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1.
Clinical Transplantation ; : e14913, 2023.
Article in English | MEDLINE | ID: covidwho-2192504

ABSTRACT

BACKGROUND: Tixagevimab and Cilgavimab (T+C) is authorized for pre-exposure prophylaxis (PrEP) against COVID-19 in solid organ transplant recipients (SOTRs), yet patient-reported outcomes after injection are not well described. Furthermore, changes in risk tolerance after T+C PrEP have not been reported, of interest given uncertain activity against emerging Omicron sublineages.

2.
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.

3.
American Journal of Transplantation ; 22(Supplement 3):1060, 2022.
Article in English | EMBASE | ID: covidwho-2063522

ABSTRACT

Purpose: Liver transplant (LT) recipients have a decreased response to 2 doses of SARS-CoV-2 vaccine compared to the general population, so we aimed to understand response to a third dose to inform vaccination strategies. Method(s): LT recipients in our observational cohort who received 3 homologous mRNA vaccines and available antibody levels pre- and post-dose 3 (D3) were identified. Those who reported a prior COVID-19 diagnosis or used belatacept were excluded. The peak anti-spike antibody level collected between the second (D2) and third dose (D3), was compared to the antibody level at 1 month post-D3. Samples were tested with Roche Elecsys Anti-Sars-CoV-2 enzyme immunoassay (EIA) (positive >=0.8 U/mL) or EUROIMMUN EIA (positive >=1.1 AU). Result(s): 146 participants completed 3 homologous doses of BNT162b2 (53%) or mRNA-1273 (47%) vaccines between 5/15/2021 - 11/8/2021. The median (IQR) time of peak pre-D3 antibody collection was 89 (31, 104) days post-D2. The median time of 1-month post-D3 antibody collection was 30 (23, 33) days. The median time between D2 and D3 was 168 (149-188) days. Overall, 125/146 (86%) were seropositive pre-D3, and 139/146 (95%) were seropositive post-D3 (Figure 1). There were no seroreversions post D3, and among the 21 seronegative recipients pre-D3, 14 (67%) seroconverted post-D3. Risk factors significantly associated with persistent seronegativity post-D3 were less time since LT (1.3 vs 6 years, p=0.042), mycophenolate use (100% vs 37%, p=0.001), BNT162b2 series (100% vs 50%, p=0.01), and pre-D3 seronegative status (86% vs 10%, p<0.001). Conclusion(s): Most LT recipients have excellent responses to a third homologous mRNA vaccine dose, greater than that seen in other transplant recipients. Persons seronegative after D2, however, show weaker response and may remain at high risk for SARS-CoV-2 infection despite D3.

4.
American Journal of Transplantation ; 22(Supplement 3):641-642, 2022.
Article in English | EMBASE | ID: covidwho-2063495

ABSTRACT

Purpose: We report the immunogenicity and safety of a third BNT162b2 vaccine in pediatric solid organ transplant recipients (pSOTRs). Method(s): Samples from pSOTRs (12-18 years) enrolled in our multicenter, observational study (COVID-19 Antibody Testing of Recipients of Solid Organ Transplants and Patients with Chronic Diseases) who received a third vaccine (V3) were analyzed for antibodies to SARS-CoV-2 spike protein receptor-binding domain, with a positive cutoff of >=0.8 and maximum titer of >2500 U/mL. Pre-V3 samples were 1-3 months after vaccine 2, and post-V3 were 1 month after vaccine 3. Result(s): Thirty-seven pSOTRs (46% heart, 24% liver, 27% kidney, 3% multi) received V3. Median (interquartile range [IQR]) age was 15 (14-16) years;42% were male and 78% white. pSOTRs were median (IQR) 9 (6-13) years from transplant. Four (11%) patients had prior SARS-CoV-2 infection. Antibody titers were positive in 26/37 (70%) patients pre-V3 and 32/37 (86%) post-V3 (Figure). Median (IQR) antibody titers were higher post-V3 (2500 [1581-2500] U/mL) than pre-V3 (211 [0.8-2500] U/mL) in paired analysis (p<0.001). 6/11 (55%) pSOTRs with negative pre-V3 titers seroconverted, with a post-V3 median (IQR) titer of 418 (132-1581) U/ mL. Transplant within 3 years was associated with negative post-V3 titer (p=0.037). Main side effects after V3 were pain (71%) and fatigue (50%). No patients reported allergic reaction, myocarditis, or rejection. One patient tested positive for SARSCoV- 2 between vaccines 2 and 3, with negative pre- and post-V3 titers. At time of first vaccine, this patient was transplanted a year ago, treated for rejection recently, and taking 3 immunosuppression agents including an antimetabolite. Conclusion(s): In this limited cohort, 86% of pSOTRs had a positive antibody response after three SARS-CoV-2 vaccines with no adverse events. Importantly, 55% of pSOTRs with prior negative response seroconverted post-V3, and 100% of pSOTRs with positive response increased their antibody titer or remained at maximum titer. Our preliminary results suggest the benefit of a third vaccine for adolescent pSOTRs based on antibody response;larger studies are needed to assess vaccine effectiveness.

