COVID-19 and Therapeutic Apheresis

Abstract:

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is an unprecedented challenge for the global community. The pathogenesis of COVID-19, its complications and long term sequelae (so called Long/Post-COVID) include, in addition to the direct virus-induced tissues injury, multiple secondary processes, such as autoimmune response, impairment of microcirculation, and hyperinflammation. Similar pathological processes, but in the settings of neurological, cardiovascular, rheumatological, nephrological, and dermatological diseases can be successfully treated by powerful methods of Therapeutic Apheresis (TA).

We describe here the rationale and the initial attempts of TA treatment in severe cases of acute COVID-19. We next review the evidence for the role of autoimmunity, microcirculatory changes and inflammation in pathogenesis of Long/Post COVID and the rationale for targeting those pathogenic processes by different methods of TA. Finally, we discuss the impact of COVID-19 pandemic on patients, who undergo regular TA treatments due to their underlying chronic conditions, with the specific focus on the patients with inherited lipid diseases being treated at the Dresden University Apheresis Center.

Source: Tselmin S, Julius U, Jarzebska N, Rodionov R. COVID-19 and Therapeutic Apheresis. Horm Metab Res. 2022 Aug;54(8):571-577. doi: 10.1055/a-1864-9482. Epub 2022 Aug 9. PMID: 35944525.  https://pubmed.ncbi.nlm.nih.gov/35944525/

Returning to work and the impact of post COVID-19 condition: A systematic review

Abstract:

Background: The COVID-19 pandemic is still ongoing, with rapidly increasing cases all over the world, and the emerging issue of post COVID-19 (or Long COVID-19) condition is impacting the occupational world.

Objective: The aim of this systematic review was to evaluate the impact of lasting COVID-19 symptoms or disability on the working population upon their return to employment.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements we performed a systematic review in December 2021, screening three databases (PubMed, ISI Web of Knowledge, Scopus), for articles investigating return to work in patients that were previously hospitalized due to COVID-19. A hand-searched was then performed through the references of the included systematic review. A quality assessment was performed on the included studies.

Results: Out of the 263 articles found through the initial search, 11 studies were included in this systematic review. The selected studies were divided based on follow-up time, in two months follow-up, follow-up between two and six months, and six months follow-up. All the studies highlighted an important impact of post COVID-19 condition in returning to work after being hospitalized, with differences based on follow-up time, home Country and mean/median age of the sample considered.

Conclusions: This review highlighted post COVID-19 condition as a rising problem in occupational medicine, with consequences on workers’ quality of life and productivity. The role of occupational physicians could be essential in applying limitations to work duties or hours and facilitating the return to employment in workers with a post COVID-19 condition.

Source: Gualano MR, Rossi MF, Borrelli I, Santoro PE, Amantea C, Daniele A, Tumminello A, Moscato U. Returning to work and the impact of post COVID-19 condition: A systematic review. Work. 2022 Aug 1. doi: 10.3233/WOR-220103. Epub ahead of print. PMID: 35938280. https://content.iospress.com/articles/work/wor220103 (Full text)

Mast cell activation syndrome and the link with long COVID

Abstract:

Mast cells are innate immune cells found in connective tissues throughout the body, most prevalent at tissue-environment interfaces. They possess multiple cell-surface receptors which react to various stimuli and, after activation, release many mediators including histamine, heparin, cytokines, prostaglandins, leukotrienes and proteases.

In mast cell activation syndrome, excessive amounts of inflammatory mediators are released in response to triggers such as foods, fragrances, stress, exercise, medications or temperature changes. Diagnostic markers may be difficult to assess because of their rapid degradation; these include urinary N-methyl histamine, urinary prostaglandins D2, DM and F and serum tryptase (which is stable) in the UK. Self-management techniques, medications and avoiding triggers may improve quality of life. Treatments include mast cell mediator blockers, mast cell stabilisers and anti-inflammatory agents. ‘Long COVID’ describes post-COVID-19 syndrome when symptoms persist for more than 12 weeks after initial infection with no alternative diagnosis.

