Long COVID-19 syndrome as a fourth phase of SARS-CoV-2 infection

Abstract

The SARS-CoV-2 pandemic has affected in the last two years a large number of subjects, with a high cost in terms of morbidity and mortality. The scientific community made progress in understanding risk factors, pathophysiology, clinical manifestations, diagnosis and treatment of acute SARS-CoV-2 infection. In the last months, another condition has become evident and caught the attention of the scientific community: the so-called long COVID syndrome. The pathophysiology of this condition is not known, even if some hypothesis have been made but not demonstrated yet. Long COVID is characterized by a very heterogeneous group of subacute and/or chronic symptoms and signs that follow the acute phase of SARS-CoV-2 infection and have a very variable duration. The presence of this syndrome in an individual is not dependent from the severity of the acute SARS-CoV-2 infection. Because of the extreme clinical heterogeneity, and also due to the lack of a shared and specific definition of the disease, it is very difficult to know the real prevalence and incidence of this condition. Some risk factors for the development of the disease have been identified: advanced age, elevated body mass index, comorbidities, specific symptoms of acute COVID-19 (in particular dyspnea), number of symptoms in the acute phase and female sex. The number of individuals affected by long COVID is high, even if it occurs only in a part of the subjects who had COVID-19. Therefore, long COVID constitutes now a major health issue and has to be managed in order to ensure an adequate access to care for all the people that need it. "Post COVID" clinics have been created in various countries, especially in Europe, for the management of people affected by long COVID syndrome. Guidelines have been written to help clinicians. An important role in the management of long COVID patients is played by the general practitioner, directly or indirectly linked to post COVID hospital clinics. The extreme heterogeneity of clinical presentation needs a patient-tailored, multidisciplinary approach. As NHS guidelines say, the three principal of care for long COVID patients are personalized care, multidisciplinary support and rehabilitation. More studies are needed in order to know better the pathophysiology of the disease. It is also necessary to create standardized and shared definitions of the disease, in order to better understand the epidemiology, the diagnostic criteria and to offer the right treatment to all the individuals who need it, without social or economic diffeences.

Keywords: COVID-19; Long COVID; SARS-CoV-2; follow up; post COVID.

Figure 1

COVID-19 phases. Three phases has been described in COVID-19 pathophysiology. Phase 1, called “early stage”, which has a predominant viral replication; it is typically asymptomatic or paucysymptomatic and is highly contagious. Phase 2, called “pulmonary” phase, characterized by lung viral replication and beginning of possible radiological findings; phase 3 or “hyperinflammatory phase” in which prevails the action of immune system ruled by the “cytokine storm”. Recently a fourth phase is being described namely “long COVID” depicted by subacute to chronic conditions and multiorgan involvement.

Figure 2

Long COVID management. Patients affected by long COVID can be managed through three pathways, depending on the severity of the acute SARS-CoV-2 infection. The main figures that lead the management of the patients are the general practitioner and the leading physician belonging to the health care centres where the patient has been hospitalized. If needed (abnormal radiological exams or persistence of symptoms after acute infections), the patient accesses the post COVID services where a specific patient-tailored treatment is offered.