5.
American Journal of Transplantation ; 22(Supplement 3):766, 2022.
Article in English | EMBASE | ID: covidwho-2063482

ABSTRACT

Purpose: This study compares SARS-CoV-2 antibody responses between the twodose mRNA-1273 and BNT162b2 vaccine series across groups of incrementally immunosuppressed patients. Method(s): Semiquantitative testing for antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was performed using the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (EIA), 15-45 days after the second vaccine dose for SARS-CoV-2 naive patients with rheumatic and musculoskeletal disease (RMD), and solid organ transplant recipients (SOTRs) from an observational cohort. Anti-RBD titers were divided into categories of >=50, >=100 and >=250 U/mL based on levels associated with plasma neutralizing capacity in COVID-19 convalescent patients. Participants were stratified by increasing intensity of immunosuppression: RMD not on immunosuppression, RMD on immunosuppression, SOTR not on mycophenolate (MMF), and SOTR on MMF. Response rates between mRNA-1273 and BNT162b2 recipients were compared using modified Poisson regression weighted for age, time since vaccination, and number of immunosuppressive medications. This analysis was repeated for several thresholds of positive response: 50, 100, and 250 U/mL. Result(s): Of 1868 participants, 55.8% of RMD and 52.7% of SOTRs received BNT162b2;the remainder received mRNA-1273. Demographics, diagnoses, and immunosuppressive regimens were similar across vaccine groups. Among RMD participants not on immunosuppression, the chance of anti-RBD >=250U/ml was comparable among BNT162b2 and mRNA-1273 recipients (IRR= 0.91 1.03 1.16 p= 0.67). mRNA-1273 recipients had a higher chance than BNT162b2 recipients to achieve anti-RBD >=250U/ml among RMD participants on immunosuppression (IRR = 1.15 1.241.34, p<0.001);SOTRs not on MMF (IRR = 1.24 1.561.96, p <0.001);and SOTRs on MMF (IRR=1.28 2.625.37, p= 0.01). Similar trends were observed with titer cutoffs of >=100 and >=50 U/mL (Table 1). Conclusion(s): The two-dose mRNA-1273 vaccine series was more likely to induce stronger humoral immunogenicity compared to BNT162b2 in immunosuppressed patients;this effect was more pronounced with greater immunosuppression. These findings suggest importance in the choice of mRNA vaccine platform in optimizing immune responses to SARS-CoV-2 vaccination and can help inform vaccination strategies for booster doses in high-risk, immunosuppressed populations.

