![]() ![]() ![]() Persistent radiological abnormalities 24, 27, 28, 29, 30 include ground-glass opacities, signs of reticulation, including course fibrous bands either with or without obvious parenchymal distortion, bronchiectasis and pulmonary fibrosis, and appeared to be related to greater severity of acute COVID-19 syndrome 27, 31. ![]() Other lung-related manifestations included prolonged oxygen requirement 18 and difficulty weaning off ventilators 26, often related to the baseline pulmonary status. Given that lung involvement characterizes severe COVID-19, pulmonary symptoms including breathlessness 17, 18, 19, 20 and cough 17, 18 are noted in a substantial proportion of patients with long COVID and may 21, 22, 23, 24 or may not 25 correlate with prior COVID-19 severity. Noteworthy clinical manifestations, summarized by specific organ systems, are detailed below, focusing mostly on patients with severe disease. Table 1 outlines the salient manifestations of acute COVID-19 and post-COVID-19 syndrome. By contrast, the most common manifestations of post-COVID-19 syndrome are systemic (fatigue and, poor concentration), neuropsychiatric (sleep abnormalities, chronic headache, ‘brain fog’, defects in memory, mood impairment and pain syndromes), cardiac (palpitations, syncope, dysrhythmias and postural symptoms) and respiratory (dyspnea and cough). Although multiple organ systems can be involved in acute COVID-19, the most common manifestations are systemic, respiratory, gastrointestinal, cardiovascular and neurological. Finally, in a recent study of home-isolated, young (16- to 30-year-old) patients with COVID-19, nearly 60% reported persistent symptoms at 6 months, independent of the severity of the initial illness 16. ![]() In another systematic review, although COVID-19-associated symptomatology was more pronounced in individuals with severe disease, individuals with mild and moderate disease also reported a wide range of symptoms after the resolution of clinical disease 15. The severity of acute COVID-19 has been linked to post-COVID-19 syndrome in one large nationwide study based on healthcase databases of the US Department of Veterans Affairs 14. Although aspects of long COVID are reminiscent of post-SARS and post-MERS syndromes, clinical and laboratory manifestations associated with long COVID appear to be protean, with the involvement of several organ systems. Notably, a subset of individuals who have had SARS or MERS are reported to demonstrate protracted neuropsychiatric symptoms 5, 6, 7, 8, 9, sleep abnormalities 9, persistent impairment of pulmonary function, including reductions in diffusion lung capacity ( D l CO) 8, 10, 11, 12, pulmonary fibrosis 13, myalgias 9 and functional disabilities such as reduced exercise tolerance 8, 9, 10, 11, 12. SARS-CoV-2, a novel β-coronavirus, is phylogenetically related to coronaviruses responsible for SARS and Middle East respiratory syndrome (MERS) (SARS-CoV and MERS-CoV, respectively). The US Centers for Disease Control and Prevention uses the term ‘post-COVID conditions’ as an umbrella term for the wide range of health consequences that are present ≥4 weeks after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Proposed guidelines from the National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network and the Royal College of General Practitioners, all in the UK, define ‘acute COVID-19’ as signs and symptoms of COVID-19 for up to 4 weeks ‘ongoing symptomatic COVID-19’ as signs and symptoms of COVID-19 present from 4 weeks to 12 weeks of infection and post-COVID-19 syndrome as signs and symptoms consistent with COVID-19 that are present for more than 12 weeks after infection and not attributable to alternative diagnoses 4. In the absence of a unifying disease definition, working constructs of long COVID have included the persistence of a constellation of symptoms for time periods varying from >4 weeks from symptom onset 2 to symptoms that last for more than 3 months after onset 3. As the world grapples with successive waves of infection fueled by the emergence of viral variants, in a subset of patients who recover, protracted disease symptoms, termed ‘long COVID’, ‘long-haul COVID’ or ‘post-COVID syndrome’, are being increasingly recognized. As of 15 November 2021, an estimated 254 million cases and 5.1 million deaths have been ascribed to COVID-19 1. ![]()
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