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1.
Embase; 28.
Preprint in English | EMBASE | ID: ppcovidwho-346602

ABSTRACT

Chronic infection with human cytomegalovirus (CMV) may contribute to poor vaccine efficacy in older adults. We assessed effects of CMV serostatus on antibody quantity and quality, as well as cellular memory recall responses, after 2 and 3 SARS-CoV-2 mRNA vaccine doses, in older adults in assisted living facilities. CMV serostatus did not affect anti-Spike and anti-RBD IgG antibody levels, nor neutralization capacity against wildtype or beta variants of SARS-CoV-2 several months after vaccination. CMV seropositivity altered T cell expression of senescence-associated markers and increased TEMRA cell numbers, as has been previously reported;however, this did not impact Spike-specific CD4+ T cell memory recall responses. CMV seropositive individuals did not have a higher incidence of COVID-19, though prior infection influenced humoral immunity. Therefore, CMV seropositivity may alter T cell composition but does not impede the durability of humoral protection or cellular memory responses after SARS-CoV-2 mRNA vaccination in older adults. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

2.
Clinical and Experimental Rheumatology ; 40(10):82-83, 2022.
Article in English | EMBASE | ID: covidwho-2067782

ABSTRACT

Objectives. The peripheral lymphocyte compartment of patients with primary Sjogren's syndrome (pSS) differs strongly from healthy individuals. Whether this altered lymphocyte composition also abnormally changes during immune reactions, especially in the context of novel mRNA-vaccines, is unknown. Methods. Peripheral blood samples from 26 pSS patients were compared to 6 healthy controls before Coronavirus-2 (CoV-2) vaccination (BNT162b2, ChAdOx1, mRNA-1273) and 7 days after secondary vaccination. Spike. 1 (S1)-receptor binding domain (RBD)-neutralizing IgG antibodies were measured in serum samples. Within peripheral blood mononuclear cells (PBMC), lymphocytes were characterized using spectral flow cytometry and B and T cell subpopulations were phenotypically analyzed. Results. Immunization induced CoV-2 specific serum antibodies in all pSS and healthy participants. When analyzing pSS and healthy individuals together, frequencies of circulating IgG+ RBD-binding antibody-secreting cells (ASC) and anti-CoV-2 serum titers correlated (r=0.42, p=0.022). Previously described alterations of peripheral B cells in pSS patients (like reduced memory B cells, increased naive and transitional B cells and higher maturity of ASCs) remained stable during vaccination. Also the subset distribution of CD4+ and CD8+ T cells mainly stayed unchanged. However, CD4+CXCR5-PD-1+ T cells phenotypically mimicking peripheral helper TPH cells increased in pSS patients comparing pre- and post-vaccination (p=0.020), while circulating CD4+CXCR5+PD-1+ follicular helper TFH cells declined (p=0.024). Conclusions. An immune reaction induced by vaccination with the novel mRNA technology yields adequate antibody production and vaccine specific lymphocytes in pSS patients and controls. However, no major changes within the typical composition of lymphocyte subpopulations of pSS patients were observed despite small changes in TPH and TFH subsets.

3.
Journal of Clinical and Diagnostic Research ; 16(9):DC12-DC17, 2022.
Article in English | EMBASE | ID: covidwho-2067199

ABSTRACT

Introduction: Bharat Biotech International Ltd in partnership with National Institute of Virology (NIV), has developed an indigenous whole virion inactivated Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) viral vaccine BBV-152 (Covaxin), formulated with Toll Like Receptors 7/8 agonist Imidazoquinoline (IMDG) molecule adsorbed to alum (Algel). Variety of factors other than environmental ones can affect vaccines efficiency outside the strict setting of clinical trials, like how the vaccine is stored or transported, and even how patients are vaccinated. In addition, the intrinsic capacity of the recipient to respond to a vaccine which is determined by sex, genetic factors, age, psychological stress, nutrition and other diseases are also likely to have an impact. Aim(s): To determine the safety, reactogenicity and immunogenicity of the inactivated whole virus vaccine (Covaxin) amongst hospital-based population groups. Material(s) and Method(s): The prospective analytical study was conducted in the Department of Microbiology, Sawai Man Singh Medical College, Jaipur, Rajasthan, India, from January 2021 to March 2021.The study primarily included Healthcare Workers (HCWs) employed at SMS Medical college and attached hospitals. In-vitro quantitative IgG antibodies against SARS-CoV-2 spike Receptor Binding Domain (RBD) were measured using Chemiluminescence Immunoassay (CLIA) based Advia centaur SARS-CoV-2 IgG, manufactured by Siemens Pvt Ltd, Munich, Germany, as per manufacture's instructions. Result(s): Out of total 223 individuals, 61.88 % (138/223) showed neutralising antibody titre of >1 index value by CLIA, rest 38.12% (85/223) were non reactive i.e., titre <1 index value, after four weeks of receiving first dose of Covaxin. After 2 to 4 weeks of receiving second dose 84.30% (188/223) showed neutralising antibody titre of >1 index value by CLIA, rest 15.70% (35/223) were non reactive i.e., titre <1 index value. After receiving first dose, 100% (223/223) of the participants developed localised pain and bodyache 33.63% (75/223). None of the participants showed any anaphylactic reaction or any emergency condition just after vaccination. Conclusion(s): Covaxin is a well-tolerated vaccine, and induces good humoral response against SARS-CoV-2 with a significant rise in the neutralising antibody titres. Copyright © 2022 Journal of Clinical and Diagnostic Research. All rights reserved.

