Intrinsic factors behind long‐COVID: I. Prevalence of the extracellular vesicles

Abstract

It can be argued that the severity of COVID-19 has decreased in many countries. This could be a result of the broad coverage of the population by vaccination campaigns, which often reached an almost compulsory status in many places. Furthermore, significant roles were played by the multiple mutations in the body of the virus, which led to the emergence of several new SARS-CoV-2 variants with enhanced infectivity but dramatically reduced pathogenicity. However, the challenges associated with the development of various side effects and their persistence for long periods exceeding 20 months as a result of the SARS-CoV-2 infection, or taking available vaccines against it, are spreading horizontally and vertically in number and repercussions. For example, the World Health Organization announced that there are more than 17 million registered cases of long-COVID (also known as post-COVID syndrome) in the European Union countries alone. Furthermore, by using the PubMed search engine, one can find that more than 10 000 articles have been published focusing exclusively on long-COVID. In light of these enormous and ever-increasing numbers of cases and published articles, most of which are descriptive of the various long-COVID symptoms, the need to know the reasons behind this phenomenon raises several important questions. Is long-COVID caused by the continued presence of the virus or one/several of its components in the recovering individual body for long periods of time, which urges the body to respond in a way that leads to long-COVID development? Or are there some latent and limited reasons related to the recovering patients themselves? Or is it a sum of both? Many observations support a positive answer to the first question, whereas others back the second question but typically without releasing a fundamental reason/signal behind it. Whatever the answer is, it seems that the real reasons behind this widespread phenomenon remain unclear. This report opens a series of articles, in which we will try to shed light on the underlying causes that could be behind the long-COVID phenomenon.

Blood Markers Show Neural Consequences of LongCOVID-19

“…Alternatively, harmful EVs secreted by cells in the periphery can cross the BBB into the brain to facilitate neurological damage. EVs have been implicated in SARS-CoV-2 infection, LongC and nLongC [ 7 , 8 ]. Our lab investigations utilized neuronal-enriched EVs (nEVs), immunopurified from plasma with anti-L1CAM monoclonal antibodies, as vehicles and biomarkers of neurological diseases [ 9 ].…”

Efficacy of Pulmonary Rehabilitation in Post-COVID-19: A Systematic Review and Meta-Analysis

“…Currently, it can be argued that the severity of COVID-19 has decreased in many countries, possibly due to the wide vaccination coverage carried out worldwide and effective treatment [ 3 ]. However, many patients affected by COVID-19 continue to experience symptoms after the acute phase, such as breathlessness, fatigue, neuropsychological symptoms, cough, and musculoskeletal pain [ 4 , 5 ].…”

Intrinsic factors behind long‐COVID: II. SARS‐CoV‐2, extracellular vesicles, and neurological disorders

“…Interestingly, the authors discovered a notable association between brain hypometabolism in this region and the presence of hyposmia/anosmia in these patients. 107 Guedj E. and colleagues, in their research, put forward the use of 18 F-FDG PET scans as a tool to investigate the hypothesis of cerebral hypometabolic dysfunction stemming from previous cerebral hypermetabolic inflammation. 108 Based on these findings, it is plausible to suggest that TSPO may play a significant role in the neuroinflammatory processes and the enduring loss of smell following acute COVID-19.…”

“…17 A general link between the long-COVID and ECVs as one of the etiological player behind the persistence of post-COVID sequelae was analyzed in the first article of the Intrinsic Factors behind long-COVID series. 18 Here, we continue this analysis by looking at the link between the long-COVID symptoms and their causes, starting from the roles of ECVs in nervous system. The main prognosis of long-COVID syndrome and neurological disorders are illustrated in Figure 1.…”

“…Exosomes have a dual action in that they are able to carry the SARS-CoV-2 inside them for a long period of time and spread the infectious component of the virus, in addition to their contribution to host defense and infection control. 18 For instance, research has shown that astrocytic ECVs are abundant in miR-873a-5p, which suppresses extracellular signal-regulated kinase phosphorylation, and the NF-b signaling pathway, which encourages the release of antiinflammatory molecules from microglia. Hence, it is thought to be a partial cytokine storm.…”