Aging and long COVID-19 syndrome: what’s new in 2023?

Abstract:

Since 2019 that saw the onset of the COVID-19 pandemic, its ongoing impact on many older adults remains a persistent public health concern, especially among those who report suffering from long or post-acute COVID-19 disease health challenges. This report presents data published largely since January 1 2023 on this topic and concerning: Long COVID or COVID-19, Older Adults, Post-Acute COVID-19 Outcomes, and Prevention.

Data show that even though long COVID-19 was discussed in 2021 at some length, it still remains a relatively unchartered poorly understood topic in which a sizeable percentage of older adult COVID-19 survivors may experience delayed features of breathing, movement, cognitive and mental health challenges. What causes the observed and perceived problems, what may help to identify who is at risk, and what will reduce these remains unknown, but may benefit from insightful research and extended observations and possible multi pronged efforts that target those symptoms of most concern.

Source: Marks R. Aging and long COVID-19 syndrome: what’s new in 2023? MOJ Gerontol Ger. 2023;8(1):9-14. DOI: 10.15406/mojgg.2023.08.00302 (Full text)

Effect of covid-19 vaccination on long covid: systematic review

Abstract:

Objective To determine the effect of covid-19 vaccination, given before and after acute infection with the SARS-CoV-2 virus, or after a diagnosis of long covid, on the rates and symptoms of long covid.

Design Systematic review.

Data sources PubMed, Embase, and Cochrane covid-19 trials, and Europe PubMed Central (Europe PMC) for preprints, from 1 January 2020 to 3 August 2022.

Eligibility criteria for selecting studies Trials, cohort studies, and case-control studies reporting on patients with long covid and symptoms of long covid, with vaccination before and after infection with the SARS-CoV-2 virus, or after a diagnosis of long covid. Risk of bias was assessed with the ROBINS-I tool.

Results 1645 articles were screened but no randomised controlled trials were found. 16 observational studies from five countries (USA, UK, France, Italy, and the Netherlands) were identified that reported on 614 392 patients. The most common symptoms of long covid that were studied were fatigue, cough, loss of sense of smell, shortness of breath, loss of taste, headache, muscle ache, difficulty sleeping, difficulty concentrating, worry or anxiety, and memory loss or confusion. 12 studies reported data on vaccination before infection with the SARS-CoV-2 virus, and 10 showed a significant reduction in the incidence of long covid: the odds ratio of developing long covid with one dose of vaccine ranged from 0.22 to 1.03; with two doses, odds ratios were 0.25-1; with three doses, 0.16; and with any dose, 0.48-1.01. Five studies reported on vaccination after infection, with odds ratios of 0.38-0.91. The high heterogeneity between studies precluded any meaningful meta-analysis. The studies failed to adjust for potential confounders, such as other protective behaviours and missing data, thus increasing the risk of bias and decreasing the certainty of evidence to low.

Conclusions Current studies suggest that covid-19 vaccines might have protective and therapeutic effects on long covid. More robust comparative observational studies and trials are needed, however, to clearly determine the effectiveness of vaccines in preventing and treating long covid.

Source: Byambasuren OStehlik PClark J, et al. Effect of covid-19 vaccination on long covid: systematic review

The role of the microbiota-gut-brain axis in post-acute COVID syndrome

Abstract:

The COVID-19 pandemic has resulted in the infection of hundreds of millions of individuals over the past three years, coupled with millions of deaths. Along with these more acute impacts of infection, a large subset of patients developed symptoms that collectively comprise “post-acute sequelae of COVID-19” (PASC, also known as long COVID), which can persist for months and maybe even years. In this review, we outline current knowledge on the role of impaired microbiota-gut-brain (MGB) axis signaling in the development of PASC and the potential mechanisms involved, which may lead to better understanding of disease progression and treatment options in the future.

Source: Gareau MG, Barrett KE. The role of the microbiota-gut-brain axis in post-acute COVID syndrome. Am J Physiol Gastrointest Liver Physiol. 2023 Mar 7. doi: 10.1152/ajpgi.00293.2022. Epub ahead of print. PMID: 36880667. https://journals.physiology.org/doi/abs/10.1152/ajpgi.00293.2022 (Full text available as PDF file)

Long COVID: An unpredicted multisystem syndrome of COVID-19 disease

Abstract:

Long COVID is multisystem syndrome with nonspecific symptoms and organic signs of unidentified pathology occurs after COVID-19 disease. Long COVID symptoms has been documented in some cases irrespective of disease severity or hospitalization.
Long COVID symptoms has significant impact on quality of life in those cases suffered from disease in recent past and lingering to almost two years since infection. Importantly, not all cases of COVID-19 were shown long COVID symptoms. Pathophysiology resulting into long COVID manifestations is still not completely validated.
Researchers have reported ‘immune dysregulation’ and ‘coagulation abnormalities’ are probable pathophysiological mechanism for long COVID. Some of the long COVID effects shown complete reversibility including post COVID lung fibrosis. Reboot system to restore immune dysregulation and recovery in long COVID is real concern. Vaccination has not shown significant effect modifying long COVID manifestation. [Editor’s note: See conclusion in full text for a contradictory statement.]
Source: Hital Vishnu Patil, Neel Tandel and Gajanan Godhali. Long COVID: An unpredicted multisystem syndrome of COVID-19 disease. World Journal of Advanced Pharmaceutical and Life Sciences, 2023, 04(01), 005012. https://www.researchgate.net/publication/368757849_Long_COVID_An_unpredicted_multisystem_syndrome_of_COVID-19_disease (Full text)

