Category: Overlapping Illnesses

Covid-19: Antibody “signature” could predict risk of long covid

Researchers have identified an immunoglobulin “signature” that could be used to predict which patients are most at risk of developing post-acute covid syndrome (PACS), otherwise known as long covid.

In a multicentre prospective study, 175 patients with covid-19 and 40 healthy control group participants were followed for up to a year. More than half of the patients with covid reported long covid symptoms lasting longer than a month. Those who developed long covid were found to have lower levels of IgM and IgG3 antibodies than those who quickly recovered, found the research, published in Nature Communications.1 A history of asthma was also highly associated with PACS, the study found.

The researchers combined data on immunoglobulin concentrations with a patient’s age, history of asthma, and five symptoms during the primary infection to develop a PACS score that could predict the risk of developing long term illness. The PACS score was then validated in an independent group of 395 people with covid-19.

The researchers, from the University of Zurich, said that the score might be especially helpful in hospital settings for early identification of those patients at a very high risk of developing PACS. It could also allow the study of targeted preventive treatments such as inhaled corticosteroids or intravenous immunoglobulin treatments.

The researchers said more research was still needed but that a PACS score or long covid risk calculator would be available soon at pacs-score.com.

The study’s limitations included that participants were infected between April 2020 and August 2021, before the omicron variant took hold. And the study didn’t take into account participants’ vaccination status.

Claire Steves, a senior clinical lecturer at King’s College London, welcomed the research, saying, “With cases high still, more people are at risk of developing long term symptoms. We urgently need to scale up research on how to prevent this happening. Tools such as these predictive models could be used to identify people at higher risk for enrolment into research trials for therapeutics.”

But she added, “This is a small study that was undertaken in a selected population, and so in particular the immune findings do need to be replicated elsewhere.”

Amitava Banerjee, professor of clinical data science and honorary consultant cardiologist at University College London, commented, “There are three implications from this research. First, the immunoglobulin signature points more clearly towards the mechanism of disease, although replication of the results in different, larger cohorts is needed. Second, this raises the possibility of being able to predict the risk of long covid in individuals post-initial infection. Third, further research is required to understand whether similar risk factor profiles can be used to predict the prognosis or speed of recovery.”

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Source: Jacqui Wise. Covid-19: Antibody “signature” could predict risk of long covid. BMJ 2022; 376 doi: https://doi.org/10.1136/bmj.o245 (Published 28 January 2022)

The Investigation of Pulmonary Abnormalities using Hyperpolarised Xenon Magnetic Resonance Imaging in Patients with Long-COVID

Abstract:

Background: Long-COVID is an umbrella term used to describe ongoing symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is one of the most common and can persist for months after the initial infection. Investigations including Computed Tomography (CT), and physiological measurements (lung function tests) are usually unremarkable. The mechanisms driving breathlessness remain unclear, and this may be hindering the development of effective treatments.

Methods: Eleven non-hospitalised Long-COVID (NHLC, 4 male), 12 post-hospitalised COVID-19 (PHC, 10 male) patients were recruited from a Post-COVID Assessment clinic, and thirteen healthy controls (6 female) were recruited to undergo Hyperpolarized Xenon Magnetic Resonance Imaging (Hp-XeMRI). NHLC and PHC participants underwent contemporaneous CT, Hp-XeMRI, lung function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Statistical analysis included group and pair-wise comparisons between patients and controls, and correlations between patient clinical and imaging data.

Results: NHLC and PHC patients were 287 ± 79 [range 190-437] and 149 ± 68 [range 68-269] days from infection, respectively. All NHLC patients had normal CT scans, and the PHC had normal or near normal CT scans (0.3/25 ± 0.6 [range 0-2] and 7/25 ± 5 [range 4-8], respectively). There was a significant difference in TLco (%) between NHLC and PHC patients (76 ± 8 % vs 86 ± 8%, respectively, p = 0.04) but no differences in other measurements of lung function. There were significant differences in RBC:TP mean between volunteers (0.45 ± 0.07, range [0.33-0.55]) and PHC (0.31 ± 0.11, [range 0.16-0.37]) and NHLC (0.35 ± 0.09, [range 0.26-0.58]) patients, but not between NHLC and PHC (p = 0.26).

