Category: Overlapping Illnesses

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Abstract:

Post-acute sequelae of COVID (PASC), usually referred to as ‘Long COVID’ (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of ‘COVID’, although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous ‘amyloid’ form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope.

Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.

Source: Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 2022 Feb 17;479(4):537-559. doi: 10.1042/BCJ20220016. PMID: 35195253. https://portlandpress.com/biochemj/article/479/4/537/230829/A-central-role-for-amyloid-fibrin-microclots-in (Full text)

Post-corona fatigue-a familiar picture in a new guise?

Abstract:

Background: Myalgic encephalitis or chronic fatigue syndrome (ME/CFS) has again come into focus as a result of coronavirus disease 2019 (COVID-19). Fundamentally problematic is the fact that ME/CFS is considered a separate entity; however, extreme fatigue is also a common symptom of an underlying disease. Our article aims to increase the acceptance of ME/CFS and extreme fatigue facing a symptomatology that is not fully understood, and to highlight the need for research, orientation for physicians, and counselling services for patients.

Materials and methods: Orientative research by focused information gathering.

Results: In various research projects, the hypothesis of post-infectious ME/CFS as an autoimmune disease could be confirmed. In general, the heterogeneity of diagnostic criteria as well as the variety of formulations to describe the symptomatology and different coding options make it difficult to clearly assign symptoms to a clinical picture. Exertion intolerance has been identified as a severe symptom of post-COVID-19 disorder. For this reason, recommendations in international guidelines are currently being revised, especially with regard to pacing. The implications for recommendations in tumor-related fatigue or due to multiple sclerosis are unclear.

Conclusion: Against the background of a decreasing burden of disease due to increasing vaccination rates, research on fatigue should not only include viral diseases.

Source: Buchberger B, Zwierlein R, Rohde V. Post-Corona-Fatigue – das bekannte Bild in neuem Gewand? [Post-corona fatigue-a familiar picture in a new guise?]. Onkologe (Berl). 2022 Feb 17:1-6. German. doi: 10.1007/s00761-022-01102-1. Epub ahead of print. PMID: 35194336; PMCID: PMC8853121. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853121/ (Article in German) (Full text)

Long COVID-19 symptoms: clinical characteristics

Abstract:

Background: To describe persistent symptoms in long COVID-19 non-severe outpatients and report the 6-month clinical recovery (CR) rate.

Methods: Observational study enrolling outpatients (≥18 years) with confirmed non-severe COVID-19 (positive nasopharyngeal RT-PCR or presence of SARS-CoV-2 antibodies) who consulted for persistent symptoms after the first pandemic wave (March-May 2020). CR was assessed at the 6-month visit and defined as complete (no symptom), partial (persistent symptoms of lower intensity) or lack of recovery (no improvement).

Results: Sixty-three patients (79% women, mean age: 48 years) enrolled; main symptoms (mean 81 days after acute infection): asthenia/myalgia (77%), dyspnea (51%), headaches (35%), cough (33%). At 6 months (n=56), 30% had complete, 57% partial, and 13% lack of recovery. The proportion of patients with >2 persistent symptoms was 27% at 6 months (main symptoms: dyspnea [54%] and asthenia/myalgia [46%]).

Conclusion: We observed a slow but high recovery rate at 6 months among these outpatients.

Source: Seang S, Itani O, Monsel G, Abdi B, Marcelin AG, Valantin MA, Palich R, Fayçal A, Pourcher V, Katlama C, Tubiana R. Long COVID-19 symptoms: clinical characteristics and recovery rate among non-severe outpatients over a six-month follow-up. Infect Dis Now. 2022 Feb 11:S2666-9919(22)00038-0. doi: 10.1016/j.idnow.2022.02.005. Epub ahead of print. PMID: 35158095; PMCID: PMC8832844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832844/ (Full text)

Assessment and Management of Long COVID

Abstract:

Almost two years into the pandemic, the scientific and healthcare communities continue to learn a great deal regarding COVID-19, the disease produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Broad variability during acute COVID-19 infection is seen, ranging from asymptomatic presentation to death. The vast majority of individuals who develop COVID-19 return to their pre-COVID-19 baseline within several weeks.

However, a portion of patients will develop a post-COVID-19 syndrome of persistent cognitive, somatic, and behavioral symptoms. This syndrome, designated as post-acute sequelae of SARS-CoV-2 infection, is more commonly known as long COVID. The objectives of this paper are to inform psychologists regarding our current understanding of the underlying pathophysiology of COVID-19, review criteria for range of severity during acute illness, present clinical manifestations of long haul phenomena, and discuss the emerging literature base of evidence-based treatment and management approaches.

Source: Rivas-Vazquez, R.A., Rey, G., Quintana, A. et al. Assessment and Management of Long COVID. J Health Serv Psychol 48, 21–30 (2022). https://doi.org/10.1007/s42843-022-00055-8  (Full study)

Determinants of Persistence of Symptoms and Impact on Physical and Mental Wellbeing in Long COVID: A Prospective Cohort Study

Abstract:

Background: Residual symptoms can be detected for several months after COVID-19. To better understand the predictors and impact of symptom persistence we analysed a prospective cohort of COVID-19 patients.

