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1.
Pulmonologiya ; 31(6):792-798, 2021.
Article in Russian | EMBASE | ID: covidwho-2033501

ABSTRACT

The main focus in the course of COVID-19 goes on assessing the overall immune response. The role of mucosal immunity in this disease has not been studied sufficiently. The study aimed to analyze published data about secretory IgA as a significant indicator of the mucosal immune response of the respiratory tract in the context of the COVID-19 pandemic. Methods. Articles were identified via PubMed bibliographic database. The time-span of research was two years (2020, 2021). Results. The search identified 54 articles. There is evidence that secretory IgA (sIgA) is the main antibody isotype of the mucosal immunity. It is produced in quantities significantly higher than those of all other isotypes of immunoglobulins combined. sIgA antibodies are effective against various pathogens, including the SARS-CoV-2 virus, due to mechanisms such as neutralization, suppression of adhesion to the mucosal surface and invasion of epithelial cells, agglutination and facilitating the removal of pathogenic microorganisms with the mucosal secretions. Virus-specific IgA antibodies in the blood serum are detected in patients with COVID-19 as early as two days after the first symptoms, while IgM or IgG class antibodies appear only after 5 days. We accessed the efficacy of intranasal immunization as to induction of predominant production of sIgA in the upper and lower respiratory tract. Conclusion. The current information on the local immune response of the respiratory mucosa is important for understanding the pathophysiological mechanisms of the disease, diagnosis, and development of new methods of treatment and prevention of COVID-19.

2.
Medical News of North Caucasus ; 17(2):202-204, 2022.
Article in English | EMBASE | ID: covidwho-2033430

ABSTRACT

The study determined the etiological structure and sensitivity to antibacterial agents of pathogens of uncomplicated and complicated forms of pneumonia in children treated in a multidisciplinary hospital. According to the study, that timely bacteriological diagnosis in the treatment of pneumonia in childhood with an adequate selection of effective antibacterial agents helps reduce hospitalizations and the development of complicated forms of pneumonia.

3.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2032772

ABSTRACT

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a cutaneous form of chronic active Epstein-Barrvirus (EBV) infection, which can develop into the extremely rare systemic lymphoma. Patients with Inborn errors of immunity (IEI), such as common variable immunodeficiency (CVID), are at higher risk of developing a severe course of infections especially viral and malignancies than the general population. The aim of the study was to present complex diagnostic and therapeutic management of HV-LPD. The clinical diagnosis was confirmed at the histological and molecular level with next generation sequencing. HV-LPD was diagnosed in a patient with CVID and chronic active Epstein–Barr virus (CAEBV) infection. The patient was refractory to CHOP chemotherapy and immunosuppressive treatment in combination with antiviral drugs (prednisone, bortezomib, gancyclovir). The third-party donor EBV-specific cytotoxic T cells (EBV-CTL, tabelecleucel) were used, which stabilised the disease course. Finally, matched unrelated donor hematopoietic cell transplantation (MUD-HCT) was performed followed by another cycle of EBV-CTL.

4.
HemaSphere ; 6:1096-1097, 2022.
Article in English | EMBASE | ID: covidwho-2032152

ABSTRACT

Background: Infectious complications are a major cause of morbidity and mortality in Chronic Lymphocytic Leukaemia (CLL). Therapeutic approaches that deplete CLL cells also affect normal B-cells. Optimal treatment would result in eradication of CLL cells and recovery of normal immune function. FLAIR (ISRCTN01844152) is a phase III trial for previously untreated CLL comparing ibrutinib plus rituximab (IR) with fludarabine, cyclophosphamide and rituximab (FCR) and subsequently amended to also compare ibrutinib plus venetoclax (I+V) and ibrutinib alone (I) with FCR. Measurable residual disease (MRD) and normal B-cell levels were assessed at multiple timepoints. Aims: To assess the depletion of normal B-cells during treatment and recovery after end of treatment. Methods: Participants aged under 75 years with <20% TP53-deleted cells were initially randomised to FCR or IR and subsequently to FCR, IR, I+V or I with the IR arm closed after randomisation of 771 participants to FCR/IR. FCR was given for 6 cycles, while treatment in the IR, I and I+V arms continued for up to 6 years except in participants attaining <0.01% MRD who continued treatment for the time taken to achieved MRD <0.01% and then stopped if MRD remained <0.01%. Month (M) 24 was earliest permitted stopping point. MRD flow cytometry was performed according to ERIC guidelines (panel: CD19/5/20/43/79/81+ROR1, acquisition of 0.5-2.2 million cells, BD Biosciences Lyric). Additional analysis of normal B-cell subsets was performed in a cohort of >500 patients (panel: CD19 to identify B-cells, CD20/5/79b+ROR1 and CD3 to exclude CLL & contaminating cells, with CD27/ 38/IgD/IgM to characterise normal B-cell subsets using a Coulter Cytoflex LX). Results: Normal B-cells were undetectable during FCR treatment and only rarely detectable until 12 months after last FCR cycle. Circulating normal B-cells were reduced in number or undetectable in participants receiving ibrutinibcontaining regimens with greater depletion in the I+V and IR arms relative to I monotherapy. B-progenitors persist through FCR treatment but were depleted during I, I+R or I+V treatment. Normal B-cell levels at 24 and 36 months after randomisation, with time off-treatment if applicable, are shown in Figure 1. In the ibrutinib-containing arms (IR, I, and I+V), there was a trend towards fewer COVID-associated SAE at any time point for participants with detectable B-cells at 24M (4/181, 2.2%) compared to those with no detectable B-cells (14/344, 4.1%) and COVID-associated SAEs were not observed in FCR-treated participants who had recovered any level of normal B-cells by 24M (0/215). However, the data on COVID infections are limited and there was no apparent association between normal B-cell levels at 24M with the proportion of participants experiencing an infectious SAE overall. Assessment of normal B-cell subsets during ibrutinib-based treatment demonstrated a mix of naïve and memory B-cells. Serological response to COVID infection/vaccination in this cohort is currently being performed. Participants stopping I+V treatment at 24-30 months post-randomisation due to MRD eradication showed rapid recovery of normal naive B-cells within 6-12 months after end of treatment in the vast majority (>95%) of evaluable cases. Summary/Conclusion: Normal circulating B-cells are depleted during treatment with rituximab but can persist at a low level during I, IR or I+V treatment. Most patients in remission after treatment with FCR or I+V show recovery of normal B-cells at 12 months of stopping treatment.

