Long COVID or Post-COVID-19 Condition: Past, Present and Future Research Directions

Abstract

The presence of symptoms after an acute SARS-CoV-2 infection (long-COVID) has become a worldwide healthcare emergency but remains underestimated and undertreated due to a lack of recognition of the condition and knowledge of the underlying mechanisms. In fact, the prevalence of post-COVID symptoms ranges from 50% during the first months after the infection up to 20% two-years after. This perspective review aimed to map the existing literature on post-COVID symptoms and to identify gaps in the literature to guide the global effort toward an improved understanding of long-COVID and suggest future research directions. There is a plethora of symptomatology that can be due to COVID-19; however, today, there is no clear classification and definition of this condition, termed long-COVID or post-COVID-19 condition. The heterogeneity in the symptomatology has led to the presence of groups/clusters of patients, which could exhibit different risk factors and different mechanisms. Viral persistence, long-lasting inflammation, immune dysregulation, autoimmune reactions, reactivation of latent infections, endothelial dysfunction and alteration in gut microbiota have been proposed as potential mechanisms explaining the complexity of long-COVID. In such an equation, viral biology (e.g., re-infections, SARS-CoV-2 variants), host biology (e.g., genetics, epigenetics) and external factors (e.g., vaccination) should be also considered. These various factors will be discussed in the current perspective review and future directions suggested.

Nirmatrelvir–Ritonavir Reduced Mortality in Hospitalized Patients with COVID-19 During the Omicron Outbreak: Real-World Evidence from Beijing

“…Hence, vaccination should be prioritized over antivirals in high-risk patients, also from the cost-effective perspective, the risk of developing anti-viral resistance in case of widespread use of antivirals, as well as its potential effect on reduction of risk of post-COVID-19 sequelae. 22,23 This study revealed some interesting findings. First, the effectiveness of nirmatrelvir-ritonavir was not ideal in patients with mild-to-moderate liver dysfunction.…”

Inflammatory Polymorphisms (IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252) Are Not Associated with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors

“…The underlying mechanisms explaining the development of post-COVID symptoms are not fully understood, and different mechanisms are proposed: viral persistence, long-lasting inflammation, immune system dysregulation, autoimmunity, the reactivation of latent infections, endothelial dysfunction, and alteration in the gut microbiota [ 32 ]. Our study did not find an association between the four SNPs associated with inflammation and the development of post-COVID symptoms.…”

Navigating the Long Haul: A Comprehensive Review of Long-COVID Sequelae, Patient Impact, Pathogenesis, and Management

“…Long COVID, also called PASC, presents as a complex and multifaceted illness affecting a significant proportion of individuals recovering from an acute COVID-19 infection [17]. Among the most common symptoms of long COVID are chronic fatigue, fever, pain, breathlessness, anxiety, chronic fatigue syndrome, and postural orthostatic tachycardia syndrome (POTS) [13,17]. Additional general symptoms may include fatigue, fever, and pain [18].…”