scholarly journals Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

BMC Medicine ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Feargal J. Ryan ◽  
Christopher M. Hope ◽  
Makutiro G. Masavuli ◽  
Miriam A. Lynn ◽  
Zelalem A. Mekonnen ◽  
...  
Keyword(s):  
Post Infection ◽  
Integrated Analysis ◽  
Transcriptional Level ◽  
T Helper ◽  
Long Term Effects ◽  
Persistent Symptoms ◽  
Adaptive Immune ◽  
Follicular Helper ◽  
Rate Of Recovery

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as “long COVID”, post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects. Methods We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection. Results Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not. Conclusions Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.

scholarly journals Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

2021 ◽  
Author(s):  
Feargal J Ryan ◽  
Christopher Martin Hope ◽  
Makutiro Ghislain Masavuli ◽  
Miriam A Lynn ◽  
Zelalem Addis Mekonnen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Dysregulation ◽  
Integrated Analysis ◽  
Transcriptional Level ◽  
T Helper ◽  
Adaptive Immune ◽  
Follicular Helper ◽  
Metabolic Dysregulation ◽  
Rate Of Recovery

Increasing evidence suggests immune dysregulation in individuals recovering from SARS-CoV-2 infection. We have undertaken an integrated analysis of immune responses at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 individuals recovering from mild, moderate, severe, or critical COVID-19. Anti-Spike and anti-RBD IgG responses were largely stable up to 24wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper and regulatory T cells) in COVID-19 convalescents compared to healthy controls, which were most strongly evident at 12 and 16wpi. RNA sequencing suggested ongoing immune and metabolic dysregulation in convalescents months after infection. Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.

scholarly journals Human Body Burden of Heavy Metals and Health Consequences of Pb Exposure in Guiyu, an E-Waste Recycling Town in China

2021 ◽  
Vol 18 (23) ◽  
pp. 12428
Author(s):  
Wenlong Huang ◽  
Xiaoling Shi ◽  
Kusheng Wu
Keyword(s):  
Heavy Metals ◽  
Body Burden ◽  
Local Environment ◽  
Waste Recycling ◽  
The Body ◽  
Health Consequences ◽  
Long Term Effects ◽  
Adaptive Immune ◽  
Pb Exposure

Guiyu accommodates millions of tons of e-waste from overseas and domestic sources each year and is notorious for its e-waste dismantling industry. As a consequence, Guiyu has been described as “the world’s most toxic place” and “junk town”. Informal e-waste recycling activities have caused severe pollution to the local environment and are associated with extensive health problems to the residents. This review provides updated insights on the body burden of heavy metals derived from e-waste and health outcomes resulted from lead (Pb) exposure. The review identified that Guiyu has been highly contaminated by heavy metals, especially Pb. Excessive exposure to Pb has been associated with multi-system and long-term effects in neonates and children, covering nervous, cardiovascular, adaptive immune, and hematologic systems as well as chromosome and DNA damage. Our review indicates strong associations that emphasize the need to develop strong regulations for prevention of exposure and health consequences in Guiyu and similar sites around the world.

scholarly journals Recovered not restored: Long-term health consequences after mild COVID-19 in non-hospitalized patients

2021 ◽  
Author(s):  
Max Augustin ◽  
Philipp Schommers ◽  
Melanie Stecher ◽  
Felix Dewald ◽  
Lutz Gieselmann ◽  
...  
Keyword(s):  
Post Infection ◽  
Baseline Level ◽  
Hospitalized Patients ◽  
Added Value ◽  
Shortness Of Breath ◽  
Health Consequences ◽  
Long Term Effects ◽  
Total Cohort ◽  
Lower Baseline

