Tag: covid-19

Long COVID symptoms and duration in SARS-CoV-2 positive children – a nationwide cohort study

Abstract:

Most children have a mild course of acute COVID-19. Only few mainly non-controlled studies with small sample size have evaluated long-term recovery from SARS-CoV-2 infection in children. The aim of this study was to evaluate symptoms and duration of ‘long COVID’ in children. A nationwide cohort study of 37,522 children aged 0-17 years with RT-PCR verified SARS-CoV-2 infection (response rate 44.9%) and a control group of 78,037 children (response rate 21.3%).

An electronic questionnaire was sent to all children from March 24th until May 9th, 2021. Symptoms lasting > 4 weeks were common among both SARS-CoV-2 children and controls. However, SARS-CoV-2 children aged 6-17 years reported symptoms more frequently than the control group (percent difference 0.8%). The most reported symptoms among pre-school children were fatigue Risk Difference (RD) 0.05 (CI 0.04-0.06), loss of smell RD 0.01 (CI 0.01-0.01), loss of taste RD 0.01 (CI 0.01-0.02) and muscle weakness RD 0.01 (CI 0.00-0.01). Among school children the most significant symptoms were loss of smell RD 0.12 (CI 0.12-0.13), loss of taste RD 0.10 (CI 0.09-0.10), fatigue RD 0.05 (CI 0.05-0.06), respiratory problems RD 0.03 (CI 0.03-0.04), dizziness RD 0.02 (CI 0.02-0.03), muscle weakness RD 0.02 (CI 0.01-0.02) and chest pain RD 0.01 (CI 0.01-0.01). Children in the control group experienced significantly more concentration difficulties, headache, muscle and joint pain, cough, nausea, diarrhea and fever than SARS-CoV-2 infected. In most children ‘long COVID’ symptoms resolved within 1-5 months.

Conclusions: Long COVID in children is rare and mainly of short duration.

What is Known:

• There are increasing reports on ‘long COVID’ in adults.

• Only few studies have evaluated the long-term recovery from COVID-19 in children, and common for all studies is a small sample size (median number of children included 330), and most lack a control group.

What is New:

• 0.8% of SARS-CoV-2 positive children reported symptoms lasting >4 weeks (‘long COVID’), when compared to a control group.

• The most common ‘long COVID’ symptoms were fatigue, loss of smell and loss of taste, dizziness, muscle weakness, chest pain and respiratory problems.

• These ‘long COVID’ symptoms cannot be assigned to psychological sequelae of social restrictions.

• Symptoms such as concentration difficulties, headache, muscle- and joint pain as well as nausea are not ‘long COVID’ symptoms.

• In most cases ‘long COVID’ symptoms resolve within 1-5 months.

Source: Borch L, Holm M, Knudsen M, Ellermann-Eriksen S, Hagstroem S. Long COVID symptoms and duration in SARS-CoV-2 positive children – a nationwide cohort study. Eur J Pediatr. 2022 Jan 9:1–11. doi: 10.1007/s00431-021-04345-z. Epub ahead of print. PMID: 35000003; PMCID: PMC8742700. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742700/ (Full text)

Cerebrospinal Fluid Analysis Post-COVID-19 Is Not Suggestive of Persistent Central Nervous System Infection

Abstract:

This study was undertaken to assess whether SARS-CoV-2 causes a persistent central nervous system infection. SARS-CoV-2-specific antibody index and SARS-CoV-2 RNA were studied in cerebrospinal fluid following COVID-19. Cerebrospinal fluid was assessed between days 1 and 30 (n = 12), between days 31 and 90 (n = 8), or later than 90 days (post-COVID-19, n = 20) after COVID-19 diagnosis. SARS-CoV-2 RNA was absent in all patients, and in none of the 20 patients with post-COVID-19 syndrome were intrathecally produced anti-SARS-CoV-2 antibodies detected. The absence of evidence of SARS-CoV-2 in cerebrospinal fluid argues against a persistent central nervous system infection as a cause of neurological or neuropsychiatric post-COVID-19 syndrome.

