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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.
Clinical and Experimental Rheumatology ; 40(10):83, 2022.
Article in English | EMBASE | ID: covidwho-2067777

ABSTRACT

Introduction. There are few studies that evaluated the response to Covid- 19 vaccines, in primary Sjogren's Syndrome (pSS) and none evaluated ChAdOx1 n-Cov19 (AstraZeneca/Fiocruz). The aim of this study was to evaluate the efficacy and safety of the ChAdOx1 n-Cov19, a viral vector vaccine, in pSS compared to healthy control (HC). Methods. Patients with pSS >18 years, classified according to ACR/EULAR 2016 were included. Neutralizing antibodies against the Receptor Binding Domain - RBD portion of the Spike protein of SARS-CoV-2 (IgGS) were measured by chemiluminescence (Abbott), before the first dose (D0) and 28 days after the second dose (D28*). The test is considered reactive if >50 AU/ml. Results. Sixty pSS patients and 62 HC were recruited from a single center (HUCAM-UFES, Vitoria, ES, Brazil). The HC group was homogeneous for sex (92% women) and younger than HC (47+/-11 vs. 39+/-13, p<0.05). In the pSS group, 45.2% were anti-Ro positive, mean ESSDAI was 3.2, 83.3% were using DMARD or immunosuppressant/biological therapy, 31.9% were in high immunosuppression. The frequency of mild adverse events (AE) was similar in both two groups. No serious AE, hospitalizations or death were reported. There was no difference between the PGA ("Patient's Global Assessment") after vaccination (4.5 vs.5, p=0.903). Among seronegative individuals at baseline, the seroconversion rate (100% vs. 89%, p=0.02) was lower, and geometric mean titers (GeoMean IgG-S) was similar in pSS=696.9(CI95%237.6 -2,043) compared to HC=1,986(CI95%1,463-2,697;p=0.316). However, in those with high immunosuppression, the seroconversion (71%, p=0.001) and GeoMean titers were lower 229.4 (CI95%14.64-3,594, p=0.004). Patients in moderate to high disease activity (ESSDAI >=5) showed lower seroconversion (60%, p=0.006) and Geomean titers 31.7 (CI95%0.06-15.4;p=0.004). Conclusions. ChAdOX1 vaccine is safe and induced high GeoMean neutralizing antibodies titers and seroconversion rate in pSS patients similar to HC. Immunossuppression therapy and disease activity decreased the immune response to the vaccine.

4.
Pakistan Journal of Medical and Health Sciences ; 16(8):335-337, 2022.
Article in English | EMBASE | ID: covidwho-2067752

ABSTRACT

Background: Occupational hazards and risks are a common public health issue, especially when healthcare workers safety is concerned;they are on high risk of catching infections such like COVID-19. The possibility of cross-infection between dental practitioners and patients is significantly higher due to the close exposure of dental staff to patient oral environment. Aim(s): To assess the prevalence of SARS-COV-2 antibodies in dental workers working in the Peshawar Dental College and Hospital, Peshawar. Study Design: Cross sectional study Place and Duration of Study: Department of Orthodontics, Peshawar Dental College & Hospital, Peshawar from 1st January 2020 to 31st December 2020. Methodology: One hundred and thirty three dental workers were enrolled. The investigation was run to detect immunoglobulin G and M antibodies against the SARS-CoV-2-2. The aspirated aerosol and air was evacuated and dissipated into the atmosphere. Result(s): Mean age was 29.4+/-1.4 years and males were dominant 74 (55.6%) and male workers found greater with positive antibodies. The prevalence of SARS-CoV-2 antibodies was 33.0%. Proportionately dental assistants (20.5% vs 16.9%) and ancillary staff (20.5% vs 10.1%) had higher prevalence. Sore throat and body aches were more common in positive antibodies cases while travel history was found significantly associated with it (40.9% vs 25.0%, p-value, 0.05). Conclusion(s): High frequency of SARS-COV-2 antibodies was found in dental workers showing a high infection rate of COVID-19 in healthcare workers in local settings. Copyright © 2022 Lahore Medical And Dental College. All rights reserved.