AbstractBackgroundWhile the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalization. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence we focus on mild COVID-19 in non-hospitalized patients.MethodsWe included 958 patients with confirmed SARS-CoV-2 infection in this study. Patients were observed for seven months from April 6th to December 2nd 2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarized presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model.FindingsWe observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8.6% (38/442) of patients presented with shortness of breath, 12.4% (55/442) with anosmia, 11.1% (49/442) with ageusia and 9.7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27.8% (123/442) and 34.8% (123/353) at month 4 and 7 post-infection, respectively. This corresponds to 12.8% patients with long-lasting symptoms relative to the initial total cohort (123/958). A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhea during acute COVID-19 were associated with higher risk to develop long-term symptoms.InterpretationThe on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalized patients was observed at four and seven months post-infection and summarized as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19.FundingCOVIM:„NaFoUniMedCovid19”(FKZ: 01KX2021)Research in contextEvidence before this studyData about long-term health consequences after SARS-CoV-2 infection and COVID-19 is scarce and most available data describe health consequences in hospitalized patients during acute COVID-19. However, these studies do not take into account the vast majority of patients with a milder course of infection (WHO score1-3).Added value of this studyOur cohort consists of mostly mild COVID-19 cases that have been prospectively followed for a median time of 6.8 months. At least one trained physician critically reviewed the patients’ reported symptoms at each visit. We assessed SARS-CoV-2 IgG at each visit to correlate reported symptoms with serological data. At 4 months after SARS-CoV-2 infection, shortness of breath occurred in 8.6% (38/442), anosmia in 12.4% (55/442), ageusia in 11.1% (49/442), and fatigue in 9.7% (43/442) of patients. At least one characteristic symptom was present in 27.8% (123/442) and 34.8% (123/353) at months 4 and 7 post-infection, respectively. Symptoms were summarized as post-COVID syndrome (PCS). Relative to our initial total cohort (123/958), this corresponds to 12.8% patients with long-lasting symptoms. Lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhea during acute COVID-19 were associated with higher risk of developing long-term symptoms.Implications of all available evidenceWe believe that our findings have important implications for the fields of infectious diseases and public health, because we show long-term health consequences may occur even after very mild COVID-19 in the outpatient setting. As up to 81% of all SARS-CoV-2 infected patients present with mild disease, it can be expected that PCS will affect a larger number of individuals than initially assumed, posing major medical, social and economic challenges.

Long COVID—The New “Invisible” Illness: How School Nurses Can Support the Nursing and Educational Teams for Student Success

2021 ◽  
pp. 1942602X2110594
Author(s):  
Megan Roesler ◽  
Patricia Fato ◽  
Barbara Obst
Keyword(s):  
School Nurses ◽  
School Age Children ◽  
Return To School ◽  
School Age ◽  
Long Term Effects ◽  
Persistent Symptoms ◽  
School Based ◽  
School Based Interventions ◽  
The Waves

School-age children are not immune to COVID-19 or the pronounced and persistent symptoms associated with a long-COVID diagnosis. Students may present with a variety of symptoms affecting their physical, cognitive, and mental health. The school community should be educated on the school-based interventions and recommendations for creating an individualized safe and successful return to school plan. As we await approval for vaccinations in school-age children younger than 12 years and continue to reposition ourselves to the waves of this pandemic and new variants of the virus, understanding the medical and educational long-term effects on our students may be a long-term need.

scholarly journals Comprehensive Flow Cytometry Profiling of the Immune System in COVID-19 Convalescent Individuals

2022 ◽  
Vol 12 ◽  
Author(s):  
Sergio Gil-Manso ◽  
Iria Miguens Blanco ◽  
Rocío López-Esteban ◽  
Diego Carbonell ◽  
Luis Andrés López-Fernández ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune System ◽  
Post Infection ◽  
Plasma Cells ◽  
Follicular Dendritic Cells ◽  
Infected People ◽  
Follicular Helper ◽  
Healthy Donors

SARS-CoV-2 has infected more than 200 million people worldwide, with more than 4 million associated deaths. Although more than 80% of infected people develop asymptomatic or mild COVID-19, SARS-CoV-2 can induce a profound dysregulation of the immune system. Therefore, it is important to investigate whether clinically recovered individuals present immune sequelae. The potential presence of a long-term dysregulation of the immune system could constitute a risk factor for re-infection and the development of other pathologies. Here, we performed a deep analysis of the immune system in 35 COVID-19 recovered individuals previously infected with SARS-CoV-2 compared to 16 healthy donors, by flow cytometry. Samples from COVID-19 individuals were analysed from 12 days to 305 days post-infection. We observed that, 10 months post-infection, recovered COVID-19 patients presented alterations in the values of some T-cell, B-cell, and innate cell subsets compared to healthy controls. Moreover, we found in recovered COVID-19 individuals increased levels of circulating follicular helper type 1 (cTfh1), plasmablast/plasma cells, and follicular dendritic cells (foDC), which could indicate that the Tfh-B-foDC axis might be functional to produce specific immunoglobulins 10 months post-infection. The presence of this axis and the immune system alterations could constitute prognosis markers and could play an important role in potential re-infection or the presence of long-term symptoms in some individuals.