Source: Schweitzer F, Goereci Y, Franke C, Silling S, Bösl F, Maier F, Heger E, Deiman B, Prüss H, Onur OA, Klein F, Fink GR, Di Cristanziano V, Warnke C. Cerebrospinal Fluid Analysis Post-COVID-19 Is Not Suggestive of Persistent Central Nervous System Infection. Ann Neurol. 2022 Jan;91(1):150-157. doi: 10.1002/ana.26262. Epub 2021 Nov 22. PMID: 34724243; PMCID: PMC8653324. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653324/ (Full text)

PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response

Abstract:

A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1β, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19.

This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cell-mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.

Source: Loretelli C, Abdelsalam A, D’Addio F, Ben Nasr M, Assi E, Usuelli V, Maestroni A, Seelam AJ, Ippolito E, Di Maggio S, Loreggian L, Radovanovic D, Vanetti C, Yang J, El Essawy B, Rossi A, Pastore I, Montefusco L, Lunati ME, Bolla AM, Biasin M, Antinori S, Santus P, Riva A, Zuccotti GV, Galli M, Rusconi S, Fiorina P. PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response. JCI Insight. 2021 Dec 22;6(24):e146701. doi: 10.1172/jci.insight.146701. PMID: 34784300. https://insight.jci.org/articles/view/146701 (Full text)

The Long-COVID Syndrome: smoking and enhanced suicide risk

Extract:

The QJM has been at the forefront in highlighting the mental health problems associated with COVID-19 infection in society.1–6 In a Commentary piece in this issue of the Journal, Leo Sher, Professor of Psychiatry from the Mount Sinai School of Medicine, highlights the role of smoking being associated with a worse prognosis in acute infections and enhancing the risk of suicide in patients suffering persistent disabling symptoms associated with the Long-COVID Syndrome.

It is well recognized that smoking is associated with suicidal ideation, suicide attempts, suicide death and a contributing factor in the pathophysiology of suicide. The author highlights the evidence that suggests that the COVID-19 pandemic has led to increased tobacco consumption as smokers use more tobacco to cope with pandemic-related stress, anxiety, depression and loneliness. Smoking will have significant psychobiological effects resulting in enhanced impulsivity and aggression which will be compounded by in particular the brain-related symptoms…

Source: Seamas C Donnelly, The Long-COVID Syndrome: smoking and enhanced suicide risk, QJM: An International Journal of Medicine, Volume 114, Issue 11, November 2021, Page 765, https://doi.org/10.1093/qjmed/hcab300

Global surveillance, research, and collaboration needed to improve understanding and management of long COVID

The scale of chronic ill health and disability after COVID-19 has been described as the next big global health challenge. Prevalence estimates of a post-COVID-19 condition, long COVID, or post-acute sequelae of SARS-CoV-2 vary according to definition, methodology, and population. A recent systematic review reported persistent symptoms at 3–6 months in a median of 57% (range 13–92) of hospitalised patients (six studies) and 26% (2–62) of non-hospitalised patients (ten studies). This study and other reviews identified few studies from low-income settings, but with more than 245 million SARS-CoV-2 infections reported globally, millions of people are likely to already be experiencing long-term illness. While COVID-19 vaccines have reduced the risk of severe COVID-19 and death, continued high rates of SARS-CoV-2 infection will lead to further disability, having a huge impact on individuals, their families, health services, and society.

Read the rest of this article HERE.

Source: Ward H, Flower B, Garcia PJ, Ong SWX, Altmann DM, Delaney B, Smith N, Elliott P, Cooke G. Global surveillance, research, and collaboration needed to improve understanding and management of long COVID. Lancet. 2021 Dec 4;398(10316):2057-2059. doi: 10.1016/S0140-6736(21)02444-2. Epub 2021 Nov 10. PMID: 34774190; PMCID: PMC8580495. (Full text)

Physiological predictors of long-term effects of covid-19 in patients with sars-cov-2: focus on lymphocyte proliferation-improving micronutrients

Abstract

Patients with long-term effects of coronavirus disease, the so-called “long-term COVID-19 syndrome” (long-COVID-19) after SARS-CoV-2 infection, have a postponed recovery lasting from 4 weeks and up to six months, spread worldwide.