Methods: Patients were followed for 9 months after COVID-19 onset. Duration and predictors of persistence of symptoms, physical health and psychological distress were assessed.

Results: 465 patients (54% males, 51% hospitalised) were included; 37% presented with at least 4 symptoms and 42% complained of symptom lasting more than 28 days. At month 9, 20% of patients were still symptomatic, showing mainly fatigue (11%) and breathlessness (8%). Hospitalisation and ICU stay vs. non-hospitalised status increased the median duration of fatigue of 8 weeks. Age > 50 years (OR 2.50), ICU stay (OR 2.35), and presentation with 4 or more symptoms (OR 2.04) were independent predictors of persistence of symptoms at month 9. A total of 18% of patients did not return to optimal pre-COVID physical health, while 19% showed psychological distress at month 9. Hospital admission (OR 2.28) and persistence of symptoms at day 28 (OR 2.21) and month 9 (OR 5.16) were independent predictors of suboptimal physical health, while female gender (OR 5.27) and persistence of symptoms at day 28 (OR 2.42) and month 9 (OR 2.48) were risk factors for psychological distress.

Conclusions: Patients with advanced age, ICU stay and multiple symptoms at onset were more likely to suffer from long-term symptoms, which had a negative impact on both physical and mental wellbeing. This study contributes to identify the target populations and Long COVID consequences for planning long-term recovery interventions.

Source: Righi E, Mirandola M, Mazzaferri F, Dossi G, Razzaboni E, Zaffagnini A, Ivaldi F, Visentin A, Lambertenghi L, Arena C, Micheletto C, Gibellini D, Tacconelli E. Determinants of Persistence of Symptoms and Impact on Physical and Mental Wellbeing in Long COVID: A Prospective Cohort Study. J Infect. 2022 Feb 9:S0163-4453(22)00065-2. doi: 10.1016/j.jinf.2022.02.003. Epub ahead of print. PMID: 35150765; PMCID: PMC8828388. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828388/ (Full text)

Exploring the Trajectory Recovery Curve of the number of Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study

Abstract:

Objective: This multicenter study investigated the recovery curve of the number of post-COVID symptoms in previously hospitalized survivors by using an exponential decay model and mosaic plots.

Methods: Patients hospitalized during the first wave of the pandemic (from March 10 to May 31, 2020) due to COVID-19 from five hospitals in Madrid (Spain) were scheduled for two telephone interviews at two follow-ups with a five-month period in between and were asked about the presence of post-COVID symptoms. The total number of post-COVID symptoms was monitored. Clinical features, symptoms at hospital admission, and hospitalization data were collected from medical records.

Results: A total of 1,593 COVID-19 survivors were assessed 8.4 (T1) and 13.2 (T2) months after hospitalization. The mean number of post-COVID symptoms was 2.6 (SD 2.0) at T1 and 1.5 (SD 1.4) at T2. The trajectory curve showed a decrease prevalence trend. The analysis also revealed that 985 (61.8%) subjects reported a greater number (T1>T2), 549 (34.5%) equal number (T1 =T2) and 59 (3.7%) lower number (T1<T2) of post-COVID symptoms in the first (T1: 8.4 months) in comparison with the second (T2: 13.2 months) assessment.

Conclusion: Current trajectory analysis revealed an overall decrease in the tendency in the number of post-COVID symptoms throughout the two years after the infection.

Source: Fernández-de-Las-Peñas C, Martín-Guerrero JD, Cancela-Cilleruelo I, Moro-López-Menchero P, Rodríguez-Jiménez J, Pellicer-Valero OJ. Exploring the Trajectory Recovery Curve of the number of Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study. Int J Infect Dis. 2022 Feb 9:S1201-9712(22)00083-2. doi: 10.1016/j.ijid.2022.02.010. Epub ahead of print. PMID: 35150911; PMCID: PMC8826603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826603/ (Full text)

Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity?

Dear editor,

We have read with great interest the review article by Sapkota et al. which has been recently published in the Clinical Rheumatology journal dealing with long COVID []. In this paper, the authors reported the symptoms and immunological findings of patients who were infected from severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2). These symptoms and laboratory features share similarities with those of patients suffering from autoimmune rheumatic diseases (ARDs). They concluded that long COVID is a mimicker of ARDs and needs to be excluded to ensure a correct diagnosis [].

