Review The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID 2023

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.

https://www.nature.com/articles/s41392-023-01640-z

 

They have a chapter on ME:

Myalgic encephalomyelitis/chronic fatigue syndrome
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neuroimmune illness characterized by intolerance to systemic exertion and chronic fatigue that cannot be alleviated via rest.87,88 The diagnostic criteria of ME/CFS comprise substantial impairment in daily activities for a minimum of 6 months and profound fatigue of new/definite onset that cannot be relieved by rest, accompanied by post-exertional malaise and unrefreshing sleep, cognitive impairment and/or orthostatic intolerance.89 For most patients with ME/CFS, ‘infectious-like’ manifestations involving fever, respiratory and digestive symptoms, myalgia, and lymphadenopathy universally emerge before illness onset.60,87,89

Fatigue syndromes after confirmed infection that might meet the diagnostic criteria of ME/CFS have been reported for multiple pathogens, including Ebola virus, Epstein-Barr virus, herpesvirus-6, SARS-CoV, and Mycoplasma pneumoniae.90,91,92,93,94 The potential correlation between long COVID and ME/CFS has also been commented by many researchers. A systematic review of 21 studies revealed that the clinical manifestations of ME/CFS exhibited many overlaps with long COVID.95 The presence of ME/CFS has also been observed in both children and adults with confirmed long COVID.96,97 Among participants over 18 years old with long COVID, 58.7% met the criteria for ME/CFS.96 In a cross-sectional survey, 40% of children and adolescents with COVID-19 were reported to have documented ME/CFS.97

The pathophysiological processes of ME/CFS could be summarized as initial immune and inflammatory responses, vascular dysregulation, and autonomic/metabolic adaptation.89,98The widespread inflammatory response triggered by SARS-CoV-2 infection has been reported in patients with varying degrees of illness severity,80,99 which could occur in the nervous system and contribute to neuropsychiatric symptoms.80,83 The interaction networks of ME/CFS and long COVID, including inflammatory cytokines comprising interleukin (IL)-6 and IL-1B, common genes, and microRNAs, have recently been depicted,100 revealing the potential mechanism of ME/CFS in the occurrence of long COVID and further emphasizing the significance of the inflammatory response. Meanwhile, the dysregulation of endothelin-1 has been found in long COVID patients and cases presenting exertion intolerance and persistent fatigue, suggesting the emergence of endothelial dysfunction and its effect on ME/CFS.101Moreover, metabolic disorders of energy probably promote exercise intolerance and nervous symptoms. The dysregulation of mitochondrial membrane potential and plasma metabolites related to mitochondria-dependent lipid catabolism are manifested in patients with long COVID,102,103 perhaps conducive to ME/CFS development. Intriguingly, a study implementing machine learning to assess antibody-binding data revealed that the microbiota-immune axis was involved in the pathophysiology of ME/CFS,104 suggesting that the microbiota could serve as a novel direction for investigating ME/CFS in post-COVID-19 syndromes.

Under certain circumstances, several diseases, such as mast cell activation syndrome, postural orthostatic tachycardia syndrome (POTS), intracranial hypertension, and craniocervical obstructions, are generally comorbid with ME/CFS.105,106,107 Quite a few studies have also documented the corresponding manifestations in patients with long COVID.26,95 However, the comorbid diseases of ME/CFS in long COVID remain enigmatic and worth further investigation.

 

Is the journal Signal Transduction and Targeted Therapy a part of Nature? So is this considered to be published by a prestigious journal?

 

Some interesting points made about one of the author on Twitter, seems reasonable to me to assume there could be some level of (undisclosed) AI writing involved in this. Another of the authors is an editor at the journal it was published in (which makes no sense for the topic). Seems pretty sketchy.

https://twitter.com/user/status/1719780431044735264

 

When this paper came up in my RSS feed a couple of days ago I skipped posting it here as I thought it was poor quality and at its best was not adding anything useful to our LC understanding.

Quite a bit more to it: see @Lucibee's thread (on Twitter via Nitter). (On BlueSky Brian Hughes has tagged Elizabeth Bik to Lucibee's post there)

https://nitter.net/_Lucibee/status/1719780431044735264

Author affiliations —

Jingwei Li1 , Yun Zhou1 , Jiechao Ma2, Qin Zhang1,3, Jun Shao1 , Shufan Liang1 , Yizhou Yu4, Weimin Li1 and Chengdi Wang1

1 Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Med-X Center for Manufacturing, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China

2 AI Lab, Deepwise Healthcare, Beijing, China

3 Department of Postgraduate Student, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China

4 Department of Computer Science, The University of Hong Kong, Hong Kong, China

Reformats to —

1) Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Med-X Center for Manufacturing, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China

Jingwei Li, Yun Zhou, Qin Zhang, Jun Shao, Shufan Liang, Weimin Li, Chengdi Wang

2) AI Lab, Deepwise Healthcare, Beijing, China

Jiechao Ma

3) Department of Postgraduate Student, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China

Qin Zhang

4) Department of Computer Science, The University of Hong Kong, Hong Kong, China

Yizhou Yu

I am a little confused about the combined listing in (1) of Department of Pulmonary and Critical Care Medicine with Med-X Center for Manufacturing but that may be an unrelated administrative/organisational quirk.

The first author (Jingwei Li) uses the same affiliation in CircRNAs in lung cancer- role and clinical application (2022 Cancer Letters)

 

Just to add:
One of the Editors in Chief of the journal - Signal Transduction and Targeted Therapy - is Prof Yu-Quan Wei, who is at the same affil (West China Hospital) as many of the listed authors. https://www.nature.com/sigtrans/editors

The corresponding authors are Weimin Li & Chengdi Wang from West China Hospital and Yizhou Yu, who is a professor of computer science from Hong Kong.

The first listed EiC is Carlo Croce, who is quite well known to Retraction Watch (for various alleged reasons I won't go into here).

This paper is seeing a lot of traffic - which will only boost its appearance in searches. I hope something is done about it soon. But I'm not sure what can be done.

 

Update: I've done something. I wrote to Springer Nature Research Integrity dept, and they are going to look into it.