Physiological predictors based on human blood biomarkers and host-virus responses to SARS-CoV-2 are still unknown. There is growing evidence about the impact of micronutrients on improving lymphocyte proliferation and their essential roles for a functioning human immune system and regulating metabolic health. This paper aims to review information about micronutrients in patients with SARS-CoV-2 infection that determines long-COVID-19 outcomes and highlight the importance of diagnostics in predictors of long-COVID-19.

We reviewed articles returned from searches on PubMed/SCOPUS/Web of Science/ EMBASE databases using a combination of terms “long COVID-19”, “long-term effects of COVID-19”, “post-COVID-19 symptoms”, “COVID-19 associated stress”, “micronutrients”. Evidence indicates the relationship between lymphocyte proliferation improving micronutrient level and long-COVID-19 induction. Zinc, selenium, iron, manganese have an immunomodulatory function in innate and adaptive immune responses to viral infection. Anti-inflammatory functions of Vits A and B groups include the regulation of lymphocyte proliferation and metabolic health. Further research using sampling and artificial intelligence-assisted algorithms could assist in the recognition of the correlation of micronutrients and long-COVID-19 clinical outcomes.

Source: Karkhut S-M, Muzyka I, Savytska M, Dzhyoieva K, Pohoretska Y, Ivanchenko N, Zayachkivska O, Schloss JV, Szabo S. PHYSIOLOGICAL PREDICTORS OF LONG-TERM EFFECTS OF COVID-19 IN PATIENTS WITH SARS-COV-2: FOCUS ON LYMPHOCYTE PROLIFERATION-IMPROVING MICRONUTRIENTS. Proc Shevchenko Sci Soc Med Sci [Internet]. 2021Dec.12 [cited 2022Jan.18];65(2). Available from: https://mspsss.org.ua/index.php/journal/article/view/560

A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19

Abstract:

SARS-CoV-2 started spreading toward the end of 2019 causing COVID-19, a disease that reached pandemic proportions among the human population within months. The reasons for the spectrum of differences in the severity of the disease across the population, and in particular why the disease affects more severely the aging population and those with specific preconditions are unclear. We developed machine learning models to mine 240,000 scientific articles openly accessible in the CORD-19 database, and constructed knowledge graphs to synthesize the extracted information and navigate the collective knowledge in an attempt to search for a potential common underlying reason for disease severity. The machine-driven framework we developed repeatedly pointed to elevated blood glucose as a key facilitator in the progression of COVID-19. Indeed, when we systematically retraced the steps of the SARS-CoV-2 infection, we found evidence linking elevated glucose to each major step of the life-cycle of the virus, progression of the disease, and presentation of symptoms.

Specifically, elevations of glucose provide ideal conditions for the virus to evade and weaken the first level of the immune defense system in the lungs, gain access to deep alveolar cells, bind to the ACE2 receptor and enter the pulmonary cells, accelerate replication of the virus within cells increasing cell death and inducing an pulmonary inflammatory response, which overwhelms an already weakened innate immune system to trigger an avalanche of systemic infections, inflammation and cell damage, a cytokine storm and thrombotic events. We tested the feasibility of the hypothesis by manually reviewing the literature referenced by the machine-generated synthesis, reconstructing atomistically the virus at the surface of the pulmonary airways, and performing quantitative computational modeling of the effects of glucose levels on the infection process.

We conclude that elevation in glucose levels can facilitate the progression of the disease through multiple mechanisms and can explain much of the differences in disease severity seen across the population. The study provides diagnostic considerations, new areas of research and potential treatments, and cautions on treatment strategies and critical care conditions that induce elevations in blood glucose levels.

Source: Logette E, Lorin C, Favreau C, et al. A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19. Front Public Health. 2021;9:695139. Published 2021 Jul 28. doi:10.3389/fpubh.2021.695139 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356061/ (Full text)

Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes

Abstract:

Background: Myocardial injury in patients with COVID-19 is associated with increased mortality during index hospitalization; however, the relationship to long-term sequelae of SARS-CoV-2 is unknown. This study assessed the relationship between myocardial injury (high-sensitivity cardiac troponin T level) during index hospitalization for COVID-19 and longer-term outcomes.

Methods and Results: This is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS-CoV-2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high-sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high-sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low-level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow-up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID-19-related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status.

Conclusions: Myocardial injury during index hospitalization for COVID-19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID-19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin-positive patients.