6.
American Journal of Transplantation ; 22(Supplement 3):763, 2022.
Article in English | EMBASE | ID: covidwho-2063481

ABSTRACT

Purpose: Kidney transplant recipients taking belatacept (KTR-B) have poor immune response to two-dose SARS-CoV-2 vaccination. We sought to characterize the impact of an additional vaccine dose on plasma neutralizing capacity and cellular responses as compared to that of KTRs controls (KTR-C) not taking belatacept. Method(s): Within an observational cohort, we tested 26 KTR-Bs and 27 KTR-Cs for anti-spike antibody responses before and after a third SARS-CoV-2 vaccine dose (D3) using two clinical assays (Roche Elecsys anti-S Ig and EUROIMMUN anti-S1 IgG). For a subset of 5 KTR-Bs and for all KTR-Cs we used a research assay (Meso Scale Diagnostics V-Plex [MSD]) to further assess anti-spike and RBD IgG, as well as surrogate plasma neutralizing activity (% ACE2 inhibition) versus the ancestral and delta variants. For 3 KTR-Bs, post D3 T cell response was assessed via IFN-y ELISpot and deemed positive if spot forming units > 20 per million PBMC and stimulation index > 3. Result(s): KTR-Bs had significant lower clinical anti-spike seroconversion than KTR-Cs (31% vs 74%, p=0.001) after D3 despite similar demographics, clinical factors, and vaccines administered (Table 1). No KTR-B (0/5) was seropositive by MSD anti-spike or anti-RBD IgG (Figure 1). % ACE2 inhibition versus the ancestral variant was significantly lower in KTR-Bs than in KTR-Cs (Median [IQR] 5.2 [2.8, 6.5] vs 12.5 [7.7, 23.9], p<0.01);all KTR-Bs were below a level consistent with detectable neutralizing antibody. All tested KTR-Bs (3/3) had a negative ELISpot, consistent with negligible cellular response. Conclusion(s): These results suggest minimal humoral or cellular immunogenicity of additional vaccine doses for KTR-Bs and indicates the need for alternative strategies to improve vaccine response such as immunosuppression alteration or use of passive immunoprophylaxis with monoclonal anti-spike antibody to improve protection versus SARS-CoV-2.

7.
American Journal of Transplantation ; 22(Supplement 3):643, 2022.
Article in English | EMBASE | ID: covidwho-2063436

ABSTRACT

Purpose: Understanding the dynamics of antibody response to a third dose (D3) of anti-SARS-CoV-2 vaccine in solid organ transplant recipients (SOTRs) is important to inform booster strategies. Method(s): We studied the the dynamics of anti-RBD (Roche, <0.8 to >2500 U/dL) and anti-S (Euroimmun, 0.1 to >8.9 AU) antibody levels in a cohort of SOTRs at 2 weeks, 1 month and 3 months after D3. We compared the proportion of seroconversion at 1 month or 3 months after D3 between mRNA and Ad.26.COV2.S D3 recipients, using Poisson regression with robust standard error, adjusting for age and numbers of immunosuppressants. Result(s): Among 928 SOTRs with 2-week (n=655), 1-month (n=651) or 3-month (n=404) post-D3 titer, 78%, 82% and 86% tested positive for antibodies. The median (IQR) anti-RBD at the three timepoints were >2500 (73, >2500), 2494 (49, >2500) and 1234 (59, >2500) U/mL (Figure 1A, blue), and there were 61% (n=436), 60% (n=491) and 53% (n=313) with anti-RBD> 1000 u/mL, respectively. The median (IQR) anti-S at the three timepoints were 3.2 (0.3, 8.4), 8 (2, >8.9) and 7.4 (2, >8.9) AU (Figure 1B, blue), and there were 47% (n=218), 61% (n=161) and 64% (n=91) who developed anti-S>4 AU. Among patients with no or minimal immune response at 2 weeks post-D3 (n=102), 3/41 (7%) had increased anti-RBD by 1 month while 11/18 (61%) had increased anti-S (Fisher exact p<0.001). 6/29 (21%) had increased anti-RBD by 3 months while 12/20 (60%) had increased anti-S (p<0.01) (Figure 1A&B, yellow). 27/102 (27%) of them seroconverted at 1 or 3 months after D3. Having received Ad.26.COV2.S as D3 is associated with 3.9X increased proportion of seroconversion at 1 month or 3 months among patients with no or minimal immune response at 2 weeks after D3 (aIRR=2.223.926.92, p<0.001). Conclusion(s): Among SOTRs who received a booster anti-SARS-CoV-2 vaccination, dynamics of Anti-RBD and Anti-S antibodies differed substantially. Anti-RBD titers on average declined only slightly after 14 days post-D3, while anti-S increased up through 30-60 days post-D3. After the peak, average titer values for both antibodies declined slightly through three months post-D3.