Both mast cell activation syndrome and long COVID cause multiple symptoms. It is theorised that COVID-19 infection could lead to exaggeration of existing undiagnosed mast cell activation syndrome, or could activate normal mast cells owing to the persistence of viral particles. Other similarities include the relapse-remission cycle and improvements with similar treatments. Importantly, however, aside from mast cell disorders, long COVID could potentially be attributed to several other conditions.

Source: Arun S, Storan A, Myers B. Mast cell activation syndrome and the link with long COVID. Br J Hosp Med (Lond). 2022 Jul 2;83(7):1-10. doi: 10.12968/hmed.2022.0123. Epub 2022 Jul 26. PMID: 35938771. https://pubmed.ncbi.nlm.nih.gov/35938771/

Long COVID Symptomatology After 12 Months and Its Impact on Quality of Life According to Initial Coronavirus Disease 2019 Disease Severity

Abstract:

Background: “Long COVID” is characterized by a variety of symptoms and an important burden for affected people. Our objective was to describe long COVID symptomatology according to initial coronavirus disease 2019 (COVID-19) severity.

Methods: Predi-COVID cohort study participants, recruited at the time of acute COVID-19 infection, completed a detailed 12-month symptom and quality of life questionnaire. Frequencies and co-occurrences of symptoms were assessed.

Results: Among the 289 participants who fully completed the 12-month questionnaire, 59.5% reported at least 1 symptom, with a median of 6 symptoms. Participants with an initial moderate or severe acute illness declared more frequently 1 or more symptoms (82.6% vs 38.6%, P < .001) and had on average 6.8 more symptoms (95% confidence interval, 4.18-9.38) than initially asymptomatic participants who developed symptoms after the acute infection. Overall, 12.5% of the participants could not envisage coping with their symptoms in the long term. Frequently reported symptoms, such as neurological and cardiovascular symptoms, but also less frequent ones such as gastrointestinal symptoms, tended to cluster.

Conclusions: Frequencies and burden of symptoms present 12 months after acute COVID-19 infection increased with the severity of the acute illness. Long COVID likely consists of multiple subcategories rather than a single entity. This work will contribute to the better understanding of long COVID and to the definition of precision health strategies.

Clinical trials registration: NCT04380987.

Source: Fischer A, Zhang L, Elbéji A, Wilmes P, Oustric P, Staub T, Nazarov PV, Ollert M, Fagherazzi G. Long COVID Symptomatology After 12 Months and Its Impact on Quality of Life According to Initial Coronavirus Disease 2019 Disease Severity. Open Forum Infect Dis. 2022 Aug 5;9(8):ofac397. doi: 10.1093/ofid/ofac397. PMID: 35983269; PMCID: PMC9379809. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379809/ (Full text)

Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis

Abstract:

Prolonged symptoms after the clearance of acute coronavirus disease 2019 (COVID-19) infection, termed long COVID, are an emerging threat to the post-COVID-19 era. Complementary and alternative medicine (CAM) interventions may play a significant role in the management of long COVID. The present study aimed to identify published studies on the use of CAM interventions for long COVID and provide an overview of the research status using bibliometric analysis.

The present scoping review searched MEDLINE, Embase, and Cochrane Library from inception until November 2021 and identified published studies on CAM interventions for long COVID. A narrative analysis of the study types and effectiveness and safety of the CAM interventions are presented and a bibliometric analysis of citation information and references of the included publications were analyzed using the Bibliometrix package for R. An electronic database search identified 16 publications (2 clinical studies and 14 study protocols of systematic reviews or clinical studies) that were included in the present study. Dyspnea or pulmonary dysfunction, quality of life, olfactory dysfunction, and psychological symptoms after COVID-19 infection were assessed in the included publications.

The two clinical studies suggested that Chinese herbal medications were effective in relieving symptoms of pulmonary dysfunction. Bibliometric analysis revealed the current trend of research publication in this area was driven by study protocols written by Chinese, Korean, and Indian authors. Thus, the present scoping review and bibliometric analysis revealed that there are few studies published about the use of CAM for long COVID and long-term management for COVID-19 survivors. Original studies on CAM interventions, including randomized controlled trials and systematic reviews, are required to actively support evidence for their use in the management of long COVID. PROSPERO registration: this trial is registered with CRD42021281526.

