Metabolic and endocrine complications of long COVID-19: A review

Abstract:

Over the past two years, the COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), centralized the interest of the health care systems and the scientific world. Majority of the COVID-19 infected individuals fully recover. However, about 12%-50% of patients experience a variety of mid- and long-term effects after recovering from the initial illness. These mid- and long-term effects are collectively known as post-COVID-19 condition or ‘long-COVID’. In the coming months, the long-term consequences of COVID-19 on the metabolic and endocrine systems may expect to rise and pose a global health care challenge. This review article aims to discuss the possible metabolic and endocrine complications of long-COVID and the relevant research findings.

Source: Bandara T, Deshmukh HA, Abdalla M, Sathyapalan T. Metabolic and endocrine complications of long COVID-19: A review. Exp Clin Endocrinol Diabetes. 2023 Mar 28. doi: 10.1055/a-2063-8697. Epub ahead of print. PMID: 36977491. https://pubmed.ncbi.nlm.nih.gov/36977491/

COVID-19 Vaccination for the Prevention and Treatment of Long COVID: A Systematic Review and Meta-analysis

Abstract:

Empirical evidence addressing the association between SARS-CoV-2 vaccination and long COVID would guide public health priorities and inform personal health decisions. Herein, the co-primary objectives are to determine the differential risk of long COVID in vaccinated versus unvaccinated patients, and the trajectory of long COVID following vaccination.

Of 2775 articles identified via systematic search, 17 were included, and 6 were meta-analyzed. Meta-analytic results determined that at least one vaccine dose was associated with a protective effect against long COVID (OR 0.539, 95% CI 0.295-0.987, p = 0.045, N= 257 817).

Qualitative analysis revealed that trajectories of pre-existing long COVID following vaccination were mixed, with most patients reporting no changes. The evidence herein supports SARS-CoV-2 vaccination for the prevention of long COVID, and recommends long COVID patients adhere to standard SARS-CoV-2 vaccination schedules.

Source: Ceban F, Kulzhabayeva D, Rodrigues NB, Di Vincenzo JD, Gill H, Subramaniapillai M, Lui LMW, Cao B, Mansur RB, Ho RC, Burke MJ, Rhee TG, Rosenblat JD, McIntyre RS. COVID-19 Vaccination for the Prevention and Treatment of Long COVID: A Systematic Review and Meta-analysis. Brain Behav Immun. 2023 Mar 27:S0889-1591(23)00079-X. doi: 10.1016/j.bbi.2023.03.022. Epub ahead of print. PMID: 36990297; PMCID: PMC10067136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067136/ (Full text)

What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?

Abstract:

Metabolic physiology plays a key role in maintaining our health and resilience. Metabolic disorders can lead to serious illnesses, including obesity. The pathogenesis of the new long COVID syndrome in individuals with long-term recovery after SARS-Co-2 infection is still incomplete. Thus there is growing attention in the study of adipose tissue activities, especially brown adipose tissue (BAT) and associated resilience which plays a crucial role in different types of obesity as potential targets for pharmacologic and nutritional interventions in the context of obesity and long COVID.

The number of studies examining mechanisms underlying BAT has grown rapidly in the last 10 years despite of role of BAT in individuals with COVID-19 and long COVID is modest. Therefore, this review aims to sum up data examining BAT activities, its resilience in health, obesity, and the possible link to long COVID.

The search was conducted on studies published in English mostly between 2004 and 2022 in adult humans and animal models. Database searches were conducted using PubMed, Scopus, and Google Scholar for key terms including adipose tissue, BAT, adipokinins, obesity, VPF/VEGF, and pathogenesis. From the initial search through the database were identified relevant articles that met inclusion and exclusion criteria and our data regarding adipose tissues were presented in this review.

It will discuss adiposity tissue activities. Current literature suggests that there are BAT integral effects to whitening and browning fat phenomenons which reflect the homeostatic metabolic adaptive ability for environmental demand or survival/adaptive mechanisms. We also review neural and vascular impacts in BAT that play a role in resilience and obesity. Finally, we discuss the role of BAT in the context of long COVID in basic research and clinical research.

