Category: Overlapping Illnesses

Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study

Abstract:

Background: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study.

Methods: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up.

Results: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1β (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome.

Conclusion: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

Source: Torres-Ruiz J, Lomelín-Gascón J, Lira Luna J, Vargas-Castro AS, Pérez-Fragoso A, Nuñez-Aguirre M, Alcalá-Carmona B, Absalón-Aguilar A, Balderas-Miranda JT, Maravillas-Montero JL, Mejía-Domínguez NR, Núñez-Álvarez C, Llorente L, Romero-Ramírez S, Sosa-Hernández VA, Cervantes-Díaz R, Juárez-Vega G, Meza-Sánchez D, Rull-Gabayet M, Martínez-Juárez LA, Morales L, López-López LN, Negrete-Trujillo JA, Falcón-Lezama JA, Valdez-Vázquez RR, Gallardo-Rincón H, Tapia-Conyer R, Gómez-Martín D. Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study. Infect Dis (Lond). 2023 Jan 13:1-12. doi: 10.1080/23744235.2022.2158217. Epub ahead of print. PMID: 36637466. https://www.tandfonline.com/doi/full/10.1080/23744235.2022.2158217 (Full text)

Towards evidence-based and inclusive models of peer support for long covid: A hermeneutic systematic review

Highlights:

• Co-produced peer support can help people living with Long COVID.
• Increasing the use of effective peer support may reduce health inequalities.
• Inclusive peer support can benefit ‘hardly reached’ Long Covid cohorts.
• Linking biomedical, relational and socio-political styles are most effective.

Abstract:

Since the first wave of COVID-19 in March 2020 the number of people living with post-COVID syndrome has risen rapidly at global pace, however, questions still remain as to whether there is a hidden cohort of sufferers not accessing mainstream clinics. This group are likely to be constituted by already marginalised people at the sharp end of existing health inequalities and not accessing formal clinics. The challenge of supporting such patients includes the question of how best to organise and facilitate different forms of support.

As such, we aim to examine whether peer support is a potential option for hidden or hardly reached populations of long COVID sufferers with a specific focus on the UK, though not exclusively. Through a systematic hermeneutic literature review of peer support in other conditions (57 papers), we evaluate the global potential of peer support for the ongoing needs of people living with long COVID.

Through our analysis, we highlight three key peer support perspectives in healthcare reflecting particular theoretical perspectives, goals, and understandings of what is ‘good health’, we call these: biomedical (disease control/management), relational (intersubjective mutual support) and socio-political (advocacy, campaigning & social context). Additionally, we identify three broad models for delivering peer support: service-led, community-based and social media. Attention to power relations, social and cultural capital, and a co-design approach are key when developing peer support services for disadvantaged and underserved groups.

Models from other long-term conditions suggest that peer support for long COVID can and should go beyond biomedical goals and harness the power of relational support and collective advocacy. This may be particularly important when seeking to reduce health inequalities and improve access for a potentially hidden cohort of sufferers.

Source: Mullard JCR, Kawalek J, Parkin A, Rayner C, Mir G, Sivan M, Greenhalgh T. Towards evidence-based and inclusive models of peer support for long covid: A hermeneutic systematic review. Soc Sci Med. 2023 Jan 14:115669. doi: 10.1016/j.socscimed.2023.115669. Epub ahead of print. PMCID: PMC9840228. https://www.sciencedirect.com/science/article/pii/S0277953623000242 (Full text)

A Systematic Review of Trials Currently Investigating Therapeutic Modalities for Post-Acute COVID-19 Syndrome and Registered on World Health Organization International Clinical Trials Platform

Abstract:

Background: Post-acute coronavirus 2019 (COVID-19) syndrome (PACS) is a well-recognized complex systemic disease that is associated with substantial morbidity. There is a paucity of established interventions to treat patients with this syndrome.

Objectives: To systematically review registered trials currently investigating therapeutic modalities for PACS.

Data sources: Search was conducted up to the 16th of September 2022 using the COVID-19 section of the World Health Organization (WHO) Internal Clinical Trials Registry Platform.

Study eligibility criteria, participants, and interventions: Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19.

Methods: Data on trial characteristics and intervention characteristics were collected and summarized.

