COVID-Pain: Acute and Late-Onset Painful Clinical Manifestations in COVID-19 – Molecular Mechanisms and Research Perspectives

Marco Cascella,1 Alfredo Del Gaudio,2 Alessandro Vittori,3 Sabrina Bimonte,1 Paola Del Prete,4 Cira Antonietta Forte,1 Arturo Cuomo,1 Elvio De Blasio2,5 1Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori-IRCCS-“Fondazione G. Pascale”, Naples, 80131, Italy; 2DSC Anestesia e Rianimazione 2, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, 71013, FG, Italy; 3Department of Anesthesiology and Critical Care, ARCO, Bambino Gesù Children’s Hospital, Rome, Italy; 4Direzione Scientifica, Istituto Nazionale Tumori-IRCCS-“Fondazione G. Pascale”, Naples, 80131, Italy; 5Multidisciplinary Emergency Unit for COVID-19 Campania, Naples, 80100, ItalyCorrespondence: Sabrina BimonteDivision of Anesthesia and Pain Medicine, Istituto Nazionale Tumori-IRCCS-“Fondazione G. Pascale”, Naples, 80131, ItalyTel +39 0815903221Email s.bimonte@istitutotumori.na.itAbstract: Although the respiratory manifestations of COVID-19 are predominant, signs and symptoms of an extra-pulmonary involvement are usually encompassed among the clinical picture of the disease. Several painful manifestations can occur during the acute phase but also as short- or long-term complications. Myalgia, joint pain, sore throat, abdominal pain, chest pain, and headache usually accompany respiratory symptoms, but they can also occur as isolated clinical findings or can be expressed regardless of the severity of COVID-19. On these premises, given the vast spectrum of clinical manifestations and the complexity of their pathogenesis, it would be more appropriate to refer to “COVID-pain”, an umbrella term useful for encompassing all these clinical manifestations in a separate chapter of the disease. In this scenario, we addressed the topic from a molecular perspective, trying to provide explanations for the underlying pathophysiological processes. Consequently, this narrative review is aimed at dissecting the mechanisms of acute and chronic painful manifestations, summarizing fundamental concepts on the matter, controversies, current research gaps, and potential developments in this field.Keywords: COVID-19, SARS-CoV-2, COVID-pain, COVID-19 complications