5.
Pediatricheskaya Farmakologiya ; 19(2):196-200, 2022.
Article in Russian | EMBASE | ID: covidwho-2067387

ABSTRACT

Background. Students, as the most active and mobile part of population, often unite into educational and informal groups, move to other regions or countries, and present a specific risk group for the spread of new coronavirus infection. Thus, they require preventive vaccination. objective. the aim of the study is to study the immunological potency, tolerance, and efficacy of GamCOVID-Vac vaccine among students of Krasnodar. methods. 119 seronegative students (18–30 years old) were examined. SARSCoV-2 IgG (ELISA method) was determined 1, 3, and 6 months after two completed rounds of vaccination. Post-vaccination adverse events and COVID-19 cases were evaluated in the study. results. SARS-CoV-2 IgG level 1 month after vaccination ranged from 6.15 to 19.38 and was to 16.39 (AU/mL) ± 1,12. Immunological potency values ranged from 4.407 to 21.5 (AU/mL) (14.74 ± 2.93) 3 months after. IgG titers were in the range of 4.14 to 17.71 (AU/mL) (10.97 ± 4.69) 6 months after. Adverse events after vaccination were revealed in 34 respondents (28.6%). Among them, local (hyperemia, pain, edema) — 21 (17.6%): slight — 90.4%, major — 9.6%;general (fever, weakness, algor, headache, arthralgia, myalgia) — 13 (10.9%): slight — 69.2%, major — 30.8%. The increase in vaccination coverage in students from 30.3 to 79.1% reduced the COVID-19 morbidity from 3.81 to 1.57%. conclusion. Gam-COVID-Vac vaccine induced stable humoral response, demonstrated sufficient safety, and reduced morbidity 2.4-fold.

6.
NeuroQuantology ; 20(11):1858-1865, 2022.
Article in English | EMBASE | ID: covidwho-2067333

ABSTRACT

Background: Fighting the Covid-19 pandemic is one of the global priorities now, and the most important type of pandemic control is vaccination. Pfizer-Biotech is considered one of the most important vaccines currently because of its high effectiveness in stimulating the immune system, despite limited data regarding the duration of the response and its side effects. The goal of this study is to assess the response ofSARS CoV-2 S1-RBD IgG andInterleukin-15 after 30 and 120days fromthe 2nd dose ofPfizer-BioNTech vaccine which applied on themedical college students at Diyala university. Methodology: This study began after the obtainment of the Medical College of the University of Diyala, the Medical College of Al-IraqiaUniversity, and the Iraqi Ministry of Health approvals . It continued from October 2021 until March 2022.A total of45 male and femaleparticipants from the College of Medicine( DiyalaUniversity)students who took thetwo doses of Pfizer-BioNTech and were divided into two groups: 1 month (30 days) and 4 months (120 days) after the full vaccination (two doses).A 5 ml of their blood was taken two times (30 days and 120 days after the 2nd dose of thePfizer-BioNTech vaccine) in the postgraduate laboratories inside the Diyala Medical College. A serological analysis to quantify IL-15 and SARS CoV-2 S1-RBD IgG has been done using BT LAB/ Bioassay Technology Laboratory/ Human Interleukin 15 ELISA Kit from CHINA andDiasino/ SARS CoV-2 S1-RBD IgG ELISA Kit/ CHINA respectively. All the lab work happened in the postgraduate laboratories inside the Diyala Medical College. Demographic information (Age and Gender) has been collected from the participants. These participants were split into two groups depending on the time after the 2nd of Pfizer-BioNTech vaccine dose (1 month and 4 months, respectively). STATISTICA (version 12 )and SPSS (version 26 ) were used to input, review and data analysis. Essential approaches of percentages and frequencies were used for qualitative variables, while, average and standard deviation were used for quantitative variables. For both IL-15 and SARS CoV-2 S1-RBD IgG, less than 0.05 of a P-value was considered considerable. Result(s): The ratio, according to gender, was (17.8: 82.2) while the age Average was (20.9 years old). The serum data of IL-15 and SARS-CoV-2 S1-RBD IgG levels after 1 month (30 days) and 4 months (120 days) were statistically non-parametric. Mann-Whitney test (Independent two samples), showeda considerabledrop(P<0.05) of IL-15as well as SARS CoV-2 S1-RBD IgGserum levels in the 4th-monthsgroup compared to the 1-monthgroup. Conclusion(s): Interleukin-15 and SARS CoV-2 S1-RBD IgG serum levels significantly droped after 120days of the 2nd dose of Pfizer-BioNTech vaccine. Copyright © 2022, Anka Publishers. All rights reserved.

7.
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.