Source: Muzyka, I., Revenko, O., Kovalchuk, I. et al. What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?. Inflammopharmacol (2023). https://doi.org/10.1007/s10787-023-01195-z (Full text)

Post-COVID Syndrome

Abstract:

Background: As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a consequence thereof. PCS is found mainly in adults, less frequently in children and adolescents. It can develop both in patients who initially had only mild symptoms or none at all and in those who had a severe course of coronavirus disease 2019 (COVID-19).

Methods: The data presented here were derived from a systematic literature review.

Results: PCS occurs in up to 15% of unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased in the most recent phase of the pandemic and is lower after vaccination. The pathogenesis of PCS has not yet been fully elucidated. Virus triggered inflammation, autoimmunity, endothelial damage (to blood vessels), and persistence of virus are thought to be causative. Owing to the broad viral tropism, different organs are involved and the symptoms vary. To date, there are hardly any evidence-based recommendations for definitive diagnosis of PCS or its treatment.

Conclusion: The gaps in our knowledge mean that better documentation of the prevalence of PCS is necessary to compile the data on which early detection, diagnosis, and treatment can be based. To ensure the best possible care of patients with PCS, regional PCS centers and networks embracing existing structures from all healthcare system sectors and providers should be set up and structured diagnosis and treatment algorithms should be established. Given the sometimes serious consequences of PCS for those affected, it seems advisable to keep the number of SARS-CoV-2 infections low by protective measures tailored to the prevailing pandemic situation.

Source: Hallek M, Adorjan K, Behrends U, Ertl G, Suttorp N, Lehmann C. Post-COVID Syndrome. Dtsch Arztebl Int. 2023 Jan 27;120(4):48-55. doi: 10.3238/arztebl.m2022.0409. PMID: 36633452; PMCID: PMC10060997. https://www.aerzteblatt.de/int/archive/article/229208 (Full text)

Risk Factors Associated With Post−COVID-19 Condition A Systematic Review and Meta-analysis

Abstract:

Importance  Post−COVID-19 condition (PCC) is a complex heterogeneous disorder that has affected the lives of millions of people globally. Identification of potential risk factors to better understand who is at risk of developing PCC is important because it would allow for early and appropriate clinical support.

Objective  To evaluate the demographic characteristics and comorbidities that have been found to be associated with an increased risk of developing PCC.

Data sources  Medline and Embase databases were systematically searched from inception to December 5, 2022.

Study Selection  The meta-analysis included all published studies that investigated the risk factors and/or predictors of PCC in adult (≥18 years) patients.

Data Extraction and Synthesis  Odds ratios (ORs) for each risk factor were pooled from the selected studies. For each potential risk factor, the random-effects model was used to compare the risk of developing PCC between individuals with and without the risk factor. Data analyses were performed from December 5, 2022, to February 10, 2023.

Main Outcomes and Measures  The risk factors for PCC included patient age; sex; body mass index, calculated as weight in kilograms divided by height in meters squared; smoking status; comorbidities, including anxiety and/or depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischemic heart disease; previous hospitalization or ICU (intensive care unit) admission with COVID-19; and previous vaccination against COVID-19.

Results  The initial search yielded 5334 records of which 255 articles underwent full-text evaluation, which identified 41 articles and a total of 860 783 patients that were included. The findings of the meta-analysis showed that female sex (OR, 1.56; 95% CI, 1.41-1.73), age (OR, 1.21; 95% CI, 1.11-1.33), high BMI (OR, 1.15; 95% CI, 1.08-1.23), and smoking (OR, 1.10; 95% CI, 1.07-1.13) were associated with an increased risk of developing PCC. In addition, the presence of comorbidities and previous hospitalization or ICU admission were found to be associated with high risk of PCC (OR, 2.48; 95% CI, 1.97-3.13 and OR, 2.37; 95% CI, 2.18-2.56, respectively). Patients who had been vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC compared with patients who were not vaccinated (OR, 0.57; 95% CI, 0.43-0.76).

