Tag: covid-19

Preliminary Guidelines for the Clinical Evaluation and Management of Long COVID

Abstract:

Long-lasting coronavirus disease 2019 (COVID-19) symptoms beyond 12 weeks, the so-called ‘long COVID’ have been increasingly reported worldwide. Long COVID can be manifested in various forms, and there is an increasing demand for proper assessment and management. However, it is challenging when trying to determine the best-practice standards of care based on the current evidence because there is no internationally agreed clinical definition or clear treatment pathway. Therefore, the present guidelines have been drafted to provide advice on diagnosis and management based on the latest updated available evidence and the consensus of expert opinion. So far, no standard test and drug treatment can be strongly recommended for patients with long COVID because of a lack of evidence. The present guidelines provide advice based on 12 key questions, including appropriate interventions for long COVID that can be used in clinical practice. Continuous careful observation and studies related to long COVID are needed for the long-term impact of COVID-19 and proper management for long COVID to be determined.

Source: Kim Y, Kim SE, Kim T, Yun KW, Lee SH, Lee E, Seo JW, Jung YH, Chong YP. Preliminary Guidelines for the Clinical Evaluation and Management of Long COVID. Infect Chemother. 2022 Sep;54(3):566-597. doi: 10.3947/ic.2022.0141. PMID: 36196612; PMCID: PMC9533168. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533168/ (Full text)

Long COVID: defining the role of rheumatology in care and research

The global pandemic of COVID-19 has had an impact on the profession of rheumatology from many perspectives, including its effects on our patients with immune-mediated conditions and immunocompromised states, the disruption of care pathways, and beyond. There also are lingering questions about how the next phase of the pandemic will evolve, with the continuing emergence of new viral variants posing a continuing threat to our patients. Beyond these formidable challenges is the uncertainty around the long-term effects of COVID-19—referred to as long COVID among other names—in the rheumatology patient population, and the role of the rheumatology practitioner in care of and research among this population. Given the current global impact of long COVID and our early stages of understanding of the condition, we pose a series of questions for the rheumatology profession, to stimulate reflection and discussion around how to address long COVID.

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Source: Calabrese LH, Calabrese CM. Long COVID: defining the role of rheumatology in care and research. Lancet Rheumatol. 2022 Oct 3. doi: 10.1016/S2665-9913(22)00266-1. Epub ahead of print. PMID: 36211989; PMCID: PMC9529216. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529216/ (Full text)

Antioxidants and Long Covid

Abstract:

Long Covid has many symptoms that overlap with ME(myalgic encephalomyelitis)/CFS(chronic fatigue syndrome), FM(fibromyalgia), EBV(Epstein-Barr virus), CMV(cytomegalovirus), CIRS (chronic inflammatory response syndrome), MCAS(mast cell activation syndrome), POTS(postural orthostatic tachycardia syndrome), and post viral fatigue syndrome. They all portend a “long haul” with an antioxidant shortfall and elevated Ca:Mg. Oxidative stress is the root cause.

Linkage between TGF(transforming growth factor)-β, IFN(interferon)-γ, the RAS(renin angiotensin system), and the KKS(kallikrein kinin system) is discussed. Technical explanations for the renin aldosterone paradox in POTS, the betrayal of TGF-β, and the commonality of markers for the Warburg effect are offered. The etiology of the common Long Covid symptoms of post exertional malaise, fatigue, and brain fog as well as anosmia, hair loss, and GI symptoms is technically discussed. Ca:Mg is critical to the glutamate/GABA balance. The role of GABA and butyrates from the “good” intestinal bacteria in the gut-brain axis and its correlation with chronic fatigue diseases are explored.

The crosstalk between the ENS(enteric nervous system) and the ANS(autonomic nervous system) and the role of the vagus in both are emphasized. HRV(heart rate variability), the fifth vital sign, points to an expanded gut-brain-heart/lung axis. A suggested approach to all of these – Long Covid, chronic fatigue diseases, post viral fatigue syndrome, and general health – is presented.

