Tag: covid-19

The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a meta-analysis of public DNA methylation and gene expression data

Abstract:

People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report a high frequency of viral infections and flu-like symptoms during their disease course. Since this reporting is in line with different immunological abnormalities and altered gene expression profiles observed in the disease, we aimed to explore whether the expression of the human angiotensin-converting enzyme-2 (ACE2), the major cell entry receptor for SARS-CoV-2, is also altered in this neglected clinical population. In particular, a low expression of ACE2 is usually indicative of a high risk of developing COVID-19.

We then performed a meta-analysis of public data on CpG DNA methylation and gene expression of this enzyme and its homologous ACE protein in peripheral blood mononuclear cells and related subsets. We found that patients with ME/CFS have decreased methylation levels of four CpG probes in the ACE locus (cg09920557, cg19802564, cg21094739, and cg10468385) and of another probe in the promoter region of the ACE2 gene (cg08559914). We also found a decreased expression of ACE2 but not of ACE in patients with ME/CFS when compared to healthy controls.

Accordingly, in newly collected data, we found evidence for a higher proportion of samples with an ACE2 expression below the limit of detection in patients with ME/CFS than in healthy controls. Altogether, patients with ME/CFS could be at a higher COVID-19 risk when infected by SARS-CoV-2. To further support this conclusion, similar research should be conducted for other human cell entry receptors and other cell types, namely, those mainly targeted by the virus.

Source: Malato J, Sotzny F, Bauer S, Freitag H, Fonseca A, Grabowska AD, Graça L, Cordeiro C, Nacul L, Lacerda EM, Castro-Marrero J, Scheibenbogen C, Westermeier F, Sepúlveda N. The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a meta-analysis of public DNA methylation and gene expression data. Heliyon. 2021 Jul 29;7(8):e07665. doi: 10.1016/j.heliyon.2021.e07665. Epub ahead of print. PMID: 34341773; PMCID: PMC8320404. https://pubmed.ncbi.nlm.nih.gov/34341773/

Shadow Burden of Undiagnosed Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) on Society: Retrospective and Prospective-In Light of COVID-19

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood, complex, multisystem disorder, with severe fatigue not alleviated by rest, and other symptoms, which lead to substantial reductions in functional activity and quality of life. Due to the unclear aetiology, treatment of patients is complicated, but one of the initial problems is the insufficient diagnostic process. The increase in the number of undiagnosed ME/CFS patients became specifically relevant in the light of the COVID-19 pandemic. The aim of this research was to investigate the issues of undiagnosed potential ME/CFS patients, with a hypothetical forecast of the expansion of post-viral CFS as a consequence of COVID-19 and its burden on society.

Methods: The theoretical research was founded on the estimation of classic factors presumably affecting the diagnostic scope of ME/CFS and their ascription to Latvian circumstances, as well as a literature review to assess the potential interaction between ME/CFS and COVID-19 as a new contributing agent. The empirical study design consisted of two parts: The first part was dedicated to a comparison of the self-reported data of ME/CFS patients with those of persons experiencing symptoms similar to ME/CFS, but without a diagnosis. This part envisaged the creation of an assumption of the ME/CFS shadow burden “status quo”, not addressing the impact of COVID-19. The second part aimed to investigate data from former COVID-19 patients’ surveys on the presence of ME/CFS symptoms, 6 months after being affected by COVID-19. Descriptive and analytical statistical methods were used to analyse the obtained data.

Results: The received data assumed that the previously obtained data on the ME/CFS prevalence of 0.8% in the Latvian population are appropriate, and the literature review reports a prevalence of 0.2-1.0% in developed countries. Regarding the reciprocity of ME/CFS and COVID-19, the literature review showed a lack of research in this field. The empirical results show quite similar self-esteem among ME/CFS patients and undiagnosed patients with longstanding disease experience, while former COVID-19 patients show a significantly lower severity of these problems. Notably, “psychological distress (anxiety)” and “episodic fatigue” are significantly predominant symptoms reported by former COVID-19 patients in comparison with ME/CFS patients and undiagnosed patients prior to the COVID-19 pandemic. The results of our analysis predict that the total amount of direct medical costs for undiagnosed patients (out-of-pocket payments) is more than EUR 15 million p.a. (in Latvia), and this may increase by at least 15% due to the consequences of COVID-19.

