Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis

Abstract:

Background: Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic.

Objectives: To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID.

Design: A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed.

Data sources and methods: Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages ‘meta’ and ‘metafor’.

Results: A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06-0.22, I 2 = 99%] and 0.22 (95% CI, 0.10-0.41, I 2 = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04-0.38, I 2 = 96%), 0.06 (95% CI, 0.03-0.11, I 2 = 98%), 0.20 (95% CI, 0.08-0.43, I 2 = 98%), and 0.17 (95% CI, 0.10-0.27, I 2 = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04-0.23, I 2 = 98%), 0.20 (95% CI, 0.06-0.50, I 2 = 97%), and 0.17 (95% CI, 0.06-0.37, I 2 = 96%), respectively.

Conclusion: GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review.

Source: Choudhury A, Tariq R, Jena A, Vesely EK, Singh S, Khanna S, Sharma V. Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis. Therap Adv Gastroenterol. 2022 Aug 19;15:17562848221118403. doi: 10.1177/17562848221118403. PMID: 36004306; PMCID: PMC9393939. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393939/ (Full text)

Myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: A mixed-methods systematic review

Abstract:

Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a fluctuating complex condition. More common in women than men, it tends to develop between mid-20s and mid-40s, including the main childbearing age (15–45 years). There are currently no systematic reviews summarising evidence relating to ME/CFS and pregnancy. The lack of quality assessed, and systematic summary evidence makes it harder for people with ME/CFS to make informed decisions about pregnancy, and harder for health care professionals to offer evidence-based care. This mixed methods systematic review aims to examine and summarise existing evidence relating to ME/CFS and pregnancy, both in relation to pregnancy outcomes and experiences of pregnancy but also the effect of pregnancy on ME/CFS severity and symptoms.

Methods This review followed a convergent segregated design. Seven electronic databases, relevant grey literature, reference lists of relevant reviews, and reference lists and citations of all included studies, were searched. Where necessary, authors were contacted for additional information. Studies of any design published in English, reporting on ME/CFS and pregnancy/postpartum (up to two years), risk of pregnancy outcomes with ME/CFS, or experiences during pregnancy for mother, partner or health and social care professionals following pregnancy with ME/CFS were included. Three researchers performed screening, data extraction and quality assessments independently. Qualitative and quantitative literature was analysed separately using thematic and descriptive syntheses, respectively (meta-analysis was not appropriate). Findings were integrated through configuration.

Results Searches identified n=2,789 studies, n=10 met our inclusion criteria. There were five quantitative studies, two qualitative studies and three pieces of grey literature. Preliminary results suggest that evidence is conflicting. In the qualitative literature, one study suggested one participant thought pregnancy improved ME/CFS symptoms while the other noted a participant commented that ME/CFS may have adversely affected her pregnancy. Of the four quantitative studies that reported on ME severity during pregnancy, two suggested pregnancy negatively impacted on ME/CFS, one study found most women had no change in ME/CFS symptoms during pregnancy, and one found ME/CFS improved during pregnancy. Only one study reported on pregnancy outcomes, finding a higher rate of spontaneous abortions, and increased developmental and learning delays in infants born to mothers with ME/CFS.

Conclusion Current evidence on ME/CFS in pregnancy is limited, and findings are inconsistent. Studies are limited by small sample size and currently, there is no UK evidence. More high-quality research into ME/CFS and pregnancy is urgently needed to support the development of evidence-based guidelines on ME/CFS and pregnancy.

Source: Pearce M, Slack E, Pears K, et alOP72 Myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: a mixed-methods systematic reviewJ Epidemiol Community Health 2022;76:A35. https://jech.bmj.com/content/76/Suppl_1/A35.1

Inequity and disparities mar existing global research evidence on Long COVID

Abstract:

Since the pandemic began in December 2019, SARS-Cov2 has accentuated the wide gap and disparities in socioeconomic and healthcare access at individual, community, country, and regional levels. More than two years into the current pandemic, up to three-fourths of the patients are reporting continued signs and symptoms beyond the acute phase of COVID-19, and Long COVID portends to be a major challenge in the future ahead.

With a comprehensive overview of the literature, we found that most studies concerning long COVID came from high and upper-middle income countries, and people of low-income and lower-and-middle income regions and vulnerable groups with comorbid conditions have been neglected. Apart from the level of income, there is a significant geographical heterogeneity in investigating the Post-Acute Sequelae of COVID-19 (PASC) or what we call now, long COVID. We believe that these recognizing health disparities is crucial from equity perspective and is the first step toward global health promotion.

