Category: Overlapping Illnesses

Neurologic manifestations of long COVID differ based on acute COVID-19 severity

Abstract:

Objective: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients.

Methods: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021.

Results: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were “brain fog” (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients.

Interpretation: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions.

Source: Perez Giraldo GS, Ali ST, Kang AK, Patel TR, Budhiraja S, Gaelen JI, Lank GK, Clark JR, Mukherjee S, Singer T, Venkatesh A, Orban ZS, Lim PH, Jimenez M, Miller J, Taylor C, Szymanski AL, Scarpelli J, Graham EL, Balabanov RD, Barcelo BE, Cahan JG, Ruckman K, Shepard AG, Slutzky MW, LaFaver K, Kumthekar PU, Shetty NK, Carroll KS, Ho SU, Lukas RV, Batra A, Liotta EM, Koralnik IJ. Neurologic manifestations of long COVID differ based on acute COVID-19 severity. Ann Neurol. 2023 Mar 26. doi: 10.1002/ana.26649. Epub ahead of print. PMID: 36966460. https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.26649 (Full text available as PDF file)

 

Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)

Abstract:

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment.

This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC.

The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, 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 specific patients.

Source: Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB; RECOVER Mechanistic Pathway Task Force. Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). Elife. 2023 Mar 22;12:e86002. doi: 10.7554/eLife.86002. PMID: 36947108; PMCID: PMC10032659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032659/ (Full text)

An Orthomolecular Protocol for Long COVID

Abstract:

A significant number of COVID-19 patients suffer from SARS-CoV-2 post-acute chronic sequelae, also known as post-COVID syndrome or long COVID. These patients report a broad range of persistent and debilitating symptoms such as fatigue, brain fog, pain, breathlessness, and dysrhythmias. These chronic symptoms are believed to be a consequence of excessive production of reactive oxygen species (ROS), inflammation, tissue damage, and mitochondrial dysfunction. Patients at higher risk of long-term sequelae are those who experienced severe COVID-19 infection, are immunocompromised and likely have depleted reserves of biological factors and micronutrients necessary for prompt recovery.

Based on biochemical principles and studies in conditions that share common traits with long COVID patients such as chronic fatigue syndrome and fibromyalgia, symptom relief and sustained recovery can be expected by administering an orthomolecular protocol consisting of a combination of precursors, cofactors, and biological response modifiers.

Source: Gonzalez MJ et al. (2023) An Orthomolecular Protocol for Long-COVID. J Orthomol Med. 38(1) https://www.researchgate.net/publication/369328211_An_Orthomolecular_Protocol_for_Long_COVID (Full text)

Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID

Abstract:

The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease.
Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease’s poor prognosis.
Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs’ phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta.
Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19.
Source: Dhawan M, Rabaan AA, Alwarthan S, Alhajri M, Halwani MA, Alshengeti A, Najim MA, Alwashmi ASS, Alshehri AA, Alshamrani SA, AlShehail BM, Garout M, Al-Abdulhadi S, Al-Ahmed SH, Thakur N, Verma G. Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID. Vaccines. 2023; 11(3):699. https://doi.org/10.3390/vaccines11030699 https://www.mdpi.com/2076-393X/11/3/699 (Full text)

Immunometabolic rewiring in long COVID patients with chronic headache

Abstract:

Almost 20% of patients with COVID-19 experience long-term effects, known as post-COVID condition or long COVID. Among many lingering neurologic symptoms, chronic headache is the most common. Despite this health concern, the etiology of long COVID headache is still not well characterized. Here, we present a longitudinal multi-omics analysis of blood leukocyte transcriptomics, plasma proteomics and metabolomics of long COVID patients with chronic headache. L

ong COVID patients experienced a state of hyper-inflammation prior to chronic headache onset and maintained persistent inflammatory activation throughout the progression of chronic headache. Metabolomic analysis also revealed augmented arginine and lipid metabolisms, skewing towards a nitric oxide-based pro-inflammation. Furthermore, metabolisms of neurotransmitters including serotonin, dopamine, glutamate, and GABA were markedly dysregulated during the progression of long COVID headache.

Overall, these findings illustrate the immuno-metabolomics landscape of long COVID patients with chronic headache, which may provide insights to potential therapeutic interventions.

Source: Foo SS, Chen W, Jung KL, Azamor T, Choi UY, Zhang P, Comhair SA, Erzurum SC, Jehi L, Jung JU. Immunometabolic rewiring in long COVID patients with chronic headache. bioRxiv [Preprint]. 2023 Mar 6:2023.03.06.531302. doi: 10.1101/2023.03.06.531302. PMID: 36945569; PMCID: PMC10028820. https://www.biorxiv.org/content/10.1101/2023.03.06.531302v1.full (Full text)

Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people

Abstract:

Objectives: To describe the physical and mental health of children and young people (CYP) 6 months after infection with SARS-CoV-2 and explore whether this varies by COVID-19 vaccination.