5.
HemaSphere ; 6:3613-3614, 2022.
Article in English | EMBASE | ID: covidwho-2032151

ABSTRACT

Background: Patients (pts) with indolent lymphomas are at increased risk of severe COVID-19 infection. We have shown limited seroconversion and live viral neutralisation (VN), but preserved COVID-specific T cell responses after 2 doses of mRNA COVID-19 vaccination in such pts. (Beaton, B ASH 2021, 149348). A 3rd vaccine dose to complete primary vaccination has since been recommended. Aims: To assess humoral & cellular immune responses to a 3rd COVID-19 (mRNA) vaccination in pts with follicular lymphoma (FL) & Waldenström Macroglobulinemia (WM), including assessment of response after pausing BTKi therapy in WM pts. Methods: Patients with WM, FL & healthy controls (HC) were enrolled in a prospective observational study to measure immune responses 21-28 days after a 3rd mRNA COVID-19 vaccine. Immune response was measured by mean fluorescence intensity (MFI) of anti-SARS-CoV-2 spike antibodies (ASAb) obtained using a high-sensitivity live cell assay, live VN to a panel of SARS-CoV-2 variants of concern, and CD4+ & CD8+ antigen-specific T cell responses. The associated TRIBECA (TReatment Interruption of BTKi to Enhance COVID-19 Antibody response) study sought to determine if a superior immune response could be gained by pause of BTKi therapy prior to and up to 4 weeks after 3rd vaccine dose. Patients were closely monitored during the BTKi pause with weekly clinical, full blood count and IgM assessments. WM pts receiving a 3rd dose while continuing on BTKi served as a control. Statistical analysis of medians between cohorts were compared by the non-parametric Mann-Whitney (Graphpad Prism). Comparison of medians between paired grouped data was assessed by 2-way ANOVA. Results: To date, 56 of 125 pts had their ASAb measured following 3rd vaccine dose administered between October 2021 and January 2022: 28 WM pts (including 6/9 WM pts on the BTKi pause sub-study), 24 FL pts and 4 HC. Median age was 68 years with 21 females and 35 males. Median follow up from 2nd dose was 140 days (range: 79- 170 days). In antibody responders, median MFI fell from 163042 (IQR 82663-249934) 28 days post 2nd dose to 52117 (IQR 19942-60973) (p<0.0001) immediately before the 3rd dose. Median MFI in all FL & WM pts pre- 3rd dose vaccine was 17111 (IQR 0-52650), rising significantly post 3rd dose to a median of 86730 (IQR 0-221937). Only 4/20 pts without measurable ASAb prior to the 3rd dose (2 WM, 2 FL) developed measurable ASAb following the 3rd dose: 16/20 patients (8 WM, 8FL, all treated) had no ASAb response. The median MFI in pts who underwent a BTKi treatment pause rose from 9151 (IQR 1671-21232) pre-3rd dose to 87720 (IQR 2785-152195) post 3rd dose, significantly higher than the median MFI in WM pts who did not pause their BTKi , which rose from 16769 (IQR 218-22447) pre- to 20252 (IQR 168-114262) post 3rd dose, (p = 0.016). Of the 5/125 with COVID infection in the study to date, only one patient (without measurable ASAb) in this 3-dose cohort had COVID, requiring intensive care support. Summary/Conclusion: Most WM & FL pts who responded to a 2nd dose COVID vaccine showed a decline in ASAb titre over time which increased following a 3rd mRNA vaccine. Only 20% of pts without detectable ASAb pre- 3rd dose showed improvement post 3rd dose, highlighting the importance of other COVID protection strategies in these pts. Although initial numbers are small, there may be a higher increment in ASAb when BTKi therapy is paused around the time of vaccination. Comprehensive immune analysis, including VN and T-cell response on the entire FL & WM cohort will be presented at the EHA congress.

