Tag: long covid pathophysiology

New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient. Here, we present a case series of four patients with a history of SARS-CoV-2 infection referred to the Post-Acute COVID-19 Syndrome (PACS) Clinic at Stanford University for evaluation of persistent symptoms, who also experienced new-onset alcohol sensitivity.

Alcohol reactions and sensitivity are not well characterized in the literature as it relates to post-viral illness. While there have been some anecdotal reports of new alcohol sensitivity in PASC patients in the media, there is a paucity of published data in the medical literature about this topic. During their medical consultation, the patients self-reported new changes in their symptoms or behaviors following the use of alcohol. A new onset of alcohol sensitivities should be assessed along with other post-COVID-19 symptoms and may provide novel avenues to explore the pathobiology of illness and potential interventions.

Source: Eastin E F, Tiwari A, Quach T C, et al. (December 29, 2023) New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series. Cureus 15(12): e51286. doi:10.7759/cureus.51286 https://www.cureus.com/articles/152512-new-alcohol-sensitivity-in-patients-with-post-acute-sequelae-of-sars-cov-2-pasc-a-case-series#!/ (Full text)

Muscle abnormalities worsen after post-exertional malaise in long COVID

Abstract:

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear.

With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

Source: Appelman, B., Charlton, B.T., Goulding, R.P. et al. Muscle abnormalities worsen after post-exertional malaise in long COVID. Nat Commun 15, 17 (2024). https://doi.org/10.1038/s41467-023-44432-3 https://www.nature.com/articles/s41467-023-44432-3 (Full text)

Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems

Abstract:

The coronavirus disease 2019 (COVID-19), instigated by the zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), rapidly transformed from an outbreak in Wuhan, China, into a widespread global pandemic. A significant post-infection condition, known as ‘long- COVID-19′ (or simply ‘long- COVID’), emerges in a substantial subset of patients, manifesting with a constellation of over 200 reported symptoms that span multiple organ systems. This condition, also known as ‘post-acute sequelae of SARS-CoV-2 infection’ (PASC), presents a perplexing clinical picture with far-reaching implications, often persisting long after the acute phase.
While initial research focused on the immediate pulmonary impact of the virus, the recognition of COVID-19 as a multiorgan disruptor has unveiled a gamut of protracted and severe health issues. This review summarizes the primary effects of long COVID on the respiratory, cardiovascular, and nervous systems. It also delves into the mechanisms underlying these impacts and underscores the critical need for a comprehensive understanding of long COVID’s pathogenesis.
Source: Sideratou C-M, Papaneophytou C. Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems. Infectious Disease Reports. 2023; 15(6):806-830. https://doi.org/10.3390/idr15060072 https://www.mdpi.com/2036-7449/15/6/72 (Full text)

Investigating the Human Intestinal DNA Virome and Predicting Disease-Associated Virus-Host Interactions in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Understanding how the human virome, and which of its constituents, contributes to health or disease states is reliant on obtaining comprehensive virome profiles. By combining DNA viromes from isolated virus-like particles (VLPs) and whole metagenomes from the same faecal sample of a small cohort of healthy individuals and patients with severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we have obtained a more inclusive profile of the human intestinal DNA virome.

Key features are the identification of a core virome comprising tailed phages of the class Caudoviricetes, and a greater diversity of DNA viruses including extracellular phages and integrated prophages. Using an in silico approach, we predicted interactions between members of the Anaerotruncus genus and unique viruses present in ME/CFS microbiomes. This study therefore provides a framework and rationale for studies of larger cohorts of patients to further investigate disease-associated interactions between the intestinal virome and the bacteriome.

Source: Hsieh SY, Savva GM, Telatin A, Tiwari SK, Tariq MA, Newberry F, Seton KA, Booth C, Bansal AS, Wileman T, Adriaenssens EM, Carding SR. Investigating the Human Intestinal DNA Virome and Predicting Disease-Associated Virus-Host Interactions in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Mol Sci. 2023 Dec 8;24(24):17267. doi: 10.3390/ijms242417267. PMID: 38139096. https://www.mdpi.com/1422-0067/24/24/17267 (Full text)

The association of insomnia with long COVID: An international collaborative study (ICOSS-II)

Abstract:

Objective: There is evidence of a strong association between insomnia and COVID-19, yet few studies have examined the relationship between insomnia and long COVID. This study aimed to investigate whether COVID-19 patients with pre-pandemic insomnia have a greater risk of developing long COVID and whether long COVID is in turn associated with higher incident rates of insomnia symptoms after infection.

