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)

NeuroCOVID-19: a critical review

Abstract:

Background: The COVID-19 pandemic has challenged neurologists since its early days. Neurology consultation services were then overloaded by emergency department and intensive-care patients with acute neurological syndromes. These complications are better explained today, but the growing number of patients with reported longstanding neurological symptoms constitute an emerging, complex, and still poorly understood phenomenon.

Objective: This review summarizes data on relevant neurological manifestations of acute SARS-CoV-2 infection and lasting post-infectious disease, also known as Long COVID. The complex history of Long COVID is examined to illustrate the upsides and challenges imposed by the active participation of patient communities in the production of medical knowledge.

Methods: Narrative review.

Results: Infection with the severe acute respiratory syndrome coronavirus 2 is associated with encephalopathy/delirium, cerebrovascular disease, headache, and peripheral nervous system involvement. Long COVID is a living concept jointly defined by patient communities, physicians and scientists, including neurologists.

Conclusion: Co-production of Long COVID knowledge between scientists and patients has initiated an era of patient-led research and evidence-based activism that acts as a two-edged sword – putting patient’s suffering in the spotlight, but with a tradeoff in methodological consistency.

Source: Guedes BF. NeuroCOVID-19: a critical review. Arq Neuropsiquiatr. 2022 May;80(5 Suppl 1):281-289. doi: 10.1590/0004-282X-ANP-2022-S136. PMID: 35976326. https://www.scielo.br/j/anp/a/v6c3Xcvq4PkkD3HvKtT7DJN/?lang=en  (Full tex)

Post COVID syndrome: A novel challenge and threat to international health

Abstract:

The global pandemic caused by the SARS-CoV-2 virus has affected every continent worldwide. The novelty of this virus, its mutations and the rapid speed and unprecedented rate at which it has torn through the global community has in turn lead to an innate lack of knowledge and information about the actual disease caused and the severity of the complications associated with COVID-19.

The SARS-CoV-2 virus has been infecting individuals since 2019 and now as of 2022 has been circulating for just over 2 years within the global populous. As the number of cases have risen globally over this period (some of which having contracted the virus twice) further endeavours have been undertaken to better understand the pathogenesis and natural progression of the disease. A condition reported in some cases with extended bouts of sickness or symptoms following the initial infection with COVID was labelled “long COVID” towards the earlier phases of the pandemic (in the spring of 2020), but has only recently gained the global media and medical attention due to its affliction of more individuals on a global basis and has thus warranted further investigation.

Long COVID is described as a persistent, long-term state of poor health following an infection with COVID-19. The effect of Long COVID is multisystemic in nature with a wide array of signs and symptoms. The most commonly reported clinical features of long COVID are: headaches, myalgia, chest pain, rashes, abdominal pain, shortness of breath, palpitations, anosmia, persistent cough, brain fogs, forgetfulness, depression, insomnia, fatigue and anxiety. This research aims to explore the symptomatology, pathophysiology as well as the treatment and prevention of Long COVID.

Source: Banerjee I, Robinson J, Leclézio A, Sathian B, Banerjee I. Post COVID syndrome: A novel challenge and threat to international health. Nepal J Epidemiol. 2022 Jun 30;12(2):1215-1219. doi: 10.3126/nje.v12i2.46149. PMID: 35974973; PMCID: PMC9374107.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374107/ (Full text)

Long Covid stigma: estimating burden and validating scale in a UK-based sample

Abstract:

Background: Stigma can be experienced as perceived or actual disqualification from social and institutional acceptance on the basis of one or more physical, behavioural or other attributes deemed to be undesirable. Long Covid is a predominantly multisystem condition that occurs in people with a history of SARSCoV2 infection, often resulting in functional disability.

Aim: To develop and validate a Long Covid Stigma Scale (LCSS); and to quantify the burden of Long Covid stigma.

Design and Setting: Follow-up of a co-produced community-based Long Covid online survey using convenience non-probability sampling.

Method: Thirteen questions on stigma were designed to develop the LCSS capturing three domains – enacted (overt experiences of discrimination), internalised (internalising negative associations with Long Covid and accepting them as self-applicable) and anticipated (expectation of bias/poor treatment by others) stigma. Confirmatory factor analysis tested whether LCSS consisted of the three hypothesised domains. Model fit was assessed and prevalence was calculated.

Results: 966 UK-based participants responded (888 for stigma questions), with mean age 48 years (SD: 10.7) and 85% female. Factor loadings for enacted stigma were 0.70-0.86, internalised 0.75-0.84, anticipated 0.58-0.87, and model fit was good. The prevalence of experiencing stigma at least ‘sometimes’ and ‘often/always’ was 95% and 76% respectively. Anticipated and internalised stigma were more frequently experienced than enacted stigma. Those who reported having a clinical diagnosis of Long Covid had higher stigma prevalence than those without.