4.
Mediterranean Journal of Infection, Microbes and Antimicrobials ; 11(1) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2066934

ABSTRACT

Introduction: Severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) antibodies are produced in persons who have been infected by the virus or have received the vaccine. Many features of these antibodies, including their dynamics and neutralization capacities, are still unclear. Understanding the immune response of the host is very important for the development of appropriate treatment methods, vaccines, and epidemiological control strategies. The present study aimed to monitor the change in antibody levels over time in individuals diagnosed with SARSCoV- 2 infections and to determine their neutralization capacity. Material(s) and Method(s): Anti-nucleocapsid and anti-spike antibody titers were measured using different kits on monthly obtained serum samples of patients of patients with SARS-CoV-2 infection. The neutralizing antibodies were evaluated using a microneutralization assay. Result(s): A total of 134 serum samples taken from 43 patients with a mild-moderate disease course were analyzed. Anti-spike antibody positivity was detected on day seven at the earliest and day 334 at the latest following a positive polymerase chain reaction (PCR) test. The mean antibody levels were observed to increase gradually to a peak after three months, and then started to decrease after month six. Anti-nucleocapsid IgM and IgG antibodies were detected alone or in combination. The highest neutralizing antibody titer was 1/80 in the first month, which was seen to drop below 1/10 after four months. Conclusion(s): The combined use of kits for the detection of antibodies against different antigens or testing total antibodies would result in a more accurate and earlier detection of the antibodies that start to emerge on the seventh day and decrease six months after SARS-CoV-2 PCR positivity. In addition, the dramatic decrease in neutralizing antibody titers after four months may be one of the causes of early reinfections. Copyright © 2022 by the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey.

5.
Archives of Disease in Childhood ; 107(Supplement 2):A267-A268, 2022.
Article in English | EMBASE | ID: covidwho-2064033

ABSTRACT

Aims To assess if there is any temporal association between the sudden high incidence of newly diagnosed Type 1 Diabetes Mellitus (T1DM) in children and the onset of Coronavirus Disease 2019 (CoviD19) in Harlow, Essex UK. Methods Design An observational study Setting Princess Alexandra Hospital NHS Trust (PAH), District General Hospital Over a period of 6 weeks between end April to start of June 2020, there were 10 cases of new onset T1DM who presented to our paediatric department. We reviewed the demographics, symptomatology and biochemical presentations of these patients (table 1). Bloods including SARS-CoV-2 IgG antibody were taken at first presentation and patients had nasal swabs for SARS-COV-2 PCR. Families of patients provided written consent to take part in the project. Antibody testing with HSL Roche kit (sensitivity of 97% at D14-21 and 100% at D40) was processed at PAH microbiology laboratory. All data collators had updated training in Good Clinical Practice GCP and Consenting in paediatric e-learning modules on NIHR Learning Management Systems platform. Primary outcomes assessed the association of new onset T1DM with COVID-19 IgG positivity. Secondary outcomes assessed the degree of severity of T1DM at presentation through severity of acidosis and level of HbA1c. Clinical presentations were evaluated to assess any patterns through the cases. We also aimed to check for any demographic similarities. We derived interquartile ranges (IQR = Q3-Q1) between Q1 25% to Q3 75% to adjust for outliers in the dataset Results Only one case was detected to have IgG antibodies at the time of presentation (not in DKA). Median age of presentation was 9.5 years. The youngest being 11 months and oldest, 14 years. There were 7 males, and 3 females in the cohort. 50% of cases were not in DKA. Of those who presented with ketosis, 2 were in severe DKA (most severe at pH 6.94). None needed intensive care management. Median HbA1c at presentation was 123.5 mmol/mol. Median duration of symptoms was 23.8 days, with those not in DKA presenting on average 17 days and those in DKA (20%) presenting longer (30 days). Those in severe DKA had higher HbA1c values (143 and 151 mmol/mol). There were comorbidities of previously diagnosed autism and hypothyroidism at diagnosis of T1DM in one solitary case (not in DKA). Covid19 antibody positive patient had a history of parent succumbing to COVID-19. Demographics - 30% cases hailed from Harlow, 20% from Broxbourne and Bishops Stortford. 10% were from Waltham abbey, Waltham cross and Epping areas each. Conclusion Our small study represents an exponential rise (three-fold increase) in cases of new onset T1DM shortly following the first pandemic peak in April 2020. Only one case showed presence of past COVID-19 infection. The sampling of antibodies was limited by lack of widespread rollout of coronavirus testing at the time. Our findings support the observation that delay in diagnosis resulted in increasing patient numbers presenting in DKA. There was no association between CoVId-19 infection and new onset T1DM in children. We look forward to outcomes of larger scale studies examining this issue.