8.
American Journal of Transplantation ; 22(Supplement 3):768-769, 2022.
Article in English | EMBASE | ID: covidwho-2063432

ABSTRACT

Purpose: nti-spike antibody response to SARS-CoV-2 vaccination is diminished in LT recipients compared to the general population so understanding durability for those that do respond is critical to mitigating risks of infection. We measured serial antibody titers in LT recipients for 6 months after two-dose mRNA vaccine series to describe kinetics and sero-reversion rates. Method(s): LT recipients without known prior COVID-19 had anti-spike antibody testing at 1, 3, and 6 months after the second dose of mRNA vaccine (D2) using two commercial assays (Roche Elecsys anti-receptor binding domain immunoassay (EIA) [positive >=0.8 U/mL] or EUROIMMUN anti-S1 EIA [positive >=1.1 AU]). We compared titer distributions over time and identified factors associated with sero-reversion. Result(s): 180 LT recipients received BNT162b2 (48%) or mRNA-1273 (52%) 2-dose series between 1/7/2021-5/7/2021. At 1 month post-D2 (n=173), 146 (84%) had positive antibody levels at a median (IQR) of 30 (28, 32) days post-D2. At 3 months post-D2 (n=164), 149 (91%) had positive levels at a median of 92 (90, 96) days post-D2. At 6 months post-D2 (n=73), 62 (85%) had positive levels at a median of 180 (176, 185) days post-D2. Among the 66 seropositive at 1 or 3 months post-D2, 58 (88%) remained seropositive by 6 months post-D2. Neither age, years since transplant, vaccine type, nor mycophenolate (MMF) use were associated with sero-reversion, though there was a trend toward more triple immunosuppressive use (25% vs 3%, p=0.07). Of those Roche-tested, the median anti-RBD levels were >=250 U/mL (14, >=250;n=120) at 1 month post-D2, >=250 U/mL (58, >=250;n=113) at 3 months, and >=250 U/mL (30, >=250;n=49) at 6 months . Of those EUROIMMUN-tested, the median anti-S1 levels were 7.25 AU (4.31, 8.71;n=53) at 1 month, 5.71 AU (1.27, 7.90;n=51) at 3 months, and 1.73 AU (0.76, 6.01;n=25) at 6 months. Conclusion(s): Overall, most LT recipients demonstrated 6 month durability of anti-spike antibody following vaccination, but a subset did sero-revert, potentially associated with heavier immunosuppression. Further investigation into clinical consequences of waning antibody levels is key to guide timing of additional vaccine doses.

