What are the main findings of the long COVID research?


In a recent review published in Nature Reviews MicrobiologyIn this study, the researchers explored the existing literature on the prolonged coronavirus disease (COVID). They highlighted key immunological findings, similarities to other diseases, symptoms, associated pathophysiologic mechanisms, and diagnostic and therapeutic options, including vaccines for coronavirus disease 2019 (COVID-19).

Study: Long COVID: main findings, mechanisms, and recommendations.  Image credit: Ralph Liebhold/Shutterstock
Stady: Long-term COVID: key findings, mechanisms, and recommendations. Image credit: Ralph Liebhold/Shutterstock

Long COVID refers to a multi-system disease among individuals infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), with prevalence rates increasing each day. Studies have reported long COVID risk factors, symptoms, pathophysiology, prognosis, and treatment options, with increasing similarities between long COVID and other diseases such as POTS (postural orthostatic tachycardia syndrome) and ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome).

About the review

In the current review, the researchers explored existing data about prolonged COVID immunity, symptoms, pathophysiology, prognosis, and treatment options.

Key Long COVID Outcomes and Similarities to Other Diseases

Studies have reported lower numbers of exhausted T lymphocytes, dendritic cells, differentiation group 4+ (CD4+) and CD8+ lymphocytes, and greater expression of PD1 (programmed cell death protein-1). In addition, an increase in the immunomodulatory activities of innate cells, atypical monocytes, and the expression of interferon (IFNs)-β, λ1, interleukin (IL)-1β, 4,6, tumor necrosis factor (TNF) was shown. Expansion of cytotoxic T lymphocytes has been linked to prolonged gastrointestinal COVID symptoms, and sustained increase in CCL11 (CXC motif chemokine 11) expression has been linked to cognitive impairment among prolonged COVID patients.

Elevated antibody counters have been reported among long-term COVID patients, such as Antibodies Against angiotensin-converting enzyme 2 (ACE-2), angiotensin II type I (AT1) receptors, beta2-adrenergic receptors, angiotensin 1-7 receptors, and M2 muscarinic receptors. Reactivation of Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) has been reported in prolonged COVID and ME/CFS patients. EBV reactivation has been linked to neurocognitive impairment and fatigue in prolonged COVID.

Persistence of SARS-CoV-2 is said to lead to prolonged COVID symptoms. SARS-CoV-2 proteins and/or RNA have been detected in cardiovascular, genital, cranial, ocular, muscular, lymphatic, hepatic, pulmonary, serum, breast, urine and fecal tissues obtained from long-term COVID patients. Similar immunophenotypes are observed between prolonged COVID and ME/CFS, with high cytokine levels in the first two to three years of disease, followed by a decrease over time, without symptom improvement in ME/CFS. Low cortisol levels, mitochondrial dysfunction, malaise after exertion, dyskinesia, mast cell activation, platelet hyperactivity, hypermotility, endometriosis, menstrual changes, and intestinal dysplasia occur in both conditions.

Prolonged COVID symptoms and underlying pathophysiologic mechanisms

The prolonged organ damage associated with COVID is said to result from the inflammation caused by COVID-19 and associated immune responses. Prolonged COVID cardiovascular symptoms such as chest pain and heart palpitations have been associated with endothelial dysfunction, microcoagulation, and decreased vascular density. Long COVID has been associated with an increased risk of kidney damage and type 2 diabetes. Ocular symptoms of long COVID, including altered pupillary responses to light, result from loss of small nerve fibers in the cornea, increased density of dendritic cells, and impairment of the microvasculature of the retina . Respiratory symptoms such as persistent cough and shortness of breath result from altered pulmonary perfusion, epithelial injury, and airway entrapment.

Prolonged cognitive and neurological symptoms of COVID include memory loss, cognitive decline, sleep difficulties, paresthesia, balance difficulties, noise and light sensitivity, tinnitus, and loss of taste and/or smell. Underlying pathophysiological mechanisms include activation of the kynurenine pathway, endothelial injury, coagulopathy, decreased cortisol levels, myelin loss, microglia reactivation, oxidative stress, hypoxia, and tetrahydrobiopterin deficiency. Gastrointestinal symptoms such as abdominal pain, nausea, loss of appetite, constipation, and heartburn have been associated with high Bacteroides vulgatus And Ruminococcus gnavus counts and less fecal stool; count. Neurological symptoms are often delayed, worsen over time and last longer than respiratory and gastrointestinal symptoms, and COVID-19 appears for a similarly prolonged period in children and adults.

Diagnostic and treatment options for prolonged coronavirus, including COVID-19 vaccines

Diagnosis and treatment of prolonged COVID is largely based on symptoms, including tilt tests for POTS, magnetic resonance imaging (MRI) to detect cardiovascular and pulmonary dysfunction, and electrocardiograms to detect complex QRS fragmentation. saliva tests and serological tests, including red blood cell abnormality, lipid profile, and complete blood count, D-dimerand C-reactive protein (CRP) assessments, to assess immune biomarker levels. PCR (polymerase chain reaction) analysis is used to detect and quantify SARS-CoV-2 RNA, and antibody testing is performed to assess humoral immune responses against SARS-CoV-2.

Pharmacological treatments include intravenous administration for immune dysfunction, low-dose naltrexone for neuroinflammation, beta-blockers for POTS, microcoagulants for microthrombi formation, and stellate ganglion blockade for dystonia. Other options include antihistamines, baxlovid, sulodexide, and pycnogenol. Non-drug options include cognitive pacing for cognitive impairment, dietary restrictions for GI symptoms, and increased salt consumption in POTS. COVID-19 vaccines have provided minimal protection against prolonged COVID, the development of which depends on the causative SARS-CoV-2 variant, and the number of vaccination doses received. Prolonged COVID infection has been reported most commonly after infection with SARS-CoV-2 Omicron BA.2.

Based on the results of the review, long-term COVID-19 is a multi-organ disease that has debilitated the lives of many people around the world, and for which diagnostic and treatment options are not sufficient. The findings underscore the need for prospective studies, clinical trials, and improved education, mass communication campaigns, policies, and financing to reduce the future burden of COVID-19.



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