Source: Chambers, P. Antioxidants and Long Covid. Preprints 2022, 2022100195 (doi: 10.20944/preprints202210.0195.v1).  https://www.preprints.org/manuscript/202210.0195/v1 (Full text available as PDF file)

Support amid uncertainty: Long COVID illness experiences and the role of online communities

Abstract:

Long COVID is characterized by persistent and debilitating long-term symptoms from COVID-19. Many persons with Long COVID began gathering in online communities during the early phases of the pandemic to share their illness experiences. This qualitative interview study explored the subjective experiences of 20 persons with Long COVID recruited from five online communities. Their understandings of illness and associated implications for social relationships with family and friends, healthcare professionals, and online community members were explored.

Three themes were identified from our analysis, including (1) complex and unpredictable illness experienced amid an evolving understanding of the pandemic; (2) frustration, dismissal, and gaslighting in healthcare interactions; and (3) validation and support from online communities. These findings highlight the significant uncertainty that persons with Long COVID navigated, the features of their often dismaying healthcare experiences, and the ways in which online communities aided them in understanding their illness.

Source: Russell D, Spence NJ, Chase JD, Schwartz T, Tumminello CM, Bouldin E. Support amid uncertainty: Long COVID illness experiences and the role of online communities. SSM Qual Res Health. 2022 Dec;2:100177. doi: 10.1016/j.ssmqr.2022.100177. Epub 2022 Oct 4. PMID: 36212783; PMCID: PMC9531408. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531408/ (Full text)

Acute COVID-19 Syndrome Predicts Severe Long COVID-19: An Observational Study

Abstract:

Introduction Tissue damage, chronic dysfunction, and symptoms that last more than 12 weeks are hallmarks of long-term chronic opportunistic viral infection (COVID-19), and the disease may have a permanent, relapsing/remitting, or gradually improving course. This study aimed to determine the risk factors of severe long COVID-19.

Methods In October 2021, primary care clinics enrolled consenting 18- to 89-year-olds to complete an online questionnaire on self-diagnosis, clinician diagnosis, testing, symptom presence, and duration of COVID-19. Long COVID-19 was identified if symptoms were beyond 12 weeks. Patients with long-lasting COVID-19 symptoms were assessed using multivariable regression to identify potential predictors of severe long COVID-19.

Results Of the 220 respondents, 108 (49%) patients were self- or clinician-diagnosed with COVID-19 or had a confirmed positive laboratory test result. Patients aged >45 years and with at least 15 COVID-19 symptoms were 5.55 and 6.02 times, respectively, more likely to acquire severe long COVID-19. Most patients with severe and moderate post-acute COVID-19 syndrome had no relevant comorbidities (p=0.0402; odds ratio [OR]=0.4; 95% confidence interval [CI]=0.18-0.98). Obesity was a significant predictor (p=0.0307; OR=6.2; 95% CI=1.1-33.2).

Conclusion The simultaneous presence of 15 or more COVID-19 symptoms, age >45 years, and obesity were related to a higher probability of severe long COVID-19.

Source: Menezes AS Jr, Botelho SM, Santos LR, Rezende AL. Acute COVID-19 Syndrome Predicts Severe Long COVID-19: An Observational Study. Cureus. 2022 Oct 2;14(10):e29826. doi: 10.7759/cureus.29826. PMID: 36204261; PMCID: PMC9527039.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527039/ (Full text)

Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics

Abstract:

Introduction: In patients with SARS-CoV-2, innate immunity is playing a central role, depicted by hyperinflammation and longer lasting inflammatory response. Reliable inflammatory markers that cover both acute and long-lasting COVID-19 monitoring are still lacking. Thus, we investigated one specific inflammatory marker involved as one key player of the immune system, kynurenine (Kyn), and its use for diagnosis/detection of the Long-/Post-COVID syndrome in comparison to currently used markers in both serum and saliva samples.

Material and methods: The study compromised in total 151 inpatients with a SARS-CoV-2 infection hospitalized between 03/2020 and 09/2021. The group NC (normal controls) included blood bank donors (n=302, 144f/158m, mean age 47.1 ± 18.3 years (range 18-75)). Two further groups were generated based on Group A (n=85, 27f/58m, mean age 63.1 ± 18.3 years (range 19-90), acute admission to the hospital) and Group B (n=66, 22f/44m, mean age 66.6 ± 17.6 years (range 17-90), admitted either for weaning or for rehabilitation period due to Long-COVID symptoms/syndrome). Plasma concentrations of Kyn, C-Reactive Protein (CRP) and interleukin-6 (IL-6) were measured on admission. In Group B we determined Kyn 4 weeks after the negative PCR-test. In a subset of patients (n=11) concentrations of Kyn and CRP were measured in sera and saliva two, three and four months after dismission. We identified 12 patients with Post-COVID symptoms >20 weeks with still significant elevated Kyn-levels.