8.
Journal of Clinical and Diagnostic Research ; 16(9):ED01-ED03, 2022.
Article in English | EMBASE | ID: covidwho-2067193

ABSTRACT

Sickle Cell Disease (SCD) is an inherited disorder with variable clinical presentation and low immunity. Coronavirus Disease-2019 (COVID-19)is a pandemic disease with a high-risk in chronic disease patients and older adults. SCD is widely distributed in Sudan;many SCD patients are infected with COVID-19. Despite this, no published data is available. This case report demonstrated the haematological and clinical course of a Sudanese sickle cell anaemia patient with COVID-19. A 20-year-old male patient was admitted to a hospital for 15 days. Demographic and clinical data were obtained from his medical records. A blood sample was taken at the time of admission and during hospitalisation. Tests were performed during admission, including Complete Blood Count (CBC), liver function test, renal function test, coagulation studies, viral screening, and urine general. The patient was diagnosed with COVID-19 using the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test based on the nasopharyngeal swab and COVID-19 IgG and IgM using Enzyme Linked Immunosorbent Assay (ELISA) for the previous infection. The patient received intravenous fluids, antibiotics, analgesia, oxygen supplementation, and blood transfusion two times during hospitalisation, and there was no need for Intensive Care Unit (ICU) admission. The patient's prognosis was good;he was discharged on day 16 with no symptoms and a negative result of the COVID-19 PCR test. A severe illness was expected because he was infected twice by COVID-19, the patient showed mild clinical symptoms with a good prognosis, so further studies are required to understand COVID-19 among Sudanese SCD patients.

9.
Journal of Clinical and Diagnostic Research ; 16(8):44-47, 2022.
Article in English | EMBASE | ID: covidwho-2067192

ABSTRACT

Introduction: The emergence of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) as a pandemic has put the global population at risk for its infection. It has also led to an accelerated effort to develop vaccines that can mitigate progression to severe infections at a minimum. The ambiguity about existence of antibodies in the human serum poses problem in formulating public health policies like suitable interval between doses of vaccines, appropriate time for vaccinating population, post natural infection, necessity of booster doses along with single dose. Aim: To estimate neutralising antibody level following vaccination of Healthcare Workers (HCWs) after three months and six months respectively. Materials and Methods: This was a prospective observational study performed in Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India after Institutional Ethics Committee (IEC) approval from January 2021 to February 2022. The study was conducted in 304 HCWs in the institute who had received two doses of Recombinant ChAdOx1 nCoV- 19 Corona Virus Vaccine (Covishield). 41 HCWs who were naturally infected with SARS-CoV-2 either before or after vaccination were also included. These participants were then subjected to IgG neutralising antibody titer estimation at three months and six months, postvaccination. Results: The study included 304 eligible HCWs. Majority of the participants belonged to the age group of 31-40 years (35.9%). Majority of the study participants were females (51%). Of the 304 participants, 263 were uninfected and 41 participants had been infected before and after vaccination. At the six month follow-up, it was observed that all but one HCW had seroconverted with majority of the participants showing more than 60% antibody level. Participants in the age group of 31-40 years showed the highest level and this observation was found to be statistically significant. Conclusion: Neutralising antibody response in HCWs is a key indicator of the efficacy of the vaccination program for Coronavirus Disease-2019 (COVID-19) in India.

10.
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.

11.
Journal of Acute Disease ; 11(4):161-164, 2022.
Article in English | EMBASE | ID: covidwho-2066827

ABSTRACT

Rationale: The impact of COVID-19 in patients with autoimmune liver disease treated with immunosuppressive therapy has not been described so far. This case report describes the clinical course of a patient with autoimmune hepatitis (AIH) who developed COVID-19 and the features of cytokine syndrome leading to its deterioration in our intensive care unit. Patient's Concern: A 28-year-old male presented with generalized anasarca for two weeks and chronic liver disease for 8 months. Diagnosis: AIH and Covid-19 with features of cytokine storm syndrome. Interventions: Intravenous furosemide, mannitol, syrup lactulose, steroids (prednisolone 40 mg), azathioprine 1 mg/kg body weight, rifaximin, vitamin K, and blood products. Outcomes: The patient had hepatic encephalopathy and AIH and died on the 10th day after admission despite ventilatory support, sustained low-efficiency hemodialysis, and resuscition. Lessons: The dramatic release of cytokines and the inflammatory-immune responses not only alter the pathophysiology but also affects the onset and severity of disease progression in patients with AIH.