9.
American Journal of Transplantation ; 22(Supplement 3):762, 2022.
Article in English | EMBASE | ID: covidwho-2063411

ABSTRACT

Purpose: Heart and lung transplant (HT/LT) recipients have impaired humoral responses to SARS-CoV-2 vaccination compared to other solid organ transplant recipients (SOTRs). The purpose of this study is to describe antibody titer kinetics and durability among HT and LT recipients. Method(s): HT or LT recipients (> 18 years) with no known COVID-19 infection were included. Demographics and clinical characteristics were collected via survey. Serologic testing was performed on the Roche Elecsys anti-SARS-CoV-2 enzyme immuno-assay (EIA) or the EUROIMMUN EIA pre- and post-dose 2 (D2). Result(s): Among 93 HT recipients, 59 (63%) were seropositive 1 month and 66 (71%) 3 months post-D2 (Table 1). Seropositive HT recipients had a higher median length of time from transplant to vaccination. 7/66 (11%) had delayed seroconversion (were negative for antibodies 1-month post-D2). Median(IQR) anti-RBD was 81 (8, 250) 1-month post-D2 (n=38) and 231 (48, 438) U/mL 3-months post-D2 (n=43) (Figure 1). Among 68 LT recipients, 29/68 (43%) were seropositive 1-month and 30 (44%) 3-months post-D2. Seronegative LT recipients were more likely to younger (18-39 years old, 15% vs 3%), or older (> 60 years, 74% vs. 50%, p=0.01). Seronegative LT recipients were more likely to be on anti-metabolite therapy (79% vs. 53%, p=0.04) and had a lower median length of time from transplant to vaccination. Among seropositive LT recipients at 3-months, 3 (10%) had delayed seroconversion. Median (IQR) anti-RBD was 61 (4, 233) U/mL 1-month post-D2 (n=26) and 45(11, 299) U/mL 3-months post-D2. Conclusion(s): HT and LT recipients develop a delayed and variable antibody response to mRNA SARS-CoV-2 vaccination. HT recipients more frequently seroconverted, and had higher anti-RBD levels, than LT recipients. Persistent negative and low antibody titers may place LT recipients at the highest risk of breakthrough SARSCoV- 2 infection among SOTRs.

10.
American Journal of Transplantation ; 22(Supplement 3):1064-1065, 2022.
Article in English | EMBASE | ID: covidwho-2063403

ABSTRACT

Purpose: Some solid-organ transplant recipients (SOTRs) with low or negative antibody levels after a 2-dose mRNA vaccine series against SARS-CoV-2 experience boosting after a third dose (D3), but long-term antibody durability after D3 is unknown. We describe six-month SARS-CoV-2 antibody kinetics and durability in 31 SOTRs who received D3. Method(s): 31 SOTRs without prior COVID-19 were identified within our national observational study. Serologic testing was performed a median of 30 (IQR 27-40) days after D3 and repeated at a median of 166 (148-184) days after D3. Semiquantitative anti-spike serologic testing using the Roche Elecsys anti-S enzyme immunoassay (EIA) or EUROIMMUN anti-S1 EIA was performed. Result(s): Over 6 months of follow-up, antibody levels increased in 16/27(59%), remained stable in 6/27(22%) (one negative, the others above the assay limit), and decreased in 5/27(19%). One-month post-D3, 24/31(77%) were seropositive and 7/31(23%) were seronegative. Six-months post-D3, 29/31(94%) were seropositive and 2/31(6%) remained seronegative. Both nonresponders received the BNT-162b2 primary series;one received Ad.26.CoV2.S and the other mRNA-1273 for D3. This difference in seroconversion after D3 was not statistically significant (Fisher exact = 0.49, between primary series). There were no reported cases of COVID-19 during the study period. Conclusion(s): We observed a very high rate of seroconversion after D3 in SOTRs, with marked heterogeneity in timing and strength of response depending on baseline antibody level and vaccine platform received. These results are encouraging evidence for the durable immunogenicity of additional vaccine doses in most SOTRs, and demonstrate the need for dedicated analysis of heterologous boosting strategies.

11.
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).