6.
HemaSphere ; 6:1930-1931, 2022.
Article in English | EMBASE | ID: covidwho-2032125

ABSTRACT

Background: Bing-Neel syndrome (BNS) is a rare complication of lymphoplasmacytic lymphoma (LPL) comprising LPL infiltration in the central nervous system (CNS). Clinical and radiological features are diverse;the diagnosis is confirmed by cerebrospinal fluid (CSF) analysis using immunological and molecular techniques. Rarely, a tissue biopsy is required. The pattern of presentation including systemic involvement and CSF features inform treatment strategies, which include CNS-penetrating therapies. Aims: To evaluate the diagnostic characteristics of patients with BNS and their influence on therapy. Methods: Data from patients referred between 2011-2021 for management of BNS to our academic neurohaematology centre were retrospectively reviewed. Those with imaging features alone or where it was not possible to distinguish from high-grade transformation were excluded. Results: Thirty-five patients (22 male, 13 female) were identified. Median age at diagnosis of BNS was 65 years (range 48-85). All patients were symptomatic. In 12 patients (34%) BNS was the de novo presentation of the IgM-related disorder, of which 3 (25%) had no detectable bone marrow (BM) infiltration of LPL at diagnosis. Approximately half (17;49%) had previously received therapy for LPL;median time to BNS diagnosis in these was 49 months (range 3-125). At BNS diagnosis, BM involvement with LPL ranged from 0-95%. More than half (14/26;54%) had <10% infiltrate and almost a fifth (4/26) >60%. All patients had leptomeningeal involvement and 8 (23%) additionally had parenchymal CNS disease. The majority had kappa light-chain predominance: IgMκ (n=26), non-IgMκ (n=5), IgMλ (n=3), one unknown. The BNS diagnosis was made on CSF analysis (n=28;80%), leptomeningeal tissue biopsy (n=3;9%) where CSF was non-informative, or by expert opinion based on supportive clinical, radiological and non-definitive CSF features (n=4;11%). Of those with a diagnosis based on CSF studies, B-cell clonality was confirmed by flow cytometry (27/28;96%), MYD88L265P mutation (18/28;64%) and immunoglobulin gene rearrangement (12/28;43%). In 22 samples with a full dataset, median CSF white cell count was 25/ul (1-233), CSF protein 1.69g/l (0.35-6), CSF IgM 9.49mg/l (1.07-61.5). The majority were treated with intensive regimens (rituximab, methotrexate (MTX), cytarabine (ARA-C) + thiotepa/idarubicin;n=30) due to the presence of CNS disease bulk and clinical need, and less commonly ibrutinib (n=3), bendamustine-rituximab (BR, n=1);one patient had intrathecal therapy (MTX, ARA-C) at the height of the COVID pandemic. Of those who received 2 cycles of intensive chemotherapy, 3 had >4 cycles followed by BCNU/thiotepa autologous stem cell transplant;10 proceeded to 'consolidation' (indefinite) ibrutinib to limit intensive chemotherapy or tackle systemic disease. At a median follow up of 26 months (range 1-121), median survival was not reached;2-year overall survival was 91% (95% CI 74-97). Three patients died during treatment (1 invasive fungal infection post COVID-19 during ibrutinib consolidation post MTX/ARA-C based therapy) and 2 during MTX-ARA-C based therapy;7 patients relapsed or progressed and were treated with ibrutinib: 1 relapsed after ibrutinib use, 1 patient was intolerant of ibrutinib and switched to BR. Image: Summary/Conclusion: Our cohort confirms that BNS may present with leptomeningeal disease and/or parenchymal disease, de novo and without systemic disease. Overall outcomes are excellent with intensive regimens, consolidated with or followed by ibrutinib;however, there are treatment-related toxicities emphasising the need for a tailored approach.

7.
The Ethiopian Journal of Health Development ; 35(4):367, 2021.
Article in English | ProQuest Central | ID: covidwho-2026938

ABSTRACT

Background: Anti-SARS-CoV-2 antibody tests are increasingly used for sero-epidemiological purposes to provide a better understanding of the extent of the infection in the community, and to monitor the progression of the COVID-19 epidemic. A sero-prevalence study was conducted to estimate prior infections with SARS-CoV-2 in Addis Ababa. Methods: A cross-sectional study was conducted from April 23 to 28, 2020 among 301 randomly selected residents of Addis Ababa;sub-city health offices, health facilities and health extension workers were contacted, to obtain a population profile and to conduct the random selection of study participants. Participants were selected, who had not been in direct contact with people who had contracted COVID-19, to maintain consistency among the study population. Interviews on socio demographic and behavioural risk factors, followed by serological tests were performed for SARS-CoV-2 IgM, and IgG antibodies, using the COVID-19 IgG/IgM Rapid Test Cassette. Based on the manufacturer information, the test has a sensitivity of 87·9% and specificity of 100% for lgM;and a sensitivity of 97·2% and specificity of 100% for IgG. A Polymerase chain reaction (RT-PCR) test was also done on combined nasopharyngeal and oropharengeal swabs. Findings: The unadjusted antibody-based crude SARS-CoV-2 prevalence was 7·6% and the adjusted (weighted average) SARS-CoV-2 prevalence was estimated at 8·8% (95% CI 5·5%-11·6%) for the study population. Higher sero-prevalence were observed for males (9.0%), age below 50 years (8.2%), students and unemployed (15.6%), as well as those with primary education (12.1%), educated above high school (37·9%), non- smokers (78·7%), with no history of regular alcohol (53·8%), no chat (70·8%), and no shisha use (94·7%). According to the findings, a significantly higher number of individuals had been infected in Addis Ababa as compared to what was being detected and reported by the RT-PCR test, which is suggestive of community transmission.

8.
Viruses ; 14(8):1742, 2022.
Article in English | ProQuest Central | ID: covidwho-2024286

ABSTRACT

In West Africa, research on the hepatitis E virus (HEV) is barely covered, despite the recorded outbreaks. The low level of access to safe water and adequate sanitation is still one of the main factors of HEV spread in developing countries. HEV infection induces acute or sub-clinical liver diseases with a mortality rate ranging from 0.5 to 4%. The mortality rate is more alarming (15 to 25%) among pregnant women, especially in the last trimester of pregnancy. Herein, we conducted a multicentric socio-demographic and seroepidemiological survey of HEV in Senegal among pregnant women. A consecutive and non-redundant recruitment of participants was carried out over the period of 5 months, from March to July 2021. A total of 1227 consenting participants attending antenatal clinics responded to a standard questionnaire. Plasma samples were collected and tested for anti-HEV IgM and IgG by using the WANTAI HEV-IgM and IgG ELISA assay. The overall HEV seroprevalence was 7.8% (n = 96), with 0.5% (n = 6) and 7.4% (n = 91) for HEV IgM and HEV IgG, respectively. One of the participant samples was IgM/IgG-positive, while four were declared indeterminate to anti-HEV IgM as per the manufacturer’s instructions. From one locality to another, the seroprevalence of HEV antibodies varied from 0 to 1% for HEV IgM and from 1.5 to 10.5% for HEV IgG. The data also showed that seroprevalence varied significantly by marital status (p < 0.0001), by the regularity of income (p = 0.0043), and by access to sanitation services (p = 0.0006). These data could serve as a basis to setup national prevention strategies focused on socio-cultural, environmental, and behavioral aspects for a better management of HEV infection in Senegal.