Design: A non-hospitalised, national cohort of people aged 11-17 years old with PCR-confirmed SARS-CoV-2 infection and PCR negatives matched at study invitation, by age, sex, region and date of testing who completed questionnaires 6 months after PCR testing. The questionnaire included 21 symptoms and standardised scales (eg, EQ-5D-Y and Chalder Fatigue Scale).

Results: 6407 test-positive and 6542 test-negative CYP completed the 6-month questionnaire: 60.9% of test-positive vs 43.2% of test-negative CYP reported at least one symptom 6 months post-test; 27.6% of test-positive vs 15.9% of test-negative CYP reported 3+ symptoms. Common symptoms at 6 months were tiredness and shortness of breath among both test-positive and test-negative CYP; however, the prevalence of both was higher in test-positive (38.4% and 22.8%, respectively) compared with test-negative CYP (26.7% and 10.9%, respectively). 24.5% test-positive vs 17.8% test-negative CYP met the Delphi research definition of long COVID. Mental health, well-being, fatigue and health-related quality of life scores were similar among test-positive and test-negative CYP 6 months post-test. Similarly, symptomatology was similar among COVID-19-vaccinated and COVID-19-unvaccinated test-positive and test-negative CYP.

Conclusions: Six-months post-PCR testing, CYP who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but test-positive CYP had higher symptom prevalence. Mental health, well-being, fatigue and health-related quality of life were similar among test-positive and test-negative CYP, and symptoms at 6 months were similar in COVID-19 vaccinated and unvaccinated.

Source: Pinto Pereira SM, Nugawela MD, Rojas NK, Shafran R, McOwat K, Simmons R, Ford T, Heyman I, Ladhani SN, Cheung EY, Fox-Smith L, Dalrymple E, Stephenson T. Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people. Arch Dis Child. 2023 Apr;108(4):289-295. doi: 10.1136/archdischild-2022-324656. Epub 2023 Jan 4. PMID: 36599625. https://adc.bmj.com/content/108/4/289.long (Full text)

Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder

Abstract:

There have been suggestions that Long COVID might be purely functional (meaning psychological) in origin. Labelling patients with neurological dysfunction in Long COVID as having functional neurological disorder (FND) in the absence of proper testing may be symptomatic of that line of thought. This practice is problematic for Long COVID patients, as motor and balance symptoms have been reported to occur in Long COVID frequently.
FND is characterized by the presentation of symptoms that seem neurological but lack compatibility of the symptom with a neurological substrate. Although diagnostic classification according to the ICD-11 and DSM-5-TR is dependent predominantly on the exclusion of any other medical condition that could account for the symptoms, current neurological practice of FND classification allows for such comorbidity. As a consequence, Long COVID patients with motor and balance symptoms mislabeled as FND have no longer access to Long COVID care, whereas treatment for FND is seldom provided and is ineffective.
Research into underlying mechanisms and diagnostic methods should explore how to determine whether motor and balance symptoms currently diagnosed as FND should be considered one part of Long COVID symptoms, in other words, one component of symptomatology, and in which cases they correctly represent FND. Research into rehabilitation models, treatment and integrated care are needed, which should take into account biological underpinnings as well as possible psychological mechanisms and the patient perspective.
Source: Van der Feltz-Cornelis CM, Moriarty AS, Strain WD. Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder. Viruses. 2023; 15(3):783. https://doi.org/10.3390/v15030783 https://www.mdpi.com/1999-4915/15/3/783 (Full text)

Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis

Abstract:

Current data suggests that coronavirus disease 2019 (COVID-19) survivors experience long-lasting problems. It is not yet understood how long these symptoms last. The goal of this study was to compile all the data that was currently available to evaluate COVID-19’s long-term effects at 12 months and above.

We looked for studies published by December 15, 2022, in PubMed and Embase that discussed follow-up findings for COVID-19 survivors who had been alive for at least a year. A random-effect model was carried out to determine the combined prevalence of different long-COVID symptoms. The Joanna Briggs Institute tool was used to assess the risk of bias for the included studies, and the I2 statistics were used to evaluate the heterogeneity. After reviewing 3,209 studies, 46 were deemed admissible, with an aggregate COVID-19 population of 17976.

At 12 months and above, 57% of patients reported a minimum of one symptom, and the five most prevalent symptoms were: dyspnea on exertion (34%, 95% CI 0.2; 0.94); difficulty in concentration (32%, 95% CI 0.16; 0.52); fatigue (31%, 95% CI 0.22; 0.40); frailty (31%, 95% CI 0.06; 0.78); and arthromyalgia (28%, 95% CI 0.09; 0.6). The findings of the present study showed that at 12 months and beyond, a sizable fraction of COVID-19 survivors still have lasting symptoms that impair several body systems. Long-COVID patients require an urgent understanding of pathophysiological processes and the development of tailored treatments.