6.
American Journal of Transplantation ; 22(Supplement 3):875-876, 2022.
Article in English | EMBASE | ID: covidwho-2063548

ABSTRACT

Purpose: The purpose of this study was to assess the clinical characteristics of serologic non-responders to COVID-19 booster vaccination in a cohort of solid organ transplant recipients. Method(s): All solid organ transplant recipients our center who received COVID-19 booster vaccination and had SARS-CoV-2 Spike IgG antibodies checked at least 4 weeks after the dose were included. We evaluated the patients who were found to have negative SARS-CoV-2 Spike IgG antibodies despite booster vaccination (i.e. serologic non-responders). Result(s): Among 657 solid organ transplant patients who had received a booster COVID-19 vaccination, 168 patients had Spike IgG antibodies checked during the study period. Forty-nine patients (29.2%) were found to be seronegative and were included in the analysis. 69% were male with a median age of 60 years. The majority of the cohort (47%) were kidney transplant recipients who had received primary vaccination series at a median of 206 days post-transplant. 65% had received basiliximab for induction immunosuppression. Most of the patients (65%) received primary vaccination with Pfizer COVID-19 vaccine and 67% received Pfizer COVID-19 booster vaccination at a median of 187 days after primary vaccination series. Spike IgG antibodies were checked at a median of 41 days from booster vaccination. No patients received rATG within 90 days of booster administration. Similarly, no patients received high dose (>250mg methylprednisolone equivalent) steroids within 30 days prior to booster vaccination. For immunosuppression, 27% were maintained on belatacept and 82% were on anti-metabolites at the time of the booster vacciantion. Ten patients (20%) experienced a COVID-19 infection postcompletion of their booster vaccination. Conclusion(s): In our solid organ transplant cohort, the majority of serologic nonresponders underwent basiliximab induction and were on an antimetabolite for maintenance immunosuppression. A limitation of our study was the use of different laboratory assays for determining IgG levels. Future work includes evaluating the clinical characteristics of COVID 19 booster serologic responders and comparing the two populations. (Table Presented).

7.
American Journal of Transplantation ; 22(Supplement 3):671, 2022.
Article in English | EMBASE | ID: covidwho-2063542

ABSTRACT

Purpose: US veterans are less likely to be transplanted. This disparity is related to donor shortage. This study seeks to increase access to transplant of US veterans to transplants using covid+ organs. This provides high quality organs to underserved population, reduce discards and is safe. Report of safety of this strategy. Early reports demonstrates safety in using these organs. Method(s): Case presentation of two veterans transplanted with covid+ organs. Recipient and donor characteristics highlighted including vaccine status, antibody level (IgG) against Sars-CoV-2 prior to and following transplant. Organ function is reported and complications. Induction agent using non-depleting agent recorded. Informed consent obtained for covid+ organ. Infectious disease consultation. IgG antibody level check prior to transplant, and post transplant. Result(s): Two cases reported. Both had no complications related to covid. Excellent donors with KDPI <30. Cycle threshold 16 and above. Sequence 193 and 225. EPTS >85. Simulect and steroids used in both cases. Cold time short >16 hours. Both brain dead donors. LOS 7 and 8 days. PRA 0%. Donor blood group A and O. DGF in one recipient which recovered after 2 weeks see figure. The recipients had initially high antibody level which declined post transplant by 50%. See fig. Conclusion(s): Using Sars-CoV-2 donors is safe and provides a source of potential high quality organs in US Veterans who are generally underserved using informed consent. Full vaccination in recipient is a prerequisite. (Table Presented).

8.
American Journal of Transplantation ; 22(Supplement 3):767, 2022.
Article in English | EMBASE | ID: covidwho-2063510

ABSTRACT

Purpose: Emerging evidence suggests that 3 doses of SARS-CoV-2 mRNA vaccine enhance immunity in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines. Here we report the results of humoral response in KT recipients in comparison with healthy control group after homologous and heterologous regimens with inactivated virus (Coronavac) and mRNA vaccine BNT162b2. Method(s): A multicenter prospective study was conducted. KT recipients received heterologous vaccine schedule (2 doses of Coronavac and a booster of mRNA BNT162b2, n= 136) or homologous (3 doses of BNT162b2 n=19). Healthy control group received 2 doses or Coronavac (n=67) or BNT162b2 (n=15). Serum IgG antibodies against Receptor Binding Domain of SARS-CoV-2 Spike protein were determined 30 and 40 days after last dose. Result(s): Seroconversion was 52.2% and 57,9% with heterologous and homologous vaccination schedules in KT, p=0.789, figure 1. Among KT patients with seroconversion, antibody levels against RBD of SARS-CoV-2 were [1012 (183-3111) and 603 (41-1255) BAU/mL, with heterologous and homologous schedule, respectively. Levels were higher in KT compared to heathy control with 2 doses of inactivated virus 308 (209-335), p=0.03 and lower than heathy control with 2 doses of BNT162b2: 2638 (2608-3808) BAU/mL, p=0.001]. Conclusion(s): Seroconversion improves after a third dose with homologous or heterologous vaccine schedules. Among patients with seroconversion antibody levels were higher than in heathy control with two doses of inactivated virus. Measurement of antibody levels could help to improve vaccination policies.