scholarly journals Mechanism of Follicular Helper T Cell Differentiation Regulated by Transcription Factors

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Long-Shan Ji ◽  
Xue-Hua Sun ◽  
Xin Zhang ◽  
Zhen-Hua Zhou ◽  
Zhuo Yu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
B Cells ◽  
T Helper Cells ◽  
Molecular Mechanisms ◽  
Transcriptional Level ◽  
T Helper ◽  
Tfh Cells ◽  
Helper Cells ◽  
Follicular Helper

Helping B cells and antibody responses is a major function of CD4+T helper cells. Follicular helper T (Tfh) cells are identified as a subset of CD4+T helper cells, which is specialized in helping B cells in the germinal center reaction. Tfh cells express high levels of CXCR5, PD-1, IL-21, and other characteristic markers. Accumulating evidence has demonstrated that the dysregulation of Tfh cells is involved in infectious, inflammatory, and autoimmune diseases, including lymphocytic choriomeningitis virus (LCMV) infection, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), IgG4-related disease (IgG4-RD), Sjögren syndrome (SS), and type 1 diabetes (T1D). Activation of subset-specific transcription factors is the essential step for Tfh cell differentiation. The differentiation of Tfh cells is regulated by a complicated network of transcription factors, including positive factors (Bcl6, ATF-3, Batf, IRF4, c-Maf, and so on) and negative factors (Blimp-1, STAT5, IRF8, Bach2, and so on). The current knowledge underlying the molecular mechanisms of Tfh cell differentiation at the transcriptional level is summarized in this paper, which will provide many perspectives to explore the pathogenesis and treatment of the relevant immune diseases.

scholarly journals One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms

2021 ◽  
Vol 10 (15) ◽  
pp. 3305
Author(s):  
Andreas Rank ◽  
Athanasia Tzortzini ◽  
Elisabeth Kling ◽  
Christoph Schmid ◽  
Rainer Claus ◽  
...  
Keyword(s):  
T Cells ◽  
Neutralizing Antibodies ◽  
Early Time ◽  
T Helper ◽  
Persistent Symptoms ◽  
Cell Responses ◽  
One Year ◽  
Antibody Levels

After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 and investigated correlations of immunity with persistent symptoms and immune longevity. Persistent complications, including headache, concentration difficulties and loss of smell/taste, were reported by 51 of 83 (61%) participants and decreased over time to 28% one year after COVID-19. Specific IgA and IgG antibodies were detectable in 78% and 66% of participants, respectively, at a 12-month follow-up. Median antibody levels decreased by approximately 50% within the first 6 months but remained stable up to 12 months. Neutralizing antibodies could be found in 50% of participants; specific INFgamma-producing T-cells were present in two thirds one year after COVID-19. Activation-induced marker assays identified specific T-helper cells and central memory T-cells in 80% of participants at a 12-month follow-up. In correlative analyses, older age and a longer duration of the acute phase of COVID-19 were associated with higher humoral and T-cell responses. A weak correlation between long-term loss of taste/smell and low IgA levels was found at early time points. These data indicate a long-lasting immunological memory against SARS-CoV-2 after mild COVID-19.

scholarly journals More complaints than findings - Long-term pulmonary function in children and adolescents after COVID-19

2021 ◽  
Author(s):  
Leona Knoke ◽  
Anne Schlegtendal ◽  
Christoph Maier ◽  
Lynn Eitner ◽  
Thomas Luecke ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Children And Adolescents ◽  
Respiratory Symptoms ◽  
Severe Infection ◽  
Preliminary Evidence ◽  
Long Term Effects ◽  
Diffusion Capacity ◽  
Persistent Symptoms ◽  
Abnormal Pulmonary Function

