POS1249 MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN DURING THE COVID-19 PANDEMIC IN TURKEY: FIRST REPORT FROM THE EASTERN MEDITERRANEAN

Background:The severity of COVID-19 symptoms can range from mild to severe. Severe COVID-19 cases with excessive hyperinflammation have many overlap features with multisystem inflammatory syndrome in children (MIS-C).Objectives:We aimed to describe the typical clinical and laboratory features and treatment of children diagnosed with MIS-C and to understand the differences as compared to severe/critical pediatric cases with COVID-19 in an eastern Mediterranean country.Methods:Children (aged <18 years) who diagnosed with MIS-C and severe/critical pediatric cases with COVID-19, were admitted to hospital between 26 March and 3 November 2020 were enrolled in the study.Results:A total of 52 patients, 22 patients diagnosed with COVID-19 with severe/critical disease course and 30 patients diagnosed with MIS-C. Although severe COVID-19 cases and cases with MIS-C share many clinical and laboratory features, MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe cases (p<0.001 for each). Of all, 53.3% of MIS-C cases had the evidence of myocardial involvement as compared to severe cases (27.2%). Additionally, C-reactive protein (CRP) and white blood cell (WBC) are the independent predictors for the diagnosis of MIS-C, particularly in the existence of conjunctival injection and rash. Corticosteroids, intravenous immunoglobulin (IVIG), and biologic immunomodulatory treatments were mainly used in MIS-C cases rather than cases with severe disease course. There were only 3 deaths among 52 patients, one of whom had Burkitt lymphoma and the two cases with severe COVID-19 of late referral.Conclusion:Differences between clinical presentations, acute phase responses, organ involvements, and management strategies indicate that MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19. Conjunctival injection and higher CRP and low WBC count seem good diagnostic parameters for MIS-C cases.Disclosure of Interests:None declared

Download Full-text

Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0369 ◽

2020 ◽

Vol 58 (7) ◽

pp. 1021-1028 ◽

Cited By ~ 297

Author(s):

Brandon Michael Henry ◽

Maria Helena Santos de Oliveira ◽

Stefanie Benoit ◽

Mario Plebani ◽

Giuseppe Lippi

Keyword(s):

Serum Ferritin ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Severe Disease ◽

Severe Illness ◽

China National Knowledge Infrastructure ◽

Discriminative Ability ◽

Laboratory Findings ◽

Liver And Kidney ◽

Wbc Count

AbstractBackgroundAs coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19.MethodsAn electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter.ResultsA total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease.ConclusionsSeveral biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.

Download Full-text

Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽

10.3390/v13030514 ◽

2021 ◽

Vol 13 (3) ◽

pp. 514

Author(s):

Denise Utami Putri ◽

Cheng-Hui Wang ◽

Po-Chun Tseng ◽

Wen-Sen Lee ◽

Fu-Lun Chen ◽

...

Keyword(s):

Immune Response ◽

Immune Cells ◽

Mononuclear Cells ◽

Immune Cell ◽

Severe Disease ◽

Viral Rna ◽

Disease Course ◽

Peripheral Blood Mononuclear ◽

Peripheral Immune Cells ◽

Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

Download Full-text

High levels of transaminases at admission predict a severe disease course in COVID-19 hospitalized patients

Digestive and Liver Disease ◽

10.1016/j.dld.2020.12.058 ◽

2021 ◽

Vol 53 ◽

pp. S22

Author(s):

F. Pelizzaro ◽

M.P. Kitenge ◽

F. Maran ◽

E. Cocconcelli ◽

E. Balestro ◽

...

Keyword(s):

Severe Disease ◽

Hospitalized Patients ◽

Disease Course

Download Full-text

COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases

International Journal of Molecular Sciences ◽

10.3390/ijms22147481 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7481

Author(s):

Pier-Angelo Tovo ◽

Silvia Garazzino ◽

Valentina Daprà ◽

Giulia Pruccoli ◽

Cristina Calvi ◽

...