9.
Archives of Disease in Childhood ; 107(Suppl 2):A214, 2022.
Article in English | ProQuest Central | ID: covidwho-2019872

ABSTRACT

AimsIntroductionCampylobacter infection is not uncommon in children, and extraintestinal manifestations following Campylobacter is a recognized entity, although hepatitis is rare. We present a case of anicteric hepatitis associated with Campylobacter infection in a 13-year-old boyMethodsCase StudyA previously healthy 13-year-old boy was admitted to the paediatric department with a 4-day history of fever and crampy abdominal pain which was localized to the right upper quadrant. He reported loss of appetite and nausea.He was not encephalopathic. His clinical examination was unremarkable, except for diffuse tenderness on deep palpation of the abdomen, especially of the right upper quadrant.His stools were normal initially but 48 hours after admission he developed severe diarrhoea.ResultsHe had elevated alanine transaminase (ALT) level (181 IU/L) on admission. The full blood count showed elevated white cell count with neutrophil leukocytosis, and C-reactive protein level was high (196mg/L). His prothrombin time (PT) and activated partial thromboplastin time (APTT) were within normal limits. The faecal molecular assay detected presence of Campylobacter by polymerase chain reaction (PCR). It did not identify any other organism.The viral hepatitis (Hepatitis A IgM, Hepatitis B surface antigen, Hepatitis C IgM, Hepatitis E IgM, and IgG) panel, Epstein-Barr virus (IgG for nuclear antigen, IgM, and IgG for viral capsid antigen), Cytomegalovirus (IgM and IgG) and Parvovirus B19 (IgM and IgG) screening were negative. Pandemic corona virus was not detected on PCR testing. The auto-antibody panel for autoimmune hepatitis (Anti-nuclear antibody, Anti-smooth muscle antibody, Anti-mitochondrial antibody, Liver kidney microsomal antibody) were normal. The ceruloplasmin level and Alpha-1 anti-trypsin levels were not low. The ultrasound scan of the abdomen revealed normal hepatic architecture, making a chronic liver disease less likely. An alternative explanation for high transaminases were not found.He improved clinically within a week and his liver functions continued to improve.ConclusionDiscussionCampylobacter infection has been associated with extra-intestinal manifestations like Guillain-Barre Syndrome, pancreatitis, erythema nodosum, haemolytic uremic syndrome, thrombotic thrombocytopenic purpura, haemolytic anaemia, glomerular nephritis, and reactive arthritis. Hepatitis is a rare complication of Campylobacterinfection and is rarely reported in medical literature.

10.
Archives of Disease in Childhood ; 107(Suppl 2):A11-A12, 2022.
Article in English | ProQuest Central | ID: covidwho-2019814

ABSTRACT

AimsPaediatric emergency departments saw an unusual increased incidence and severity of disease presentation in children with new onset diabetes in the early phase of the COVID-19 pandemic. The DIMPLES study(Diabetes Mellitus in children and young people presenting to the Emergency Department during the SARS-CoV-2 pandemic) aimed to characterise the features of children presenting to Paediatric Emergency Department with new onset diabetes in the COVID-19 pandemic, exploring the incidence and severity of diabetic ketoacidosis (DKA).MethodsThe DIMPLES study is a retrospective multicentre study done across 49 paediatric emergency departments providing a unique perspective of new onset diabetes paediatric diabetes from the frontline.We compared the characteristics of children aged 6 months to 16 years presenting to the Paediatric Emergency Departments across UK and Ireland with new onset diabetes in the pandemic (March 1, 2020 to February 28, 2021) with the children presenting in the same time period over the pre pandemic period (March 1, 2019 to February 28, 2020).ResultsDuring the COVID pandemic year, there were increase from the pre-pandemic year in children with new onset diabetes presenting with DKA (pH <7.3;from 395 to 566;43% rise), severe DKA (pH <7.1;from 141 to 252;a 79% rise), and admissions to intensive care (from 38 to 72;89% rise), suggesting an increase in incidence and severity of new-onset diabetes. An increase in the incidence of new onset diabetes from 1015 to 1176 was noted in the pandemic(16% increase compared to an estimated increase of 2-4% per year).The median age of children who presented with new onset diabetes in the pandemic, the duration of symptoms before presentation and the ethnicity was similar to the pre pandemic period. Delay did not appear to be a significant factor in the pandemic compared to the pre pandemic period in the majority of cases.There was a paucity in testing for COVID-19 antibodies, 37/1176 children with new onset diabetes were tested with n=8 children testing positive for IgG/IgM COVID-19 antibodies. 12 children with new onset diabetes tested positive for SARS-CoV-2 on nasopharyngeal swabs, 7 presented with moderate to severe DKA and 3 presented with mild DKA.ConclusionThe DIMPLES study showed an increase in the number and severity of children presenting to the Paediatric Emergency Department with new onset diabetes and DKA in the COVID -19 pandemic. Proving association or causation was challenging given the small number of children tested for COVID-19 antibodies. When the incidence and severity at presentation is interpreted in the context of high levels of SARS-CoV-2 in the community and a low incidence of other viral infectious triggers it appears that COVID -19 may have a role as an accelerator or possibly even a precipitator of new onset diabetes in a genetically predisposed child.

11.
25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021 ; : 851-852, 2021.
Article in English | Scopus | ID: covidwho-2010980

ABSTRACT

In this work, we report the initial development steps of a finger stick point-of-care device (adhesive bandage) for timely detection/screening of immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The bandage, comprising vertically stacked serum separation membrane, conjugate pad, and detection (readout) zone, aims to colloid-capture SARS-CoV-2-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies from a pinprick (~10 µL) of blood in one step, and visually display results in forms of no immune IgM-/IgG-, early immune IgM+/IgG-, active immune IgM+/IgG+, and immune IgM-/IgG+ in short time (minutes). © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

12.
NeuroQuantology ; 20(8):7591-7595, 2022.
Article in English | EMBASE | ID: covidwho-2010532

ABSTRACT

The current research aimedto demonstrate the extent such as increase in the rate of immune response to antibodies (IgG, IgM) for people who received the first dose of the Pfizer mRNA vaccine at (1-3) weeks times period and to compare them with people who were not taken for the first dose of the same vaccine and none infected with COVID-19.Also the results appearedsignificant variations in immunoglobulin (IgG) levels (P≤ 0.05) between case (Recipients mRNA vaccination) and control patients, there were. In terms of age and gender, however, there were no significant changes (P≥ 0.05) in immunoglobulin (IgM) levels between case (Recipients mRNA vaccination) and control patients.