Source: Taghrir MH, Akbarialiabad H, Abdollahi A, Ghahramani N, Bastani B, Paydar S, Razani B, Mwangi J, Asadi-Pooya AA, Roozbeh J, Malekmakan L, Kumar M. Inequity and disparities mar existing global research evidence on Long COVID. Glob Health Promot. 2022 Aug 12:17579759221113276. doi: 10.1177/17579759221113276. Epub ahead of print. PMID: 35962520. https://pubmed.ncbi.nlm.nih.gov/35962520/

Returning to work and the impact of post COVID-19 condition: A systematic review

Abstract:

Background: The COVID-19 pandemic is still ongoing, with rapidly increasing cases all over the world, and the emerging issue of post COVID-19 (or Long COVID-19) condition is impacting the occupational world.

Objective: The aim of this systematic review was to evaluate the impact of lasting COVID-19 symptoms or disability on the working population upon their return to employment.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements we performed a systematic review in December 2021, screening three databases (PubMed, ISI Web of Knowledge, Scopus), for articles investigating return to work in patients that were previously hospitalized due to COVID-19. A hand-searched was then performed through the references of the included systematic review. A quality assessment was performed on the included studies.

Results: Out of the 263 articles found through the initial search, 11 studies were included in this systematic review. The selected studies were divided based on follow-up time, in two months follow-up, follow-up between two and six months, and six months follow-up. All the studies highlighted an important impact of post COVID-19 condition in returning to work after being hospitalized, with differences based on follow-up time, home Country and mean/median age of the sample considered.

Conclusions: This review highlighted post COVID-19 condition as a rising problem in occupational medicine, with consequences on workers’ quality of life and productivity. The role of occupational physicians could be essential in applying limitations to work duties or hours and facilitating the return to employment in workers with a post COVID-19 condition.

Source: Gualano MR, Rossi MF, Borrelli I, Santoro PE, Amantea C, Daniele A, Tumminello A, Moscato U. Returning to work and the impact of post COVID-19 condition: A systematic review. Work. 2022 Aug 1. doi: 10.3233/WOR-220103. Epub ahead of print. PMID: 35938280. https://content.iospress.com/articles/work/wor220103 (Full text)

Repeated maximal exercise tests of peak oxygen consumption in people with myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and meta-analysis

Abstract:

Background: Repeated maximal exercise separated by 24 hours may be useful in identifying possible objective markers in people with ME/CFS that are not present in healthy controls.

Aim: We aimed to synthesise studies in which the test-to-retest (24 hours) changes in VO2 and work rate have been compared between people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and controls.

Methods: Seven databases (CINAHL, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus and MEDLINE) were searched. Included studies were observational studies that assessed adults over the age of 18 years with a clinical diagnosis of ME/CFS compared to healthy controls. The methodological quality of included studies was assessed using the Systematic Appraisal of Quality for Observational Research critical appraisal framework. Data from included studies were synthesised using a random effects meta-analysis.

Results: The pooled mean decrease in peak work rate (five studies), measured at retest, was greater in ME/CFS by −8.55 (95% CI −15.38 to –1.72) W. The pooled mean decrease in work rate at anaerobic threshold (four studies) measured at retest was greater in ME/CFS by −21 (95%CI −38 to −4, tau = 9.8) W. The likelihood that a future study in a similar setting would report a difference in work rate at anaerobic threshold which would exceed a minimal clinically important difference (10 W) is 78% (95% CI 40%–91%).

Conclusion: Synthesised data indicate that people with ME/CFS demonstrate a clinically significant test–retest reduction in work rate at the anaerobic threshold when compared to apparently healthy controls.

Source: John Derek Franklin & Michael Graham (2022) Repeated maximal exercise tests of peak oxygen consumption in people with myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review and meta-analysis, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2108628  https://www.tandfonline.com/doi/full/10.1080/21641846.2022.2108628 (Full text)

Long COVID, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence

Abstract:

Objective: The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging challenge of which ENT specialists must be aware. This systematic review aims to evaluate the prevalence of persistent audiovestibolar and olfactory/gustatory symptoms in patients with “long-COVID”.