Conclusion: There are RBC:TP abnormalities in NHLC and PHC patients, with NHLC patients also demonstrating lower TLco than PHC patients despite their having normal CT scans. These abnormalities are present many months after the initial infection.

Summary statement: Hyperpolarized Xenon MRI and TLco demonstrate significantly impaired gas transfer in non-hospitalised long-COVID patients when all other investigations are normal.

Source:  James T. Grist, Guilhem J. Collier, Huw Walters, Mitchell Chen, Gabriele Abu Eid, Aviana Laws, Violet Matthews, Kenneth Jacob, Susan Cross, Alexandra Eves, Marianne Durant, Anthony Mcintyre, Roger Thompson, Rolf F. Schulte, Betty Raman, Peter A. Robbins, Jim M. Wild, Emily Fraser, Fergus Gleeson. The Investigation of Pulmonary Abnormalities using Hyperpolarised Xenon Magnetic Resonance Imaging in Patients with Long-COVID.
medRxiv 2022.02.01.22269999; doi: https://doi.org/10.1101/2022.02.01.22269999

Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort

Abstract:

Background: The burden of long-term symptoms (i.e. long-COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCW), frequency and risk factors for symptoms compatible with long-COVID are assessed.

Methods: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long-COVID (including psychometric scores) were asked and compared between HCW with positive NPS, seropositive HCW without positive NPS (presumable a-/pauci-symptomatic infections), and negative controls. Also, the effect of time since diagnosis and quantitative anti-S was evaluated. Poisson regression was used to identify risk factors for symptom occurrence.

Results: Of 3’334 HCW (median 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCW with positive NPS more frequently reported ≥1 symptom compared to controls (73%vs.52%, p<0.001); seropositive HCW without positive NPS did not score higher than controls (58%vs.52%, p=0.13), although impaired taste/olfaction (16%vs.6%, p<0.001) and hair loss (17%vs.10%, p=0.004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores.

Conclusions: Seropositive HCW without positive NPS are only mildly affected by long-COVID. Exhaustion/burnout is common, even in non-infected HCW. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Source: Strahm C, Seneghini M, Güsewell S, Egger T, Leal O, Brucher A, Lemmenmeier E, Meier Kleeb D, Möller JC, Rieder P, Ruetti M, Rutz R, Schmid HR, Stocker R, Vuichard-Gysin D, Wiggli B, Besold U, Kuster SP, McGeer A, Risch L, Friedl A, Schlegel M, Schmid D, Vernazza P, Kahlert CR, Kohler P. Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort. Clin Infect Dis. 2022 Jan 28:ciac054. doi: 10.1093/cid/ciac054. Epub ahead of print. PMID: 35090015. https://pubmed.ncbi.nlm.nih.gov/35090015/  (Full text available as PDF file)

Diagnostic challenges posed by intersections between post-acute covid syndrome and neurocognitive disorders

Introduction:

COVID-19 initially was considered an acute respiratory illness. Its severity was classified on the basis of symptoms of respiratory distress for example, tachypnoea and hypoxia. Accordingly, 80% cases reported asymptomatic or mild illness, about 5–15% being moderate severity and the last 5% requiring hospital-based care (COVID, 2021). Almost everyone was expected to tide over the infection in a couple of weeks. In the acute phase of the illness, central nervous system (CNS) involvement manifests as headaches, confusion, cerebrovascular events like strokes, dizziness and seizures (Wang et al., 2020–Pezzini et al., 2020). Infecting cells bearing the ACE- 2 receptor, it involves multiple organ systems, some of which are now known to run a chronic course. Its understanding as an acute infection has changed as more and more persons now report persistent symptoms running over months (Revised Guidelines on Clinical Management, 2021).

Studies report that between 30% and 40% of those recovered from COVID-19 infections report of lasting symptoms (Chopra et al., 2021). Accurate estimates of persons suffering from Post Acute Covid Syndrome (PACS) are unreliable as yet considering ongoing community transmissions and limitations in health care access. With over 215 million reported cases (coronavirus.jhu.edu, 2021), numbers of those with PACS can overrun any health system. Symptoms persisting beyond 4 weeks after recovery from acute infection range from chest pain and palpitations, shortness of breath, muscle and joint aches and pains, headaches, neuropathy and paraesthesia, fatigue, anosmia, ageusia, myalgia, cardiopulmonary insufficiency, increased propensity for thromboembolic phenomena, micro vascular coagulopathies, demyelinating conditions, cognitive dysfunctions, psychological distress and even sleep and mood disturbances. Collectively, these neuropsychiatric symptoms are sometimes referred to as “brain fog” and can be incapacitating. It is also unclear how long these symptoms will last.