Keyword(s):

Viral Infections ◽

Severe Disease ◽

Endogenous Retroviruses ◽

Type I ◽

Human Endogenous Retroviruses ◽

Moderate Disease ◽

Amplification Assay ◽

Positive Correlations ◽

Inducible Genes ◽

Inflammatory Syndrome

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. RIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children nd in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19-infected children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

Download Full-text

Pathological findings in rotation thromboelastometry associated with thromboembolic events in COVID-19 patients

Thrombosis Journal ◽

10.1186/s12959-021-00263-0 ◽

2021 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Kristina Boss ◽

Andreas Kribben ◽

Bartosz Tyczynski

Keyword(s):

Severe Sepsis ◽

Severe Disease ◽

Study Data ◽

Sepsis Group ◽

Similar Data ◽

Disease Course ◽

Thromboembolic Events ◽

Pathological Findings ◽

Fibrinolysis Shutdown ◽

Maximum Clot Firmness

Abstract Background Severe thromboembolic events are one of the major complications associated with COVID-19 infection, especially among critically ill patients. We analysed ROTEM measurements in COVID-19 patients with a severe disease course and in patients with severe sepsis. Methods In this study, data obtained by extended analysis of haemostasis with standard laboratory tests and thromboelastometry of 20 patients with severe course of COVID-19 were retrospectively analysed and compared with similar data from 20 patients with severe sepsis but no COVID-19. Results The thromboelastometry values obtained from 20 sepsis patients contained a maximum clot firmness above the normal range but among COVID-19 patients, hypercoagulability was much more pronounced, with significantly higher maximum clot firmness (FIBTEM: 38.4 ± 10.1 mm vs. 29.6 ± 10.8 mm; P = 0.012; EXTEM: 70.4 ± 10.4 mm vs. 60.6 ± 14.8 mm; P = 0.022). Additionally, fibrinogen levels were significantly higher among COVID-19 patients (757 ± 135 mg/dl vs. 498 ± 132 mg/dl, P < 0.0001). Furthermore, thromboelastometry showed fibrinolysis shutdown among COVID-19 patients with significantly lower maximum of lysis than among sepsis patients (EXTEM: 0.6 ± 1.2 % vs. 3.3 ± 3.7 %; P = 0.013). Seven of 20 COVID-19 patients experienced thromboembolic events, whereas no patient in the sepsis group experienced such events. Conclusions ROTEM analysis showed significantly different pathological findings characterized by hypercoagulability and fibrinolysis shutdown among COVID-19 patients with a severe disease course compared to patients with severe sepsis. These abnormalities seem to be associated with thromboembolic events.

Download Full-text

Multisystem inflammatory syndrome in children during the COVID-19 pandemic in Turkey: first report from the Eastern Mediterranean

Clinical Rheumatology ◽

10.1007/s10067-021-05631-9 ◽

2021 ◽

Cited By ~ 2

Author(s):

Yasemin Ozsurekci ◽

Sibel Gürlevik ◽

Selman Kesici ◽

Ummusen Kaya Akca ◽

Pembe Derin Oygar ◽

...

Keyword(s):

Eastern Mediterranean ◽

First Report ◽

Inflammatory Syndrome

Download Full-text

Repeated SARS-CoV-2 Positivity: Analysis of 123 Cases

Viruses ◽

10.3390/v13030512 ◽

2021 ◽

Vol 13 (3) ◽

pp. 512

Author(s):

Szilárd Váncsa ◽

Fanni Dembrovszky ◽

Nelli Farkas ◽

Lajos Szakó ◽

Brigitta Teutsch ◽

...

Keyword(s):

Individual Patient Data ◽

Case Reports ◽

Severe Disease ◽

Descriptive Analysis ◽

Case Series ◽

Disease Course ◽

Chain Reaction ◽

Baseline Characteristics ◽

Polymerase Chain ◽

Meta Analyses

Repeated positivity and reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is a significant concern. Our study aimed to evaluate the clinical significance of repeatedly positive testing after coronavirus disease 2019 (COVID-19) recovery. We performed a systematic literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. With available individual patient data reporting on repeatedly SARS-CoV-2 positive (RSP) patients, case reports, and case series were included in this analysis. We performed a descriptive analysis of baseline characteristics of repeatedly positive cases. We assessed the cases according to the length of their polymerase chain reaction (PCR) negative interval between the two episodes. Risk factors for the severity of second episodes were evaluated. Overall, we included 123 patients with repeated positivity from 56 publications, with a mean repeated positivity length of 47.8 ± 29.9 days. Younger patients were predominant in the delayed (>90 days) recurrent positive group. Furthermore, comparing patients with RSP intervals of below 60 and above 60 days, we found that a more severe disease course can be expected if the repeated positivity interval is shorter. Severe and critical disease courses might predict future repeatedly positive severe and critical COVID-19 episodes. In conclusion, our results show that the second episode of SARS-CoV-2 positivity is more severe if it happens within 60 days after the first positive PCR. On the other hand, the second episode’s severity correlates with the first.