Potential of Black Seeds (Nigella Sativa) in the Management of Long COVID or Post-acute Sequelae of COVID-19 (PASC) and Persistent COVID-19 Symptoms – An Insight

Abstract:

Background: Some individuals may experience symptoms persisting for many months after the recovery from COVID-19 and patients with Long COVID are managed mainly with symptomatic treatment and supportive care.

Objective: This review article focuses on the beneficial effects of black seeds (Nigella Sativa) in the management of long COVID and persistent COVID symptoms.

Methods: The literature was searched in databases such as LitCOVID, Web of Science, Google Scholar, bioRxiv, medRxiv, Science Direct, EBSCO, Scopus, Embase, and reference lists to identify studies, which evaluated various effects of black seeds (N. sativa) related to signs and symptoms of Long COVID.

Results: Black seeds (N. sativa) have shown potential anti-COVID, antiviral, anti-inflammatory, antioxidant, immunomodulatory, antihypertensive, anti-obesity, antidiabetic, antihyperlipidemic, and antiasthmatic properties in various clinical, animal, in-vitro, in-vivo, and in-silico studies, which would help the patients recovered from COVID to mitigate Long COVID complications.

Conclusion: Patients experiencing Long COVID may use black seeds (N. sativa) as adjunctive therapy in combination with symptomatic treatment and supportive care to prevent further deterioration and hospitalization. The safety and efficacy of N. sativa in patients with Long-COVID would further be established by future randomized controlled clinical trials.

Source: Pakkir Maideen NM, Hassan Jumale A, Ramadan Barakat I, Khalifa Albasti A. Potential of Black Seeds (Nigella Sativa) in the Management of Long COVID or Post-acute Sequelae of COVID-19 (PASC) and Persistent COVID-19 Symptoms – An Insight. Infect Disord Drug Targets. 2023 Feb 23. doi: 10.2174/1871526523666230223112045. Epub ahead of print. PMID: 36825730.

Living with “long COVID”: A systematic review and meta-synthesis of qualitative evidence

Abstract:

Objectives: Long-term health consequences of coronavirus disease (COVID-19), also known as “long COVID,” has become a global health concern. In this systematic review, we aimed to synthesize the qualitative evidence on lived experiences of people living with long COVID that may inform health policymaking and practice.

Methods: We searched six major databases and additional sources and systematically retrieved relevant qualitative studies and conducted a meta-synthesis of key findings using the Joanna Briggs Institute (JBI) guidelines and reporting standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist.

Results: We found 15 articles representing 12 studies out of 619 citations from different sources. These studies provided 133 findings that were categorized into 55 categories. All categories were aggregated to the following synthesized findings: living with complex physical health problems, psychosocial crises of long COVID, slow recovery and rehabilitation, digital resources and information management, changes in social support, and experiences with healthcare providers, services, and systems. Ten studies were from the UK, and others were from Denmark and Italy, which highlights a critical lack of evidence from other countries.

Conclusions: More representative research is needed to understand long COVID-related experiences from diverse communities and populations. The available evidence informs a high burden of biopsychosocial challenges among people with long COVID that would require multilevel interventions such as strengthening health and social policies and services, engaging patients and caregivers in making decisions and developing resources, and addressing health and socioeconomic disparities associated with long COVID through evidence-based practice.

Source: Hossain MM, Das J, Rahman F, Nesa F, Hossain P, Islam AMK, Tasnim S, Faizah F, Mazumder H, Purohit N, Ramirez G. Living with “long COVID”: A systematic review and meta-synthesis of qualitative evidence. PLoS One. 2023 Feb 16;18(2):e0281884. doi: 10.1371/journal.pone.0281884. PMID: 36795701; PMCID: PMC9934341. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934341/ (Full text)

Unfavorable Outcome and Long-Term Sequelae in Cases with Severe COVID-19

Abstract:

