About this Research Topic
About half of hospitalized COVID-19 patients (31%-69%) and 10% of SARS-COV-2-infected individuals present long-term sequelae of COVID-19 (long-COVID). Long-COVID has been defined in October 2021 by the World Health Organization as de novo or persisting symptoms present usually 3 months after COVID-19 onset and lasting at least 2 months. The manifestations of long-COVID are usually organized as systemic (as fatigue, weakness, loss of appetite), respiratory (dyspnea, cough), neuropsychiatric (memory or concentration impairment, headache, sleep disorders, anxiety or depression), musculoskeletal (pain and loss of function), cardiac (chest pain, palpitations), vascular (thrombosis and embolism), gastrointestinal (nausea, vomiting, diarrhea), endocrine, renal, dermatological and miscellaneous, being clinical, laboratorial or radiological. These symptoms may fluctuate or relapse over time and are not explicated by any other cause. Of note, sequelae have also been previously reported after SARS-CoV-1 and MERS-CoV infections.
Several pathophysiological hypotheses have been proposed to explain the onset of the post-COVID-19 condition. Firstly, as ACE2, the SARS-CoV-2 receptor, is expressed at the surface of a myriad of epithelial and endothelial cells, the cytopathic effect of SARS-CoV-2 may drive long-term tissue damage. Secondly, the persistence of SARS-CoV-2 or of some of its components in the human body, particularly in the intestine, but also in other tissues as shown by autopsy, has been documented and may be common for more than 6 months after the acute infection. This presence could cause immune dysregulation. Thus, persistent immune inflammation (high levels of TNF, IL-1, IL-6, CXCL10) and interferon overproduction have been reported in patients with sequelae. Thirdly, autoimmune phenomena have been also reported in long-term recovered patients, and may also explain some forms of long-COVID. Finally, a link between long-COVID and anti-EBV antibody titer, as well as EBV viremia has been reported. The frequency of anti-CMV cytotoxic CD8 T cells has also been associated with gastrointestinal sequelae of COVID-19. Thus, CMV or EBV reactivation could drive long-COVID.
This Research Topic welcomes original articles and reviews, with the aim of:
• Increasing our understanding of the immunological causes of the various symptoms of long-COVID, including neurological outcomes, by unveiling the immune dysregulation predicting and/or associated with sequelae.
• Identifying continental specificities of long-COVID in terms of frequency, symptomatology, severity, and outcome.
• Describing its association with other infections, including HIV, CMV, and EBV.
• Exploring the effect of potential preventive and curative immune therapies.
This topic is of crucial importance given that over 550 million individuals have already been infected by SARS-CoV-2.
Several pathophysiological hypotheses have been proposed to explain the onset of the post-COVID-19 condition. Firstly, as ACE2, the SARS-CoV-2 receptor, is expressed at the surface of a myriad of epithelial and endothelial cells, the cytopathic effect of SARS-CoV-2 may drive long-term tissue damage. Secondly, the persistence of SARS-CoV-2 or of some of its components in the human body, particularly in the intestine, but also in other tissues as shown by autopsy, has been documented and may be common for more than 6 months after the acute infection. This presence could cause immune dysregulation. Thus, persistent immune inflammation (high levels of TNF, IL-1, IL-6, CXCL10) and interferon overproduction have been reported in patients with sequelae. Thirdly, autoimmune phenomena have been also reported in long-term recovered patients, and may also explain some forms of long-COVID. Finally, a link between long-COVID and anti-EBV antibody titer, as well as EBV viremia has been reported. The frequency of anti-CMV cytotoxic CD8 T cells has also been associated with gastrointestinal sequelae of COVID-19. Thus, CMV or EBV reactivation could drive long-COVID.
This Research Topic welcomes original articles and reviews, with the aim of:
• Increasing our understanding of the immunological causes of the various symptoms of long-COVID, including neurological outcomes, by unveiling the immune dysregulation predicting and/or associated with sequelae.
• Identifying continental specificities of long-COVID in terms of frequency, symptomatology, severity, and outcome.
• Describing its association with other infections, including HIV, CMV, and EBV.
• Exploring the effect of potential preventive and curative immune therapies.
This topic is of crucial importance given that over 550 million individuals have already been infected by SARS-CoV-2.
Keywords: Long COVID, Long term tissue damage, immune dysregulation
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