13.
Pharmacia ; 69(3):791-800, 2022.
Article in English | EMBASE | ID: covidwho-2010396

ABSTRACT

The aim of current study was to determine, retrospectively, possible correlations between smoking and the incidence, course severity, intubation rate, and mortality (by gender and age) in patients treated for complicated coronavirus infection in the internal medicine clinic at UMHATEM ”N. I. Pirogov” Sofia for the period 01.03.2020–31.12.2020. In a prospective study, the recovery period and immunogenesis in smokers and non-smokers within a one-year period after hospital discharge was investigated. The applied methods were: 1) computed tomography and blood gas analysis 2) chemiluminescent immunoassay for the qualitative determination of total IgM, IgA and IgG anti-SARS-CoV2 AB. Results showed that the part of non-smokers with a positive PCR test is significantly higher compared to the group of former and current smokers. The data obtained from the study confirmed that Covid infection is much more severe among smokers and former smokers with a higher levels of inflammatory markers noticed among the smoking group.

14.
Annals of the Rheumatic Diseases ; 81:760, 2022.
Article in English | EMBASE | ID: covidwho-2009136

ABSTRACT

Background: Pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov2/COVID19) determines the life of clinicians and patients since 2 years. Limited information is available on the nature, prognosis, and complications of SARS-Cov2 virus infection in patients with idiopathic infammatory myopathies (IIM). There are also few data on triggered humoral response, side effects and disease course after COVID19 infection or vaccination in IIM. Objectives: The primary goals of the current research were to assess frequency and outcome of COVID-19 disease and to determine the vaccination rate and effect in our IIM cohort. Secondary objectives were to search for risk factors of infection, predictive factors of hospitalization and to assess incidence of vaccination adverse events, complications and post vaccination breakthrough infections. Methods: We retrospectively identifed the confrmed COVID19 positive patients and assessed the symptoms, disease course and outcome on 01/06/2021 then patients were prospectively followed. Incidence and complications of vaccination were determined by questionnaires. Anti-SARS-CoV-2 S enzyme electrochemilu-minescent immunoassay has been used to assess seroconversion, which measures total antibody (IgM and IgG) to the SARS-CoV2 S protein and SARS-CoV2 N protein. Disease activity was determined by physician global activity. Results: A total of 176 patients were screened and 101 participated in the study. By 01/06/2021, the COVID infection rate was 34,7% (mean age: 49.54 years, 72.72% women), which was signifcantly higher than the national prevalence at that time (8.2%). A third of these infections occurred asymptomatically or mild but 20% of the infected patients were hospitalized, one patient died. Longer disease duration (8.67 vs. 17.87 years;p=0.003) and higher incidence of anti-Jo-1 antibody (57% vs. 10% p=0.018) were signifcantly associated with hospitaliza-tion. All of COVID infected patients became seropositive regardless of immu-nosuppressive therapy or symptoms severity. 53,4 % of the patients received anti-COVID19 vaccine, 75,9 % choose the mRNA type. The titer of antibodies against the spike protein induced by vaccines showed high variance, but 72,3% of patients became seropositive after vaccination. Higher antibody titer against spike protein was detected after Pfzer-BioNTech vaccination compared to others (177,1 U/ml vs. 81.1 U/ml;p <001). Patients receiving steroid therapy had decreased post-vaccination antibody response compared to those without steroid treatment (94,03 U/ml vs. 165.6 U/ml;p = 0.008). With the follow-up of vaccinated patients, we did not found short term vaccine related major adverse events, but long term data revealed 7, 4 % post vaccination disease relapse. Breakthrough infection was detected in 9.25 % of the vaccinated patients, one cancer associated patient without post vaccination seroconversion died due to COVID pneumonia. All the fatal COVID infections occurred in patients with seron-egativity to anti-SARS-CoV2 S protein. Conclusion: Based on our results, myositis may be associated with an increased risk of infection with SARS-CoV-2. Independent risk factor for hospitalization is anti-Jo1 positivity and longer disease duration. Anti-SARS-CoV2 vaccines are safe, tolerable and strongly recommended for IIM population, but further investigation is required to assess clinical signifcance of post-vaccination disease fare.

15.
Annals of the Rheumatic Diseases ; 81:1699-1700, 2022.
Article in English | EMBASE | ID: covidwho-2009132

ABSTRACT

Background: SARS-CoV-2 infection is a public health problem due to its high contagiousness and mortality. Spectrum of symptoms ranges from no symptoms to interstitial pneumonia. Patients with rheumatic disease present an increased infectious risk, especially those treated with immunosuppressants or biologic therapy. Since the beginning of the pandemic, risk of contagion and development of complications in these patients has been questioned. Objectives: To describe hospitalization prevalence, seroconversion, and symptoms in patients under follow-up by the rheumatology department of a tertiary hospital. Methods: Observational, cross-sectional study conducted by phone interview including patients with different diagnosis of rhematic diseases. Data about symptoms, hospital admission, serology by ELISA (when >15 days of evolution), diagnosis and baseline treatment, from March 2020 to February 2021 were collected. Results: Eighty-six patients with different rheumatic diseases and positive COVID-19 PCR were included (82.35% women) in Table 1. Mean age was 49.30 years (16.16). The 48.71% received biological therapy, JAK inhibitors or apremi-last, with a median of 3.11 years (Q1 1,08;Q3 3,17). Secukinumab was the biological therapy most often used (24,32%), followed by Tocilizumab (13,51%). The 34,18% received DMARDs or immunosuppressors, with a median of 5.09 years (Q1 12,25;Q3 11.09). The most frequent symptoms were asthenia (72.15%), headache (66.23%) and cough (59.49%). Nine patients (11.25%) were admitted to hospital, eight of them (10%) for pneumonia. Three of them were admitted to intensive care and one died. Seroconversion occurred in 53.25%. low IgG titers were present in 2.94% and IgM persisted positive in 56.25% of this group. In 6.45% the result was indeterminate. Conclusion: Hospitalization and mortality rate obtained was low and the most frequent symptoms were mild. Seroconversion occurred in more than 50% of patients and the result of 6.45% was indeterminate. It's important to highlight that since March 2020 to May 2020 IgG positive prevalence was 25%, while since September 2021 to February 2021, this prevalence increased until 57,45%. This difference is due to a modifcation of autoantibody detection technique since summer 2020.