Conclusions and Relevance  This systematic review and meta-analysis demonstrated that certain demographic characteristics (eg, age and sex), comorbidities, and severe COVID-19 were associated with an increased risk of PCC, whereas vaccination had a protective role against developing PCC sequelae. These findings may enable a better understanding of who may develop PCC and provide additional evidence for the benefits of vaccination.

Trial Registration  PROSPERO Identifier: CRD42022381002

Source: Tsampasian V, Elghazaly H, Chattopadhyay R, et al. Risk Factors Associated With Post−COVID-19 ConditionA Systematic Review and Meta-analysisJAMA Intern Med. Published online March 23, 2023. doi:10.1001/jamainternmed.2023.0750 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2802877 (Full text)

Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)

Abstract:

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment.

This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC.

The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.

Source: Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB; RECOVER Mechanistic Pathway Task Force. Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). Elife. 2023 Mar 22;12:e86002. doi: 10.7554/eLife.86002. PMID: 36947108; PMCID: PMC10032659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032659/ (Full text)

Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder

Abstract:

There have been suggestions that Long COVID might be purely functional (meaning psychological) in origin. Labelling patients with neurological dysfunction in Long COVID as having functional neurological disorder (FND) in the absence of proper testing may be symptomatic of that line of thought. This practice is problematic for Long COVID patients, as motor and balance symptoms have been reported to occur in Long COVID frequently.
FND is characterized by the presentation of symptoms that seem neurological but lack compatibility of the symptom with a neurological substrate. Although diagnostic classification according to the ICD-11 and DSM-5-TR is dependent predominantly on the exclusion of any other medical condition that could account for the symptoms, current neurological practice of FND classification allows for such comorbidity. As a consequence, Long COVID patients with motor and balance symptoms mislabeled as FND have no longer access to Long COVID care, whereas treatment for FND is seldom provided and is ineffective.
Research into underlying mechanisms and diagnostic methods should explore how to determine whether motor and balance symptoms currently diagnosed as FND should be considered one part of Long COVID symptoms, in other words, one component of symptomatology, and in which cases they correctly represent FND. Research into rehabilitation models, treatment and integrated care are needed, which should take into account biological underpinnings as well as possible psychological mechanisms and the patient perspective.
Source: Van der Feltz-Cornelis CM, Moriarty AS, Strain WD. Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder. Viruses. 2023; 15(3):783. https://doi.org/10.3390/v15030783 https://www.mdpi.com/1999-4915/15/3/783 (Full text)

Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis

Abstract:

Current data suggests that coronavirus disease 2019 (COVID-19) survivors experience long-lasting problems. It is not yet understood how long these symptoms last. The goal of this study was to compile all the data that was currently available to evaluate COVID-19’s long-term effects at 12 months and above.

We looked for studies published by December 15, 2022, in PubMed and Embase that discussed follow-up findings for COVID-19 survivors who had been alive for at least a year. A random-effect model was carried out to determine the combined prevalence of different long-COVID symptoms. The Joanna Briggs Institute tool was used to assess the risk of bias for the included studies, and the I2 statistics were used to evaluate the heterogeneity. After reviewing 3,209 studies, 46 were deemed admissible, with an aggregate COVID-19 population of 17976.

At 12 months and above, 57% of patients reported a minimum of one symptom, and the five most prevalent symptoms were: dyspnea on exertion (34%, 95% CI 0.2; 0.94); difficulty in concentration (32%, 95% CI 0.16; 0.52); fatigue (31%, 95% CI 0.22; 0.40); frailty (31%, 95% CI 0.06; 0.78); and arthromyalgia (28%, 95% CI 0.09; 0.6). The findings of the present study showed that at 12 months and beyond, a sizable fraction of COVID-19 survivors still have lasting symptoms that impair several body systems. Long-COVID patients require an urgent understanding of pathophysiological processes and the development of tailored treatments.

