What is the evidence for the consequences of Post-Acute COVID-19 (Coronavirus Disease 2019) Syndrome or Long COVID-19 (Coronavirus Disease 2019) Syndrome?

From the Guidelines

Yes, there is substantial proof of post-COVID or long COVID syndrome, with research documenting persistent symptoms in many COVID-19 survivors, including fatigue, brain fog, shortness of breath, chest pain, joint pain, and cognitive difficulties that can last for months after initial infection, as reported in a 2023 study published in Nature Reviews Microbiology 1. The symptoms of long COVID have been verified through multiple large-scale studies tracking patients over time, with medical imaging and laboratory tests showing objective evidence of organ damage in some long COVID patients, including lung scarring, cardiac inflammation, and neurological abnormalities. Some of the key findings from the 2023 study include:

• T cell alterations, including exhausted T cells, reduced CD4 and CD8 effector memory cell numbers, and elevated PD1 expression on central memory cells, persisting for at least 13 months 1
• Long COVID is associated with all ages and acute phase disease severities, with the highest percentage of diagnoses between the ages of 36 and 50 years, and most long COVID cases are in non-hospitalized patients with a mild acute illness 1
• Hundreds of biomedical findings have been documented, with many patients experiencing dozens of symptoms across multiple organ systems, including cardiovascular, thrombotic and cerebrovascular disease, type 2 diabetes, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and dysautonomia, especially postural orthostatic tachycardia syndrome (POTS) 1 The syndrome appears to affect between 10-30% of COVID-19 survivors, including those who had mild initial infections, with significant proportions of individuals with long COVID unable to return to work, contributing to labor shortages. The management of long COVID typically involves symptom-based approaches, such as pacing for postexertional malaise, pharmacological and non-pharmacological treatments for POTS, and cognitive pacing for cognitive dysfunction, as outlined in a 2023 study published in Nature Reviews Microbiology 1. The underlying mechanisms likely involve persistent inflammation, autoimmune reactions, viral persistence in tissues, and microvascular damage, with multiple, potentially overlapping, causes of long COVID, including persisting reservoirs of SARS-CoV-2 in tissues, immune dysregulation, and autoimmunity. Healthcare systems worldwide have established specialized long COVID clinics to address this growing medical challenge, recognizing it as a legitimate post-viral condition requiring comprehensive care. Some of the treatment options that have been suggested include:
• Paxlovid for viral persistence and antivirals (COVID-19) 1
• Valaciclovir, famciclovir, valganciclovir, and other antivirals for viral persistence and antivirals (reactivations such as of EBV, HCMV, and VZV) 1
• Sulodexide for endothelial dysfunction 1
• Probiotics for gastrointestinal symptoms 1
• Stellate ganglion block for dysautonomia 1
• Pycnogenol for endothelial function, microcirculation, inflammatory markers, and oxidative stress 1
• H and H antihistamines, particularly famotidine, for MCAS 1
• Transcutaneous vagal stimulation for autonomic dysfunction 1

From the Research

Post-COVID Syndrome: Incidence and Clinical Spectrum

• The incidence of post-COVID syndrome is estimated at 10-35%, while for hospitalized patients it may reach 85% 2.
• Fatigue is the most common symptom reported in 17.5-72% of post-COVID cases, followed by residual dyspnea with an incidence ranging from 10-40% 2.
• Mental problems, chest pain, and olfactory and gustatory dysfunction may affect up to 26,22, and 11% of patients, respectively 2.

Persistent Symptoms and Pulmonary Function

• Fatigue or weakness were the most prevalent physical effects of post-acute COVID-19 syndrome, while psychosocial symptoms were the most common manifestations among several systems 3.
• Abnormalities in lung function of recovering patients, i.e., DLCO <80% persisted for long periods 3.
• Severe patients were more likely to present joint pain and decreased lung functions compared with non-severe patients 3.

Impact on Physical Function, Cognitive Function, and Health-Related Quality of Life

• Persistent symptoms associated with post-acute COVID-19 syndrome seem to impact physical and cognitive function, health-related quality of life, and participation in society 4.
• Increased levels of fatigue and dyspnea were reported, alongside reductions in levels of regularly completed physical activity 4.
• Ninety-eight patients (63%) scored for at least mild cognitive impairment, and the domain of the EuroQol: 5 dimension, 5 level most impacted was Self-care, Anxiety/Depression, and Usual Activities 4.

Biological Factors Contributing to Persistent Symptoms

• Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens, and autoimmunity due to molecular mimicry between pathogen and host proteins 5.
• The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis 5.

Treatment and Rehabilitation

• Outpatient pulmonary rehabilitation in patients with long COVID improves exercise capacity, functional status, dyspnea, fatigue, and quality of life 6.
• A 6-week interdisciplinary individualized pulmonary rehabilitation program resulted in significant improvements across secondary endpoints, including presence of dyspnea, fatigue, and quality of life 6.