Source: Tae-Hun Kim, Sae-Rom Jeon, Jung Won Kang, Sunoh Kwon, “Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis“, Evidence-Based Complementary and Alternative Medicine, vol. 2022, Article ID 7303393, 7 pages, 2022. https://doi.org/10.1155/2022/7303393 https://www.hindawi.com/journals/ecam/2022/7303393/ (Full text)

A Review of Respiratory Post-Acute Sequelae of COVID-19 (PASC) and the Potential Benefits of Pulmonary Rehabilitation

Abstract:

With the SARS-CoV-2 pandemic continuing into its third year, the number of patients who survive acute COVID-19 infection but go on to develop long-term symptoms is increasing daily. Those individuals who experience one or more of a variety of persistent symptoms post-COVID-19 are now diagnosed with the syndrome called post-acute sequelae of COVID-19 (PASC), often colloquially called “Long COVID.” This article discusses relevant research and current hypotheses regarding the pathophysiology and management of respiratory symptoms of PASC, in order to provide primary care physicians with context for management of this heterogeneous population. We focus on the growing body of research that supports the use of pulmonary rehabilitation for patients with PASC to improve symptoms and quality of life.

Source: Simon M, Simmons JE. A Review of Respiratory Post-Acute Sequelae of COVID-19 (PASC) and the Potential Benefits of Pulmonary Rehabilitation. R I Med J (2013). 2022 Sep 1;105(7):11-15. PMID: 35930484.  https://pubmed.ncbi.nlm.nih.gov/35930484/ http://rimed.org/rimedicaljournal/2022/09/2022-09-11-covid-simon.pdf (Full text available as PDF file)

Cognitive Complications of COVID-19 Infection

Abstract:

SARS-CoV-2 is associated with a post-infectious neurocognitive syndrome characterized by fatigue and deficits in attention, memory, and executive function. As screening cognitive testing generally remains normal, the pathophysiologic basis of these symptoms remains controversial and there is no standardized treatment paradigm.

We present a clinical case demonstrative of typical neurocognitive sequelae of SARS-CoV-2 infection, highlighting medical and social factors that may have contributed to the severity of symptoms. We discuss the pathophysiologic evidence for cognitive “brain fog” following COVID-19 infection as well as lifestyle changes and rehabilitation strategies that may improve recovery. As the benefits of pharmacologic therapy remain unproven, we close with a brief discussion of medication options that might be appropriate targets for future clinical trials in the context of rehabilitative treatment.

Source: Warren S, Drake J, Wu CK. Cognitive Complications of COVID-19 Infection. R I Med J (2013). 2022 Sep 1;105(7):27-30. PMID: 35930487. https://pubmed.ncbi.nlm.nih.gov/35930487/ http://rimed.org/rimedicaljournal/2022/09/2022-09-27-covid-warren.pdf  (Full text available as PDF file)

Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC)

Abstract:

Background: Fibrin(ogen) amyloid microclots and platelet hyperactivation previously reported as a novel finding in South African patients with the coronavirus 2019 disease (COVID-19) and Long COVID/Post-Acute Sequelae of COVID-19 (PASC), might form a suitable set of foci for the clinical treatment of the symptoms of Long COVID/PASC. A Long COVID/PASC Registry was subsequently established as an online platform where patients can report Long COVID/PASC symptoms and previous comorbidities.

Methods: In this study, we report on the comorbidities and persistent symptoms, using data obtained from 845 South African Long COVID/PASC patients. By using a previously published scoring system for fibrin amyloid microclots and platelet pathology, we also analysed blood samples from 80 patients, and report the presence of significant fibrin amyloid microclots and platelet pathology in all cases.