9.
American Journal of Transplantation ; 22(Supplement 3):1066, 2022.
Article in English | EMBASE | ID: covidwho-2063484

ABSTRACT

Purpose: The purpose of this study was to study our cohort of adult solid organ transplant recipients who had been infected with SARS-CoV-2 to describe the incidence density of SARS-CoV-2 re-infection, as well as the clinical features and convalescent immunity profile. Method(s): Incidence density was calculated as the total cases of re-infection divided by total days after initial diagnosis with active graft. We included those with initial infection diagnosed by polymerase chain reaction before or after transplantation, and cycle threshold values were obtained when possible. Two recipients had immunity evaluated in the weeks prior to re-infection, by measuring IgG antibody titer to the SARS-CoV-2 receptor binding domain and virus-specific CD4+ and CD8+ T-cell reactivity following stimulation with SARS-CoV-2 peptide pools and using activation induced marker assays. Result(s): Out of 210 infected recipients, 5 (2.4%) developed re-infection, including two that had received full mRNA vaccination, but none developed hypoxia. The incidence density was 9.4 (95% confidence interval 3.9-22.6) cases/100,000 patient days. Two cases of re-infection had participated in our immunity study and had convalescent immunity data from a blood draw approximately six months after initial infection and prior to re-infection. Both mounted virus specific CD4 T cell responses prior to re-infection (1.19% and 0.28% of total CD4 T cells) and both had reactive IgG testing (1.30 and 4.99 signal/cut off ratio). Conclusion(s): This suggests that SOT recipients infected with SARS-CoV-2 remain at high risk for re-infection even after generating reactive cellular and humoral immune responses.

10.
American Journal of Transplantation ; 22(Supplement 3):637, 2022.
Article in English | EMBASE | ID: covidwho-2063479

ABSTRACT

Purpose: COVID-19-related morbidity and mortality is high among kidney patients. Several studies recently suggested low humoral and cellular immune responses after two doses of mRNA-1273 (Moderna) in these patients. Interleukin (IL)-21 is key in orchestrating an effective immune response against viral infections, is mainly produced by activated CD4+ T-cells and stimulates both humoral and cellular immunity. However, T-cell function may be impaired in kidney patients and this may explain the poor response to vaccination. Currently, there is limited data available on the vaccine-induced IL-21 memory T-cell response in these patients. We studied the induction of SARS-CoV-2-specific IL-21 memory T-cell response after mRNA- 1273 vaccination in 3 groups of kidney patients. Method(s): 113 participants were randomly selected from a prospective controlled multicenter cohort study, including 38 controls, 19 chronic kidney disease (CKD) stages G4/5 (eGFR <30 mL/min/1.73m2), 20 dialysis and 36 kidney transplant patients. All participants received 2 doses of mRNA-1273. To assess the vaccineinduced IL-21 memory T-cell response, we performed an IL-21 ELISpot (per 3.105 PBMCs) in these participants at baseline and 28 days after the second vaccination. SARS-CoV-2 S1-specific IgG antibody levels were already measured in the context of the multicenter cohort study. Result(s): Kidney transplant recipients had a significantly lower number of SARSCoV- 2-specific IL-21 producing memory T-cells when compared to controls (median of 46 versus 146, P<0.001). Participants with CKD G4/5 or on dialysis also had reduced SARS-CoV-2-specific IL-21 producing memory T-cells compared to controls (median of 128 [19-658] and 124 [7-654] versus 146 [10-635], p=0.43 and p=0.45, respectively), but the difference was less pronounced. In addition, a positive correlation was found between the number of SARS-CoV-2-specific IL-21 producing memory T-cells and SARS-CoV-2 S1-specific IgG antibody levels for all groups (Pearson correlation coefficient of 0.2, p=0.028). Conclusion(s): Kidney transplant recipients have an impaired antibody response after two doses of mRNA-1273 (Moderna), which correlates with poor SARS-CoV- 2-specific T-cell reactivity. These findings suggest that poor IL-21 memory T-cell response might hamper protection against COVID-19.

11.
American Journal of Transplantation ; 22(Supplement 3):770, 2022.
Article in English | EMBASE | ID: covidwho-2063470

ABSTRACT

Purpose: The impact of antigenic imprinting, when immune memory of one antigen influences the response to subsequent similar antigens, on the antibody response in solid organ transplant recipients (SOTRs) after SARS-CoV-2 vaccination is currently unknown. This study examines the relationship between seasonal coronaviruses (sCoV) and SARS-CoV-2 antibody levels pre- and post-vaccination in SOTRs. Method(s): Plasma from 52 SOTRs pre- and post-SARS-CoV-2 vaccination (2 doses, mRNA) was analyzed using the Meso Scale Diagnostic Coronavirus Panel 3 (an electrochemiluminescence detection-based multiplexed sandwich immunoassay) for IgG antibodies against alpha sCoVs (229E, NL63), beta sCoVs (HKU1, OC43), and SARS-CoV-2 spike proteins. Changes in IgG titers were determined by paired Wilcoxon rank-sum tests. Spearman correlation analysis was used to determine associations between pre-vaccination anti-sCoVs and post-vaccination anti-SARS-CoV-2 IgG. Result(s): Vaccination increased both anti-SARS-CoV-2 (fold change (FC) 1.9, p<0.001) and anti-beta sCoV (HKU1 [FC 0.05, p<0.001], OC43 [FC 0.8, p<0.001]) IgG titers in SOTRs, but did not increase anti-alpha sCoV IgG. Furthermore, prevaccination anti-beta sCoV (HKU1 [rho= -0.3, p=0.03], OC43 [rho= -0.3, p<0.03]) IgG titers were negatively correlated with post-vaccination anti-SARS-CoV-2 IgG. Conclusion(s): These exploratory findings suggest that prior exposure to seasonal betacoronaviruses may lead to antigenic imprinting in SOTRs that negatively impacts the antibody response to vaccination against the novel pandemic betacoronavirus, SARS-CoV-2.