Results: Mean values for NC used as reference were 2.79 ± 0.61 µM, range 1.2-4.1 µM. On admission, patients showed significantly higher concentrations of Kyn compared to NC (p-values < 0.001). Kyn significantly correlated with IL-6 peak-values (r=0.411; p-values <0.001) and CRP (r=0.488, p-values<0.001). Kyn values in Group B (Long-/Post-COVID) showed still significant higher values (8.77 ± 1.72 µM, range 5.5-16.6 µM), whereas CRP values in Group B were in the normal range.

Conclusion: Serum and saliva Kyn are reflecting the acute and long-term pathophysiology of the SARS-CoV-2 disease concerning the innate immune response and thus may serve a useful biomarker for diagnosis and monitoring both Long- and Post-COVID syndrome and its therapy.

Source: Bizjak DA, Stangl M, Börner N, Bösch F, Durner J, Drunin G, Buhl JL, Abendroth D. Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics. Front Immunol. 2022 Sep 23;13:1004545. doi: 10.3389/fimmu.2022.1004545. PMID: 36211365; PMCID: PMC9537769. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537769/ (Full text)

Plasma cytokine levels reveal deficiencies in IL-8 and gamma interferon in Long-COVID

Abstract:

Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood.

We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of interferon gamma (IFNγ) and interleukin-8 (IL-8). Additionally, we found significant reductions in levels of IL-6, IL-2, IL-17, IL-13, and IL-4 in individuals with long-COVID.

We propose immune exhaustion as the driver of long-COVID, with the complete absence of IFNγ and IL-8 preventing the lungs and other organs from healing after acute infection, and reducing the ability to fight off subsequent infections, both contributing to the myriad of symptoms suffered by those with long-COVID.

Source: Williams ESCP, Martins TB, Hill HR, Coiras M, Shah KS, Planelles V, Spivak AM. Plasma cytokine levels reveal deficiencies in IL-8 and gamma interferon in Long-COVID. medRxiv [Preprint]. 2022 Oct 5:2022.10.03.22280661. doi: 10.1101/2022.10.03.22280661. PMID: 36238724; PMCID: PMC9558442. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558442/ (Full text)

Pathophysiology of Post-COVID syndromes: a new perspective

Abstract:

Most COVID-19 patients recovered with low mortality; however, some patients experienced long-term symptoms described as “long-COVID” or “Post-COVID syndrome” (PCS). Patients may have persisting symptoms for weeks after acute SARS-CoV-2 infection, including dyspnea, fatigue, myalgia, insomnia, cognitive and olfactory disorders. These symptoms may last for months in some patients.

PCS may progress in association with the development of mast cell activation syndrome (MCAS), which is a distinct kind of mast cell activation disorder, characterized by hyper-activation of mast cells with inappropriate and excessive release of chemical mediators. COVID-19 survivors, mainly women, and patients with persistent severe fatigue for 10 weeks after recovery with a history of neuropsychiatric disorders are more prone to develop PCS. High D-dimer levels and blood urea nitrogen were observed to be risk factors associated with pulmonary dysfunction in COVID-19 survivors 3 months post-hospital discharge with the development of PCS. PCS has systemic manifestations that resolve with time with no further complications. However, the final outcomes of PCS are chiefly unknown.

Persistence of inflammatory reactions, autoimmune mimicry, and reactivation of pathogens together with host microbiome alterations may contribute to the development of PCS. The deregulated release of inflammatory mediators in MCAS produces extraordinary symptoms in patients with PCS. The development of MCAS during the course of SARS-CoV-2 infection is correlated to COVID-19 severity and the development of PCS. Therefore, MCAS is treated by antihistamines, inhibition of synthesis of mediators, inhibition of mediator release, and inhibition of degranulation of mast cells.