Pathophysiology of COVID-19 related complications is largely unknown. Current research suggests that the chronic inflammation and aberrant immune responses in the host can be a cause of chronic inflammation, resulting in long-term neuropsychiatric symptoms (weeks – months post-acute infection) (Bechter, 2013). Inflammatory markers take much longer to return to pre morbid levels: correlations with PACS are however unclear. Data from the National Survey of Residential Care Facilities in the United States showed that 70% of individuals in these facilities had some cognitive issues, out of which 29% had mild and 19% had severe cognitive impairment (Zimmerman et al., 2014). Coronavirus infection outbreaks in the past like for Severe Acute Respiratory Syndrome (2002–04) and Middle East Respiratory Syndrome (2012) have also had neuropsychiatric symptoms: depressed mood, anxiety, insomnia, irritability, and memory impairments were noted. Psychological factors may also contribute to the development of some long term neuropsychiatric symptoms.

Roughly, 10% of the current global population is aged 65 or older (United Nations, 2021). Estimates of people living with neurocognitive disorder (NCDs) hover around 50 million worldwide with 10 million new cases added yearly. Globally, 80% of the deaths attributable to COVID-19 infections have occurred amongst persons 65 or older: however, age disaggregated data for COVID-19 infection, survival, lasting morbidity and mortality are unavailable.

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Source: Philip S, Shoib S, Gregor Issac T, Javed S. Diagnostic challenges posed by intersections between post-acute covid syndrome and neurocognitive disorders. Asian J Psychiatr. 2022 Jan;67:102936. doi: 10.1016/j.ajp.2021.102936. Epub 2021 Nov 21. PMID: 34844177; PMCID: PMC8606183. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606183/ (Full text)

Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC)

Introduction:

The emergence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought with it a plethora of new challenges. In the beginning of the pandemic, efforts were focused on pathogenesis and acute treatment; however, over time, understanding and managing post-COVID sequelae have become the new frontier.1, 2 Generally, the majority of individuals show symptom resolution within 3–4 weeks of COVID-19, but a substantial number of people continue to experience lingering effects and develop protracted illness, regardless of initial symptom severity. Although still being defined, these effects can be collectively referred to as postacute sequelae of SARS-CoV-2 infection (PASC),3 which is the term used in this report. Notably, there are a number of other terms that are found in the literature (eg, long COVID, postacute COVID-19 syndrome, long-haul COVID, chronic COVID). At the time of development, much of the literature focused on patients who were not vaccinated, and the incidence and trajectory of PASC in vaccinated patients with “breakthrough” cases (including but not limited to current and emerging variants of the virus) are evolving. The PASC Collaborative took this into account during the development process and these guidance statements generally apply to individuals who develop PASC regardless of their vaccination status.

This guidance statement has a specific focus on the cognitive-related symptoms of PASC that can occur in people who have been diagnosed with acute COVID-19 infection or presumed to have had the infection and initially experienced mild to severe symptoms. Some patients required hospital acute care, whereas many others were managed in nonhospitalized community settings. This consensus guidance statement is one in a series extending across the breadth of the most prevalent or recognized PASC sequelae. Published and in-process guidance statements from this collaborative include the assessment and management of PASC associated fatigue, breathing and respiratory sequelae, cardiovascular complications, autonomic dysfunction, mental health, and neurologic sequelae. These statements are intended to provide consensus-driven practice guidance to clinicians in the assessment and treatment of individuals presenting with PASC.

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Source: Fine JS, Ambrose AF, Didehbani N, Fleming TK, Glashan L, Longo M, Merlino A, Ng R, Nora GJ, Rolin S, Silver JK, Terzic CM, Verduzco-Gutierrez M, Sampsel S. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R. 2022 Jan;14(1):96-111. doi: 10.1002/pmrj.12745. Epub 2022 Jan 12. PMID: 34902226. https://onlinelibrary.wiley.com/doi/10.1002/pmrj.12745 (Full text)

Improvement of a Long Covid patient after vaccinations, a case report in family practice

Abstract:

Since 2019, primary care has been under great pressure from Covid-19 patients and now from those affected by Long Covid. The issue of this new condition, its diagnosis and available treatments, were investigated on the occasion of an anecdotal and unexpected recovery of a patient with Long Covid.