16.
Annals of the Rheumatic Diseases ; 81:1683, 2022.
Article in English | EMBASE | ID: covidwho-2009025

ABSTRACT

Background: It is assumed that patients with immuno-infammatory rheumatic diseases (IIRDs) in old age are susceptible to a more severe course of COVID-19 both due immunological disorders (autoimmune disease and its activity, immuno-suppressive therapy, immunosenescence leading to systemic subclinical chronic infammation with increased secretion of IL-6, IL-1, IL-18, TNF-α) and due to the presence of comorbid pathology. There are no Russian data on the course of COVID-19 in elderly patients with IIRDs. Objectives: To study the features of the course of COVID-19 in elderly patients with IIRDs. Methods: The study included 93 patients with IIRDs: 72 women, 21 men, average age 67.5±6.1 years. Of them, 62 patients suffered from rheumatoid arthritis, 9-systemic sclerosis, 5-ankylosing spondylitis, 4-Sjogren's disease, 4-systemic vasculitis, 3-psoriatic arthritis, 2-osteoarthritis, 1 systemic lupus erythematosus, 1-polymyositis, 1-rheumatic polymyal-gia, 1-gout. At the moment of COVID-19, 10 patients had high activity of IIRDs, 26-moderate, 40-low, 17-remission. 69 patients were treated with disease-modifying antirheumatic drugs-DMARDs (40-methotrexate, 12-lefunomide, 8-sulfasalazine, 7-hydroxychloroquine), 45-glucocorticoids (34-low doses, 11-medium or high doses). 36 patients received biologic or target DMARDs: 24-rituximab (the interval from the last administration to the development of COVID-19 symptoms averaged 7 months), 4-TNF-α inhibitors, 3-abatacept, 2-secukinumab, 1-tofacitinib, 1-baricitinib, 1 ustekinumab. Comorbidities included hypertension (n=74), coronary artery disease (n=27), obesity (n=17), diabetes mellitus (n=8), bronchial asthma (n=5), chronic obstructive pulmonary disease (n=4), chronic kidney disease (n=3). The patients were interviewed by a research doctor, additional information was obtained from medical documentation. Results: The most common symptoms of COVID-19 were fever-67.7%, weakness/drowsiness-53.7%, cough-48.4%, as well as anosmia and dyspnea-35.5% each, headache-20.4%, body aches-16.1%, congestion nose-8.6%, chest pain-7.5%, dysgeusia-5.4%, diarrhea/vomiting-3.2%. According to CT chest scan, 8 patients had 0% of lung damage, 31-25%, 32-50%, 12-75%, in other cases the study was not carried out (n=9) or data are not available (n=1). In 2 patients the course of COVID-19 was complicated by bacterial pneumonia, in 1-bacterial-fungal. An asymptomatic course was noted only in 2 patients (PCR+/IgM +, CT 0, close contact with a confrmed case of COVID-19). Recovery was noted in 90 patients, fatal outcome-in 3. Exacerbation of IIRDs after COVID-19 was noted in 48.4% of patients, which required intensifying antirheu-matic therapy. Conclusion: Preliminary data indicate that COVID-19 is characterized by moderate and severe course in elderly patients with IIRDs. Further studies are required to identify risk factors for severe course and complications in order to provide timely qualifed care.

17.
Annals of the Rheumatic Diseases ; 81:954, 2022.
Article in English | EMBASE | ID: covidwho-2009014

ABSTRACT

Background: Coronavirus Disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by a wide range of clinical manifestations 1. Although COVID-19 was initially considered a respiratory infection, it was shortly recognized as a multisystemic disorder associated with heightened infammatory responses, including autoimmune phenomena 1. The presence of autoantibodies (AAbs) has been described in COVID-19 patients, highlighting the state of immune dysregulation in COVID-19 1. The clinical signifcance of AAbs, however, is still elusive. Objectives: To assess the prevalence of AAbs in critically ill, mechanically ventilated COVID-19 patients admitted to the intensive care unit (ICU) and investigate whether AAbs influence the clinical outcome of these patients. Methods: The current study evaluated prospectively from March 8th, 2021 to May 10th, 2021 the presence of AAbs against nuclear antigens (ANA), extracta-ble nuclear antigens (ENA), neutrophil cytoplasmic antigens (ANCA), cyclic cit-rullinated peptides (anti-CCP), double stranded-DNA (anti-dsDNA), cardiolipin (anti-CL), β2-glycoprotein-I (anti-β2-GPI), thyroid peroxidase (anti-TPO), and thyroglobulin (anti-TG) in critically ill COVID-19 patients upon admission in the ICU (n=217). Samples from 60 COVID-19 patients that were available 15 days after ICU admission were further analyzed for the evaluation of de novo AAbs production. Serum samples of age and sex matched healthy individuals before the COVID-19 pandemic were used as a control group (n=117). Results: COVID-19 patients treated in ICU had more commonly at least one AAb compared to age and sex matched controls (174/217, 80.2% vs 73/217, 62,4%, p< 0,001). More specifcally, COVID-19 patients expressed more frequently ANAs (48.4% vs 21.4%, p<0.001), anti-dsDNA (5.1% vs 0%, p=0.01), anti-CCP (8.3% vs 1.7%, p=0.014) and anti-CL IgM AAbs (21.7% vs 9.4%, p=0.005) than controls. The majority of critical COVID-19 patients who were positive for AAbs (144, 82.8%) expressed reactivity in up to three autoantigens with the most prominent being ANA, anti-phospholipid, ANCA and anti-TPO AAbs. AAbs-positive patients demonstrated more robust anti-SARS-CoV-2 humoral responses compared to AAbs-negative patients [detectable anti-SARS-CoV-2 S1-protein IgG antibodies: 150 (86.2%) vs 28 (65.1%), p=0.001;adequate neutralizing activity: 159 (91.4%) vs. 33 (76.7%), p=0.007]. The two groups, however, did not differ in terms of clinicoepidemiologic characteristics or the incidence of death in the ICU. Convalescent COVID-19 patients (n=111) compared to those who died (n=106), did not differ in the prevalence of serum AAbs or antibody responses against SARS-CoV-2. Differences were only shown in clinicolaboratory parameters including patients' age, comorbidities, O2 saturation, infammatory markers, and in-hospi-tal prognostic scores as expected. Paired samples testing (n=60) revealed that 45 patients had at least one newly induced AAb, 28 patients lost at least one reactivity and only 6 patients didn't show any seroconversion. The most common new-onset AAb reactivity was against anti-CL (IgG isotype) (n=21) followed by ANA (n=20), anti-β2-GPI (IgG isotype) (n=11), myositis-related antigens (n=13) and ENAs (n=9);nevertheless, no associations with clinicoepidemiologic features or COVID-19 outcome were revealed. Conclusion: Patients with severe COVID-19 express AAbs more commonly than age and sex matched controls, suggesting that SARS-COV-2 infection may induce a hitherto unknown B-cell autoreactivity. The presence of autoantibodies does not play a role in the outcome of SARS-COV-2 infection. However, further studies are needed to defne their role in future development of systemic autoimmune disorders or the long-COVID syndrome.

