, chest pain, dyspnea, and fatigue was 2.5%, 6.5%, 23.3%, and 61.2%, respectively. Clinical and hospitalization factors were not associated with long-term post-COVID-19 cough. In conclusion, the prevalence of post-COVID-19 cough one year after SARS-CoV-2 infection was 2.5% in subjects who had survived hospitalization for COVID-19. No clear risk factor associated to long-term post-COVID-19 cough was identified.