A 48-year-old woman, a single mother of two and patient in our family practice for several years, became sick from Covid-19 in October 2020. She never recovered, and 9 months later was still showing signs of severe Long Covid with somatic, behavioral, cognitive and memory disorders.

After her two vaccinations by Comirnaty – Pfizer/BioNTech, she reported severe side effects, followed at day 12 after the first vaccine by an unexpected improvement still present at day 30 and 44 of the Long Covid symptoms from which she had suffered for several months. SARSCoV-2 antibodies were very high and although Magnetic Resonance Imaging were not very contributory, cerebral tomoscintigraphic examination was compatible with a cerebral pathology of vascular type.

While no conclusions can be drawn from an isolated case, this case allows us to show that post Covid patients, who may already be highly comorbid, should be accompanied on a long-term basis. The disease is not yet precisely defined and symptoms may be non-specific family practice or may vary depending on the organs affected. Diagnostic procedures are not always helpful. A post Covid heartsink patient with medically unexplained symptoms may well be a Covid long hauler. This makes listening to the patient‘s words and narrative medicine very powerful.

Source: Jamoulle M, Kazeneza-Mugisha G, Zayane A. Improvement of a Long Covid patient after vaccinations, a case report in The Permanente Journal. Accepted. Oct. 2021. In press. https://orbi.uliege.be/bitstream/2268/267459/1/in_press_Long_Covid_revised_full_final_draft_20212610.pdf (Full text)

Restless legs syndrome is associated with long-COVID in women

Abstract:

Study Objectives: Sleep disturbance is common in long-COVID (LC). Restless legs syndrome (RLS) is characterized by sleep disturbance and has been reported after viral infections. Therefore, we evaluated RLS symptoms cross-sectionally in individuals with LC at both current and pre-COVID19 timepoints.

Methods: LC-focused Facebook adults were recruited for an online assessment of symptoms before COVID-19 infection and during their present LC state in a cross-sectional manner. The LC group documented baseline symptoms retrospectively. Questions were included about the presence/severity of RLS symptoms and assessments of fatigue, quality of life, and sleep apnea. A control group was recruited and included individuals ≥18 years of age who never had overt symptoms of COVID-19. Pregnancy was exclusion criteria for both groups.

Results: There were 136 LC participants (89.7% females, age 46.9 ±12.9 years) and 136 controls (65.4% females, age 49.2 ±15.5). RLS prevalence in LC-females was 5.7% pre-COVID-19 and 14.8% post-COVID-19 (p<0.01) vs. 6.7% in control-females. Severity of RLS was moderate in both groups. Logistic regression predicting post-COVID-19 RLS among LC-females failed to find significant effects of hospitalization, sleep apnea, neuropathic pain severity or use of antihistamines and antidepressants.

Conclusions: The baseline prevalence of RLS in LC-females was similar to the general population group as well as to patients in epidemiological studies. The prevalence significantly increased in the LC state. Post-infectious immunological mechanisms may be at play in the production for RLS symptoms.

Source: Leonard B. Weinstock, MD, FACG ; Jill B. Brook, MA ; Arthur S. Walters,  MD ;  Ashleigh Goris, RN, BSN, MPH, CIC, FAPIC ; Lawrence B. Afrin, MD ; Gerhard J. Molderings, MD. Restless legs syndrome is associated with long-COVID in women. Journal of Clinical Sleep Medicine. Published Online:January 25, 2022. https://doi.org/10.5664/jcsm.9898 https://jcsm.aasm.org/doi/pdf/10.5664/jcsm.9898 (Full study)

Persistent Autoimmune Activation and Proinflammatory State in Post-COVID Syndrome

Abstract:

Background: The immunopathological pathways enabling post-COVID syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition.

Methods: Thirty-three patients were included for longitudinal clinical and autoantibody analyses of whom 12 patients were assessed for cytokines and lymphocyte populations. Patients were followed during 7-11 months after acute COVID-19. Autoimmune profile and immunological status were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry.

Results: Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by upregulated IFN-α, TNF-α, G-CSF, IL-17A, IL-6, IL-1β, and IL-13, whereas IP-10 was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of IgG S1-SARS-CoV-2 antibodies remained elevated over time.