18.
Annals of the Rheumatic Diseases ; 81:331-332, 2022.
Article in English | EMBASE | ID: covidwho-2008925

ABSTRACT

Background: Thrombosis is a unique complication in coronavirus disease 2019 (COVID-19). We have reported that elevated ferritin and D-dimer on admission were the risk factors of thromboses by analyzing the patients sequentially admitted to our hospital due to COVID-19 (1). However, we have not analyzed throm-botic complications in the view of the antiphospholipid antibodies (aPLs), which are frequently detected in the COVID-19 patients. Objectives: To elucidate the thrombogenic effects of aPLs in COVID-19, we analyzed the development of thrombosis in three lupus models after SARS-CoV-2 infection. Additionally, we evaluated the association of thrombotic events and the serum profile of aPLs in Japanese patients with COVID-19. Methods: Three animal models of lupus (MRL-lpr/lpr, NZBxNZW F1 and NZW×BXSB F1) were evaluated in this study. NZW×BXSB F1 was also considered as a model of antiphospholipid syndrome (APS) since aPLs were detected with a high titer (2). Experimental SARS-CoV-2 infection was induced using mouse-passaged virus strain (3). The incidence of thromboses in the lungs and kidneys were identifed by evaluating H&E staining and PTAH staining of paraf-fn-embedded sections. We have experienced 44 thrombotic events in 34 out of 594 patients admitted to our institute. As a non-thrombotic COVID-19, 68 patients were selected to make a 1 to 2 matched-pair based on the propensity score. In total 102 patients, seven types of aPLs (anti-cardiolipin (CL) IgG/IgM, anti-β2GP1 IgG/IgA/IgM, and anti-phosphatidyl serine/prothrombin complex (PS/PT) IgG/IgM) were measured using specifc ELISA kits. The patients' clinical characteristics and serological profile of aPLs were further evaluated. Results: We identifed the development of thromboses in the lungs or kidneys in 6 out of 12 (50%) NZW×BXSB F1 mice after the SARS-CoV-2 infection, whereas no thrombosis was observed in non-infected mice. Further, there was no thrombosis in the other lupus models (0%) after the infection. These fndings might suggest the pathogenic role of aPLs under the SARS-CoV-2 infection. Among our COVID-19 patients, 39 out of 102 (38%) were tested positive for one or more aPLs. The positive ratios of any aPLs were statistically indifferent between the patients with or without thrombosis;anti-CL IgG (8.8% vs 5.9%)/IgM (0% vs 5.9%), anti-β2GP1 IgG (21% vs 12%)/IgA (8.8% vs 15%)/IgM (0% vs 1.5%), and anti-PS/PT IgG (0% vs 2.9%)/IgM (12% vs 13%), respectively. In addition, their titers were relatively lower than those observed in APS patients. The patients' characteristics and the prognosis of COVID-19 were comparable regardless of the detection of any aPLs. These fndings suggested that COVID-19 associated aPLs were irrelevant to thrombotic complications. Conclusion: Thromboses were induced after the infection of SARS-CoV-2 only in the APS model. However, aPLs detected in COVID-19 patients have little impact on the development of thrombosis. SARS-CoV-2 infection might have a high risk of thrombosis, especially in APS patients, as shown in the case report (4). The discrepancy of its thrombogenic effects of aPLs might be explained by the low titer of the antibody or the diversity of antibody epitope. Further analyses are required to clarify the mechanisms of aPLs production and the development of thrombosis in COVID-19.