12.
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.

13.
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).

14.
American Journal of Transplantation ; 22(Supplement 3):638-639, 2022.
Article in English | EMBASE | ID: covidwho-2063546

ABSTRACT

Purpose: Solid organ transplant recipients (SOTR) develop weak antibody responses after SARS-CoV-2 vaccination. Published data on neutralizing activity of plasma, a better measure of protection, in SOTR following an additional dose of SARSCoV- 2 vaccine is limited. Method(s): Plasma was longitudinally collected from SOTR following initial COVID- 19 vaccination. Neutralizing activity against SARS-CoV-2 was assessed using the cPass Neutralization Antibody Detection Kit (GenScript, Biotech). ELISAs were performed against SARS-CoV-2 proteins (S1, N, RBD), CMV (glycoprotein B), Influenza A H1N1 (nucleoprotein), HSV-1, EBV glycoprotein (gp350), and tetanus toxoid for comparison. Result(s): Demographic and clinical characteristics are summarized in table 1. No participants had evidence of COVID-19 infection as IgG titers to SARS-CoV-2 N protein were low. Neutralizing activity against SARS-CoV-2 RBD was observed in 39.6% of individuals (N=21/53) ~93 days after initial vaccination. Participants with neutralizing activity were more likely to have received a liver transplant (47.6% vs 6.25%, p=0.001), and less likely to be on an anti-metabolite (52.4% vs. 87.5%, p=0.009) or triple immunosuppression (14.3% vs. 53.1%, p=0.008). After an additional vaccine dose, 78.1% (N=25/32) of participants developed neutralizing activity with significant increases in viral neutralization (figure 1, median 36.8% [95%CI 18.9-64.6] to 97.2% [95%CI 74.0-98.9], p<0.0001). Participants with low neutralizing activity demonstrated adequate antibody titers to other microbial antigens (figure 2). Conclusion(s): An additional dose of SARS-CoV-2 vaccine increased the number of SOTR with neutralizing activity and the magnitude of the seroresponse. SOTR with low neutralizing activity maintain humoral responses to other microbial antigens suggesting the diminished seroresponse might be related to inhibition of new B cell responses.

15.
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).

16.
American Journal of Transplantation ; 22(Supplement 3):640-641, 2022.
Article in English | EMBASE | ID: covidwho-2063541

ABSTRACT

Purpose: Kidney transplant recipients (KTRs) have diminished immune response and protection after 2-dose mRNA COVID-19 vaccination. It is unknown if additional doses improve neutralization of variants of concern (VOC) in KTRs with prior poor seroresponse. Method(s): Adult KTRs with negative (<0.8 U/mL) or low (<=50 U/ml) anti-RBD Ig (Roche Elecsys anti-SARS-CoV-2-S) after 2-dose mRNA series were given a homologous 3rd dose (D3). Anti-RBD and VOC surrogate neutralization (%ACE2i) were measured 30 days post D3;responses were stratified by baseline anti-RBD. Reactogenicity, serial SARS-CoV-2 swabs, and donor-specific antibody (DSA) were assessed. Result(s): 81 KTRs (50% negative anti-RBD) received D3 (72% BNT162b2, 28% mRNA-1273) at median 167 days post D2 (Table). Median (IQR) anti-RBD increase was 410 (8-2309) U/mL with 69% (40% negative vs 98% low anti-RBD) achieving day 30 anti-RBD >50 U/ml (Fig1a). 22% remained seronegative. Non-response was associated with lower baseline lymphocyte count (median 770 vs 1160 cells/ uL;p=0.05) and IgG (median 779 vs 979 mg/dL;p<0.01), but not demographics, vaccine, or immunosuppressives. Median (IQR) delta variant %ACE2i increased from 6% (3-7) to 10% (4-22) (p<0.001), a 1% (0-5) increase in negative vs 13% (5-25) in low anti-RBD. %ACE2i was linearly associated with anti-RBD >=100 U/ mL (all VOC shown in Fig1b);64% of KTRs with anti-RBD >=250 U/mL had delta %ACE2i >20. There were 3 cases of mild-moderate COVID-19 >=7 days post-D3, with pre-infection anti-RBD <0.4, 22, 76 U/mL and delta %ACE2i 6, 9, and 16, respectively. There was no acute rejection, nor increased or de novo DSA. Conclusion(s): A 3rd mRNA vaccine dose increased anti-RBD and VOC neutralization in KTRs without inducing clinical alloimmunity, yet 45% with negative baseline anti-RBD remained seronegative without delta variant neutralization. Trials are ongoing to test immune response augmentation in this subgroup via temporary immunosuppression reduction or heterologous boosting.