Methods: Data were collected cross-sectionally (May-Dec 2021) as part of an international collaborative study involving participants from 16 countries. A total of 2311 participants (18-99 years old) with COVID-19 provided valid responses to a web-based survey about sleep, insomnia, and health-related variables. Log-binomial regression was used to assess bidirectional associations between insomnia and long COVID. Analyses were adjusted for age, sex, and health conditions, including sleep apnea, attention and memory problems, chronic fatigue, depression, and anxiety.

Results: COVID-19 patients with pre-pandemic insomnia showed a higher risk of developing long COVID than those without pre-pandemic insomnia (70.8% vs 51.4%; adjusted relative risk [RR]: 1.33, 95% confidence interval [CI]: 1.07-1.65). Among COVID-19 cases without pre-pandemic insomnia, the rates of incident insomnia symptoms after infection were 24.1% for short COVID cases and 60.6% for long COVID cases (p < .001). Compared with short COVID cases, long COVID cases were associated with an increased risk of developing insomnia symptoms (adjusted RR: 2.00; 95% CI: 1.50-2.66).

Conclusions: The findings support a bidirectional relationship between insomnia and long COVID. These findings highlight the importance of addressing sleep and insomnia in the prevention and management of long COVID.

Source: Chen SJ, Morin CM, Ivers H, Wing YK, Partinen M, Merikanto I, Holzinger B, Espie CA, De Gennaro L, Dauvilliers Y, Chung F, Yordanova J, Vidović D, Reis C, Plazzi G, Penzel T, Nadorff MR, Matsui K, Mota-Rolim S, Leger D, Landtblom AM, Korman M, Inoue Y, Hrubos-Strøm H, Chan NY, Bjelajac AK, Benedict C, Bjorvatn B. The association of insomnia with long COVID: An international collaborative study (ICOSS-II). Sleep Med. 2023 Dec;112:216-222. doi: 10.1016/j.sleep.2023.09.034. Epub 2023 Oct 24. PMID: 37922783. https://www.sciencedirect.com/science/article/abs/pii/S1389945723003672

Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles

Abstract:

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as “long COVID”. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms.

We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues.

In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.

Source: Aschman, T., Wyler, E., Baum, O. et al. Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles. acta neuropathol commun 11, 193 (2023). https://doi.org/10.1186/s40478-023-01662-2 https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-023-01662-2 (Full text)

Sex differences in vascular endothelial function related to acute and long COVID-19

Abstract:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been at the forefront of health sciences research since its emergence in China in 2019 that quickly led to a global pandemic. As a result of this research, and the large numbers of infected patients globally, there were rapid enhancements made in our understanding of Coronavirus disease 2019 (COVID-19) pathology, including its role in the development of uncontrolled immune responses and its link to the development of endotheliitis and endothelial dysfunction.

There were also some noted differences in the rate and severity of infection between males and females with acute COVID. Some individuals infected with SARS-CoV-2 also experience long-COVID, an important hallmark symptom of this being Myalgic Encephalomyelitis-Chronic Fatigue Syndrome (ME-CFS), also experienced differently between males and females.

The purpose of this review is to discuss the impact of sex on the vasculature during acute and long COVID-19, present any link between ME-CFS and endothelial dysfunction, and provide evidence for the relationship between ME-CFS and the immune system. We also will delineate biological sex differences observed in other post viral infections and, assess if sex differences exist in how the immune system responds to viral infection causing ME-CFS.

Source: Kayla KA, Bédard-Matteau J, Rousseau S, Tabrizchi R, Noriko D. Sex differences in vascular endothelial function related to acute and long COVID-19. Vascul Pharmacol. 2023 Dec 1:107250. doi: 10.1016/j.vph.2023.107250. Epub ahead of print. PMID: 38043758. https://www.sciencedirect.com/science/article/abs/pii/S1537189123001106 (Full text)

Catalytic Antibodies May Contribute to Demyelination in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Here we report preliminary data demonstrating that some patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may have catalytic autoantibodies that cause the breakdown of myelin basic protein (MBP). We propose that these MBP-degradative antibodies are important to the pathophysiology of ME/CFS, particularly in the occurrence of white matter disease/demyelination. This is supported by magnetic resonance imagining studies that show these findings in patients with ME/CFS and could explain symptoms of nerve pain and muscle weakness.

In this work, we performed a series of experiments on patient plasma samples where we isolated and characterized substrate-specific antibodies that digest MBP. We also tested glatiramer acetate (copaxone), an FDA approved immunomodulator to treat multiple sclerosis, and found that it inhibits ME/CFS antibody digestion of MBP. Furthermore, we found that aprotinin, which is a specific serine protease inhibitor, specifically prevents breakdown of MBP while the other classes of protease inhibitors had no effect. This coincides with the published literature describing catalytic antibodies as having serine protease-like activity. Postpandemic research has also provided several reports of demyelination in COVID-19.