12.
American Journal of Transplantation ; 22(Supplement 3):457, 2022.
Article in English | EMBASE | ID: covidwho-2063392

ABSTRACT

Purpose: While SARS-CoV-2 vaccination has dramatically reduced COVID-19 severity in the general population, fully vaccinated solid organ transplant recipients (SOTRs) demonstrate reduced seroconversion and increased breakthrough infection rates. Furthermore, a third vaccine dose only increases antibody and T cell responses in a proportion of SOTRs. We sought to investigate the underlying mechanisms resulting in varied humoral responses in SOTRs. Method(s): Within a longitudinal prospective cohort of SOTRs, anti-spike IgG, total and spike-specific B cells were evaluated in 44 SOTR participants before and after a third vaccine dose using high dimensional flow cytometry to assess immunologic and metabolic phenotypes. B cell phenotypes were compared to those of 10 healthy controls who received a standard two-dose mRNA series. Result(s): Notably, even in the absence anti-spike antibody after two doses, spikespecific B cells were detectable in most SOTRs (76%). While 15% of participants were seropositive before the third dose, 72% were seropositive afterward. B cells, however, were differentially skewed towards non-class switched B cells in SOTRs as compared to healthy control B cells. Expansion of spike-specific class-switched B cells in SOTRs following a third vaccine dose correlated with increased classswitched (IgG) antibody titers. Antibody response to a third vaccine dose was associated with expanded populations of germinal center-like (CD10+CD27+) B cells, as well as CD11c+ alternative lineage B cells with specific upregulation of CPT1a, the rate limiting enzyme of fatty acid oxidation and a preferred energy source of germinal center B cells. Conclusion(s): This analysis defines a distinct B cell phenotype in SOTRs who respond to a third SARS-CoV-2 vaccine dose, specifically identifying fatty acid oxidation as pathway that could be targeted to improve vaccine response such as through targeted immunosuppressive modulation. (Figure Presented).

13.
American Journal of Transplantation ; 22(Supplement 3):406, 2022.
Article in English | EMBASE | ID: covidwho-2063381

ABSTRACT

Purpose: This study aims to compare the immunogenicity of a third dose of the heterologous BNT262b2 mRNA vaccine versus the homologous inactivated wholevirion CoronaVac vaccine in adult kidney transplant recipients (KTR). Method(s): This prospective, single-center, phase 4 interventional study included KTR aged 30-69 years, with more than 30days of transplantation, and no previous confirmed COVID-19. The patients received the 3rd heterologous (BNT162b2 mRNA) or homologous dose, at least four weeks after the standard two-dose schedule of CoronaVac vaccine, at the transplant center. Antibody response immediately before and after the 3rd dose was assessed by the AdviseDx SARS-CoV-2 IgG II assay. For those positive assays, neutralizing anti-SARS-CoV-2 antibodies were assessed through the cPassTM SARS-CoV-2 Neutralization Antibody Detection Kit. Result(s): There were 307 patients in the heterologous group and 777 patients in the homologous group. KTR in the heterologous group were older (median age 54 vs. 50 years,p<0.0001), with a lower prevalence of diabetes (7% vs. 11%,p=0.032), lower percentage of deceased donors (60% vs. 68%,p=0.006) and longer time since transplant (median 11 vs. 6 years,p< 0.0001).Immediately before the 3rd dose, seroprevalence for IgG antibodies (36% vs. 34%,p=0.597) and the median antibody titers among those seroprevalent (246 AU/mL vs. 268 AU/mL,p=0.279) were similar. At a median of 25 days after the heterologous and 35 days after the homologous 3rddose vaccine, seroconversion rate was higher in the heterologous group (49% vs. 32%,p<0.0001), resulting in a higher seroprevalence rate (67% vs. 55%,p=0.0003). Overall, 42% remained seronegative after the third dose. The median antibody titers after booster among those seroprevalent patients was higher in those in whom the 3rd heterologous vaccine was administered (7,771 AU/mL vs 599 AU/mL,p<0.0001). The analysis of the neutralizing activity is ongoing. Conclusion(s): This prospective interventional study suggests that a 3rd heterologous dose is associated with a higher seroconversion rate and median antibody titers compared to a homologous dose in kidney transplant recipients fully vaccinated with inactivated whole-virion CoronaVac vaccine. In addition, 42% of subjects did not produce humoral immune response after the third dose, urging the development of alternative strategies.

