Tag: long covid review

Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms

Abstract:

Numerous investigations have demonstrated significant and long-lasting neurological manifestations of COVID-19. It has been suggested that as many as four out of five patients who sustained COVID-19 will show one or several neurological symptoms that can last months after the infection has run its course. Neurological symptoms are most common in people who are less than 60 years of age, while encephalopathy is more common in those over 60. Biological mechanisms for these neurological symptoms need to be investigated and may include both direct and indirect effects of the virus on the brain and spinal cord. Individuals with Alzheimer’s disease (AD) and related dementia, as well as persons with Down syndrome (DS), are especially vulnerable to COVID-19, but the biological reasons for this are not clear.
Investigating the neurological consequences of COVID-19 is an urgent emerging medical need, since close to 700 million people worldwide have now had COVID-19 at least once. It is likely that there will be a new burden on healthcare and the economy dealing with the long-term neurological consequences of severe SARS-CoV-2 infections and long COVID, even in younger generations. Interestingly, neurological symptoms after an acute infection are strikingly similar to the symptoms observed after a mild traumatic brain injury (mTBI) or concussion, including dizziness, balance issues, anosmia, and headaches. The possible convergence of biological pathways involved in both will be discussed. The current review is focused on the most commonly described neurological symptoms, as well as the possible molecular mechanisms involved.
Source: Granholm A-C. Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms. Journal of Clinical Medicine. 2023; 12(9):3190. https://doi.org/10.3390/jcm12093190 https://www.mdpi.com/2077-0383/12/9/3190 (Full text)

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

Abstract:

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms.
The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses.
In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.
Source: Gonzalez-Garcia P, Fiorillo Moreno O, Zarate Peñata E, Calderon-Villalba A, Pacheco Lugo L, Acosta Hoyos A, Villarreal Camacho JL, Navarro Quiroz R, Pacheco Londoño L, Aroca Martinez G, Moares N, Gabucio A, Fernandez-Ponce C, Garcia-Cozar F, Navarro Quiroz E. From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID. International Journal of Molecular Sciences. 2023; 24(9):8290. https://doi.org/10.3390/ijms24098290 https://www.mdpi.com/1422-0067/24/9/8290 (Full text)

Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder

Abstract:

Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge.
One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can alter the mitochondria responsible for energy production in cells. This alteration leads to mitochondrial dysfunction which, in turn, increases oxidative stress. Ultimately, this results in a loss of mitochondrial integrity and cell death. Moreover, viral proteins can bind to mitochondrial complexes, disrupting mitochondrial function and causing the immune cells to over-react. This over-reaction leads to inflammation and potentially long COVID symptoms.
It is important to note that the roles of mitochondrial damage and inflammatory responses caused by SARS-CoV-2 in the development of long COVID are still being elucidated. Targeting mitochondrial function may provide promising new clinical approaches for long-COVID patients; however, further studies are needed to evaluate the safety and efficacy of such approaches.
Source: Chen T-H, Chang C-J, Hung P-H. Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder. International Journal of Molecular Sciences. 2023; 24(9):8034. https://doi.org/10.3390/ijms24098034 https://www.mdpi.com/1422-0067/24/9/8034 (Full text)

Identification and diagnosis of long COVID-19: A scoping review

Abstract:

Long COVID-19 (LC-19) is a condition that has affected a high percentage of the population that recovered from the initial disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LC-19 diagnosis is currently poorly defined because of its variable, multisystem, episodic symptoms, and lack of uniformity in the critical time points associated with the disease. Considering the number of cases, workers’ compromised efficiency or inability to return to their duties can affect organizations and impact economies. LC-19 represents a significant burden on multiple levels and effectively reduces quality of life. These factors necessitate the establishment of firm parameters of diagnoses to provide a foundation for ongoing and future studies of clinical characteristics, epidemiology, risk factors, and therapy.

In this scoping review, we conducted a literature search across multiple publication sites to identify papers of interest regarding the diagnosis of LC-19. We identified 225 records of interest and categorized them into seven categories. Based on our findings, there are only 11 original papers that outline the diagnostic process in detail with little overlap. This scoping review highlights the lack of consensus regarding the definition and, thereby, the LC-19 diagnosis processes. Due to no clear directive and considering the many unknowns surrounding the natural history of the disease and further recovery/sequelae from COVID-19, continued discussion and agreement on a definition/diagnosis will help future research and management of these patients.

Source: Srikanth S, Boulos JR, Dover T, Boccuto L, Dean D. Identification and diagnosis of long COVID-19: A scoping review. Prog Biophys Mol Biol. 2023 May 12;182:1-7. doi: 10.1016/j.pbiomolbio.2023.04.008. Epub ahead of print. PMID: 37182545; PMCID: PMC10176974. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176974/ (Full text)

Viral persistence, reactivation, and mechanisms of long COVID

Abstract:

The COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has infected hundreds of millions of individuals. Following COVID-19 infection, a subset can develop a wide range of chronic symptoms affecting diverse organ systems referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. A National Institutes of Health-sponsored initiative, RECOVER: Researching COVID to Enhance Recovery, has sought to understand the basis of long COVID in a large cohort. Given the range of symptoms that occur in long COVID, the mechanisms that may underlie these diverse symptoms may also be diverse.