Methods: The literature was systematically reviewed according to PRISMA guidelines; PubMed, Scopus and Google Scholar were screened by searching articles on audiovestibular symptoms and olfactory/gustatory dysfunction after SARS-CoV-2 infection. The keywords used were hearing loss, tinnitus, vertigo, smell disorders, parosmia, anosmia, hyposmia, dysgeusia combined with COVID-19 or SARS-CoV-2.

Results: 1100 articles were identified. After removal of duplicates (382), 702 articles were excluded, and 16 were included in the systematic review. All articles included identified an association between SARS-CoV-2 infection and persistent hearing or chemosensory impairment. The studies were published over a period of 2 years, between 2019 and 2021.

Conclusions: The likelihood of patients with persistent audiovestibular symptoms related to COVID-19 was different among the articles; however, olfactory and gustatory disturbances were more consistently reported. Studies with longer follow-up are required to fully evaluate the long-term impact of these conditions.

Source: De Luca P, Di Stadio A, Colacurcio V, Marra P, Scarpa A, Ricciardiello F, Cassandro C, Camaioni A, Cassandro E. Long COVID, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence. Acta Otorhinolaryngol Ital. 2022 Apr;42(Suppl. 1):S87-S93. doi: 10.14639/0392-100X-suppl.1-42-2022-10. PMID: 35763279; PMCID: PMC9137376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137376/ (Full text)

COVID-19 Pandemic-Revealed Consistencies and Inconsistencies in Healthcare: A Medical and Organizational View

Abstract:

The circumstances of the Coronavirus disease caused by the SARS-CoV-2 virus (COVID-19) pandemic have had a significant impact on global and national developments, affecting the existence of society in all its expressions, as well as the lives of people themselves. In the context of the pandemic, increased attention has been focused on acute measures, but the ending of the pandemic is expected as a resolution of the related healthcare problems. However, there are several indicators that the COVID-19 pandemic might induce long-term consequences for individual and public health. Some of the consequences are inferred and predictable, but there are also areas of medicine that have been indirectly affected by the pandemic, and these consequences have not yet been sufficiently explored.

This study is focused on drawing attention to some of the COVID-19 pandemic consistencies and the pandemic-revealed inconsistencies in healthcare. Content analysis and statistical analysis were applied to achieve the aim of the study. The main findings of the study address chronic disease burden (particularly, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)), healthcare governance and organizational issues, and the synergy between health policy perspectives and innovative solutions in practice.

The study provides insight into the particular healthcare issues affected by the COVID-19 pandemic, such as the increase in mortality in some diagnoses besides COVID-19 and the possible emergence of a new type of resistance-vaccine-resistance-contemporaneously supporting the identification of the tendencies and currently unnoticed indirect consistencies and inconsistencies revealed by the pandemic.

Source: Araja D, Berkis U, Murovska M. COVID-19 Pandemic-Revealed Consistencies and Inconsistencies in Healthcare: A Medical and Organizational View. Healthcare (Basel). 2022 May 31;10(6):1018. doi: 10.3390/healthcare10061018. PMID: 35742069. https://www.mdpi.com/2227-9032/10/6/1018/htm  (Full text)

What Do We Need to Know About Musculoskeletal Manifestations of COVID-19?: A Systematic Review

Abstract:

»: COVID-19 is a disease that is challenging science, health-care systems, and humanity. An astonishingly wide spectrum of manifestations of multi-organ damage, including musculoskeletal, can be associated with SARS-CoV-2.

»: In the acute phase of COVID-19, fatigue, myalgia, and arthralgia are the most common musculoskeletal symptoms.

»: Post-COVID-19 syndrome is a group of signs and symptoms that are present for >12 weeks. The associated musculoskeletal manifestations are fatigue, arthralgia, myalgia, new-onset back pain, muscle weakness, and poor physical performance.

»: Data on COVID-19 complications are growing due to large absolute numbers of cases and survivors in these 2 years of the pandemic. Additional musculoskeletal manifestations encountered are falls by the elderly, increased mortality after hip fracture, reduced bone mineral density and osteoporosis, acute sarcopenia, rhabdomyolysis, Guillain-Barré syndrome, muscle denervation atrophy, fibromyalgia, rheumatological disease triggering, septic arthritis, adhesive capsulitis, myositis, critical illness myopathy, onset of latent muscular dystrophy, osteonecrosis, soft-tissue abscess, urticarial vasculitis with musculoskeletal manifestations, and necrotizing autoimmune myositis.

