Tag: covid-19

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/

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)

Long COVID: to investigate immunological mechanisms and sex/gender related aspects as fundamental steps for tailored therapy

Introduction:

Around a quarter of people who have had coronavirus disease 2019 (COVID-19) experience symptoms that continue for at least 1 month, but one in ten are still unwell after 12 weeks. This very debilitating condition has been defined by patient groups as “long COVID”, elsewhere called post-COVID, whereas the patients are frequently called COVID-19 long-haulers [1]. Long COVID has a serious impact on patient ability to go back to work or school, to have a social life and may have significant economic consequences for patients, their families and for society.

The condition is characterised by long-term sequelae and can involve a range of about 200 different and overlapping symptoms, such as persistent fatigue, chest and muscle pain, headache, shortness of breath, anosmia, muscle weakness, fever, cognitive dysfunction (brain fog), tachycardia, intestinal disorders and skin manifestations. It can affect anyone, but women appear to be twice as likely to develop long COVID as men, but only until around age 60 years, when the risk level becomes similar [2–4]. Long COVID has also been described in paediatric patients [5]. An Italian study reported that at least one symptom persisted 4 months after COVID-19 infection [6] whereas an Australian analysis suggested that only 8% of children had ongoing symptoms 3–6 months after mild SARS-CoV-2 infection [7]. No gender difference was observed in the prevalence of long COVID in this population [5].

Source: Elena Ortona, Walter Malorni. Long COVID: to investigate immunological mechanisms and sex/gender related aspects as fundamental steps for tailored therapy. European Respiratory Journal Feb 2022, 59 (2) 2102245; DOI: 10.1183/13993003.02245-2021. https://erj.ersjournals.com/content/59/2/2102245?rss=1  (Full text)

Pathological sequelae of long-haul COVID

Abstract:

The world continues to contend with successive waves of coronavirus disease 2019 (COVID-19), fueled by the emergence of viral variants. At the same time, persistent, prolonged and often debilitating sequelae are increasingly recognized in convalescent individuals, named ‘post-COVID-19 syndrome’ or ‘long-haul COVID’. Clinical symptomatology includes fatigue, malaise, dyspnea, defects in memory and concentration and a variety of neuropsychiatric syndromes as the major manifestations, and several organ systems can be involved. The underlying pathophysiological mechanisms are poorly understood at present.

This Review details organ-specific sequelae of post-COVID-19 syndromes and examines the underlying pathophysiological mechanisms available so far, elaborating on persistent inflammation, induced autoimmunity and putative viral reservoirs. Finally, we propose diagnostic strategies to better understand this heterogeneous disorder that continues to afflict millions of people worldwide.

Source: Mehandru, S., Merad, M. Pathological sequelae of long-haul COVID. Nat Immunol (2022). https://doi.org/10.1038/s41590-021-01104-y https://www.nature.com/articles/s41590-021-01104-y (Full text)

Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome

Abstract:

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which – combined with age, history of asthma bronchiale, and five symptoms during primary infection – is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.

Source: Cervia C, Zurbuchen Y, Taeschler P, Ballouz T, Menges D, Hasler S, Adamo S, Raeber ME, Bächli E, Rudiger A, Stüssi-Helbling M, Huber LC, Nilsson J, Held U, Puhan MA, Boyman O. Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome. Nat Commun. 2022 Jan 25;13(1):446. doi: 10.1038/s41467-021-27797-1. PMID: 35078982. https://www.nature.com/articles/s41467-021-27797-1 (Full text)

Long covid in children and adolescents

Editorial:

Risk appears low, but many questions remain

Symptoms involving almost every organ system have been reported after SARS-CoV-2 infection.123 Estimates of the prevalence of long covid (also called post-covid-19 condition, post-acute sequelae of covid-19, or chronic covid syndrome) vary considerably, partly because of confusion around the definition. The term long covid encompasses a broad range of symptoms, including objective complications of covid-19 (pulmonary fibrosis, myocardial dysfunction), mental health conditions, and more subjective, non-specific symptoms resembling those seen in post-viral chronic fatigue syndrome (myalgic encephalomyelitis). Most studies to date have substantial limitations, including small cohorts, absence of control groups, non-standardised capture of symptoms, lack of correction for pre-existing medical conditions, participant reported infection, and variation in follow-up, as well as selection, non-response, misclassification, and recall biases.4

In children and adolescents, acute covid-19 is less severe than in adults.56 Concern among many parents has therefore focused more on the potential long term effects of SARS-CoV-2 infection. Unfortunately, fewer data are available on long covid in young people compared with adults.7 The widely quoted one in seven frequency in children is based on a study with a 13% response rate.78

The linked study by Magnusson and colleagues (doi:10.1136/bmj-2021-066809) used nationwide register data from Norway to estimate the impact of covid-19 on long term healthcare use among 1.3 million children and adolescents.9 The authors identified a short term increase in primary (but not specialist) care use after covid-19 in all the studied age groups. This increase was related to respiratory and general or non-specific conditions, mostly in the four weeks after infection. The increase in primary care use persisted for up to six months among children aged 1-5 years. Notably, covid-19 in children had limited overall impact on healthcare services.

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Source: Petra Zimmermann. Long covid in children and adolescents. BMJ 2022; 376 doi: https://doi.org/10.1136/bmj.o143 (Published 20 January 2022) https://www.bmj.com/content/376/bmj.o143.full (Full article)