In this review, we focus on the emerging literature supporting the role(s) that viral persistence or reactivation of viruses may play in PASC. Persistence of SARS-CoV-2 RNA or antigens is reported in some organs, yet the mechanism by which they do so and how they may be associated with pathogenic immune responses is unclear. Understanding the mechanisms of persistence of RNA, antigen or other reactivated viruses and how they may relate to specific inflammatory responses that drive symptoms of PASC may provide a rationale for treatment.

Source: Chen B, Julg B, Mohandas S, Bradfute SB; RECOVER Mechanistic Pathways Task Force. Viral persistence, reactivation, and mechanisms of long COVID. Elife. 2023 May 4;12:e86015. doi: 10.7554/eLife.86015. PMID: 37140960; PMCID: PMC10159620. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159620/ (Full text)

A Narrative Review on the Potential Role of Vitamin D3 in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19

Abstract:

Purpose of Review: The coronavirus disease 2019 (COVID-19) pandemic has challenged global health systems and economies from January 2020. COVID-19 caused by the infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) has acute respiratory and cardiometabolic symptoms that can be severe and lethal. Long-term physiological and psychological symptoms, known as long COVID-19, persist affecting multiple organ systems. While vaccinations support the fight against SARS-CoV-2, other effective mechanisms of population protection should exist given the presence of yet unvaccinated and at-risk vulnerable groups, global disease comorbidities, and short-lived vaccine responses. The review proposes vitamin D3 as a plausible molecule for prevention, protection, and disease mitigation of acute and long COVID-19.

Recent Findings: Epidemiological studies have shown that individuals who were deficient in vitamin D3 had worse COVID-19 health outcomes and mortality rates. Higher doses of vitamin D3 supplementation may improve health and survivorship in individuals of various age groups, comorbidities, and severity of disease symptoms.

Summary: Vitamin D3’s biological effects can provide protection and repair in multiple organ systems affected by SARS-CoV-2. Vitamin D3 supplementation can potentially support disease-mitigation in acute and long COVID-19.

Source: Moukayed, M. A Narrative Review on the Potential Role of Vitamin D3 in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19. Curr Nutr Rep (2023). https://doi.org/10.1007/s13668-023-00471-2 https://link.springer.com/article/10.1007/s13668-023-00471-2 (Full text)

Long-COVID and its Physical and Neurological Symptoms in Adults: A Systematic Review

Abstract:

This review was carried out with the objective to study patterns of neurological, psychological and other physical consequences of COVID-19 in the long term. The guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) had been followed; 22 articles, published during January 2020 to September 2021, were selected. Original research, review articles, editorial and viewpoints were included. Google Scholar, Medline, and PubMed were searched through 2020 till 2021.

Data collection in selected studies was performed mainly through the online survey, telephone survey, use of medical records, and patient interviews. This systematic review contains the studies conducted in the American, Asian and European countries. The major outcomes identified were the neurological, psychological, and other long-term chronic manifestations of COVID‐19.

This review demonstrates that long-COVID has started to bring a huge wave of patients, the count of them being millions now, who can enter a phase of disability due to neurological damages if not treated during the early course of illness. Though more disabling than lethal, long-COVID patients with a neurological deficit is expected to overburden the healthcare system globally which is already been struggling to handle acute COVID-19 patients in this once-in-a-lifetime pandemic.

Source: Abdul Mannan Baig, Sameera Rizvi, Shahla Pardhan, Joachim Gerlach, Tazeen Saeed Ali. Long-COVID and its Physical and Neurological Symptoms in Adults: A Systematic Review. Vol. 17 No. 04 (2023): Pakistan Journal of Medical & Health Sciences. https://pjmhsonline.com/index.php/pjmhs/article/view/4549/4498 (Full text)

Long COVID: a review and proposed visualization of the complexity of long COVID

Abstract:

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose a visual description of the complexity of Long COVID and its pathogenesis that can be used by researchers, clinicians, and public health officials to guide the global effort toward an improved understanding of Long COVID and the eventual mechanism-based provision of care to afflicted patients. The proposed visualization or framework for Long COVID should be an evidence-based, dynamic, modular, and systems-level approach to the condition.

Furthermore, with further research such a framework could establish the strength of the relationships between pre-existing conditions (or risk factors), biological mechanisms, and resulting clinical phenotypes and outcomes of Long COVID. Notwithstanding the significant contribution that disparities in access to care and social determinants of health have on outcomes and disease course of long COVID, our model focuses primarily on biological mechanisms. Accordingly, the proposed visualization sets out to guide scientific, clinical, and public health efforts to better understand and abrogate the health burden imposed by long COVID.