Source: Weber B, Siddiqi H, Zhou G, Vieira J, Kim A, Rutherford H, Mitre X, Feeley M, Oganezova K, Varshney AS, Bhatt AS, Nauffal V, Atri DS, Blankstein R, Karlson EW, Di Carli M, Baden LR, Bhatt DL, Woolley AE. Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes. J Am Heart Assoc. 2022 Jan 4;11(1):e022010. doi: 10.1161/JAHA.121.022010. Epub 2021 Dec 31. PMID: 34970914. https://www.ahajournals.org/doi/10.1161/JAHA.121.022010 (Full text)

Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis

Abstract:

Importance: COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.

Objective: To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.

Data sources: Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.

Study selection: Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.

Data extraction & synthesis: Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Turkey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.

Main outcomes & measures: The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks after COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences of post-COVID-19 syndrome.

Results: The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2=99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I2=98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.

Conclusions & relevance: A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.

Study Registration PROSPERO (CRD42021256965).

Source: Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, Rodrigues NB, Subramaniapillai M, Di Vincenzo JD, Cao B, Lin K, Mansur RB, Ho RC, Rosenblat JD, Miskowiak KW, Vinberg M, Maletic V, McIntyre RS. Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis. Brain Behav Immun. 2021 Dec 29;101:93–135. doi: 10.1016/j.bbi.2021.12.020. Epub ahead of print. PMID: 34973396; PMCID: PMC8715665. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715665/ (Full text)

Sulodexide in the treatment of patients with long COVID 19 symptoms and endothelial dysfunction: The results of TUN-EndCOV study

Abstract:

Background: Endothelial dysfunction is probably one of the mechanisms of long COVID-19 symptoms. Sulodexide has pleiotropic properties within the vascular endothelium that can prove beneficial in the long COVID-19 symptoms.

Purpose: We aimed to evaluate the effect of sulodexide when used in patients with endothelial dysfunction and long COVID-19 symptoms.

Methods: We conducted a prospective multicenter longitudinal case-control study. Endothelial function was evaluated with DTM “E4-Diagnose” Polymath based on the Endothelium Quality Index (EQI). A group of patients with endothelial dysfunction (EQI < 2.0) received sulodexide. All the patients were followed-up 21 days after inclusion. Primary outcomes were defined as endothelial function amelioration (delta EQI) and long COVID-19 symptoms evolution during the follow-up.

Results: A total of 410 patients were included in this study. Patients were included at an average time of 1.89 ± 1.2 month after COVID-19 infection. At inclusion, 210 (51.2%) patients had an EQI < 2. The median age was 49 ± 13.8 (18–80) years. Among the patients with endothelial dysfunction, only 79 patients received sulodexide. Patients in sulodexide group had lower EQI than the non-medical intervention group (0.94 ± 0.6 vs. 1.52 ± 0.4; P < 10−3). They were more diabetic, hypertensive, had more coronary artery disease and received more long-term medications (aspirin, Bblockers and statins) than the others (P = 0.01, 0.002, 0.01, 0.009, 0.001 and 0.01, respectively). At the 21-days follow-up, patients in sulodexide group presented lower long COVID symptoms especially chest pain, palpitations, fatigue and neuro-cognitive difficulties associated to a significant amelioration of endothelial function (delta EQI 1.26 ± 1.07 vs. 0.22 ± 0.7; P < 10−3).

Conclusion: Sulodexide in patients with long COVID-19 may be a good intervention to ameliorate chest pain, palpitations, fatigue and neuro-cognitive difficulties associated to endothelial dysfunction.

Source: S. Charfeddine, H. Ibn Hadjamor, S. Torjmen, S. Kraiem, R. Hammami, A. Bahloul, N. Kallel, N. Moussa, I. Touil, J. Jdidi, S. Abdesselem, L. Abid. Sulodexide in the treatment of patients with long COVID 19 symptoms and endothelial dysfunction: The results of TUN-EndCOV study,
Archives of Cardiovascular Diseases Supplements. Volume 14, Issue 1, 2022, Page 127, ISSN 1878-6480,
https://doi.org/10.1016/j.acvdsp.2021.10.007. (https://www.sciencedirect.com/science/article/pii/S1878648021006455)