12.
American Journal of Transplantation ; 22(Supplement 3):440, 2022.
Article in English | EMBASE | ID: covidwho-2063372

ABSTRACT

Purpose: Mycophenolate mofetil (MMF) use is associated with decreased antibody response to the SARS-CoV-2 mRNA vaccine series in heart and lung transplant recipients (HLTRs). Higher MMF doses have been associated with poor immunogenicity in kidney transplant recipients, but limited data exist on HLTRs. We evaluated the relationship between daily MMF dose and vaccine-induced antibody response in HLTRs. Method(s): HLTRs (n= 212) from an observational cohort were categorized by daily MMF doses (None, Low: <1000mg, Moderate: 1000-2000mg, High: >=2000mg). Semi-quantitative antibody testing was performed at 1, 3, and 6-months post-dose 2 (D2) using the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (EIA), testing for antibodies to SARSCoV2 spike protein receptor binding domain, and the EUROIMMUN EIA, testing for S1 domain of SARS-CoV-2 spike protein. Multivariable Poisson regression was used to estimate the risk of a negative antibody response with increasing MMF dose. Result(s): At the time of vaccination, 94 (44.3%) HLTRs reported receiving no MMF, 33 (15.6%) reported a low dose, 54 (25.7%) reported a moderate dose, and 31 (14.8%) reported a high dose regimen. There were statistically significant differences in the number of participants on mTOR inhibitors and Triple immunosuppression among the groups but the participants in all 4 dose categories were otherwise comparable (Table 1) The risk ratio of a negative post-D2 titer with low, moderate and high dose regimens compared to no MMF was 0.65 1.15 2.05 (p=0.63), 1.34 2.043.10 (p=0.001) and 1.83 2.77 4.21 (p<0.001) after adjusting for age, sex, vaccine type, time since transplant, and corticosteroid use. Conclusion(s): HLTRs taking MMF >1000mg/day are at higher risk of remaining seronegative after mRNA vaccination, with evidence of a dose-nonresponse effect. The findings support the exploration of whether targeted MMF reduction strategies in HLTRs increase SARS-CoV-2 vaccine immunogenicity. (Table Presented).

13.
American Journal of Transplantation ; 22(Supplement 3):566, 2022.
Article in English | EMBASE | ID: covidwho-2063341

ABSTRACT

Purpose: Understanding risk factors for impaired vaccine responses can guide strategies for testing, additional dose recommendations, and vaccine schedules to provide improved protection in solid organ transplant recipients (SOTRs). Our purpose was to use machine learning to characterize risk factors and create a prediction model for seroconversion after 2-dose mRNA SARS-CoV-2 vaccination. Method(s): Using our national observational cohort of 1031 SOTRs we created a machine learning model using gradient boosting to explore, rank, and quantify the association of 19 clinical factors with antibody responses to 2-dose mRNA vaccination. Gradient boosting is a general-purpose machine learning algorithm that generates a sequence of parsimonious prediction models based on the residual error of the previous models. We measured the area under the receiver operating characteristic curve (AUROC) via a 10-fold cross validation to evaluate the model's performance. Finally, we evaluated the prediction performance of the models in discrimination and calibration with an external cohort of 512 SOTRs from Houston Methodist. Result(s): Mycophenolate mofetil (MMF) use, shorter time since transplant, and older age were the strongest predictors of seronegativity, collectively contributing to 76% of the model's prediction performance (Figure 1). Other clinical factors, including organ type, vaccine type, sex, race, and other immunosuppression medications, showed weaker associations with seronegativity. Longer time since transplant was associated with higher odds of seropositivity, especially during the first 5 years post-transplant (Figure 2a). Older age among those <65 years old (Figure 2b) and MMF (Figure 2c) were associated with lower odds of seropositivity. The model had moderate prediction performance, with an AUROC of 0.79 (our cohort) and 0.67 (Houston Methodist cohort). Conclusion(s): Our machine learning model allows us to identify SOTRs at highest risk of suboptimal immunogenic response to vaccination, highlighting opportunities for improving protection from COVID-19 including more targeted vaccination strategies. (Figure Presented).