Recently, we reported a patient who contracted SARS-CoV-2 infection and developed an erosive seronegative arthritis six months after infection []. Musculoskeletal, cutaneous, and other systemic manifestations, along with the presence of autoantibodies, are frequently observed in these patients. On the other hand, SARS-CoV-2 may trigger autoimmune responses and the development of de-novo manifestations of ARDs, as in our patient []. The pathogenesis of these phenomena is not well defined. One hypothesis implies the presence of autoantibodies against interferon (IFN) type-I, or inborn errors in the type-I IFN immunity [, ]. Another hypothesis is that SARS-CoV-2 might trigger autoimmune responses through molecular mimicry []. Several viruses have been implicated as possible etiological factors for the development of ARDs, mostly systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and others. Between viruses Epstein-Barr virus (EBV) is implicated in the pathogenesis of the above disorders [, ]. Indeed, EBV can trigger immune responses through molecular mimicry and is a polyclonal activator of B-cells and increases the production of rheumatoid factor (RF). Several studies suggested that molecular mimicry is a possible mechanism responsible for the development of ARDs in SARS-CoV-2 infection [, ]. Thus, SARS-CoV-2 may trigger autoimmunity and the possible development of the de novo manifestations of ARDs.

Read the full article HERE.

Source: Drosos AA, Pelechas E, Voulgari PV. Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity? Clin Rheumatol. 2022 Feb 11:1–2. doi: 10.1007/s10067-022-06092-4. Epub ahead of print. PMID: 35147823; PMCID: PMC8831874. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831874/ (Full text)

Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection

Abstract:

Postacute sequelae of SARS-CoV2 (PASC) infection is an emerging global health crisis, variably affecting millions worldwide. PASC has no established treatment. We describe 2 cases of PASC in response to opportune administration of over-the-counter antihistamines, with significant improvement in symptoms and ability to perform activities of daily living. Future studies are warranted to understand the potential role of histamine in the pathogenesis of PASC and explore the clinical benefits of antihistamines in the treatment of PASC.

Source: Melissa D. Pinto, Natalie Lambert, Charles A. Downs, Heather Abrahim, Thomas D. Hughes, Amir M. Rahmani, Candace W. Burton, Rana Chakraborty. Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection. The Journal for Nurse Practitioners, 2022, ISSN 1555-4155, https://doi.org/10.1016/j.nurpra.2021.12.016.
https://www.sciencedirect.com/science/article/pii/S155541552100547X  (Full text)

Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review

Abstract:

Background: Long COVID-19 may affect patients after hospital discharge.

Aims: This study aims to describe the burden of the long-term persistence of clinical symptoms in COVID-19 patients.

Methods: We conducted a systematic review by using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. The PubMed and Google Scholar databases were searched for studies that included information on the prevalence of somatic clinical symptoms lasting at least 4 weeks after the onset of a PCR- or serology-confirmed diagnosis of COVID-19. The prevalence of persisting clinical symptoms was assessed and risk factors were described when investigated. Psychological symptoms and cognitive disorders were not evaluated in this study.

Results: Thirty-seven articles met the inclusion criteria. Eighteen studies involved in-patients only with a duration of follow-up of either less than 12 weeks, 12 weeks to 6 months, or more. In these studies, fatigue (16-64%), dyspnea (15-61%), cough (2-59%), arthralgia (8-55%), and thoracic pain (5-62%) were the most frequent persisting symptoms. In nineteen studies conducted in a majority of out-patients, the persistence of these symptoms was lower and 3% to 74% of patients reported prolonged smell and taste disorders. The main risk factors for persisting symptoms were being female, older, having comorbidities and severity at the acute phase of the disease.

Conclusion: COVID-19 patients should have access to dedicated multidisciplinary healthcare allowing a holistic approach. Effective outpatient care for patients with long-COVID-19 requires coordination across multiple sub-specialties, which can be proposed in specialized post-COVID units.

Source: Nguyen NN, Hoang VT, Dao TL, Dudouet P, Eldin C, Gautret P. Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review. Eur J Clin Microbiol Infect Dis. 2022 Feb 10:1–31. doi: 10.1007/s10096-022-04417-4. Epub ahead of print. PMID: 35142947; PMCID: PMC8830952. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830952/ (Full text)

Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study

Abstract:

Background: We describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11-17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status.

Methods: In this national cohort study, adolescents aged 11-17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192).

Findings: 23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710 [23·2%]), and shortness of breath (717 [23·4%]), and among the test-negative group were tiredness (911 [24·4%]), headache (530 [14·2%]), and other (unspecified; 590 [15·8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29·6% (95% CI 27·4-31·7) for the test-positive group and 19·3% (17·7-21·0) for the test-negative group (risk ratio 1·53; 95% CI 1·35-1·70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15-17 years than those aged 11-14 years, and in those with lower pretest physical and mental health.

Interpretation: Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship.

Funding: UK Department of Health and Social Care, in their capacity as the National Institute for Health Research, and UK Research and Innovation.

Source: Stephenson T, Pinto Pereira SM, Shafran R, de Stavola BL, Rojas N, McOwat K, Simmons R, Zavala M, O’Mahoney L, Chalder T, Crawley E, Ford TJ, Harnden A, Heyman I, Swann O, Whittaker E; CLoCk Consortium, Ladhani SN. Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study. Lancet Child Adolesc Health. 2022 Feb 7:S2352-4642(22)00022-0. doi: 10.1016/S2352-4642(22)00022-0. Epub ahead of print. PMID: 35143770; PMCID: PMC8820961. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820961/  (Full text)