Source: Batiha, G.ES., Al-kuraishy, H.M., Al-Gareeb, A.I. et al. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J 19, 158 (2022). https://doi.org/10.1186/s12985-022-01891-2  https://virologyj.biomedcentral.com/articles/10.1186/s12985-022-01891-2 (Full text)

Sleep symptoms are essential features of long-COVID – Comparing healthy controls with COVID-19 cases of different severity in the international COVID sleep study (ICOSS-II)

Abstract:

Many people report suffering from post-acute sequelae of COVID-19 or “long-COVID”, but there are still open questions on what actually constitutes long-COVID and how prevalent it is. The current definition of post-acute sequelae of COVID-19 is based on voting using the Delphi-method by the WHO post-COVID-19 working group. It emphasizes long-lasting fatigue, shortness of breath and cognitive dysfunction as the core symptoms of post-acute sequelae of COVID-19.

In this international survey study consisting of 13,628 subjects aged 18-99 years from 16 countries of Asia, Europe, North America and South America (May-Dec 2021), we show that post-acute sequelae of COVID-19 symptoms were more prevalent amongst the more severe COVID-19 cases, i.e. those requiring hospitalisation for COVID-19. We also found that long-lasting sleep symptoms are at the core of post-acute sequelae of COVID-19 and associate with the COVID-19 severity when COVID-19 cases are compared with COVID-negative cases.

Specifically, fatigue (61.3%), insomnia symptoms (49.6%) and excessive daytime sleepiness (35.8%) were highly prevalent amongst respondents reporting long-lasting symptoms after hospitalisation for COVID-19. Understanding the importance of sleep-related symptoms in post-acute sequelae of COVID-19 has a clinical relevance when diagnosing and treating long-COVID.

Source: Merikanto I, Dauvilliers Y, Chung F, Wing YK, de Gennaro L, Holzinger B, Bjorvatn B, Morin CM, Penzel T, Benedict C, Koscec Bjelajac A, Chan NY, Espie CA, Hrubos-Strøm H, Inoue Y, Korman M, Landtblom AM, Léger D, Matsui K, Mota-Rolim S, Nadorff MR, Plazzi G, Reis C, Yordanova J, Partinen M. Sleep symptoms are essential features of long-COVID – Comparing healthy controls with COVID-19 cases of different severity in the international COVID sleep study (ICOSS-II). J Sleep Res. 2022 Oct 8:e13754. doi: 10.1111/jsr.13754. Epub ahead of print. PMID: 36208038. https://onlinelibrary.wiley.com/doi/10.1111/jsr.13754 (Full text)

Symptomatology and microbiology of the gastrointestinal tract in post-COVID conditions

Abstract:

Post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 (PASC), refer to the persistence of symptoms in COVID-19 long-haulers. Various manifestations of post-COVID conditions are general symptoms and/or manifestations of damage in multiple organs. Besides, SARS-CoV-2 can involve the gastrointestinal tract, resulting in sequelae such as diarrhea, abdominal pain, nausea, anorexia, vomiting, constipation, abdominal distension, acid reflux, and/or gastrointestinal bleeding.
Previous investigations point to SARS-CoV-2 entry into enterocytes enhances by the angiotensin-converting enzyme 2 (ACE2) receptors. Interestingly, ACE2 receptors are abundantly expressed in the gut, implying infection with SARS-CoV-2 might occur through this route as well as in the respiratory tract. According to mounting evidence, SARS-CoV-2 RNA has been identified in fecal specimens of patients with COVID-19 during and beyond the acute phase.
In addition, studies have shown gut microbiome composition is altered in patients with PASC, hence, another putative mechanism linked to gastrointestinal symptoms is gut dysbiosis. The presence of the gut-lung axis in COVID-19 might have major implications for disease pathogenesis and treatment.
This review discussed the prevalence of gastrointestinal symptoms and pathophysiology underlying possible infection of the gut in patients with PASC. Also, SARS-COV-2 induced NLRP3 inflammasome-dependent inflammatory pathways are briefly addressed.
Source: Norouzi Masir M, Shirvaliloo M. Symptomatology and microbiology of the gastrointestinal tract in post-COVID conditions. JGH Open : an Open Access Journal of Gastroenterology and Hepatology. 2022 Aug. DOI: 10.1002/jgh3.12811. PMID: 36247234; PMCID: PMC9538198. https://europepmc.org/article/pmc/pmc9538198 (Full text)