Cardiac impairments in postacute COVID-19 with sustained symptoms: A review of the literature and proof of concept

Abstract:

Although acute COVID-19 is known to cause cardiac damage in some cases, there is still much to learn about the duration and relative permanence of the damage that may occur. Long COVID is a condition that can occur when COVID-19 symptoms remain in the postviral acute period. Varying accounts of long COVID have been described across the literature, however, cardiac impairments are sustained in many individuals and cardiovascular assessment is now considered to be an expected follow-up examination.

The purpose of this review and proof of concept is to summarize the current research related to the assessment of cardiac function, including echocardiography and blood biomarker data, during the follow-up period in patients who recovered from COVID-19. Following a literature review, it was found that right ventricular dysfunction along with global longitudinal strain and diastolic dysfunction are common findings.

Finally, more severe acute myocardial injury during the index hospitalization appears to exacerbate cardiac function. The available literature implies that cardiac function must be monitored in patients recovered from COVID-19 who remain symptomatic and that the impairments and severity vary from person-to-person.

The proof-of-concept analysis of patients with cardiac disease and respiratory disease in comparison to those with sustained symptoms from COVID-19 suggests elevated systolic time interval in those with sustained symptoms from COVID-19, thus reducing heart performance indices. Future research must consider the details of cardiac complications during the acute infection period and relate this to the cardiac function in patients with long COVID during mid- and long-term follow-up.

Source: Singh J, Bhagaloo L, Sy E, Lavoie AJ, Dehghani P, Bardutz HA, Mang CS, Buttigieg J, Neary JP. Cardiac impairments in postacute COVID-19 with sustained symptoms: A review of the literature and proof of concept. Physiol Rep. 2022 Aug;10(16):e15430. doi: 10.14814/phy2.15430. PMID: 35993433; PMCID: PMC9393908.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393908/ (Full text)

Autonomic and neuropathic complaints of long-COVID objectified: an investigation from electrophysiological perspective

Abstract:

Purpose: Here , we aimed to assess the frequency and phenomenology of autonomic and neuropathic complaints of long-COVID and to evaluate them by means of electrophysiology.

Methods: Step 1. Patients with prior COVID-19 infection were screened by COMPASS-31 and mTORONTO to create the target population for further evaluation. Step 2. Patients with high scores were invited for a detailed history of their complaints and electrophysiological analysis, which included nerve conduction studies, cutaneous silent period (CSP), and sympathetic skin response (SSR). We also constituted a control group composed of healthy subjects of similar age and sex for electrophysiological analysis.

Results: There were 106 patients, who matched the study criteria. Among them, thirty-eight patients (%35.8) had neuropathic or autonomic complaints or both. Fatigue and headache were significantly more frequent in patients with autonomic and neuropathic complaints. Detailed examination and electrophysiological evaluation were performed in 14 of 38 patients. Neuropathic complaints were patchy and proximally located in the majority. The entire CSP suppression index was higher in the patients (p = 0.002). There was no difference in palmar and plantar SSR between patients and healthy subjects. mTORONTO scores were negatively correlated with palmar and plantar SSR amplitudes, and the correlation was moderate.

Conclusion: Neuropathic or autonomic complaints were seen in more than one-third of patients with long-COVID. Neuropathic complaints were generally patchy, proximally predominant, asymmetric, or diffuse. The CSP suppression index was abnormal whereas SSRs were normal.

Source: Ser MH, Çalıkuşu FZ, Tanrıverdi U, Abbaszade H, Hakyemez S, Balkan İİ, Karaali R, Gündüz A. Autonomic and neuropathic complaints of long-COVID objectified: an investigation from electrophysiological perspective. Neurol Sci. 2022 Aug 22:1–11. doi: 10.1007/s10072-022-06350-y. Epub ahead of print. PMID: 35994135; PMCID: PMC9395948. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395948/ (Full text)

Sex-dependent characteristics of Neuro-Long-COVID: Data from a dedicated neurology ambulatory service

Abstract:

“Long-COVID” is a clinical entity that consists of persisting post-infectious symptoms that last for more than three months after the onset of the first acute COVID-19 symptoms. Among these, a cluster of neurological persisting symptoms defines Neuro-Long-COVID. While the debate about the pathogenesis of Long-COVID is still ongoing, sex differences have been individuated for both the acute and the chronic stage of the infection.

We conducted a retrospective study describing sex differences in a large sample of patients with Neuro-Long-COVID. Demographic and clinical data were collected in a specifically designed Neuro-Long-Covid outpatient service. Our sample included 213 patients: 151 were females and 62 were males; the mean age was similar between females (53 y, standard deviation 14) and males (55 y, standard deviation 15); no significant differences was present between the demographic features across the two groups.