Discussion: The clinical manifestations of PCS are associated with the persistence of a proinflammatory, and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.

Source: Acosta-Ampudia Y, Monsalve DM, Rojas M, Rodríguez Y, Zapata E, Ramírez-Santana C, Anaya JM. Persistent Autoimmune Activation and Proinflammatory State in Post-COVID Syndrome. J Infect Dis. 2022 Jan 25:jiac017. doi: 10.1093/infdis/jiac017. Epub ahead of print. PMID: 35079804. https://pubmed.ncbi.nlm.nih.gov/35079804/

Impact of Q-fever on physical and psychosocial functioning until 8 years after Coxiella burnetii infection: An integrative data analysis

Abstract:

Background: This study aimed to determine short- and long-term physical and psychosocial impact of Coxiella burnetii infection in three distinct entities: Q-fever fatigue syndrome (QFS), chronic Q-fever, and patients with past acute Q-fever without QFS or chronic Q-fever.

Methods: Integrative data analysis was performed, combining original data from eight studies measuring quality of life (QoL), fatigue, physical and social functioning with identical validated questionnaires, from three months to eight years after onset infection. Linear trends in each outcome were compared between Q-fever groups using multilevel linear regression analyses to account for repeated measures within patients.

Results: Data included 3947 observations of 2313 individual patients (228 QFS, 135 chronic Q-fever and 1950 patients with past acute Q-fever). In the first years following infection, physical and psychosocial impact was highest among QFS patients, and remained high without significant improvements over time. In chronic Q-fever patients, QoL and physical functioning worsened significantly over time. Levels of fatigue and social participation in patients with past acute Q-fever improved significantly over time.

Conclusion: The impact differs greatly between the three Q-fever groups. It is important that physicians are aware of these differences, in order to provide relevant care for each patient group.

Source: Reukers DFM, van Jaarsveld CHM, Akkermans RP, Keijmel SP, Morroy G, van Dam ASG, Wever PC, Wielders CCH, van der Velden K, van Loenhout JAF, Hautvast JLA. Impact of Q-fever on physical and psychosocial functioning until 8 years after Coxiella burnetii infection: An integrative data analysis. PLoS One. 2022 Feb 2;17(2):e0263239. doi: 10.1371/journal.pone.0263239. PMID: 35108330; PMCID: PMC8809529. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263239 (Full text)

Pediatric Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Overlaps and Opportunities

David Spodick once wrote: “We must view published material critically (if not biblically), for too often the ‘Conclusions’ giveth, but the ‘Materials and Methods’ taketh away.” In the December 2021 issue of the Pediatric Infectious Diseases Journal, Zimmermann et al provide a masterful application of Spodick’s exhortation. Their review of the existing evidence regarding long COVID in children enumerates important methodologic challenges in interpreting this literature, including the heterogeneity of available case definitions for long COVID, differences in the time intervals in which symptoms are ascertained, variability regarding which symptoms are included under the rubric of long COVID, and whether laboratory confirmation of the initial COVID infection is required. Additionally, the authors emphasize that without control groups in many of these studies, and in light of the overlap of some long COVID symptoms with symptoms of prolonged social isolation, it is difficult to discern which symptoms are attributable to the general pandemic circumstances rather than the COVID-19 infection itself. Despite such limitations, it is clear that pediatric patients are at risk for prolonged symptoms following acute SARS-CoV-2 infection. Although many persistent symptoms, such as anosmia, dysgeusia and shortness of breath are unique to the post-COVID state, many other symptoms such as fatigue, cognitive dysfunction, lightheadedness and postexertional malaise overlap with symptoms found in myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). In this commentary, we review case definitions for long COVID and ME/CFS, emphasize recent research findings on the biologic basis of ME/CFS, discuss the overlap with long COVID, and consider opportunities posed by the pandemic to improve the understanding of both conditions

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Source: Siberry VGR, Rowe PC. Pediatric Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Overlaps and Opportunities. Pediatr Infect Dis J. 2022 Feb 4. doi: 10.1097/INF.0000000000003477. Epub ahead of print. PMID: 35121715. https://journals.lww.com/pidj/Citation/9000/Pediatric_Long_COVID_and_Myalgic.95546.aspx (Full text)