Conclusion: This study establishes a scale to measure Long Covid stigma and highlights common experiences of stigma in people living with Long Covid.

Source: Marija PantelicNida ZiauddeenMark BoyesMargaret E O’HaraClaire HastieNisreen A Alwan. Long Covid stigma: estimating burden and validating scale in a UK-based sample. 

A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity

Abstract:

A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively.

Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy.

Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.

Source: Kedor C, Freitag H, Meyer-Arndt L, Wittke K, Hanitsch LG, Zoller T, Steinbeis F, Haffke M, Rudolf G, Heidecker B, Bobbert T, Spranger J, Volk HD, Skurk C, Konietschke F, Paul F, Behrends U, Bellmann-Strobl J, Scheibenbogen C. A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nat Commun. 2022 Aug 30;13(1):5104. doi: 10.1038/s41467-022-32507-6. PMID: 36042189. https://www.nature.com/articles/s41467-022-32507-6 (Full text)

Long-COVID Clinical Features and Risk Factors: A Retrospective Analysis of Patients from the STOP-COVID Registry of the PoLoCOV Study

Abstract:

Despite recovering from the acute phase of coronavirus disease (COVID-19), many patients report continuing symptoms that most commonly include fatigue, cough, neurologic problems, hair loss, headache, and musculoskeletal pain, a condition termed long-COVID syndrome. Neither its etiopathogenesis, nor its clinical presentation or risk factors are fully understood. Therefore, the purpose of this study was to retrospectively evaluate the most common symptoms of long-COVID among patients from the STOP COVID registry of the PoLoCOV study, and to search for risk factors for development of the syndrome.

The registry includes patients who presented to the medical center for persistent clinical symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The analysis included data from initial presentation and at three-month follow-up. Of the 2218 patients, 1569 (70.7%) reported having at least one symptom classified as long-COVID syndrome three months after recovery from the initial SARS-CoV-2 infection. The most common symptoms included chronic fatigue (35.6%\), cough (23.0%), and a set of neurological symptoms referred to as brain fog (12.1%).

Risk factors for developing long-COVID syndrome included female gender (odds ratio [OR]: 1.48, 95% confidence intervals [CI] [1.19-1.84]), severe COVID-19 (OR: 1.56, CI: 1.00-2.42), dyspnea (OR: 1.31, CI: 1.02-1.69), and chest pain (OR: 1.48, CI: 1.14-1.92). Long-COVID syndrome represents a significant clinical and social problem. The most common clinical manifestations are chronic fatigue, cough, and brain fog. Given the still-limited knowledge of long-COVID syndrome, further research and observation are needed to better understand the mechanisms and risk factors of the disease.

Source: Chudzik M, Babicki M, Kapusta J, Kałuzińska-Kołat Ż, Kołat D, Jankowski P, Mastalerz-Migas A. Long-COVID Clinical Features and Risk Factors: A Retrospective Analysis of Patients from the STOP-COVID Registry of the PoLoCOV Study. Viruses. 2022 Aug 11;14(8):1755. doi: 10.3390/v14081755. PMID: 36016376; PMCID: PMC9415629. https://www.mdpi.com/1999-4915/14/8/1755/htm (Full text)

Predicting the efficacy of variant-modified COVID-19 vaccine boosters

Abstract:

As a result of the emergence and circulation of antigenically distinct SARS-CoV-2 variants, a number of variant-modified COVID-19 vaccines have been developed. Here we perform a meta-analysis of the available data on neutralisation titres from clinical studies comparing booster vaccination with either the current ancestral-based vaccines or variant-modified vaccines. We then use this to predict the relative efficacies of these booster vaccines under different scenarios.

Source: David S Khoury, Steffen S Docken, Kanta Subbarao, Stephen Kent, Miles Philip Davenport, Deborah Cromer. Predicting the efficacy of variant-modified COVID-19 vaccine boosters. medRxiv 2022.08.25.22279237; doi: https://doi.org/10.1101/2022.08.25.22279237 (Full article available as PDF file)

COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis

Abstract:

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with acute and postacute cognitive and neuropsychiatric symptoms including impaired memory, concentration, attention, sleep and affect. Mechanisms underlying these brain symptoms remain understudied.