Results: Hypertension, high cholesterol levels (dyslipidaemia), cardiovascular disease and type 2 diabetes mellitus (T2DM) were found to be the most important comorbidities. The gender balance (70% female) and the most commonly reported Long COVID/PASC symptoms (fatigue, brain fog, loss of concentration and forgetfulness, shortness of breath, as well as joint and muscle pains) were comparable to those reported elsewhere. These findings confirmed that our sample was not atypical. Microclot and platelet pathologies were associated with Long COVID/PASC symptoms that persisted after the recovery from acute COVID-19.

Conclusions: Fibrin amyloid microclots that block capillaries and inhibit the transport of O2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. Removal and reversal of these underlying endotheliopathies provide an important treatment option that urgently warrants controlled clinical studies to determine efficacy in patients with a diversity of comorbidities impacting on SARS-CoV-2 infection and COVID-19 severity. We suggest that our platelet and clotting grading system provides a simple and cost-effective diagnostic method for early detection of Long COVID/PASC as a major determinant of effective treatment, including those focusing on reducing clot burden and platelet hyperactivation.

Source: Pretorius E, Venter C, Laubscher GJ, Kotze MJ, Oladejo SO, Watson LR, Rajaratnam K, Watson BW, Kell DB. Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Cardiovasc Diabetol. 2022 Aug 6;21(1):148. doi: 10.1186/s12933-022-01579-5. PMID: 35933347; PMCID: PMC9356426. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356426/ (Full text)

Long COVID: which symptoms can be attributed to SARS-CoV-2 infection?

Comment:

Mortality rates following SARS-CoV-2 infection have decreased as a consequence of public health policies, vaccination, and acute antiviral and anti-inflammatory theBrightling CE, Evans RA. Long COVID: which symptoms can be attributed to SARS-CoV-2 infection? Lancet. 2022 Aug 6;400(10350):411-413. doi: 10.1016/S0140-6736(22)01385-X. PMID: 35933996; PMCID: PMC9352303.rapies. However, in the wake of the pandemic, post-acute sequelae of COVID-19, or long COVID, has emerged: a chronic illness in people who have ongoing multidimensional symptomatology and disability weeks to years after the initial infection. Early reports of long COVID prevalence, summarised in a systematic review examining the frequency and variety of persistent symptoms after COVID-19, found that the median proportion of people who had at least one persistent symptom 60 days or more after diagnosis or at least 30 days after recovery from COVID-19 infection was 73%. However, the estimated prevalence depends on the duration, population, and symptoms used to define long COVID. More recently, community-based studies have suggested a lower prevalence of persistent symptoms; whereas among people who were hospitalised following COVID-19 infection, a high proportion do not fully recover (50–70%).

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Source: Brightling CE, Evans RA. Long COVID: which symptoms can be attributed to SARS-CoV-2 infection? Lancet. 2022 Aug 6;400(10350):411-413. doi: 10.1016/S0140-6736(22)01385-X. PMID: 35933996; PMCID: PMC9352303. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352303/ (Full text)

Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches

Abstract:

SARS-CoV-2–infected individuals may suffer a multi–organ system disorder known as “long COVID” or post-acute sequelae of SARS-CoV-2 infection (PASC). There are no standard treatments, the pathophysiology is unknown, and incidence varies by clinical phenotype.

Acute COVID-19 correlates with biomarkers of systemic inflammation, hypercoagulability, and comorbidities that are less prominent in PASC. Macrovessel thrombosis, a hallmark of acute COVID-19, is less frequent in PASC. Female sex at birth is associated with reduced risk for acute COVID-19 progression, but with increased risk of PASC. Persistent microvascular endotheliopathy associated with cryptic SARS-CoV-2 tissue reservoirs has been implicated in PASC pathology.

Autoantibodies, localized inflammation, and reactivation of latent pathogens may also be involved, potentially leading to microvascular thrombosis, as documented in multiple PASC tissues. Diagnostic assays illuminating possible therapeutic targets are discussed.

Source: Ahamed J, Laurence J. Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches. J Clin Invest. 2022 Aug 1;132(15):e161167. doi: 10.1172/JCI161167. PMID: 35912863; PMCID: PMC9337829. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337829/ (Full text)