Because COVID-19 has been described as a trigger for ME/CFS, demyelination could play a bigger role in patient symptoms for those recently diagnosed with ME/CFS. Therefore, by studying proteolytic antibodies in ME/CFS, their target substrates, and inhibitors, a new mechanism of action could lead to better treatment and a possible cure for the disease.

Source: Jensen MA, Dafoe ML, Wilhelmy J, Cervantes L, Okumu AN, Kipp L, Nemat-Gorgani M, Davis RW. Catalytic Antibodies May Contribute to Demyelination in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Biochemistry. 2023 Nov 27. doi: 10.1021/acs.biochem.3c00433. Epub ahead of print. PMID: 38011893. https://pubs.acs.org/doi/10.1021/acs.biochem.3c00433 (Full text)

Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID

Abstract:

In the COVID-19 pandemic, caused by SARS-CoV-2, many individuals experience prolonged symptoms, termed long-lasting COVID-19 symptoms (long COVID). Long COVID is thought to be linked to immune dysregulation due to harmful inflammation, with the exact causes being unknown. Given the role of the microbiome in mediating inflammation, we aimed to examine the relationship between the oral microbiome and the duration of long COVID symptoms.

Tongue swabs were collected from patients presenting with COVID-19 symptoms. Confirmed infections were followed until resolution of all symptoms. Bacterial composition was determined by metagenomic sequencing. We used random forest modeling to identify microbiota and clinical covariates that are associated with long COVID symptoms. Of the patients followed, 63% developed ongoing symptomatic COVID-19 and 37% went on to long COVID.

Patients with prolonged symptoms had significantly higher abundances of microbiota that induced inflammation, such as members of the genera Prevotella and Veillonella, which, of note, are species that produce LPS. The oral microbiome of patients with long COVID was similar to that of patients with chronic fatigue syndrome.

Altogether, our findings suggest an association with the oral microbiome and long COVID, revealing the possibility that dysfunction of the oral microbiome may have contributed to this draining disease.

Source: Haran JP, Bradley E, Zeamer AL, Cincotta L, Salive MC, Dutta P, Mutaawe S, Anya O, Meza-Segura M, Moormann AM, Ward DV, McCormick BA, Bucci V. Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID. JCI Insight. 2021 Oct 22;6(20):e152346. doi: 10.1172/jci.insight.152346. PMID: 34403368; PMCID: PMC8564890. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564890/ (Full text)

Role of Tau protein in long COVID and potential therapeutic targets

Abstract:

Introduction: Long COVID is an emerging public health burden and has been defined as a syndrome with common symptoms of fatigue, shortness of breath, cognitive dysfunction, and others impacting day-to-day life, fluctuating or relapsing over, occurring for at least two months in patients with a history of probable or confirmed SARS CoV-2 infection; usually three months from the onset of illness and cannot be explained by an alternate diagnosis. The actual prevalence of long-term COVID-19 is unknown, but it is believed that more than 17 million patients in Europe may have suffered from it during pandemic.

Pathophysiology: Currently, there is limited understanding of the pathophysiology of this syndrome, and multiple hypotheses have been proposed. Our literature review has shown studies reporting tau deposits in tissue samples of the brain from autopsies of COVID-19 patients compared to the control group, and the in-vitro human brain organoid model has shown aberrant phosphorylation of tau protein in response to SARS-CoV-2 infection. Tauopathies, a group of neurodegenerative disorders with the salient features of tau deposits, can manifest different symptoms based on the anatomical region of brain involvement and have been shown to affect the peripheral nervous system as well and explained even in rat model studies.

Long COVID has more than 203 symptoms, with predominant symptoms of fatigue, dyspnea, and cognitive dysfunction, which tauopathy-induced CNS and peripheral nervous system dysfunction can explain. There have been no studies up till now to reveal the pathophysiology of long COVID. Based on our literature review, aberrant tau phosphorylation is a promising hypothesis that can be explored in future studies.

Therapeutic approaches for tauopathies have multidimensional aspects, including targeting post-translational modifications, tau aggregation, and tau clearance through the autophagy process with the help of lysosomes, which can be potential targets for developing therapeutic interventions for the long COVID. In addition, future studies can attempt to find the tau proteins in CSF and use those as biomarkers for the long COVID.

Source: Marwaha B. Role of Tau protein in long COVID and potential therapeutic targets. Front Cell Infect Microbiol. 2023 Oct 25;13:1280600. doi: 10.3389/fcimb.2023.1280600. PMID: 37953801; PMCID: PMC10634420. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634420/ (Full text)