Download Full-text

Multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid level of the suggested prognostic marker CXCL13

Multiple Sclerosis Journal ◽

10.1177/1352458512463482 ◽

2012 ◽

Vol 19 (7) ◽

pp. 863-870 ◽

Cited By ~ 14

Author(s):

M Lindén ◽

M Khademi ◽

I Lima Bomfim ◽

F Piehl ◽

M Jagodic ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Neurological Diseases ◽

Severe Disease ◽

Human Leukocyte ◽

Disease Course ◽

Nucleotide Polymorphisms ◽

Treatment Protocols ◽

Tnfaip3 Gene ◽

Cerebrospinal Fluid Level

Background: The mechanisms of multiple sclerosis (MS) pathogenesis are still largely unknown. The heterogeneity of disease manifestations make the prediction of prognosis and choice of appropriate treatment protocols challenging. Recently, increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was proposed as a possible marker for a more severe disease course and conversion from clinically isolated syndrome (CIS) to relapsing–remitting MS (RRMS). Objective: To investigate whether there are genetic susceptibility variants in MS that correlate with the levels of CXCL13 present in the CSF of MS patients. Methods: We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a panel of single nucleotide polymorphisms (SNPs) that have been associated with susceptibility to MS and then correlated the genotypes with the levels of CXCL13, as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other neurological diseases (OND) or OND with an inflammatory component (iOND). Results: Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased levels of CXCL13. Conclusion: Our results pointed towards a genetic predisposition for increased CXCL13 levels, which in MS patients correlates with the severity of the disease course. These findings encourage further investigation and replication, in an independent patient cohort.

Download Full-text

Mechanistic Inferences from Clinical Reports of SARS-CoV-2

10.31219/osf.io/6q5bg ◽

2020 ◽

Author(s):

Meagan M Jenkins ◽

Tyler R McCaw ◽

Paul A Goepfert

Keyword(s):

Randomized Clinical Trials ◽

Severe Disease ◽

Treatment Options ◽

Management Strategies ◽

Type I ◽

Interferon Signaling ◽

Adaptive Responses ◽

Initial Clinical Trial ◽

Inflammatory State ◽

Clinical Trial Results

SARS-CoV-2 was identified as the causative pathogen in an outbreak of viral pneumonia cases originating in Wuhan, China, with an ensuing rapid global spread that led it to be declared a pandemic by the WHO on March 11, 2020. Given the threat to public health posed by sequelae of SARS-CoV-2 infection, the literature surrounding patient presentation in severe and non-severe cases, transmission rates and routes, management strategies, and initial clinical trial results have become available at an unprecedented pace. In this review we collate current clinical and immunologic reports, comparing these to reports of previous coronaviruses to identify mechanisms driving progression to severe disease in some patients. In brief, we propose a model wherein dysregulated type I interferon signaling leads to aberrant recruitment and accumulation of innate immune lineages in the lung, impairing establishment of productive adaptive responses, and permitting a pathologic pro-inflammatory state. Finally, we extend these findings to suggest possible treatment options that may merit investigation in randomized clinical trials.

Download Full-text

Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients

10.1101/2020.03.30.20047852 ◽

2020 ◽

Cited By ~ 3

Author(s):

Amr H. Sawalha ◽

Ming Zhao ◽

Patrick Coit ◽

Qianjin Lu

Keyword(s):

Oxidative Stress ◽

Immune Response ◽

Viral Entry ◽

Viral Infections ◽

Severe Disease ◽

Disease Course ◽

Vicious Cycle ◽

Respiratory Complications ◽

Disease Remission ◽

Functional Receptor

SummaryInfection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specially, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.

Download Full-text