Results: After screening 17125 trials, 388 trials from 42 countries were eligible. 331 trials tested mono-therapeutic strategies, while 39 trials included a combination of interventions. Among the 824 primary outcomes identified, there were more than 300 different outcomes. Rehabilitation was the most employed class of intervention with 169 trials. We encountered 76 trials examining pharmacological agents of various classes with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring Traditional Chinese Medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed with 12 and 4 trials, respectively. Other interventions including transcranial current direct stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions were also employed.

Conclusion: We identified 388 registered trials with a high degree of heterogeneity exploring 144 unique interventions for PACS. Most target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials conducted with standardization of outcomes while following WHO’s recommendation for uniform evaluation and treatment.

Source: Fawzy NA, Shaar BA, Taha R, Arabi TZ, Sabbah BN, Alkodaymi MS, Omrani OA, Makhzoum T, Almahfoudh NE, Al-Hammad QA, Hejazi W, Obeidat Y, Osman N, Al-Kattan KM, Berbari EF, Tleyjeh IM. A Systematic Review of Trials Currently Investigating Therapeutic Modalities for Post-Acute COVID-19 Syndrome and Registered on World Health Organization International Clinical Trials Platform. Clin Microbiol Infect. 2023 Jan 12:S1198-743X(23)00009-5. doi: 10.1016/j.cmi.2023.01.007. Epub ahead of print. PMID: 36642173; PMCID: PMC9837206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837206/ (Full text)

Long COVID Symptomatology and Associated Factors in Primary Care Patients: The EPICOVID-AP21 Study

Abstract:

Persistent COVID-19 condition includes a wide variety of symptoms and health problems of indeterminate duration. The present study examined the sociodemographic and clinical characteristics of the population with Long COVID seen in Primary Care using a questionnaire based on the existing scientific literature. It was an observational and descriptive study of the characteristics of the Spanish population with Long COVID over 14 years of age.
The responses were analysed by means of a descriptive analysis of the variables recorded, in addition to a bivariate analysis to determine the existence of a relationship between persistent COVID-19 and variables such as gender, age, vaccination status or concomitant pathology. The results obtained clearly describe the sociodemographic characteristics of the population, highlighting the predominance of female gender and the prevalence of tiredness and fatigue.
Furthermore, relevant information was obtained on the differences in symptomatology according to gender, age, previous pathologies and alterations derived from infection and/or vaccination. These data are important for better detection, diagnosis and treatment of Long COVID and the improvement of the quality of life of this population.
Source: Romero-Rodríguez E, Perula-de-Torres LÁ, González-Lama J, Castro-Jiménez RÁ, Jiménez-García C, Priego-Pérez C, Vélez-Santamaría R, Simón-Vicente L, González-Santos J, González-Bernal JJ. Long COVID Symptomatology and Associated Factors in Primary Care Patients: The EPICOVID-AP21 Study. Healthcare. 2023; 11(2):218. https://doi.org/10.3390/healthcare11020218 https://www.mdpi.com/2227-9032/11/2/218 (Full text)

Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study

Abstract:

Objectives: To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status.

Design: Retrospective nationwide cohort study.

Setting: Electronic medical records from an Israeli nationwide healthcare organisation.

Population: 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021.

Main outcome measures: Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection.

Results: Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients.

Conclusions: This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.

Source: Mizrahi B, Sudry T, Flaks-Manov N, Yehezkelli Y, Kalkstein N, Akiva P, Ekka-Zohar A, Ben David SS, Lerner U, Bivas-Benita M, Greenfeld S. Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study. BMJ. 2023 Jan 11;380:e072529. doi: 10.1136/bmj-2022-072529. PMID: 36631153; PMCID: PMC9832503. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832503/ (Full text)

Long COVID in the Older Adult and Vitamin D

Abstract:

Background: The coronavirus COVID-19 strain that emerged in December 2019 continues to produce a widespread and seemingly intractable negative impact on health and longevity and life quality in all parts of the world, especially, among older adults with chronic health conditions.

Objectives: The first aim of this updated review article was to examine, summarize, synthesize, and report on the research base concerning the possible use of vitamin D in the realm of the recently emergent syndrome termed long or post-acute COVID-19 disease. A second was to establish any health associated preventive and intervention recommendations for the older adult with long COVID-19 manifestations, who may yet be susceptible to future COVID-19 variant infections and others.