Source: Mudgal S K, Gaur R, Rulaniya S, et al. (March 18, 2023) Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis. Cureus 15(3): e36325. doi:10.7759/cureus.36325 https://www.cureus.com/articles/143288-pooled-prevalence-of-long-covid-19-symptoms-at-12-months-and-above-follow-up-period-a-systematic-review-and-meta-analysis#!/ (Full text)

A Review of Possible Supplements to Relieve the Symptoms of Fatigue after COVID-19

Abstract:

Background: The highly infectious coronavirus has become a global pandemic; the effective medication is yet to be developed. The health care system was strained; millions of people have been suffered from infection and complications. Post COVID-19 fatigue is a dominant characteristic of coronavirus infection. It affects general state of health, muscle strength, sleeping quality, mental health, and life quality. This paper is emphasizing and summarizing the potential beneficial supplementations of post COVID-19 fatigue symptoms.

Methods: The knowledge gained from PubMed and from the National Library of Medicine. Clinical studies and systematic review articles were collected in this topic.

Results: Herein, we discuss the possible therapeutic supplementations with anti-inflammatory, immunomodulatory and antioxidant effect. Vitamin complexes, trace elements, antioxidants, coenzymes, probiotics, essential fatty acids; one and creatine as amino acid derivatives have been appeared to be effective in relieving post COVID-19 fatigue symptoms.

Conclusions: Based on the data, these nutrients and supplements might be important to alleviate the post COVID-19 fatigue symptoms and they could be considered as a supportive therapy

Source: Boglárka Bernadett Tisza, Gyöngyi Iván, Viola Keczeli, Melinda Kóró, Patricia Szántóri, Zsófia Gyócsiné Varga, Henriett Müller, Olivia Pribéli, Zoltán Szabó, Zsófia Verzár, Monika Sélleyné Gyuró, Andrea Gubicskóné Kisbendek and Tímea Stromájer-Rácz. A Review of Possible Supplements to Relieve the Symptoms of Fatigue after COVID-19.  J Med Public Health. 2023;4(2):JMPH-04-1062. https://www.medtextpublications.com/open-access/a-review-of-possible-supplements-to-relieve-the-symptoms-of-1309.pdf (Full text)

The prevalence of stigma in a UK community survey of people with lived experience of long COVID

Abstract:

Background: Stigma can be experienced as perceived or actual disqualification from social and institutional acceptance on the basis of one or more physical, health-related, behavioural, or other attributes deemed to be undesirable. Long COVID is a predominantly multisystem condition that occurs in people with a history of SARS-CoV-2 infection, often resulting in functional disability, which limits day-to-day activities. We aimed to quantify the burden of stigma experienced in a community-based sample of people with lived experience of long COVID.

Methods: Data from the follow-up of a long COVID longitudinal online survey was used. The survey was coproduced with people living with long COVID. 13 questions on stigma were included to develop a Long COVID Stigma Scale capturing three domains: enacted (overt experiences of discrimination due to long COVID), internalised (internalising negative associations with long COVID and accepting them as self-applicable), and anticipated (expectation of bias or poor treatment by others) stigma. Data were collected through a social media survey with convenience non-probability sampling.

Findings: 966 (47·9%) of 2016 participants from the UK completed the follow-up survey and 888 responded to the questions on stigma. The mean age of respondents was 48·3 years (SD 10·7), and 84·6% identified as female. Roughly half (n=460, 50·4%) reported having a formal, clinical, long COVID diagnosis, and of these, 440 responded to the questions on stigma. The prevalence of people experiencing overall stigma at least sometimes was 95·4% (n=847), prevalence of enacted stigma was 62·7% (n=557), internalised stigma was 86·4% (n=767), and anticipated stigma was 90·8% (n=806). Prevalence of stigma was higher in respondents with a formal diagnosis of long COVID (97·5%; n=429) than in those without (93·2%; n=413).

Interpretation: This study highlights widespread and multilayered stigmas experienced by people living with long COVID in the UK, which presents a serious public health concern. The broader literature on stigmatised health conditions consistently suggests that stigma drives people away from health services, contributes to psychological distress, and compromises long-term physical outcomes. The higher proportion experiencing stigma in those with clinical diagnosis of long COVID might be indicative of stigma within the health-care system. Findings from this study should be taken into consideration within clinical practice and health care, social care, employment, and education policies.

Source: Pantelic M, Ziauddeen N, Boyes M, O’Hara ME, Hastie C, Alwan NA. The prevalence of stigma in a UK community survey of people with lived experience of long COVID. Lancet. 2022 Nov;400 Suppl 1:S84. doi: 10.1016/S0140-6736(22)02294-2. Epub 2022 Nov 24. PMID: 36930033. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02294-2/fulltext