17.
American Journal of Transplantation ; 22(Supplement 3):1058-1059, 2022.
Article in English | EMBASE | ID: covidwho-2063534

ABSTRACT

Purpose: To evaluate the safety and generation rate of Ab anti spike rate in SOT patients at 28 and 90 days after completing the Covid 19 vaccination scheme. Method(s): Multicenter prospective study in SOT with a complete vaccination scheme who agreed to participate in the study . Demographic , vaccination: schedule;time;adverse effects and transplant variables were collected. The generation rate of antispike antibodies was evaluated by the COVIDAR-IgG method at the Universidad de Buenos Aires School of Medicine. Result(s): 113 SOT patients were included (September 6th to October 4th). Median age was 53 (IQR 42.5-63, women 36.8%). Transplant type: 72.8% renal , 13.1% cardiac, 12.3% liver, 0.9% pancreas and 0.9% lung. Deceased donors 71.1%. The median time after transplantation to vaccination was 65 months (IQR 30 120 R 2-429). Only 7% of patients developed rejection within the year prior to vaccination and no patient rejected post vaccination. 74.3% (n 84) had triple immunosuppressive maintenance regimen (steroids + calcineurin inhibitors (ICN) + antiproliferative), 24 pts (21.1%) double regimen WITHOUT steroids and 5 (4.3%) monotherapy with IC. Vaccination schedule: Sputnik 14.5%, Sputnik-Astrazeneca 4.4%, Sputnik-Moderna 28.9%, Sinopharm 3.5%, Astrazeneca 34.2%. Vaccine-related adverse events were observed in 18.4% of patients, 82% were mild. 40% of SOT responded with Antispike Ab , with a lower response rate in kidney transplantation p <0.0007 RR 0.48 (0.32-0.71) and use of triple immunosuppressive maintenance regimen p <0.00009 RR 0.419 (0.26 -0.66). Patients previously infected with Covid-19 prior to vaccine (11.45% pts), had a higher response rate p <0.0001 RR 2.58 (1.90-3.51).No patients developed COVID-19 after vaccination. Conclusion(s): In our SOT population, a lower generation rate of anti-spike Ab was observed, compared to the reported in the general population. Renal Tx and the triple IS regimen were associated with a lower response rate. Covid-19 prior to vaccination was associated with a higher antibody response to the vaccine.

18.
American Journal of Transplantation ; 22(Supplement 3):1016, 2022.
Article in English | EMBASE | ID: covidwho-2063533

ABSTRACT

Purpose: Torque tenovirus (TTV), a highly prevalent virus which is not known to cause pathology in humans, is currently being investigated as a marker of immunosuppression. In this study we investigated if the TTV load measured prior to COVID-19 vaccination can predict the serological response to the COVID-19 vaccine, measured 28 days after the second vaccination dose. Method(s): The humoral response to the mRNA 1273 vaccine (Moderna) was assessed in Lung transplant recipients (LTR) who received a transplant between 4 and 237 months prior, by measuring Spike-specific IgG levels at 28 days after the second vaccination. Antibody concentrations of >10 BAU/ml were considered reactive. TTV loads were determined by PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. Patient characteristics, including reasons for transplantation, antirejection treatment, age and time since transplantation, were recorded to assess associations between these factors and vaccination response or TTV levels. Result(s): 103 LTR were included of which 41 (40%) showed some response (>10 BAU/ml) to the vaccine at 28 days after the second vaccination. 61 (60%) were non-responders. TTV loads at baseline varied between negative and 10E9 copies/ ml. The TTV loads were found to correlate with IgG levels and the with the percentage of responders 28 days after the second vaccination (=<0.001). TTV loads also correlated strongly with the time since transplantation. High TTV levels occurred predominantly in patients who were shorter after transplantation (p=0.0001). Conclusion(s): This study shows an association between pre-vaccination TTV load and humoral response to the SARS-CoV-2 vaccine, which correlate with the time after transplantation. We recommend that TTV load measurements are included in further vaccination efficacy studies in immunocompromised cohorts. If the TTV load is indeed a predictor of vaccine response, this could be used as a potential guidance for optimizing vaccination response.