19.
Annals of the Rheumatic Diseases ; 81:367-368, 2022.
Article in English | EMBASE | ID: covidwho-2008923

ABSTRACT

Background: Rheumatic musculoskeletal diseases (RMD) are pathological conditions characterized by an impaired immunological system that is determinant both in the pathogenesis and in the inadequate response to infections. The use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) or biologic and targeted synthetic (b/ts) DMARDs, contribute to compromise immunological reactivity. Objectives: To analyze the immune response to SARS-CoV-2 in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) receiving treatment with DMARDs and to investigate the effect of the different classes of drugs on humoral and cellular response. Methods: Patients were tested for anti-SARS-CoV-2 IgG, IgM and IgA antibodies to nucleoprotein (N) and receptor-binding domain (RBD) through ELISA and neutralization assays. Then, we performed a fow cytometry analysis of monocytes, NK cells, B and T lymphocytes from PBMCs of serologically positive patients. We also included a cohort of non-RMD individuals recovered from COVID-19 as a reference group of non-immunosuppressed subjects. A frst recruitment occurred in May-June 2020 (T1) and a second recruitment, 3-4 months after (T2), allowed to evaluate the persistence of the antibody response over time and to investigate the cellular immune response to SARS-CoV-2 in RMD patients having resolved the infection. Results: During T1, 358 patients with RA (n=200) or SpA (n=158) were recruited. Mean age was 52.8, 64% were female. All patients were treated with DMARDs, 299 with b/tsDMARDs and 59 received csDMARDs alone. One third was also receiving corticosteroids (CS). At T2, 36 subjects were recruited. We found a seroprevalence rate of 18.4%, which did not signifcantly differ between RA and SpA groups, and between patients treated with b/ts-DMARD or csDMARDs, either alone or in combination with CS (Table 1). Antibody levels of RMD patients were lower than non-RMD individuals (Figure 1), with CTLA4-Ig-treated patients having the lowest IgG levels. This difference was less marked in symptomatic RMD patients. 72% of seropositive patients elicited neutralizing sera. Despite an overall decrease in anti-RBD and anti-N titers, more than two-third of patients maintained antibodies titers above positivity threshold at T2. Concerning cellular response, we found that CD8+ T-cells frequency was overall comparable between RMD and non-RMD convalescents, and did not differ in b-or cs-DMARD treated ones. Conversely, CD4+ T-cell frequencies were signifcantly lower in RMD patients, especially those treated with anti-IL6R and CTLA4-Ig. B-cell subpopulations (class-switched, memory, and IgG+ memory B-cells) had sustained frequencies in anti-TNFα treated patients, while they had a trend of reduction in patients treated with anti-IL6R and CTLA4-Ig. Conclusion: Our data provide a comprehensive picture of the humoral and cellular immune responses to SARS-CoV-2 infection in RMD patients. We showed that DMARDs treatments did not alter a successful antibody response to the virus and did not hamper the antibody neutralizing ability. However, the magnitude of antibody response was slightly reduced compared to non-RMD individuals, especially in patients receiving CTLA4-Ig. We did not observe marked differences in the B-and T-cell populations between RMD patients compared to non-RMD individuals. However, in patients receiving anti-TNFα we found a higher relative abundance of effector adaptive population compared to other bDMARDs.

20.
Annals of the Rheumatic Diseases ; 81:115, 2022.
Article in English | EMBASE | ID: covidwho-2008913

ABSTRACT

Background: Patients with autoimmune systemic diseases have an increased risk to contract infections and develop severe complications;infections in turn can reactivated and worsen the disease itself in a vicious circle. Thus, vaccination is the main weapon to prevent infectious diseases and represents an important and safe instrument of care for rheumatic patients that needs to be further promoted. However, the immunosuppressive drugs used to treat rheumatic diseases may impair response to vaccines, in particular those targeting B or T cells directly (1). Objectives: The aim of this study is to evaluate the B and T-cell mediated immune response to mRNA vaccination in patients with systemic autoimmune diseases, such as vasculitis or systemic connective tissue diseases, early or continuously treated with B-cell targeting therapies, rituximab (RTX) or beli-mumab (BEL), by comparing with controls and each other. Secondary we evaluated the in vitro effective neutralizing capacity in belimumab-exposed patients. Methods: Twenty-eight consecutive patients under treatment with rituximab (RTX, n=11) or belimumab (BEL, n=17) and 13 age/sex matched controls (non-rheumatic healthcare personnel) were enrolled in the study. Nobody presented anti-SARS-CoV2 antibodies related to previous viral contact and all were always negative at the molecular swab monthly control. All patients and controls received mRNA vaccines and were tested three to four weeks after complete vaccination. All RTX patients started vaccination within 5 months from the last infusion, and all but one of them were B-cell depleted. Anti-SARS-CoV-2 RBD total antibodies were analysed by a diagnostic assay (Elecsys, Roche) while T-cell response was evaluated using the IGRA test (Euroimmun). A subgroup of BEL-patients was tested with pseudovirus neutralization assay. Results: Detectable anti-SARS-CoV2 RBD antibodies were documented in 1/11 RTX patients versus 16/17 BEL patients (p<0.0001). The median concentration was signifcantly lower than that observed in controls (39.6 AU/ml vs 1133 AU/ml, p<0.0001). A very low titer of anti-RBD antibodies were documented only in 1 out of 11 patients in the RTX subgroup (0.93 U/ml, positive if >0,79 U/ml) and the patient was the only one who showed an initial B-cell recovery (CD19+ B-cell 5 cells/microL). Anti-RBD antibodies were documented in 16 out 17 of patients in the BEL subgroup. The median anti-RBD antibody titer in patients receiving BEL was 243 [77.55-744.0] U/ml, and it was signifcantly lower compared to the controls (p=0.002). The IGRA test was positive in 8/11 (72.7%) RTX patients vs 16/17 (94.1%) BEL patients (p=0.7), with interferon release comparable to control subjects (p=0.2). Six patients with BEL were also stratifed according to total antibodies (IgG+I-gA+IgM) against-RBD into high responders (>800 AU/mL, n=3) and low responders (≤45 AU/mL, n=3) and tested with pseudovirus neutralization assay. Two thirds of low titer group of patients neutralized the Wuhan-Hu1 strain at medium-low titer (IC50 ≈102) but were almost ineffective in inhibiting the B.1.1.7 entry into target cells (IC50 =10). Regarding high responders, while two patients were able to inhibit both the strains at medium-high titer (approximately IC50 ≈103 for Wuhan-Hu1 and B.1.1.7), one patient neutralized only the WT strain. Conclusion: B-cell targeting therapies do not preclude SARS-CoV-2 vaccination since a cellular immunity can raise even in the absence of circulating B cells. Most importantly, the immunogenicity of COVID-19 vaccination in SLE patients treated with belimumab is supported. However, patients showing the lowest humoral response to vaccine could remain at higher risk of infections, due to low neutralizing capacity.

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