14.
American Journal of Transplantation ; 22(Supplement 3):570, 2022.
Article in English | EMBASE | ID: covidwho-2063350

ABSTRACT

Purpose: Data shows COVID vaccine response after 2 doses in patients on Belatacept immunosuppression (IS) is low, with reported rates of seroconversion (as measured by COVID spike IgG antibody (IgG Ab) detection) of <10%. It is suggested that T cell immunity provides more nuanced marker of immunity. We seek to describe immune response with third dose of vaccine using T cell immunity and spike Ab as surrogate markers. Method(s): 12 kidney transplant patients on long term belatacept maintenance therapy were included. All patients received induction rabbit anti thymocyte globulin at transplant and were maintained on triple IS with mycophenolate and steroids. All patients received 3 doses of the Pfizer BioNTech SARS CoV2 mRNA vaccine. IgG Ab and T cell immunity response were monitored after 2 doses of vaccine, on the date of 3rd dose with repeat testing done about 4 weeks after 3rd dose. Due to small sample size, T cell response detection was treated qualitatively as "detected" and "negative" results based upon manufacturer instructions (Eurofins Viracor). IgG Ab response was treated qualitatively as "detected" and "negative", as many responses were too low to be reliably quantifiable. Result(s): Of the 12 included patients, 58% were female, 50% were African American, at mean of 77 months post transplant. After 2 vaccine doses, immunity was detected using the T cell based assay in 6/12 [50.0%, 95% CI: (21.1%-78.9%)];after 3 doses, T cell immunity detection remained the same (6/12). After 2 doses, IgG was detected in 2/12 patients [16.7%, 95% CI: (2.1%-48.4%)]. After 3 doses, this rate doubled to 4/12 [33.3%, 95% CI: (9.9%-65.1%)]. All IgG Ab detected patients were within the T Cell detected patients. There were statistically significant differences between patients that showed a response vs those that did not although patients with no response had been on a numerically higher duration of belatacept (mean=56 months) vs those with any response (mean=34 months;p=0.23). No patients developed a COVID 19 infection during the study period. Conclusion(s): In this cohort, T cell response identified a bigger subset of patients with vaccine response with 2 mRNA vaccine doses compared with those identified with an IgG response only. However, both T cell immunity and IgG Ab response remained low after 2 or 3 doses, and no patient in in the 2 dose group developed new T cell immunity response after third vaccination. IgG Ab response increased in half of the patients, but these were patients who already had developed a T cell immune response after second dose of vaccine. Total change in COVID spike IgG response after the third dose was up to 33% from an initial 16%, which may demonstrate improved total response to 3 doses. Further research is needed to assess if response rates improve with additional (fourth) doses of COVID vaccine or 'mix and match' strategies.

15.
American Journal of Transplantation ; 22(Supplement 3):597, 2022.
Article in English | EMBASE | ID: covidwho-2063338

ABSTRACT

Purpose: To investigate the effect of mycophenolate mofetil (MMF) on SARSCoV- 2 vaccination response in kidney transplant recipients using the standard immunosuppressive regimen of tacrolimus (TAC) and MMF. Method(s): A randomized controlled trial in immunologically low risk kidney transplant recipients was performed (EudraCT nr.: 2014-001372-66). Patients were randomized to standard TAC/MMF or TAC monotherapy (TACmono) from 9 months onwards, without steroids. Antibody based immune responses to SARS-CoV-2 vaccination (mRNA-1273 or BNT162b2) were investigated in a central laboratory, as part of the RECOVAC Antibody study (EudraCT nr.: 2021-283 001520-18), 4-8 weeks after the second vaccination. Measurement involved the presence of antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 S-protein (IgG anti-RBD antibody) using the Sanquin anti-SARS-CoV-2 RBD IgG ELISA assay. Patients were classified as non-responders (<=50 BAU/mL), low-responders (50-300 BAU/ mL) and responders (>300 BAU/mL). Result(s): Between 2015 and 2018, 79 recipients were randomized to TAC/MMF (n=41) and TACmono (n=38). At the outbreak of the COVID-19 pandemic in early 2020, 67 patients were alive with a functioning graft (TAC/MMF n=35, TACmono n=32). In 27 patients antibody responses could be established: Ten patients were excluded from the analyses due to symptomatic COVID-19 infection and 1 due to a positive nucleocapsid test, possibly from an asymptomatic infection. The rest did not participate in the vaccination study, because of ChAdOx1-S, age >80 years or lack of informed consent. Mean age was 64 (43-75) years, median time after transplantation 4.2 (3.0-6.5) years and eGFR was 53 (36-105) ml/min/1.73m2. TAC trough levels were 6.6 (+/-0.3) mug/L in both groups, and MMF dose was 1000 mg daily (range 500- 2000) in TAC/MMF. Median SARS-CoV-2 Spike S1-specific IgG antibody levels were 37.3 BAU/ml in TAC/MMF (5 non, 7 low, 1 responder) and 715.6 BAU/ml in TACmono (1 non, 6 low, 7 responders, p =0.004, figure 1). Of note is that antibody levels of >1000 BAU/ml, as a presumed threshold for protection against Omicron (B.1.1.529), was reached in 1/13 TAC/MMF and 7/14 TACmono patients (p=0.03). Conclusion(s): In this controlled study mycophenolate mofetil on top of tacrolimus severely hampered serological COVID-19 vaccination response.

