The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID

Abstract

There have been hundreds of millions of cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the growing population of recovered patients, it is crucial to understand the long-term consequences of the disease and management strategies. Although COVID-19 was initially considered an acute respiratory illness, recent evidence suggests that manifestations including but not limited to those of the cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, and musculoskeletal systems may persist long after the acute phase. These persistent manifestations, also referred to as long COVID, could impact all patients with COVID-19 across the full spectrum of illness severity. Herein, we comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific sequelae, pathophysiological mechanisms, and multidisciplinary management strategies. In addition, the impact of psychological and psychosomatic factors is also underscored. Despite these crucial findings on long COVID, the current diagnostic and therapeutic strategies based on previous experience and pilot studies remain inadequate, and well-designed clinical trials should be prioritized to validate existing hypotheses. Thus, we propose the primary challenges concerning biological knowledge gaps and efficient remedies as well as discuss the corresponding recommendations.

Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition

“…Viral infections have long been considered a major cause of myalgic encephalomyelitis–chronic fatigue syndrome . Although the exact mechanisms of postviral syndrome are unclear, viruses are thought to trigger aberrant immune responses that cause persistent mild inflammation and immune cell dysregulation, leading to long-lasting symptoms . We speculate that COVID-19 may affect muscle cells and autonomic neurons directly or via inflammatory pathways, causing myopathy and/or dysautonomia in some patients.…”

The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches

“…The main L-C19 symptoms reported in children and adolescents were neuropsychiatric: mood, fatigue, sleep disorder, headache, cognition, dizziness, neurological abnormalities (pins, tremor), balance problems; cardiorespiratory: respiratory symptoms, sputum/nasal congestion. orthostatic intolerance, exercise intolerance, chest pain, rhinorrhea, cough, sore throat, chest tightness, variation in heart rate, palpitations; dermatologic/teguments: hyperhidrosis, dermatologic (dry skin, rashes, hives), hair loss; gastrointestinal: abdominal pain, constipation, diarrhea, vomiting/nausea; and other: loss of appetite, altered smell, body weight variations, myalgia, altered smell, otalgia, ophthalmologic (conjunctivitis, dry eyes), fever, changes in menstruation, urinary symptoms, dysphagia, speech disturbances ( 157 – 159 ).…”

Type I interferon pathway genetic variants in severe COVID-19

“…As COVID-19 patients recovered, a subset has experienced persistent symptoms lasting for weeks past primary viral infection, giving rise to a post-infectious syndrome known as Long COVID or post-acute sequelae of COVID-19 ( Pagaduan and Altawallbeh, 2020 ; Phetsouphanh et al, 2022 ; Rio et al, 2020 ). This multisystemic condition often includes severe symptoms persisting for at least two months, following a history of probable or confirmed SARS-CoV-2 infection without an alternative diagnosis ( Davis et al, 2023 ; Li et al, 2023 ; Nalbandian et al, 2023 ). While estimates suggests that at least 65 million individuals worldwide may be affected by Long COVID, the actual number is difficult to ascertain, and it is likely higher due to undocumented cases ( Davis et al, 2023 ; Nalbandian et al, 2023 ).…”

“…While estimates suggests that at least 65 million individuals worldwide may be affected by Long COVID, the actual number is difficult to ascertain, and it is likely higher due to undocumented cases ( Davis et al, 2023 ; Nalbandian et al, 2023 ). Some common manifestations are similar to the acute disease, such as fatigue, shortness of breath, and a dysfunctional sense of smell, while others are different, such as neurocognitive impairment, autonomic dysfunction, and psychiatric ailments such as anxiety and depression ( Davis et al, 2023 ; Li et al, 2023 ; Nalbandian et al, 2023 ; Shaffer, 2022 ). Obese and older patients have a higher risk of developing Long COVID and this may be due to their association with acute COVID-19 severity, since severely ill patients are more likely to exhibit persistent symptoms.…”

“…SARS-CoV-2 variants may play a role in the progression of long COVID, with data from studies suggesting that Omicron infection is associated with fewer clinical manifestations of this post-infectious syndrome. However, the increased transmissibility and relatively low morbidity of this variant have the potential to expose more people to acute COVID-19 and the risk of progressing to persistent symptoms ( Fernández-de-las-Peñas et al, 2022 ; Li et al, 2023 ; Torjesen, 2021 ). Conversely, vaccination may prevent long COVID, since they can prevent acute COVID-19 or severe illness progression.…”