The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with the virus, a significant proportion of them continue to experience health issues weeks, months and even years after acute infection with SARS-CoV-2. This persistence of clinical symptoms in infected individuals for at least three months after the onset of the disease or the emergence of new symptoms lasting more than two months, without any other explanation and alternative diagnosis have been named long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Long COVID has been characterized as a constellation of symptoms and disorders that vary widely in their manifestations. Further, the mechanisms underlying long COVID are not fully understood, which hamper efficient treatment options. This review describes predictors and the most common symptoms related to long COVID’s effects on the central and peripheral nervous system and other organs and tissues. Furthermore, the transcriptional markers, molecular signaling pathways and risk factors for long COVID, such as sex, age, pre-existing condition, hospitalization during acute phase of COVID-19, vaccination, and lifestyle are presented. Finally, recommendations for patient rehabilitation and disease management, as well as alternative therapeutical approaches to long COVID sequelae are discussed. Understanding the complexity of this disease, its symptoms across multiple organ systems and overlapping pathologies and its possible mechanisms are paramount in developing diagnostic tools and treatments.

Editorial: The NeuroCOVID-19 syndrome: cognitive and psychological profiles, physiopathology, and impact on neurologically vulnerable populations

“…The Coronavirus Disease 2019 (COVID-19) global pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has led to the identification of a broad range of post-acute COVID-19 neurological symptoms including cognitive impairments, executive dysfunctions, changes in sleep, emotional distress, pain and fatigue ( 1 ). Alarmingly, those post-acute sequelae of COVID-19 (PASC) can occur several weeks after infection, arise after severe, mild, or even asymptomatic SARS-CoV-2 infection, and are characterized by the persistence, worsening, or new onset of chronic and debilitating neurological symptoms, which have led to the use of NeuroCOVID syndrome terminology ( 2 , 3 ).…”

“…Despite a global research effort in describing PASC, there are still many research challenges and many open questions, particularly relating to pathophysiology, specific biomarkers, effective treatments ( 3 ) and risk factors of cognitive deficits and other neurological manifestations ( 4 ).…”