Conclusions: ME/CFS creates a significant shadow burden on society, even considering only the direct medical costs of undiagnosed patients-the number of whom in Latvia is probably at least five times higher than the number of discerned patients. Simultaneously, COVID-19 can induce long-lasting complications and chronic conditions, such as post-viral CFS, and increase this burden. The Latvian research data assume that ME/CFS patients are not a high-risk group for COVID-19; however, COVID-19 causes ME/CFS-relevant symptoms in patients. This increases the need for monitoring of patients for even longer after recovering from COVID-19’s symptoms, in order to prevent complications and the progression of chronic diseases. In the context of further epidemiological uncertainty, and the possibility of severe post-viral consequences, preventive measures are becoming significantly more important; an integrated diagnostic approach and appropriate treatment could reduce this burden in the future.

Source: Araja D, Berkis U, Lunga A, Murovska M. Shadow Burden of Undiagnosed Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) on Society: Retrospective and Prospective-In Light of COVID-19. J Clin Med. 2021 Jul 6;10(14):3017. doi: 10.3390/jcm10143017. PMID: 34300183. https://pubmed.ncbi.nlm.nih.gov/34300183/

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Abstract:

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive.

This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, 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 care for specific patients with the diagnosis

Source: Proal AD, VanElzakker MB. Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms. Front Microbiol. 2021 Jun 23;12:698169. doi: 10.3389/fmicb.2021.698169. PMID: 34248921; PMCID: PMC8260991. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260991/ (Full study)

Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome is a serious illness of unknown etiology, characterized by debilitating exhaustion, memory impairment, pain and sleep abnormalities. Viral infections are believed to initiate the pathogenesis of this syndrome although the definite proof remains elusive. With the unfolding of COVID-19 pandemic, the interest in this condition has resurfaced as excessive tiredness, a major complaint of patients infected with the SARS-CoV-2 virus, often lingers for a long time, resulting in disability, and poor life quality.

In a previous article, we hypothesized that COVID-19-upregulated angiotensin II triggered premature endothelial cell senescence, disrupting the intestinal and blood brain barriers. Here, we hypothesize further that post-viral sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome, are promoted by the gut microbes or toxin translocation from the gastrointestinal tract into other tissues, including the brain. This model is supported by the SARS-CoV-2 interaction with host proteins and bacterial lipopolysaccharide. Conversely, targeting microbial translocation and cellular senescence may ameliorate the symptoms of this disabling illness.

Source: Sfera A, Osorio C, Zapata Martín Del Campo CM, Pereida S, Maurer S, Maldonado JC, Kozlakidis Z. Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis. Front Cell Neurosci. 2021 Jun 25;15:673217. doi: 10.3389/fncel.2021.673217. PMID: 34248502; PMCID: PMC8267916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267916/ (Full study)

Assessment of Prolonged Physiological and Behavioral Changes Associated With COVID-19 Infection

Introduction: Long-term COVID symptoms marked by autonomic dysfunction1 and cardiac damage2 following COVID-19 infection have been noted for up to 6 months after symptom onset,3 but to date have not been quantified, to our knowledge. Previous studies have found that wearable data can improve real-time detection of viral illness4 or discrimination of individuals with COVID-19 vs other viral infections.5 Wearable devices provide a way to continuously track an individual’s physiological and behavioral metrics beginning when healthy (ie, before infection), during the course of infection, and recovery back to baseline. In this cohort study, we aimed to examine the duration and variation of recovery among COVID-19–positive vs COVID-19–negative participants.
Methods: DETECT (Digital Engagement and Tracking for Early Control and Treatment) is a remote, app-based, longitudinal research study enrolling adult participants from all over the US and collecting their wearable data to better understand individual changes associated with viral illness, including COVID-19. All participants provided informed consent electronically. The protocol for this study was reviewed and approved by the Scripps Office for the Protection of Research Subjects. This study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

From March 25, 2020, through January 24, 2021, 37 146 participants were enrolled. This analysis focuses on 875 individuals who reported symptoms of an acute respiratory illness and underwent swab testing for COVID-19 and were found to be either positive (234 individuals) or negative (641 individuals) (eFigure in the Supplement).