Here we report that SARS-CoV-2-infected hamsters exhibit a lack of viral neuroinvasion despite aberrant blood-brain barrier permeability. Hamsters and patients deceased from coronavirus disease 2019 (COVID-19) also exhibit microglial activation and expression of interleukin (IL)-1β and IL-6, especially within the hippocampus and the medulla oblongata, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uraemia or trauma. In the hippocampal dentate gyrus of both COVID-19 hamsters and humans, we observed fewer neuroblasts and immature neurons.

Protracted inflammation, blood-brain barrier disruption and microglia activation may result in altered neurotransmission, neurogenesis and neuronal damage, explaining neuropsychiatric presentations of COVID-19. The involvement of the hippocampus may explain learning, memory and executive dysfunctions in COVID-19 patients.

Source: Soung AL, Vanderheiden A, Nordvig AS, Sissoko CA, Canoll P, Mariani MB, Jiang X, Bricker T, Rosoklija GB, Arango V, Underwood M, Mann JJ, Dwork AJ, Goldman JE, Boon ACM, Boldrini M, Klein RS. COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis. Brain. 2022 Aug 25:awac270. doi: 10.1093/brain/awac270. Epub ahead of print. PMID: 36004663. https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awac270/6672950?login=false  (Full text)

Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways

Abstract:

The physio-affective phenome of Long COVID-19 is predicted by (a) immune-inflammatory biomarkers of the acute infectious phase, including peak body temperature (PBT) and oxygen saturation (SpO2), and (b) the subsequent activation of immune and oxidative stress pathways during Long COVID. The purpose of this study was to delineate the effects of PBT and SpO2 during acute infection, as well as the increased neurotoxicity on the physical, psychological, social and environmental domains of health-related quality of life (HR-QoL) in people with Long COVID.

We recruited 86 participants with Long COVID and 39 normal controls, assessed the WHO-QoL-BREF (World Health Organization Quality of Life Instrument-Abridged Version, Geneva, Switzerland) and the physio-affective phenome of Long COVID (comprising depression, anxiety and fibromyalgia-fatigue rating scales) and measured PBT and SpO2 during acute infection, and neurotoxicity (NT, comprising serum interleukin (IL)-1β, IL-18 and caspase-1, advanced oxidation protein products and myeloperoxidase, calcium and insulin resistance) in Long COVID.

We found that 70.3% of the variance in HR-QoL was explained by the regression on the physio-affective phenome, lowered calcium and increased NT, whilst 61.5% of the variance in the physio-affective phenome was explained by calcium, NT, increased PBT, lowered SpO2, female sex and vaccination with AstraZeneca and Pfizer. The effects of PBT and SpO2 on lowered HR-QoL were mediated by increased NT and lowered calcium yielding increased severity of the physio-affective phenome which largely affects HR-QoL.

In conclusion, lowered HR-Qol in Long COVID is largely predicted by the severity of neuro-immune and neuro-oxidative pathways during acute and Long COVID.

Source: Maes M, Al-Rubaye HT, Almulla AF, Al-Hadrawi DS, Stoyanova K, Kubera M, Al-Hakeim HK. Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways. Int J Environ Res Public Health. 2022 Aug 19;19(16):10362. doi: 10.3390/ijerph191610362. PMID: 36011997. https://www.mdpi.com/1660-4601/19/16/10362/htm (Full text)

Correlation of respiratory muscle function and cardiopulmonary exercise testing in post-acute COVID-19 syndrome

To the editors,

We read the paper published by Hennigs et al. [] with great interest and thank the authors for shifting the focus to studying respiratory muscle function in Post-COVID-19 patients. The authors report striking pathological findings of mouth occlusion pressure (MOP) measurements in previously hospitalized but also non-hospitalized patients presenting with post-acute COVID-19 syndrome (PACS). In their study, Hennigs and co-authors found a high proportion of patients, more frequently females, with decreased maximum inspiratory pressure (MIP, or PImax), suggesting impairment of respiratory muscle strength. Additionally, their data indicate that increased neuroventilatory or central ventilatory drive (P0.1) may have a role in perceived respiratory distress in patients suffering from Post-COVID-19 fatigue. With this letter, we would like to share complementary data from a case series correlating MIP and P0.1 with cardiopulmonary exercise testing (CPET) in patients with PACS. Furthermore, we aim to elaborate on the limitations of MOP measurements, particularly MIP.

Read the rest of this article HERE.

Source: Leo F, Bülau JE, Semper H, Grohé C. Correlation of respiratory muscle function and cardiopulmonary exercise testing in post-acute COVID-19 syndrome. Infection. 2022 Aug 16:1–4. doi: 10.1007/s15010-022-01899-4. Epub ahead of print. PMID: 35972679; PMCID: PMC9379900. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379900/ (Full text)