Pathophysiology and mechanism of long COVID: a comprehensive review

Castanares-Zapatero, Diego; Chalon, Patrice; Kohn, Laurence; Dauvrin, Marie; Detollenaere, J; Noordhout, Charline Maertens de; Jong, C Primus-de; Cleemput, Irina; Heede, Koen Van den

doi:10.1080/07853890.2022.2076901

Cited by 388 publications

(361 citation statements)

References 116 publications

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“…Оригинальность исследования ЛИРА-КОВИД заключается в том, что впервые продемонстрировано наличие синдрома ГА у больных ПКС. Причинами ее возникновения, по-видимому, является сохраняющиеся печеночная и церебральная дисфункции, вызванные как самой инфекцией COVID-19, так и последствиями предшествующих инфицированию -хронических печеночных и/или церебральных расстройств [12].…”

Section: Discussionunclassified

Results of a multicenter prospective observational study “Clinical significance of hyperammonemia in patients with post-Covid syndrome (LIRA - COVID)”: efficacy of L-ornithine L-aspartate

Лазебник

Туркина

Myazin

et al. 2023

jour

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Epidemiological data suggests that approximately 10-65% of patients with mild to moderate COVID-19 have persistent symptoms already after an acute infection, which may last for six months or more. Previous clinical studies have shown that similar symptoms may also occur in the liver. Russian scientists have studied the phenomenon of hyperammonemia in the acute phase of COVID-19, but the problem of elevated blood ammonia levels in post -COVID syndrome has not been studied before. One possible option for the correction of hyperammonemia is the L-ornithine -L-aspartate (LOLA) preparation. The aim of the study was to investigate the manifestation of hyperammonemia in post -COVID syndrome and the possibility of its correction by using LOLA.Eighty-three patients (mean age 51.71 ± 12.82) with post-COVID syndrome, attention and memory impairment, chronic fatigue, hyperammonemia, 2-fold increase of alanine transaminase (ALT) and aspartate transaminase (AST) levels were included into multicenter, prospective observational study. L-ornithine-L-aspartate (LOLA) was given (3 g 3 times per day orally) for 4 weeks to correct hyperammonemia. Patients were accessed by the number connection test (NCT), fatigue evaluation test, measurement of ammonia and ALT, AST levels at baseline, and after 4 weeks.At week 4 the ammonia level was signifi cantly decreased in 81 patients (97.6%). Time (sec) to complete the NCT was 49,43 ± 15,85 vs 64.67 ± 24.95 at baseline (p<0.001). Before treatment, the majority of patients had stage 1 hepatic encephalopathy (HE) -50.6% and stage 1-2 (intermediate) HE -30.1%, stage 2 HE -10.9%, stage 3 HE -2.4%. After LOLA treatment, the distribution changed: 41% of patients had no HE, 36.1% had stage 1 of HE, 22.9% had stage 1-2 (intermediate) of HE, and stage 2 and 3 of HE was no longer defi ned. The mean score in fatigue evaluation test was 46,27 ± 10.0 vs 64,71 ± 19,18 at baseline (p<0.001). ALT and AST levels were 47,83 ± 38,21 units/l vs 95,75 ± 68.99 units/l at baseline and 40,10 ± 35,97 units/l vs 78,51 ± 90,90 units/l at baseline respectively (p<0.001).This study showed that the inclusion of LOLA in a dose of 3 g 3 times a day for 4 weeks was associated with signifi cant improvement in the objective and subjective outcomes in patients with post-COVID syndrome.