Despite the prevalence of the specific chronic symptoms between male and females showed no significant differences, the total number of females accessing our service was higher than that of males, confirming the higher prevalence of Neuro-Long-COVID in female individuals. Conversely, a worse acute phase response in males rather than females was confirmed by a significant difference in the rates of acute respiratory symptoms (p = 0.008), dyspnea (p = 0.018), respiratory failure (p = 0.010) and the consequent need for ventilation (p = 0.015), together with other acute symptoms such as palpitations (p = 0.049), headache (p = 0.001) and joint pain (p = 0.049).

Taken together, these findings offer a subgroup analysis based on sex-dependent characteristics, which can support a tailored-medicine approach.

Source: Michelutti M, Furlanis G, Buoite Stella A, Bellavita G, Frezza N, Torresin G, Ajčević M, Manganotti P. Sex-dependent characteristics of Neuro-Long-COVID: Data from a dedicated neurology ambulatory service. J Neurol Sci. 2022 Jul 28;441:120355. doi: 10.1016/j.jns.2022.120355. Epub ahead of print. PMID: 35994869; PMCID: PMC9328838. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328838/ (Full text)

Predictors of post-COVID-19 and the impact of persistent symptoms in non-hospitalized patients 12 months after COVID-19, with a focus on work ability

Abstract:

Background: Better knowledge of long-term symptoms following coronavirus disease 2019 (COVID-19), the so-called post-COVID-19, in non-hospitalized patients is needed. The aim of this study was to study persisent symptoms up to 12 months after COVID-19 in non-hospitalized patients and their impact on work ability. We also investigated predictors of persistent symptoms.

Methods: This study encompassed non-hospitalized adult subjects with a COVID-19 infection confirmed via positive nasopharyngeal swab polymerase chain reaction test during the first wave of the pandemic in Uppsala, Sweden. In total, 566 subjects were sent a survey via e-mail or post with an invitation to participate in the survey 12 months post-diagnosis. The majority of subjects were healthcare workers, as this group was prioritized for testing.

Results: A total of 366 subjects responded, with 47% reporting persistent symptoms 12 months after their COVID-19 diagnosis. The most commonly reported symptoms at this time were impaired sense of smell and/or taste and fatigue. Among the predictors of persistent symptoms were being born abroad, lower physical fitness compared with peers before COVID-19, body mass index >25 kg/m2, cooccurrence of hypertension and chronic pain, and having more than seven of the general COVID-19 symptoms at the onset. Respondents with symptoms after 12 months self-reported negatively about their general health and work ability.

Conclusions: This study indicated that many people who had mild COVID-19 might have a variety of long-term symptoms. It highlights the importance of considering work ability after mild COVID-19.

Source: Kisiel MA, Janols H, Nordqvist T, Bergquist J, Hagfeldt S, Malinovschi A, Svartengren M. Predictors of post-COVID-19 and the impact of persistent symptoms in non-hospitalized patients 12 months after COVID-19, with a focus on work ability. Ups J Med Sci. 2022 Aug 9;127. doi: 10.48101/ujms.v127.8794. PMID: 35991464; PMCID: PMC9383047. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9383047/ (Full text)

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)

Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A critical review of the literature

Abstract:

Introduction: Persistent debilitating fatigue is a frequent complaint in patients with systemic autoimmune rheumatic diseases (SARDs). Fatigue is, however, frequently overlooked in the clinic, and patients who successfully achieve remission of their disease, often still have a lowered quality of life due to its persistence. How similar is this fatigue to Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), what is this fatigue associated with, and what tools/approaches (if any), have resulted in the improvement of fatigue in these patients is poorly defined.

Areas covered: Similarities between the pathophysiology of ME/CFS, systemic sclerosis (SSc) and primary systemic vasculitides (PSV) are discussed, followed by an in-depth review of the prevalence and correlates of fatigue in these diseases. The authors reviewed literature from MEDLINE, APA PsycInfo, Embase, and CINAHL.

Expert opinion: Persistent fatigue is a prominent feature in SARDs and may not be associated with components commonly associated with disease activity and/or progression. Immune and metabolic commonalities exist between ME/CFS, SSc, and PSVs – suggesting that common pathways inherent to the diseases and fatigue may be present. We suggest that patients with features of ME/CFS need to be identified by treating physicians, as they may require alternative approaches to therapy to improve their quality of life.

Source: van Eeden C, Osman MS, Cohen Tervaert JW. Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A critical review of the literature. Expert Rev Clin Immunol. 2022 Aug 31:1-22. doi: 10.1080/1744666X.2022.2116002. Epub ahead of print. PMID: 36045606. https://pubmed.ncbi.nlm.nih.gov/36045606/

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)