Methods: To examine the association between vitamin D and long COVID-19 illness manifestations, articles responding to several key words entered into leading data bases were examined: These included the terms: Vitamin D, Long/Post-Acute COVID-19 and/or COVID-19. Databases employed were PUBMED, PubMed Central and Google Scholar. All relevant articles were carefully examined and those meeting the review criteria were carefully read, and described in narrative form.

Results: Data reveal some possible benefits may accrue in the context of COVID-19 illness prevention and rehabilitation by efforts to ensure optimal vitamin D serum levels among high risk, vitamin D deficient, and chronically challenged post-acute COVID-19 older adults.

Conclusion: More rigorous and carefully construed research efforts to examine vitamin D implications and its moderating or mediating role in averting or mitigating long COVID-19 health complications are strongly warranted.

Source: Ray Marks (2023) Long COVID in the Older Adult and Vitamin D. J Gerontol Geriatr Med 9: 155. https://www.heraldopenaccess.us/openaccess/long-covid-in-the-older-adult-and-vitamin-d (Full text)

Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective

Abstract:

Background: Risk factors for developing long COVID are not clearly established. The present study was designed to determine if any sign, symptom, or treatment of the acute phase, or personal characteristics of the patient, is associated with the development of long COVID.
Methods: A cohort study was carried out, randomly selecting symptomatic COVID-19 patients and not vaccinated. The severity of the acute illness was assessed through the number of compatible COVID-19 symptoms, hospitalizations, and the symptom severity score using a 10-point visual analog scale.
Results: After multivariate analysis, a severity score ≥8 (RR 2.0, 95%CI 1.1–3.5, p = 0.022), hospitalization (RR 2.1, 95%CI 1.0–4.4, p = 0.039), myalgia (RR 1.9, 95%CI 1.08–3.6, p = 0.027), tachycardia (RR 10.4, 95%CI 2.2–47.7, p = 0.003), and use of antibiotics (RR 2.0, 95%CI 1.1–3.5, p = 0.022), was positively associated with the risk of having long COVID. Higher levels of education (RR 0.6, 95%CI 0.4–0.9, p = 0.029) and type positive B blood group (B + AB, RR 0.44, 95%CI 0.2–0.9, p = 0.044) were protective factors. The most important population attributable fractions (PAFs) for long COVID were myalgia (37%), severity score ≥8 (31%), and use of antibiotics (27%).
Conclusions: Further studies in diverse populations over time are needed to expand the knowledge that could lead us to prevent and/or treat long COVID.
Source: Guzman-Esquivel J, Mendoza-Hernandez MA, Guzman-Solorzano HP, Sarmiento-Hernandez KA, Rodriguez-Sanchez IP, Martinez-Fierro ML, Paz-Michel BA, Murillo-Zamora E, Rojas-Larios F, Lugo-Trampe A, Plata-Florenzano JE, Delgado-Machuca M, Delgado-Enciso I. Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective. Healthcare. 2023; 11(2):197. https://doi.org/10.3390/healthcare11020197 https://www.mdpi.com/2227-9032/11/2/197 (Full text)

SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19

Abstract:

Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties. While escape from humoral immunity certainly contributes to intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin’s lymphoma who received treatment with rituximab and lacked neutralizing antibodies.

Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented the binding of known immunogenic SARS-CoV-2 HLA class I antigens. By experimentally assessing the effect of a subset of the escape mutations, we show that they resulted in a loss of as much as ~1% of effector CD8 T cell response. Our results indicate that CD8 T cell escape represents a major underappreciated contributor to SARS-CoV-2 evolution in humans.

Source: Stanevich OV, Alekseeva EI, Sergeeva M, Fadeev AV, Komissarova KS, Ivanova AA, Simakova TS, Vasilyev KA, Shurygina AP, Stukova MA, Safina KR, Nabieva ER, Garushyants SK, Klink GV, Bakin EA, Zabutova JV, Kholodnaia AN, Lukina OV, Skorokhod IA, Ryabchikova VV, Medvedeva NV, Lioznov DA, Danilenko DM, Chudakov DM, Komissarov AB, Bazykin GA. SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19. Nat Commun. 2023 Jan 10;14(1):149. doi: 10.1038/s41467-022-34033-x. PMID: 36627290; PMCID: PMC9831376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9831376/ (Full text)