Background: The frequency of persistent symptoms after coronavirus disease 2019 (COVID-19) in adults varies from 4.5% to 87%. Pulmonary function can also show long-term impairment in adults: 10% of hospitalised adults had reduced spirometry values, and 24% had decreased diffusion capacity. To date, only preliminary evidence is available on persistent respiratory sequelae in children and adolescents, therefore our objective was to examine the long-term effects of COVID-19 on pulmonary function in this age group. Methods: Multiple-breath washout, body plethysmography, and diffusion capacity testing were performed after an average of 2.6 months (range 0.4-6.0) following COVID-19 in 73 children and adolescents (age 5-18 years) with different disease severity. Cases were compared to 45 controls with and without infection within six months prior to assessment after exclusion of severe acute respiratory coronavirus-2 infection (SARS-CoV-2). Results: Of the 19 patients (27.1%) who complained about persistent or newly emerged symptoms since COVID-19, 8 (11.4%) reported respiratory symptoms. Comparing patients with COVID-19 to controls, no significant differences were detected in frequency of abnormal pulmonary function (COVID-19: 12, 16.4%; controls: 12, 27.7%; OR 0.54, 95% CI 0.22-1.34). Only two patients with persistent respiratory symptoms showed abnormal pulmonary function. Multivariate analysis revealed reduced forced vital capacity (p=0.045) in patients with severe infection regardless of SARS-CoV-2 infection. Discussion: Pulmonary function is rarely impaired in children and adolescents after COVID-19, except of those with severe infection. The discrepancy between persistent respiratory symptoms and normal pulmonary function suggests a different underlying pathology such as dysfunctional breathing.

scholarly journals Long covid—mechanisms, risk factors, and management

BMJ ◽  
2021 ◽  
pp. n1648
Author(s):  
Harry Crook ◽  
Sanara Raza ◽  
Joseph Nowell ◽  
Megan Young ◽  
Paul Edison
Keyword(s):  
Risk Factors ◽  
Traumatic Stress ◽  
Sleep Disturbances ◽  
Long Term Effects ◽  
Post Traumatic Stress ◽  
Persistent Symptoms ◽  
Multiple Organs ◽  
Post Traumatic ◽  
Musculoskeletal Systems

Abstract Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.

scholarly journals Living with ‘Long COVID-19’: The long-term complications and sequelae

2021 ◽  
Vol 5 (1) ◽  
pp. 011-021
Author(s):  
Nikhra Vinod
Keyword(s):  
Healthcare Providers ◽  
Clinical Manifestations ◽  
Organ Damage ◽  
Long Term Effects ◽  
Genomic Changes ◽  
Persistent Symptoms ◽  
Inflammatory Changes ◽  
Symptoms And Signs ◽  
Variable Presentation

Introduction - the perennial pandemic: It is being increasingly realised that the COVID-19 may have become the new reality associated with human existence world over and the mankind may have to live with it for years or even decades. Further, the grievous nature of the disease is evolving further with the genomic changes in the virus in form of mutations and evolution of variants, with enhanced infectivity and probably virulence. There are serious challenges posed by the SARS-CoV-2 virus and COVID-19 as the disease. COVID-19 as acute and chronic disease: On exposure to the SARS-CoV-2 virus, not all patients develop a disease. Further, for those who develop the disease, there is a large variation in disease severity. The known factors including the constituent factors and several still unknown factors influence the disease manifestations, its course, and later the convalescent phase as well. In fact, substantial continuing morbidity after resolution of the infection indicates persisting multisystem effects of COVID-19. The ‘long COVID-19’ or ‘long haulers’: The patients who continue to suffer with persisting symptoms have been described as long haulers and the clinical condition has been called post-COVID-19 or ‘long COVID-19’. The diagnosis should be entertained if various symptoms and signs linger well beyond the period of convalescence in COVID-19. With the chronicity, there occur inflammatory changes and damage in various organs, and the extent of organ damage determines the long-term effects. Management of ‘long COVID’ syndrome: The ‘long COVID’ syndrome has multi-system involvement, variable presentation, and unpredictable course. Following clinical and investigational assessment, the patients should be managed as per clinical manifestations, extent of organ damage and associated complications. The findings from various studies indicate that preventing further organ damage in ‘long COVID’ is crucial. The long COVID’s prognostic challenges: As apparent, the ‘long COVID’ afflictions are more common than realized earlier. The symptoms can escalate in patients with co-morbid conditions. The persistent symptoms among COVID-19 survivors pose new challenges to the healthcare providers and may be suitably managed with a combination of pharmacological and non-pharmacological treatments, and holistic healthcare.

Sign in / Sign up

Export Citation Format

Share Document