Emerging evidence shows that individuals with COVID-19 who survive the acute phase of illness may experience lingering symptoms in the following months. There is no clear indication as to whether these symptoms persist for a short time before resolving or if they persist for a long time. In this review, we will describe the symptoms that persist over time and possible predictors in the acute phase that indicate long-term persistence.
Based on the literature available to date, fatigue/weakness, dyspnea, arthromyalgia, depression, anxiety, memory loss, slowing down, difficulty concentrating and insomnia are the most commonly reported persistent long-term symptoms. The extent and persistence of these in long-term follow-up is not clear as there are still no quality studies available.
The evidence available today indicates that female subjects and those with a more severe initial disease are more likely to suffer permanent sequelae one year after the acute phase. To understand these complications, and to experiment with interventions and treatments for those at greater risk, we must first understand the physio-pathological mechanisms that sustain them.
Source: Fabbri A, Voza A, Riccardi A, Vanni S, De Iaco F on behalf of the Study & Research Center of the Italian Society of Emergency Medicine (SIMEU). Unfavorable Outcome and Long-Term Sequelae in Cases with Severe COVID-19. Viruses. 2023; 15(2):485. https://doi.org/10.3390/v15020485 (Full text)

Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review

Abstract:

The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19.
The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms.
A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a.
The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood–nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.
Source: Reyes-Long S, Cortés-Altamirano JL, Bandala C, Avendaño-Ortiz K, Bonilla-Jaime H, Bueno-Nava A, Ávila-Luna A, Sánchez-Aparicio P, Clavijo-Cornejo D, Dotor-LLerena AL, Cabrera-Ruiz E, Alfaro-Rodríguez A. Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review. International Journal of Molecular Sciences. 2023; 24(4):3574. https://doi.org/10.3390/ijms24043574 https://www.mdpi.com/1422-0067/24/4/3574 (Full text)

Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected

Abstract:

Long COVID is an emerging problem in the current health care scenario. It is a syndrome with common symptoms of shortness of breath, fatigue, cognitive dysfunction, and other conditions that have a high impact on daily life. They are fluctuating or relapsing states that occur in patients with a history of SARS-CoV-2 infection for at least 2 months. They are usually conditions that at 3 months after onset cannot be explained by an alternative diagnosis. Currently very little is known about this syndrome.

A thorough review of the literature highlights that the cause is attributable to deposits of tau protein. Massive phosphorylation of tau protein in response to SARS-CoV-2 infection occurred in brain samples from autopsies of people previously affected with COVID-19. The neurological disorders resulting from this clinical condition are termed tauopathies and can give different pathological symptoms depending on the involved anatomical region of the brain.

Peripheral small-fiber neuropathies are also evident among patients with Long COVID leading to fatigue, which is the main symptom of this syndrome. Certainly more research studies could confirm the association between tau protein and Long COVID by defining the main role of tau protein as a biomarker for the diagnosis of this syndrome that is widespread in the post-pandemic period.

Source: Ferrara, F., Zovi, A., Masi, M. et al. Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected. Naunyn-Schmiedeberg’s Arch Pharmacol (2023). https://doi.org/10.1007/s00210-023-02417-5 https://link.springer.com/article/10.1007/s00210-023-02417-5 (Full text)

Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis

Abstract:

Background: The relationship between coronavirus disease 2019 (COVID-19) vaccination and long COVID has not been firmly established. We conducted a systematic review and meta-analysis to evaluate the association between COVID-19 vaccination and long COVID.

Methods: PubMed and EMBASE databases were searched on September 2022 without language restrictions (CRD42022360399) to identify prospective trials and observational studies comparing patients with and without vaccination before severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We also included studies reporting symptomatic changes of ongoing long COVID following vaccination among those with a history of SARS-CoV-2 infection. Odds ratios (ORs) for each outcome were synthesized using a random-effects model. Symptomatic changes after vaccination were synthesized by a one-group meta-analysis.

Results: Six observational studies involving 536,291 unvaccinated and 84,603 vaccinated (before SARS-CoV-2 infection) patients (mean age, 41.2-66.6; female, 9.0-67.3%) and six observational studies involving 8,199 long COVID patients (mean age, 40.0 to 53.5; female, 22.2-85.9%) who received vaccination after SARS-CoV-2 infection were included. Two-dose vaccination was associated with a lower risk of long COVID compared to no vaccination (OR, 0.64; 95% confidence interval [CI], 0.45-0.92) and one-dose vaccination (OR, 0.60; 95% CI, 0.43-0.83). Two-dose vaccination compared to no vaccination was associated with a lower risk of persistent fatigue (OR, 0.62; 95% CI, 0.41-0.93) and pulmonary disorder (OR, 0.50; 95% CI, 0.47-0.52). Among those with ongoing long COVID symptoms, 54.4% (95% CI, 34.3-73.1%) did not report symptomatic changes following vaccination, while 20.3% (95% CI, 8.1-42.4%) experienced symptomatic improvement after two weeks to six months of COVID-19 vaccination.

Conclusions: COVID-19 vaccination before SARS-CoV-2 infection was associated with a lower risk of long COVID, while most of those with ongoing long COVID did not experience symptomatic changes following vaccination.

Source: Watanabe A, Iwagami M, Yasuhara J, Takagi H, Kuno T. Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis. Vaccine. 2023 Feb 8:S0264-410X(23)00134-2. doi: 10.1016/j.vaccine.2023.02.008. Epub ahead of print. PMID: 36774332; PMCID: PMC9905096. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905096/ (Full text)