The Draft Report by the Institute for Quality and Efficiency in Healthcare Does Not Provide Any Evidence That Graded Exercise Therapy and Cognitive Behavioral Therapy Are Safe and Effective Treatments for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

The German Institute for Quality and Efficiency in Healthcare (IQWiG) recently published its draft report to the government about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The IQWiG concluded that graded exercise therapy (GET) and cognitive behavioral therapy (CBT) should be recommended in the treatment for mild and moderate ME/CFS based on two CBT and two GET studies. In this article, we reviewed the evidence used by IQWiG to support their claims, because their conclusion is diametrically opposed to the conclusion by the British National Institute for Health and Care Excellence (NICE) in its recently updated ME/CFS guidelines.

Our analysis shows that the trials IQWiG used in support suffered from serious flaws, which included badly designed control groups; relying on subjective primary outcomes in non-blinded studies; alliance and response shift bias, including patients in their trials who did not have the disease under investigation, selective reporting, making extensive endpoint changes and low to very low adherence of treatments.

Our analysis also shows that the report itself used one CBT and one GET study that both examined a different treatment. The report also used a definition of CBT that does not reflect the way it is being used in ME/CFS or was tested in the studies. The report noted that one study used a wrong definition of post-exertional malaise (PEM), the main characteristic of the disease, according to the report. Yet, it ignored the consequence of this, that less than the required minimum percentage of patients had the disease under investigation in that study.

It also ignored the absence of improvement on most of the subjective outcomes, as well as the fact that the IQWiG methods handbook states that one should use objective outcomes and not rely on subjective outcomes in non-blinded studies. The report concluded that both treatments did not lead to objective improvement in the six-minute walk test but then ignored that. The report did not analyze the other objective outcomes of the studies (step test and occupational and benefits status), which showed a null effect.

Finally, the report states that the studies do not report on safety yet assumes that the treatments are safe based on a tendency towards small subjective improvements in fatigue and physical functioning, even though the adherence to the treatments was (very) low and the studies included many patients who did not have the disease under investigation and, consequently, did not suffer from exertion intolerance contrary to ME/CFS patients. At the same time, it ignored and downplayed all the evidence that both treatments are not safe, even when the evidence was produced by a British university.

In conclusion, the studies used by the report do not provide any evidence that CBT and GET are safe and effective. Consequently, the report and the studies do not provide any support for the recommendation to use CBT and GET for ME/CFS or long COVID, which, in many cases, is the same or resembles ME/CFS, after an infection with SARS-CoV-2.

Source: Vink M, Vink-Niese A. The Draft Report by the Institute for Quality and Efficiency in Healthcare Does Not Provide Any Evidence That Graded Exercise Therapy and Cognitive Behavioral Therapy Are Safe and Effective Treatments for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Diseases. 2023 Jan 16;11(1):11. doi: 10.3390/diseases11010011. PMID: 36648876; PMCID: PMC9844345. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844345/ (Full text)

Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis

Abstract:

The purpose of this article is to review the evidence of similar symptomatology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of SARS-CoV-2 infection (PASC).
Reanalysis of data from a study by Jason comparing symptom reports from two groups of ME/CFS and PASC patients shows a notably similar symptomatology. Symptom scores of the PASC group and the ME/CFS group correlated 0.902 (p < 0.0001) across items. The hypothesis is presented that ME/CFS and PASC are caused by a chronic state of multisystemic disequilibrium including endocrinological, immunological, and/or metabolic changes.
The hypothesis holds that a changed set point persistently pushes the organism towards a pathological dysfunctional state which fails to reset. To use an analogy of a thermostat, if the ‘off switch’ of a thermostat intermittently stops working, for periods the house would become warmer and warmer without limit. The hypothesis draws on recent investigations of the Central Homeostasis Network showing multiple interconnections between the autonomic system, central nervous system, and brain stem.
The hypothesis helps to explain the shared symptomatology of ME/CFS and PASC and the unpredictable, intermittent, and fluctuating pattern of symptoms of ME/CFS and PASC. The current theoretical approach remains speculative and requires in-depth investigation before any definite conclusions can be drawn.
Source: Marks DF. Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis. Biomedicines. 2023; 11(1):180. https://doi.org/10.3390/biomedicines11010180 https://www.mdpi.com/2227-9059/11/1/180 (Full text)