16.
Cardiology in the Young ; 32(Supplement 2):S239, 2022.
Article in English | EMBASE | ID: covidwho-2062096

ABSTRACT

Background and Aim: Cardiac involvement in multisystem inflam-matory syndrome in children (MIS-C) associated with Coronavirus 2019 disease (COVID-19) is often observed with high risk of hearth failure. Early diagnosis and treatment are man-datory for a good outcome. The aim is to describe cardiovascular involvement, management and early outcome for patients with MIS-C and to analyze the differences in cardiovascular manifesta-tions between two groups: younger and older than 6 years old. Method(s): This retrospective observational study describes cardio-vascular clinical manifestations, laboratory findings, cardiac imag-ing, according to different age groups, and treatment in patients with diagnosis of MIS-C admitted to the Pediatric Istitute Giannina Gaslini between March 2020 and September 2021. Result(s): We collected 25 patients. Median age at onset of symptoms was 5 years old (interquartile range IQR, 3-12 y), 12 boys (56%). Immunoglobulin G antibodies were positive in 70% cases, Polymerase chain reaction (PCR) nasal/throat swab test for COVID-19 was positive in 15% cases, at the admission. The remaining cases had close contacts of COVID-19 positive cases. Predominant coronary artery abnormalities were observed in age group up to 6 years old (n.13) with development of small and medium aneurysms in half of cases and low rate of mild ventricular dysfunction. While children between 7-18 years of age present myopericardial involvement with ventricular dysfunction in 67% cases, from mild to moderate. Only two cases of transient coronary dilatation. Frequent electrocardiogram abnormalities: ventricular repolarization anomalies and reversibile QTc prolon-gation interval. Laboratory findings showed rised inflammatory markers and only mild elevation of cardiac enzymes compared to an early and significant NT-pro-BNP increase. All patients were treated with intravenous immunoglobulin and corticosteroids. Some cases needed anakinra. Aspirin and heparin was adminis-trated. No inotropes requied but only cardioprotective therapy. No need of Intensive Care Unit. Conclusion(s): This case-series shows the frequent cardiovascular involvement in MIS-C with a peculiar distribution, according to differents age's group: coronary artery anomalies in young ones, myopericardial disease in old ones. Prompt multi target anti-inflammatory therapy could have an effect to favorable outcome.

17.
Chest ; 162(4):A537, 2022.
Article in English | EMBASE | ID: covidwho-2060622

ABSTRACT

SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Persistent acute symptoms of coronavirus disease 2019 (Covid-19) have been previously described in patients receiving immunosuppression, and have additionally been associated with the development of new variants of the SARS-CoV-2 virus. Here follows a report of a similar case which eventually responded to treatment with antiviral and monoclonal antibody therapies. CASE PRESENTATION: The patient is a 51 year old male with a past medical history of bilateral optic neuritis (treated with rituximab), polysubstance use disorder, bipolar disorder, and hypertension. He initially presented to the emergency department in January 2022 with symptoms of shortness of breath, cough, and worsening fatigue over the preceding 3-4 weeks. On presentation he required intubation for hypoxia. A PCR test for SARS-CoV-2 returned positive and he was initiated on treatment with intravenous dexamethasone and antibiotics for presumed community acquired pneumonia. He was extubated 4 days later, but remained hospitalized for a further 6 weeks due to recurrent fevers and a persistent supplemental oxygen requirement. Due to concern for viral-induced cryptogenic organizing pneumonia he was started on high-dose intravenous steroids. However, he developed escalating oxygen requirements resulting in a second intubation to facilitate bronchoscopy, results of which were non-diagnostic. Serum testing for SARS COV2 IgG antibody, 10 weeks after the initial onset of his symptoms, returned negative, therefore he was then treated with a 5 day course of remdesivir, as well as monoclonal antibody therapy with casirivimab-imdevimab. He additionally underwent a VATS lung biopsy for definitive tissue diagnosis, which revealed interstitial inflammation with patchy fibroblastic linear nodules, consistent with diffuse alveolar damage. He was extubated and had improvement in his oxygen requirements and respiratory function, and was planned for discharge to pulmonary rehabilitation almost 3 months after his initial presentation. DISCUSSION: Patients receiving immunosuppression remain at risk for persistent symptoms, prolonged hospitalization, and increased morbidity and mortality, when infected with SARS-CoV-2. Notably, the patient described here had received only 2 doses of an FDA-approved COVID-19 vaccine at the time of his infection, and was being treated with rituximab for optic neuritis, with his last infusion being approximately one month before the onset of his symptoms. Such prolonged, symptomatic infection from SARS-CoV-2 remains a clinical concern, especially due to its association with the development of new viral variants, and further research into appropriate treatment for these patients continues to be investigated. CONCLUSIONS: This case demonstrates an immunocompromised patient with persistent symptoms of Covid-19 who eventually responded to treatment with the antiviral remdesivir, as well as monoclonal antibodies. Reference #1: Choi B, Choudhary MC, Regan J, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med 2020;383:2291-2293. DISCLOSURES: No relevant relationships by Vivek Sinanan

