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It's not over till it's over: a narrative review of Long COVID

  • Joseph V. Pergolizzi1
  • Jo Ann LeQuang1
  • Peter Magnusson2,3
  • Dariusz Myrcik4,5
  • Giustino Varrassi5

1NEMA Research Group, Naples, FL 34108-1852, USA

2Centre for Research and Development, Uppsala University/Region Gävleborg, 80188 Gävle, Sweden

3Cardiology Research Unit, Department of Medicine, Solna, Karolinska Institutet, 17177 Stockholm, Sweden

4Department of Internal Medicine, University of Silesia, 41813 Katoviche, Poland

5Paolo Procacci Foundation, Via Tacito 7, 00193 Rome, Italy

DOI: 10.22514/sv.2021.067 Vol.17,Issue 3,May 2021 pp.21-30

Submitted: 19 March 2021 Accepted: 26 March 2021

Published: 08 May 2021

*Corresponding Author(s): Jo Ann LeQuang E-mail:


Viral persistence following acute COVID infection is increasingly being reported by patients and gradually being recognized as a medical syndrome. Like much about COVID, this so-called Long COVID is perplexing. It is associated with numerous symptoms, foremost among them profound fatigue, and often occurs in a relapsing/remitting pattern. There is one “living” guideline for managing Long COVID and even terminology and definitions of the syndrome are in flux. Long COVID occurs in patients who have recovered from the acute infection and this may be viral persistence, a form of autoimmunity, or the long-term results of organ damage sustained during the acute infection. Symptoms have been reported up to six months after acute infection with no clear association between the severity of the acute infection and the presence or absence of Long COVID. The symptoms of the acute illness do not necessarily align with the symptoms of Long COVID. Disruptions to the autonomic function in Long COVID are particularly puzzling, including orthostatic intolerance syndrome (which may not have occurred during the acute infection). Loss of the sense of smell and taste is one symptom that appears common in both acute and Long COVID; on the other hand, fever is more prevalent in acute than Long COVID. Research is urgently needed to better understand Long COVID, for example: what is the role of elevated biomarkers such as D-dimer and C-reactive protein in Long COVID? Is Long COVID one or more than one syndrome? How can patients with Long COVID be appropriately treated?


COVID-19; COVID therapy; Fatigue; Immunobiography; Long COVID; Long-haul COVID; Oxidative stress; Therapy

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Joseph V. Pergolizzi,Jo Ann LeQuang,Peter Magnusson,Dariusz Myrcik,Giustino Varrassi. It's not over till it's over: a narrative review of Long COVID. Signa Vitae. 2021. 17(3);21-30.


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