The following calculation was used for resting heart rate (RHR): deviation from baseline = daily RHR − baseline RHR mean. Individuals with COVID-19 were also grouped by their mean RHR deviation from baseline 28 to 56 days after symptom onset (<1, 1-5, or >5 beats per minute).

Data analysis was conducted in SAS statistical software version 9.4 (SAS Institute). Significance was set at P < .05. P values were calculated with 1-way ANOVA (for mean age) or χ2 tests. Additional details about our methods can be found in the eAppendix in the Supplement.

Results: For this analysis, our study population consisted of 234 COVID-19–positive individuals (mean [range] age, 45.3 [18-76] years; 164 women [70.9%]) and 641 COVID-19–negative symptomatic individuals (mean [range] age, 44.7 [19-75] years; 455 women [71.1%]). Individuals with COVID-19 took longer to return to their RHR (Figure, A and B), sleep (Figure, C and D), and activity (Figure, E and F) baselines compared with symptomatic individuals who were COVID-19 negative. This difference was most marked for RHR, with COVID-19–positive individuals initially experiencing a transient bradycardia followed by a prolonged relative tachycardia that did not return to baseline, on average, until 79 days after symptom onset. Step count and sleep quantity returned to baseline sooner than RHR at 32 and 24 days, respectively. During recovery, individuals with COVID-19 experienced different trajectories in the return of their RHR to their normal compared with COVID-19–negative individuals (Figure, B). A small subset of COVID-19–positive participants (32 participants [13.7%]) maintained an RHR more than 5 beats per minute greater than their baseline RHR that did not return to their normal for more than 133 days. During the acute phase of COVID-19, individuals in this group reported higher frequencies of cough (27 participants [84.4%] vs 57 participants [55.3%] in the <1 beat per minute group and 57 participants [57.6%] in the 1-5 beats per minute group), body ache (20 participants [62.5%] vs 42 participants [40.8%] in the <1 beat per minute group and 35 participants [35.4%] in the 1-5 beats per minute group), and shortness of breath (9 participants [28.1%] vs 9 participants [8.7%] in the <1 beat per minute group and 6 participants [6.1%] in the 1-5 beats per minute group) compared with the other groups (Table).
Discussion: To our knowledge, this is the first study to examine longer duration wearable sensor data. We found a prolonged physiological impact of COVID-19 infection, lasting approximately 2 to 3 months, on average, but with substantial intraindividual variability, which may reflect various levels of autonomic nervous system dysfunction or potentially ongoing inflammation. Transient bradycardia has been noted in a case study6 approximately 9 to 15 days after symptom onset, which was also seen in our population. Our data suggest that early symptoms and larger initial RHR response to COVID-19 infection may be associated with the physiological length of recovery from this virus.

Symptom data were collected only during the acute phase of infection, which limited our ability to compare long-term physiological and behavioral changes with long-term symptoms. In the future, with larger sample sizes and more comprehensive participant-reported outcomes, it will be possible to better understand factors associated with interindividualized variability in COVID-19 recovery.

