Tag: long covid review

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)

Nutritional Support During Long COVID: A Systematic Scoping Review

Abstract:

Introduction: Long COVID is a term that encompasses a range of signs, symptoms, and sequalae that continue or develop after an acute COVID-19 infection. The lack of early recognition of the condition contributed to delays in identifying factors that may contribute toward its development and prevention. The aim of this study was to scope the available literature to identify potential nutritional interventions to support people with symptoms associated with long COVID.

Methods: This study was designed as a systematic scoping review of the literature (registration PROSPERO CRD42022306051). Studies with participants aged 18 years or older, with long COVID and who underwent a nutritional intervention were included in the review.

Results: A total of 285 citations were initially identified, with five papers eligible for inclusion: two were pilot studies of nutritional supplements in the community, and three were nutritional interventions as part of inpatient or outpatient multidisciplinary rehabilitation programs. There were two broad categories of interventions: those that focused on compositions of nutrients (including micronutrients such as vitamin and mineral supplements) and those that were incorporated as part of multidisciplinary rehabilitation programs. Nutrients included in more than one study were multiple B group vitamins, vitamin C, vitamin D, and acetyl-l-carnitine.

Discussion: Two studies trialed nutritional supplements for long COVID in community samples. Although these initial reports were positive, they are based on poorly designed studies and therefore cannot provide conclusive evidence. Nutritional rehabilitation was an important aspect of recovery from severe inflammation, malnutrition, and sarcopenia in hospital rehabilitation programs. Current gaps in the literature include a potential role for anti-inflammatory nutrients such as the omega 3 fatty acids, which are currently undergoing clinical trials, glutathione-boosting treatments such as N-acetylcysteine, alpha-lipoic acid, or liposomal glutathione in long COVID, and a possible adjunctive role for anti-inflammatory dietary interventions.

This review provides preliminary evidence that nutritional interventions may be an important part of a rehabilitation program for people with severe long COVID symptomatology, including severe inflammation, malnutrition, and sarcopenia. For those in the general population with long COVID symptoms, the role of specific nutrients has not yet been studied well enough to recommend any particular nutrient or dietary intervention as a treatment or adjunctive treatment.

Clinical trials of single nutrients are currently being conducted, and future systematic reviews could focus on single nutrient or dietary interventions to identify their nuanced mechanisms of action. Further clinical studies incorporating complex nutritional interventions are also warranted to strengthen the evidence base for using nutrition as a useful adjunctive treatment for people living with long COVID.

Source: Bradbury J, Wilkinson S, Schloss J. Nutritional Support During Long COVID: A Systematic Scoping Review. J Integr Complement Med. 2023 Apr 26. doi: 10.1089/jicm.2022.0821. Epub ahead of print. PMID: 37102680. https://pubmed.ncbi.nlm.nih.gov/37102680/

A Post-Pandemic Enigma: The Cardiovascular Impact of Post-Acute Sequelae of SARS-CoV-2

Abstract:

COVID-19 has become the first modern-day pandemic of historic proportion, affecting >600 million individuals worldwide and causing >6.5 million deaths. While acute infection has had devastating consequences, postacute sequelae of SARS-CoV-2 infection appears to be a pandemic of its own, impacting up to one-third of survivors and often causing symptoms suggestive of cardiovascular phenomena. This review will highlight the suspected pathophysiology of postacute sequelae of SARS-CoV-2, its influence on the cardiovascular system, and potential treatment strategies.

Source: Singh TK, Zidar DA, McCrae K, Highland KB, Englund K, Cameron SJ, Chung MK. A Post-Pandemic Enigma: The Cardiovascular Impact of Post-Acute Sequelae of SARS-CoV-2. Circ Res. 2023 May 12;132(10):1358-1373. doi: 10.1161/CIRCRESAHA.122.322228. Epub 2023 May 11. PMID: 37167358; PMCID: PMC10171306. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171306/ (Full text)

Long COVID: Where Are We in 2023?

Introduction:

The term “COVID Long-Hauler” or “Long-Haul COVID” was first created by patients within few months of the onset of the pandemic., The first publication of persistent symptoms following acute COVID-19 was from Italy in July 2020, where-in, 143 hospitalized patients with acute COVID-19 between April and May 2020, who eventually tested negative by polymerase chain reaction (PCR), were followed for two months as out-patient and 87.4% had at least one persistent symptom. The database study from the United States (U.S.) Department of Veterans Affairs (VA) was the first largest study to show that beyond a month of illness, there existed a higher risk for death and healthcare utilization because of a variety of incident respiratory, cardiovascular, neurological, musculoskeletal, gastrointestinal and metabolic disorders. Subsequently, multiple other observational studies have been published.– The systematic reviews that followed, were limited by the low quality of such studies, lack of standardized definition and representative biologic markers for the different organ systems involved as a part of this syndrome.

Source: Regunath H, Goldstein NM, Guntur VP. Long COVID: Where Are We in 2023? Mo Med. 2023 Mar-Apr;120(2):102-105. PMID: 37091941; PMCID: PMC10121126. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121126/ (Full text)

Long COVID and especially headache syndromes

Abstract:

Purpose of review: This is an expert overview on recent literature about the complex relationship between coronavirus disease 2019 (COVID-19) and headache.

Recent findings: Long COVID is a clinical syndrome characterized by the presence of persistent symptoms following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Headache is one of the most common symptoms and is described most often as throbbing pain, associated with photo and phonofobia and worsening with physical exercise. In acute COVID-19, headache is usually described as moderate or severe, diffuse and oppressive although sometimes it has been described with a migraine-like phenotype, especially in patients with a previous history of migraine.

Headache intensity during acute phase seems to be the most important predictor of duration of headache over time. Some COVID-19 cases can be associated with cerebrovascular complications, and red flags of secondary headaches (e.g. new worsening or unresponsive headache, or new onset of neurological focal signs) should be urgently investigated with imaging. Treatment goals are the reduction of number and intensity of headache crises, and the prevention of chronic forms.

Summary: This review can help clinicians to approach patients with headache and infection from SARS-CoV-2, with particular attention to persistent headache in long COVID.

Source: Tana C, Giamberardino MA, Martelletti P. Long COVID and especially headache syndromes. Curr Opin Neurol. 2023 Jun 1;36(3):168-174. doi: 10.1097/WCO.0000000000001153. Epub 2023 Apr 4. PMID: 37078648. https://pubmed.ncbi.nlm.nih.gov/37078648/