19.
American Journal of Transplantation ; 22(Supplement 3):1095, 2022.
Article in English | EMBASE | ID: covidwho-2063528

ABSTRACT

Purpose: Kidney transplant recipients (KTR) have inadequate responses to 2-dose COVID vaccination schedules and are at increased risk of severe COVID-19. Formation of T cell memory following vaccination is regulated by mTOR complex 1. mTOR inhibitors have been used in pre-clinical models to boost vaccine-elicited cytotoxic T cell memory responses. In observational studies, KTR receiving mTOR inhibitors had improved serological neutralisation and SARS-CoV-2 reactive T cell responses to 2 doses of COVID-19 vaccine, including cytotoxic T cells and circulating T follicular helper cells. We performed a clinical trial in stable KTR using sirolimus as a substitute for mycophenolate prior to a 3rd dose of COVID-19 vaccine to enhance COVID-19 vaccine responses. Method(s): KTR receiving tacrolimus, mycophenylate and corticosteroid with inadequate response to 2 doses of a COVID vaccine (defined by anti-RBD IgG <100U/ mL) and no history of COVID infection were recruited from 2 Australian transplant centres. Patients were randomised in a 1:1 ratio to continue mycophenolate maintenance or switch to sirolimus (trough level target 6 ng/mL). All patients received a 3rd dose of BNT162b2 COVID-19 vaccine and had immunological responses measured 4-6 weeks later. Result(s): 54 patients were randomised to sirolimus switch (n = 28), or control (n = 26). Patients were 70% male, mean age 57.5 years (SD10.4), with mean graft age 6.2 years (SD 5.4). Mean serum trough concentrations of sirolimus and tacrolimus were 6.4 and 6.1 respectively. There have been no safety or tolerability issues in the sirolimus cohort with stable serum creatinine (mean 117.8 vs 119.3, p=0.6), and mild increase in urinary ACR (mean 5.4 vs 17.4, p=0.1). Final results including immunological testing will be collated March 2022. Conclusion(s): Sirolimus switch is safe and well-tolerated. This trial will determine whether the strategy of mTOR inhibitor therapy peri-vaccination can optimise vaccine immune responses against COVID-19 in KTR.

20.
American Journal of Transplantation ; 22(Supplement 3):949-950, 2022.
Article in English | EMBASE | ID: covidwho-2063519

ABSTRACT

Purpose: The COVID-19 pandemic portends significant morbidity and mortality in immunocompromised individuals. Vaccination against COVID-19 among immunocompromised population is an essential step to minimize deadly complications. Numerous studies have shown an association between immune status, disease severity, and suboptimal responsiveness to vaccination. Additionally, data suggests that elevated IgG levels correlated with host viral neutralization. We herein present data indicating that induction and maintenance immunosuppression therapy affects responsiveness to vaccination among kidney transplant recipients. Method(s): The study data was retrospectively analyzed for 48 kidney transplant patients who received mRNA type COVID-19 vaccine at our institution. Majority of patients received vaccination between January and March 2021;two doses in total. The 30 days post-vaccination SARS-CoV-2 spike antigen-specific IgG levels were measured to assess immunological response to vaccine. Result(s): The included patients underwent kidney transplantation between 1983 and 2020. Among these patients, 35% showed detectable peak COVID IgG serum levels 30 days after the 2nd vaccine dose. A total of 31 patients (65%) did not show any response;majority of these non-responders (62%) were heavily immunocompromised, either on high dose Mycophenolate (at least 720 mg twice daily) in addition to standard Calcineurin inhibitor/Sirolimus+/-Prednisone), or had received high dose Thymoglobulin (6 mg/kg or more) within a year of vaccination. Among immunocompetent patients, over 95% immunological responsiveness or viral neutralization after the second vaccination dose has been reported. Conclusion(s): Anti-thymocyte globulin as induction immunosuppression and antimetabolites like Mycophenolate as maintenance immunosuppression serve as the cornerstone of transplantation management. However, their utilization impacts B cell proliferation, thereby reducing antibody production and the effectiveness of the SARS-CoV-2 vaccine in transplant patients. The ability of these immunosuppressive medications to suppress responsiveness to the SARS CoV-2 vaccine supports the need for 1) regular immunological surveillance post-vaccination among transplant patients, and 2) the need for a third or possibly fourth booster dose to achieve a sustained and effective response.

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