»: A wide range of signs and symptoms involving the musculoskeletal system that affect quality of life and can result in a decrease in disability-adjusted life years. This powerful and unpredictable disease highlights the importance of multimodality imaging, continuing education, and multidisciplinary team care to support preventive measures, diagnosis, and treatment.

Source: Pires RE, Reis IGN, Waldolato GS, Pires DD, Bidolegui F, Giordano V. What Do We Need to Know About Musculoskeletal Manifestations of COVID-19?: A Systematic Review. JBJS Rev. 2022 Jun 3;10(6). doi: 10.2106/JBJS.RVW.22.00013. PMID: 35658089. https://pubmed.ncbi.nlm.nih.gov/35658089/

Clinical overlap between fibromyalgia and myalgic encephalomyelitis. A systematic review and meta-analysis

Abstract:

Myalgic encephalomyelitis is an illness characterized by profound malaise after mental or physical effort occurring in patients already suffering from constant fatigue. On the other hand, widespread pain and widespread allodynia are the core fibromyalgia clinical features. There is controversy on these two syndromes alikeness. Through the years, different diagnostic and/or classification criteria have been put forward to appraise both fibromyalgia and myalgic encephalomyelitis. The epidemiology of these two illnesses, and their overlap, may vary accordingly to the used definition. The most recent Wolfe et al. 2016 fibromyalgia diagnostic criteria incorporates three myalgic encephalomyelitis features including fatigue, waking unrefreshed and dyscognition. The objective of this meta-analysis was to define the clinical overlap between fibromyalgia and myalgic encephalomyelitis based on a systematic literature review.

Methods: PubMed, Embase, Lilacs, and Cochrane data bases were searched on January 25, 2021 linking the medical subject heading “Fibromyalgia” to the following terms “chronic fatigue syndrome”, “myalgic encephalomyelitis” and “systemic exertion intolerance disease”. Our review included all original articles in which the clinical overlap between fibromyalgia and myalgic encephalomyelitis could be quantified based on recognized diagnostic or classification criteria. Articles scrutiny and selection followed the PRISMA guidelines. Each study quality was assessed according to GRADE recommendations. The global clinical overlap was calculated using a fixed effect model with inverse variance-weighted average method.

Results: Twenty one publications were included in the meta-analysis. Reviewed studies were highly dissimilar in their design, objectives, sample size, diagnostic criteria, and/or outcomes yielding a 98% heterogeneity index. Nevertheless, the clinical overlap between fibromyalgia and myalgic encephalomyelitis was a well defined outcome that could be reliably calculated despite the high heterogeneity value. All reviewed publications had moderate GRADE evidence level. Most evaluated articles used the old 1990 Wolfe et al. fibromyalgia diagnostic criteria. Myalgic encephalomyelitis and fibromyalgia diagnoses overlapped in 47.3% (95% CI: 45.97-48.63) of the reported cases.

Conclusion: This meta-analysis found prominent clinical overlap between fibromyalgia and myalgic encephalomyelitis. It seems likely that this concordance would be even higher when using the most recent Wolfe et al. 2016 fibromyalgia diagnostic criteria.

Source: Ramírez-Morales R, Bermúdez-Benítez E, Martínez-Martínez LA, Martínez-Lavín M. Clinical overlap between fibromyalgia and myalgic encephalomyelitis. A systematic review and meta-analysis. Autoimmun Rev. 2022 Jun 8:103129. doi: 10.1016/j.autrev.2022.103129. Epub ahead of print. PMID: 35690247. https://pubmed.ncbi.nlm.nih.gov/35690247/

Pathophysiology and mechanism of long COVID: a comprehensive review

Abstract:

Background: After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as “long COVID”, and it was defined more recently as “Post COVID-19 condition” by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic.

Aim: To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID.

Method: We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation.

Results: A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far.

Conclusion: Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms.

KEY MESSAGES:

  • Long-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms.
  • The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well.
  • Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.

Source: Castanares-Zapatero D, Chalon P, Kohn L, Dauvrin M, Detollenaere J, Maertens de Noordhout C, Primus-de Jong C, Cleemput I, Van den Heede K. Pathophysiology and mechanism of long COVID: a comprehensive review. Ann Med. 2022 Dec;54(1):1473-1487. doi: 10.1080/07853890.2022.2076901. PMID: 35594336; PMCID: PMC9132392. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132392/ (Full text)