Source: Radin JM, Quer G, Ramos E, et al. Assessment of Prolonged Physiological and Behavioral Changes Associated With COVID-19 Infection. JAMA Netw Open. 2021;4(7):e2115959. doi:10.1001/jamanetworkopen.2021.15959 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781687 (Full article)

Post COVID syndrome: a new challenge for medicine

Abstract:

The huge concern raised by SARS-CoV2 pandemic about public health management and social impact is still under debate, particularly because COVID-19 may affect infected people much longer than expected from a typical air-borne viral disease. The scientific community is actually wondering about the etiopathogenesis and clinical development of this “post-COVID” complex symptomatology, very close to symptoms typically observed in chronic fatigue syndrome, so recently named as “post-acute sequelae of COVID-19 (PASC)”. This commentary tries to focus on the most recent news about this issue.

Source: Tirelli U, Taibi R, Chirumbolo S. Post COVID syndrome: a new challenge for medicine. Eur Rev Med Pharmacol Sci. 2021 Jun;25(12):4422-4425. doi: 10.26355/eurrev_202106_26154. PMID: 34227079. https://pubmed.ncbi.nlm.nih.gov/34227079/

Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known?

Abstract:

Post-Acute COVID-19 Syndrome (PACS) is defined by persistent symptoms >3-4 weeks after onset of COVID-19. The mechanism of these persistent symptoms is distinct from acute COVID-19 although not completely understood despite the high incidence of PACS. Cardiovascular symptoms such as chest pain and palpitations commonly occur in PACS, but the underlying cause of symptoms is infrequently known. While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. Additionally, patients hospitalized with acute COVID-19 who display biomarker evidence of myocardial injury may have underlying coronary artery disease revealed by the physiological stress of SARS-CoV-2 infection and may benefit from medical optimization. We review what is known about PACS and the cardiovascular system and propose a framework for evaluation and management of related symptoms.

Source: Dixit NM, Churchill A, Nsair A, Hsu JJ. Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known? Am Heart J Plus. 2021 May;5:100025. doi: 10.1016/j.ahjo.2021.100025. Epub 2021 Jun 24. PMID: 34192289; PMCID: PMC8223036. https://pubmed.ncbi.nlm.nih.gov/34192289/

Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys, and brain that may produce a variety of symptoms. PASC also includes a post-coronavirus disease 2019 (COVID-19) syndrome (‘long COVID’) with features that can follow other acute infectious diseases and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Here we summarize what is known about the pathogenesis of ME/CFS and of ‘acute’ COVID-19, and we speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses, and we suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.

Source: Komaroff AL, Lipkin WI. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med. 2021 Jun 7:S1471-4914(21)00134-9. doi: 10.1016/j.molmed.2021.06.002. Epub ahead of print. PMID: 34175230. https://pubmed.ncbi.nlm.nih.gov/34175230/

Insights from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome

Abstract:

SARS-CoV-2 can cause chronic and acute disease. Post-Acute Sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys and brain, that may produce a variety of symptoms. PASC also includes a post-COVID-19 syndrome (“long COVID”) with features that can follow other acute infectious diseases as well as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we summarize what is known about the pathogenesis of ME/CFS and of acute COVID-19, and speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses, and suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.

Source: A.L. Komaroff and W.I. Lipkin, Insights from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome, Trends in Molecular Medicine (2021), https://doi.org/ 10.1016/j.molmed.2021.06.002  https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(21)00134-9 (Full text)

Report on the impact of Covid-19 on ME

Summary:

This summary report provides the preliminary findings from responses to the survey we are carrying out, in partnership with Action for ME, to identify the impact that Covid-19 has on people with ME. The report is based on the analysis of the 220 responses received in the three weeks after the survey went live in late March.

These initial responses show clearly that Covid-19 had a significant impact on respondents, with more than three quarters (76%) of respondents saying that Covid-19 made their ME symptoms worse. This impact appears to be long lasting, with over two thirds of respondents reporting that the worsening in symptoms has lasted more than 6 months and have still not resolved.

The wider impact of Covid-19 is illustrated by the negative impacts on the health of respondents, including 72% reporting new symptoms. The analysis also shows that respondents’ ability to attend education or work had decreased and their use of health services had increased significantly, highlighting the potential economic impact of Covid-19.

Read the full report HERE.