Source: Perumal R, Shunmugam L, Naidoo K, Abdool Karim SS, Wilkins D, Garzino-Demo A, Brechot C, Parthasarathy S, Vahlne A, Nikolich JŽ. Long COVID: a review and proposed visualization of the complexity of long COVID. Front Immunol. 2023 Apr 20;14:1117464. doi: 10.3389/fimmu.2023.1117464. PMID: 37153597; PMCID: PMC10157068. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157068/ (Full text)

Intrinsic factors behind long-COVID: I. Prevalence of the extracellular vesicles

Abstract:

It can be argued that the severity of COVID-19 has decreased in many countries. This could be a result of the broad coverage of the population by vaccination campaigns, which often reached an almost compulsory status in many places. Furthermore, significant roles were played by the multiple mutations in the body of the virus, which led to the emergence of several new SARS-CoV-2 variants with enhanced infectivity but dramatically reduced pathogenicity.

However, the challenges associated with the development of various side effects and their persistence for long periods exceeding 20 months as a result of the SARS-CoV-2 infection, or taking available vaccines against it, are spreading horizontally and vertically in number and repercussions. For example, the World Health Organization announced that there are more than 17 million registered cases of long-COVID (also known as post-COVID syndrome) in the European Union countries alone. Furthermore, by using the PubMed search engine, one can find that more than 10 000 articles have been published focusing exclusively on long-COVID.

In light of these enormous and ever-increasing numbers of cases and published articles, most of which are descriptive of the various long-COVID symptoms, the need to know the reasons behind this phenomenon raises several important questions. Is long-COVID caused by the continued presence of the virus or one/several of its components in the recovering individual body for long periods of time, which urges the body to respond in a way that leads to long-COVID development? Or are there some latent and limited reasons related to the recovering patients themselves? Or is it a sum of both?

Many observations support a positive answer to the first question, whereas others back the second question but typically without releasing a fundamental reason/signal behind it. Whatever the answer is, it seems that the real reasons behind this widespread phenomenon remain unclear. This report opens a series of articles, in which we will try to shed light on the underlying causes that could be behind the long-COVID phenomenon.

Source: El-Maradny YA, Rubio-Casillas A, Uversky VN, Redwan EM. Intrinsic factors behind long-COVID: I. Prevalence of the extracellular vesicles. J Cell Biochem. 2023 May;124(5):656-673. doi: 10.1002/jcb.30415. Epub 2023 May 1. PMID: 37126363. https://pubmed.ncbi.nlm.nih.gov/37126363/

Review of Neurological Manifestations of SARS-CoV-2

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect any part of the neuraxis. Many neurological conditions have been attributed to be caused by SARS-CoV-2, namely encephalopathy (acute necrotizing encephalopathy and encephalopathy with reversible splenial lesions), seizures, stroke, cranial nerve palsies, meningoencephalitis, acute disseminated encephalomyelitis (ADEM), transverse myelitis (long and short segment), Guillain-Barré syndrome (GBS) and its variants, polyneuritis cranialis, optic neuritis (ON), plexopathy, myasthenia gravis (MG), and myositis.

The pathophysiology differs depending on the time frame of presentation. In patients with concomitant pulmonary disease, for instance, acute neurological illness appears to be caused by endotheliopathy and cytokine storm. Autoimmunity and molecular mimicry are causative for post-coronavirus disease 2019 (COVID-19)-sequelae. It has not yet been shown that the virus can penetrate the central nervous system (CNS) directly.

This review aims to describe the disease and root pathogenic cause of the various neurological manifestations of COVID-19. We searched Pubmed/Medline and Google Scholar using the keywords “SARS-CoV-2” and “neurological illness” for articles published between January 2020 and November 2022. Then, we used the SWIFT-Review (Sciome LLC, North Carolina, United States), a text-mining workbench for systematic review, to classify the 1383 articles into MeSH hierarchical tree codes for articles on various parts of the nervous system, such as the CNS, peripheral nervous system, autonomic nervous system, neuromuscular junction, sensory system, and musculoskeletal system. Finally, we reviewed 152 articles in full text. SARS-CoV-2 RNA has been found in multiple brain areas without any histopathological changes.

Despite the absence of in vivo virions or virus-infected cells, CNS inflammation has been reported, especially in the olfactory bulb and brain stem. SARS-CoV-2 genomes and proteins have been found in affected individuals’ brain tissues, but corresponding neuropathologic changes are seldom found in these cases. Additionally, viral RNA can rarely be identified in neurological patients’ CSF post hoc SARS-CoV-2 infection.

Most patients with neurological symptoms do not have active viral replication in the nervous system and infrequently have typical clinical and laboratory characteristics of viral CNS infections. Endotheliopathy and the systemic inflammatory response to SARS-CoV-2 infection play a crucial role in developing neuro-COVID-19, with proinflammatory cytokine release mediating both pathological pathways. The systemic inflammatory mediators likely activate astrocytes and microglia across the blood-brain barrier, indirectly affecting CNS-specific immune activation and tissue injury. The management differs according to co-morbidities and the neurological disorder.

Source: P, Sehgal V, Kapila S, et al. (April 27, 2023) Review of Neurological Manifestations of SARS-CoV-2. Cureus 15(4): e38194. doi:10.7759/cureus.38194 https://www.cureus.com/articles/149269-review-of-neurological-manifestations-of-sars-cov-2#!/ (Full text)