Source: Mudgal S K, Gaur R, Rulaniya S, et al. (March 18, 2023) Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis. Cureus 15(3): e36325. doi:10.7759/cureus.36325 https://www.cureus.com/articles/143288-pooled-prevalence-of-long-covid-19-symptoms-at-12-months-and-above-follow-up-period-a-systematic-review-and-meta-analysis#!/ (Full text)

A Review of Possible Supplements to Relieve the Symptoms of Fatigue after COVID-19

Abstract:

Background: The highly infectious coronavirus has become a global pandemic; the effective medication is yet to be developed. The health care system was strained; millions of people have been suffered from infection and complications. Post COVID-19 fatigue is a dominant characteristic of coronavirus infection. It affects general state of health, muscle strength, sleeping quality, mental health, and life quality. This paper is emphasizing and summarizing the potential beneficial supplementations of post COVID-19 fatigue symptoms.

Methods: The knowledge gained from PubMed and from the National Library of Medicine. Clinical studies and systematic review articles were collected in this topic.

Results: Herein, we discuss the possible therapeutic supplementations with anti-inflammatory, immunomodulatory and antioxidant effect. Vitamin complexes, trace elements, antioxidants, coenzymes, probiotics, essential fatty acids; one and creatine as amino acid derivatives have been appeared to be effective in relieving post COVID-19 fatigue symptoms.

Conclusions: Based on the data, these nutrients and supplements might be important to alleviate the post COVID-19 fatigue symptoms and they could be considered as a supportive therapy

Source: Boglárka Bernadett Tisza, Gyöngyi Iván, Viola Keczeli, Melinda Kóró, Patricia Szántóri, Zsófia Gyócsiné Varga, Henriett Müller, Olivia Pribéli, Zoltán Szabó, Zsófia Verzár, Monika Sélleyné Gyuró, Andrea Gubicskóné Kisbendek and Tímea Stromájer-Rácz. A Review of Possible Supplements to Relieve the Symptoms of Fatigue after COVID-19.  J Med Public Health. 2023;4(2):JMPH-04-1062. https://www.medtextpublications.com/open-access/a-review-of-possible-supplements-to-relieve-the-symptoms-of-1309.pdf (Full text)

Pain Management in the Post-COVID Era-An Update: A Narrative Review

Abstract:

An extensive computer search (from January 2020 to January 2023) was conducted including literature from the PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases. According to preset criteria, a total of 58 articles were included in this review article. Generally, any patient who becomes infected with COVID-19 can develop post-COVID-19 conditions. The course of COVID-19 is divided into three main stages: acute COVID-19 (up to 4 weeks), post-acute COVID-19 (from 4 to 12 weeks), and post-COVID (from 12 weeks to 6 months). If a more protracted course of COVID (over 6 months) is demonstrated, the term “long-COVID” is used.

Although the acute stage of COVID-19 infection most commonly manifests with acute respiratory symptoms, one very common symptom of the disease is pain, while the most common symptoms of post-COVID syndrome are shortness of breath, dry cough, fatigue, loss of olfactory and gustatory function, tightness and chest pain, sleep and mood disturbances, body aches, muscle and joint pain, sore throat, fever, and persistent headaches.

All observations demonstrated a high incidence of chronic pain syndromes of various localization in the post- and long-COVID period. Post-COVID chronic pain might include a newly developed chronic pain as a part of post-viral syndrome; worsening of preexisting chronic pain due to the associated changes in the medical services, or a de novo chronic pain in healthy individuals who are not infected with COVID.

Chronic pain during and post-COVID-19 pandemic is an important health issue due to the significant impacts of pain on the patients, health care systems, and society as well. Therefore, it is important that patients with chronic pain receive effective treatment according to their specific needs. Accordingly, the main goal of this review article is to provide a broad description about the post-COVID pain and to explore the impact of long COVID-19 on chronic pain patients, and also to give brief reports about the prevalence, risk factors, possible mechanisms, different presentations, and the management tools through a systematic approach.

Source: El-Tallawy SN, Perglozzi JV, Ahmed RS, Kaki AM, Nagiub MS, LeQuang JK, Hadarah MM. Pain Management in the Post-COVID Era-An Update: A Narrative Review. Pain Ther. 2023 Apr;12(2):423-448. doi: 10.1007/s40122-023-00486-1. Epub 2023 Feb 28. PMID: 36853484; PMCID: PMC9971680. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971680/ (Full text)