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Section: Discussionunclassified

Results of a multicenter prospective observational study “Clinical significance of hyperammonemia in patients with post-Covid syndrome (LIRA - COVID)”: efficacy of L-ornithine L-aspartate

Лазебник

Туркина

Myazin

et al. 2023

jour

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“…Considering the staggering amount of patients reporting prolonged symptoms even as long as 15 months after the initial onset of COVID-19 2,7,46,47 , further research into potential pathomechanisms of this protracted recovery is urgently needed 48 . A possible explanation for the mechanisms underlying some PASC symptoms, such as dyspnea, shortness of breath and exercise intolerance, could be an impaired regeneration of alveolar tissue and lung fibrosis 3,9 . It has also been suggested that the persistence of CK8 + ADI cells might be the cause of prolonged hypoxemia in COVID-19 patients 8 .…”

Section: Discussionmentioning

confidence: 99%

Hamsters are a model for post-COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2

Heydemann

Ciurkiewicz

Beythien

et al. 2022

Preprint

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A relevant number of coronavirus disease 2019 (COVID-19) survivors suffers from post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC). Current evidence suggests a dysregulated alveolar regeneration in COVID-19 as a possible explanation for respiratory PASC symptoms, a phenomenon which deserves further investigation in a suitable animal model. This study investigates morphologic and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+ alveolar differentiation intermediate (ADI) cells accumulate following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of p53 at 6- and 14-days post infection (dpi), indicating a prolonged block in the ADI state. Transcriptome data shows the expression of gene signatures driving ADI cell senescence, epithelial-mesenchymal transition, and angiogenesis. Moreover, we show that multipotent CK14+ airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, persistence of ADI cells, peribronchiolar proliferates, M2-type macrophages, and sub-pleural fibrosis is observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The study provides a suitable translational model for future research on the pathomechanims of PASC and testing of prophylactic and therapeutical approaches.

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“…Inflammation via the trigeminal nerve has been postulated as a possible mechanism of headache 115 . SARS‐CoV‐2 has been detected in the trigeminal ganglion in autopsy studies 55 .…”

Section: Representative Neurological Symptoms Of Pascmentioning

confidence: 99%

“…22 Inflammation via the trigeminal nerve has been postulated as a possible mechanism of headache. 115 SARS-CoV-2 has been detected in the trigeminal ganglion in autopsy studies. 55 However, there may be a variety of factors associated with headache in COVID-19 cases.…”

Section: Headachementioning

confidence: 99%

Neurological post‐acute sequelae of SARS‐CoV‐2 infection

Takao

Ohira

2022

Psychiatry Clin Neurosci

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The novel corona virus infectious disease, COVID‐19, caused by SARS‐CoV‐2, can have two phases: acute (generally 4 weeks after onset) and chronic (> 4 weeks after onset). Both phases include a wide variety of signs and symptoms including neurological and psychiatric symptoms. The signs and symptoms that are considered sequelae of COVID‐19 are termed post‐COVID condition, long COVID‐19, and post‐acute sequelae of SARS‐CoV‐2 infection (PASC). PASC symptoms include fatigue, dyspnea, palpitation, dysosmia, sub‐fever, hypertension, alopecia, sleep problems, loss of concentration, amnesia, numbness, pain, gastrointestinal symptoms, depression, and anxiety. Because the specific pathophysiology of PASC has not yet been clarified, there are no definite criteria of the condition, hence the World Health Organization’s definition is quite broad. Consequently, it is difficult to correctly diagnose PASC. Approximately 50% of patients may show at least one PASC symptom up to 12 months after COVID‐19 infection; however, the exact prevalence of PASC has not been determined. Despite extensive research in progress worldwide, there are currently no clear diagnostic methodologies or treatments for PASC. In this review, we discuss the currently available information on PASC and highlight the neurological sequelae of COVID‐19 infection. Furthermore, we provide clinical suggestions for diagnosing and caring for PASC patients based on our outpatient clinic experience. This article is protected by copyright. All rights reserved.

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Pathophysiology and mechanism of long COVID: a comprehensive review

Cited by 388 publications

References 116 publications

Results of a multicenter prospective observational study “Clinical significance of hyperammonemia in patients with post-Covid syndrome (LIRA - COVID)”: efficacy of L-ornithine L-aspartate

Results of a multicenter prospective observational study “Clinical significance of hyperammonemia in patients with post-Covid syndrome (LIRA - COVID)”: efficacy of L-ornithine L-aspartate

Hamsters are a model for post-COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2

Neurological post‐acute sequelae of SARS‐CoV‐2 infection

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