Pathological sequelae of long-haul COVID

Abstract

an estimated 254 million cases and 5.1 million deaths have been ascribed to COVID-19 1 . 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. 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 . 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 . 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).Organ-specific sequelae. 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). Notably, a subset of individuals who have had SARS or MERS are reported to demonstrate protracted neuropsychiatric symptoms 5-9 , sleep abnormalities 9 , persistent impairment of pulmonary function, including reductions in diffusion lung capacity (Dl CO ) 8,10-12 , pulmonary fibrosis 13 , myalgias 9 and functional disabilities such as reduced exercise tolerance [8][9][10][11][12] . 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.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 . 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 . Finally, in a recent study of home-isolated, young (16to 30-year-old) patients with COVID-19, nearly 60% reported persistent symptoms at 6 months, independent of the severity of the initial illness 16 . Although multiple organ systems can be involved in acute COVID-19, the most common manifestations are systemic, respiratory, gastrointestinal, cardiovascular and neurological. By c...

Post-COVID-19 tele-survey for persistent symptoms in a single center hospital cohort in India along with a parallel country-wide web-survey

“…The PCS found to be most prevalent in our study have also been reported by previous studies done in different parts of the world (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), although the relative distribution varied among cohorts, as did the demographic and clinical associations. The most extensive and long physical follow-up study, done in Wuhan, China, reported fatigue and muscle weakness (63%) and sleep difficulties (26%) to be the most prevalent PCS at a median of 186 days since symptom onset (N=1655) (9).…”

“…A major concern amidst this pandemic has been the long term morbidities in the individuals recovering from COVID-19 disease, the so-called 'long COVID' (6,7). The 'long-haul COVID', which has emerged as a definite clinical entity all over the world, has largely been attributed to the undue lingering of the systemic inflammation for variable time periods (8). Exploring the factors that make convalescent subjects more susceptible to long-COVID is a domain of active research.…”

ACE2-independent SARS-CoV-2 infection and mouse adaption emerge after passage in cells expressing human and mouse ACE2

“…The pathological consequences of ACE-2 independent infection remain to be characterized, and one might speculate that ACE-independent infection may play a role in long-COVID 56,57 .…”

Repurposing Probenecid to Inhibit SARS-CoV-2, Influenza Virus, and Respiratory Syncytial Virus (RSV) Replication

“…Interestingly, CoVs and RSV replicate in the host cell’s cytosol, while flu replicates in the nucleus; however, all of these viruses are susceptible to probenecid. As viruses modify host genes and pathways to facilitate viral replication, it is possible that probenecid treatment may modify viral-mediated changes that contribute to the treatment of “long COVID” symptoms [ 73 , 74 ], where PANX1 expression in the brain and synaptic plasticity are modified by COVID [ 75 , 76 ].…”