Post by Nadica (She/Her) on Sept 23, 2024 1:46:40 GMT
A review of cytokine-based pathophysiology of Long COVID symptoms - Published March 30, 2023
Abstract
The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production. In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines. There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.
Highlights
- Long COVID patients include millions of people worldwide, and persistent symptoms following COVID-19 can continue for months.
- Varied and relapsing symptoms of Long COVID can be attributed to elevated peripheral and central cytokines, generated by an abnormal immune response.
- Chronic inflammation linked to immunothrombosis with microclot formation leads to decreased tissue perfusion and ischemia.
- CNS effects may be due to direct viral invasion, indirect immune response, or immunothrombosis.
- Dysregulated activation of brain microglia, due to neuroinflammation, can cause centrally mediated symptoms.
- Upregulation of the p38 MAPK pathway by SARS-Cov-2 can be a possible mechanism by which the virus increases cytokine production.
- Progression to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia occurs in some patients and could involve development of autoimmunity.
Abstract
The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production. In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines. There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.
Highlights
- Long COVID patients include millions of people worldwide, and persistent symptoms following COVID-19 can continue for months.
- Varied and relapsing symptoms of Long COVID can be attributed to elevated peripheral and central cytokines, generated by an abnormal immune response.
- Chronic inflammation linked to immunothrombosis with microclot formation leads to decreased tissue perfusion and ischemia.
- CNS effects may be due to direct viral invasion, indirect immune response, or immunothrombosis.
- Dysregulated activation of brain microglia, due to neuroinflammation, can cause centrally mediated symptoms.
- Upregulation of the p38 MAPK pathway by SARS-Cov-2 can be a possible mechanism by which the virus increases cytokine production.
- Progression to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia occurs in some patients and could involve development of autoimmunity.