18.
Swiss Medical Weekly ; 152(Supplement 261):2S, 2022.
Article in English | EMBASE | ID: covidwho-2058360

ABSTRACT

Patients with inflammatory rheumatic diseases (IRD) have an increased risk for a worse COVID-19 outcome, and impaired immune responses following mRNA COVID-19 vaccines have been observed. In this prospective observational study, we compared the anti-S1 response following vaccination with BNT162b2 and mRNA- 1273 in a large cohort of IRD patients and assessed the effect of different immunomodulatory treatments. Patients from SCQM, the Swiss IRD cohort, who assented to an mRNA COVID-19 vaccine were recruited into the study between 3/2021-9/2021. Participants answered the study questionnaire via the mySCQM patient app and provided self-collected capillary blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose. Samples were tested for IgG antibodies against the S1 domain of the SARS-CoV-2 spike protein using the EUROIMMUN ELISA. We examined differences in antibody titres depending on the vaccine and treatment received, while adjusting for age and history of SARSCoV- 2 infection, by applying mixed effects continuous outcome logistic regression models at each timepoint. Eligible samples were obtained from 564 IRD patients (mean age 53 y (s.d. 12 y), 66% female) with 36% RA, 37%, axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARD & no steroids 15%), csDMARD (9%), TNFi (48%), IL-6/17/23i (14%), JAKi (6%), rituximab (4%), abatacept (3%), and PDE4i (1%) in mono/combination therapy at baseline. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. Independently of the disease, treatment, and history of SARS-CoV- 2 infection, the odds of having higher anti-S1 titres at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.3, 3.9, and 3.8 times higher with mRNA-1273 compared to BNT162b2 for the average-aged patient of this population (p <0.0001). Moreover, with every year of age, the odds of higher anti-S1 levels increased by 3% to 5% following mRNA-1273 vs BNT162b2 vaccination (p <0.05), indicating an additional benefit for elderly IRD patients. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly reduced antibody responses compared to respective monotherapies. Our results suggest that in IRD patients, vaccination with mRNA- 1273 vs BNT162b2 results in higher anti-S1 antibody titres, and has an additional benefit in elderly patients.

19.
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.

20.
HemaSphere ; 6:1862-1863, 2022.
Article in English | EMBASE | ID: covidwho-2032105

ABSTRACT

Background: In patients (pts) with hematological malignancies, COVID-19 is considered to be associated with a high risk of severe morbidity and mortality. While anti-COVID-19 vaccination of such pts has become the standard of care, pts undergoing lymphodepleting therapy fail to generate protective serological response due to either the nature of their underlying disease or exposure to therapy. Aims: This study aimed to assess serological response to vaccination with BNT162b2 (Pfizer) as well as COVID-19-related morbidity and mortality in Hodgkin lymphoma (HL) pts. Methods: The above vaccine was available in Israel from January 2021 and all pts with hematological malignancies were recommended to undergo vaccination with 2 doses of this vaccine, injected 21 days apart. Six months later a 3rd dose was recommended and in another 3 months a 4th dose was available for pts at risk. Serology tests were performed at least 2 weeks after the 2nd vaccination. The SARS-CoV-2 IgG II Quant (Abbott©) assay was used to measure levels of IgG antibodies (Abs) against the SARS-CoV-2 spike protein. A result was considered positive if the IgG level was ≥150 AU/ml, which was defined as an adequate serological response. Results: The current non-interventional single-center study evaluated the outcome of 55 HL pts (median age 46 years, 53% females);51% of pts had advanced HL. Study participants received 1-9 lines of therapy (median 1 line). Six pts had COVID-19 prior to vaccination, 49 were vaccinated: 9 with 2 doses, 36 with 3 doses and 4 with 4 doses of BNT162b2. Following initial 2 vaccine doses and after a 3rd dose Ab levels >150 AU/ml were developed in 85% and 89.5% of pts, respectively. At a median of 95 days post-2nd vaccination, Ab levels were 2024 (1-29400) and 4 (0-7539) in 48 patients with no background disease versus 7 pts treated with lymphodepleting drugs or having a background disease, respectively. During the follow-up, 5 vaccinated pts were diagnosed with COVID-19 when the Delta variant was prevalent and 9-during the Omicron wave. Notably, similar Ab levels were observed in those infected with Omicron and in non-infected pts, reflecting the genetic drift of this variant. A further analysis was performed to compare findings in a subgroup of 7 pts who had an additional background disease along with HL, such as chronic lymphocytic leukemia, s/p kidney transplantation, solid tumor, or those who were heavily pretreated, including therapy with bendamustine, versus the values observed in the rest 48 pts. The median age in the former subgroup was 58 (31-80) years, which was significantly older than in the remaining pts [median 45 (18-78) years] and median Ab levels were 4 (0-7539) AU/ml and 2024 (1-2940) AU/ml, respectively. Notably, after the 3rd vaccination, the median Ab level in both groups was 7000 AU/ml. Summary/Conclusion: The results of the current study show that at least 85% of HL pts develop a high titer of anti-spike antibodies after vaccination with 2 BNT162b2 doses. These titers substantially increased post the 3rd vaccine dose. Only a minority of HL pts who had additional background diseases or were heavily pretreated, failed to develop an adequate serological response;however, some of them had high Ab titers post-3rd and 4th vaccinations. In this study, morbidity and mortality rates of HL pts infected with COVID-19 were lower than those reported in pts with other lymphoma types.

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