14.
American Journal of Transplantation ; 22(Supplement 3):406, 2022.
Article in English | EMBASE | ID: covidwho-2063340

ABSTRACT

Purpose: To compare antibody response to a third dose (D3) of SARS-CoV-2 vaccine in solid organ transplant recipients (SOTRs) with negative or low-positive antibody levels after 2-dose mRNA vaccination across D3 platforms. Method(s): From our observational study, 532 SOTRs who developed suboptimal antibody responses to 2-dose mRNA vaccination (Roche<50 U/mL or EUROIMMUN <1.1 AU) were selected. Belatacept recipients and persons with any COVID-19 diagnosis were excluded. We compared post-D3 antibody levels among SOTRs who received an mRNA vaccine for D3 (n=487) versus Ad.26.COV2.S for D3 (n=45). Poisson regression with robust standard error was used to study the association between vaccine platform and seroconversion, adjusting for immunosuppression, age, time since transplant, and liver transplant status. Result(s): Pre-D3, 342 SOTRs (64%) were seronegative, of whom 107 (31%) developed high-positive antibody levels post-D3. In contrast, of the 190 (36%) with low-positive pre-D3 antibody levels, 172 (91%) were high-positive post-D3 (Figure 1). Among SOTRs seronegative pre-D3, 1.8x more Ad.26.COV2.S D3 recipients seroconverted compared to mRNA D3 recipients (49.7% vs 27.8%, Fisher's exact=0.014) (Figure 2). Among the pre-D3 seronegative group, there was a 2x higher chance of developing high-positive post-D3 levels with Ad.26.COV2.S compared to mRNA D3 (IRR =1.42.02.9, p<0.001). This was despite the Ad.26. COV2.S D3 group having fewer younger patients and liver transplant recipients, factors that are associated with higher odds of positive antibody response. 165 SOTRs (31%) remained seronegative after D3 (22% of Ad.26.COV2.S recipients vs 32% of mRNA recipients). Conclusion(s): Heterologous boosting with Ad.26.COV2.S may be a promising vaccination option for SOTRs with poor response to the 2-dose mRNA series, particularly among those who are seronegative. (Table Presented).

15.
American Journal of Transplantation ; 22(Supplement 3):405, 2022.
Article in English | EMBASE | ID: covidwho-2063339

ABSTRACT

Purpose: Post-acute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon manifested by long lasting cognitive, mental, and physical symptoms. We aimed to estimate the prevalence of PASC symptoms in solid organ transplant recipients (SOTRs) in the short (1- 6 months) and long-term (> 6 months) periods after SARS-CoV-2 infection. We also compared the prevalence of these symptoms between those with SARS-CoV-2 infection requiring hospitalization and those not requiring hospitalization. Method(s): We surveyed 111 SOTRs with self-reported SARS-CoV-2 infection diagnosed more than 4 weeks prior to survey administration. The survey consisted of 7 validated questionnaires ("Quick Dementia Rating System (QDRS)", "Patient Health Questionnaire (PHQ9)", "Generalized Anxiety Disorder 7 (GAD-7)", "Impact of Events Scale (IES-6)", "EuroQol- 5 Dimension (EQ-5D)", "PROMIS global physical health scale (GHS) "and "Breathlessness, Cough and Sputum Scale (BCSS)"). Result(s): Of the 111 survey participants, 32 (33%) had been hospitalized and 35 (36%) had SARS-CoV-2 infection >6 months ago. Median (IQR) age was 58 years (46, 65). Median time from SARS-CoV-2 diagnosis was 167 days (138, 221). Cognitive impairment, anxiety, depression, insomnia, feeling of trauma, fatigue, pain, breathing problems, cough, abnormal smell, abnormal taste, and diarrhea were reported by 40%, 23%, 36%, 55%, 53%, 41%, 19%, 33%, 33%, 21%, 22%, and 32% of patients respectively. Hospitalized patients had poorer scores in cognition (QDRS survey score of 2 versus 0.75, p=0.048) (Figure 1), quality of life (EQ-5D survey score of 2 versus 1, p=0.043), physical health (PROMIS GHS survey score of 10 versus 11, p=0.013), respiratory status (BCSS survey score of 1 versus 0, p=0.056), and pain (Pain score of 3 versus 0, p 0.006). Among patients who had SARS-CoV-2 infection >6 months ago, abnormal breathing, cough, abnormal smell, abnormal taste, and diarrhea continued to be reported by 31%, 31%, 29%, 32%, and 32% of patients respectively. Conclusion(s): After SARS-CoV-2 infection, SOTRs had a high prevalence of PASC symptoms. Some of the symptoms are more severe in patients who had required hospitalization and persist beyond 6 months. Further studies are needed to understand the long term sequalae of SARS-CoV-2 infection in SOTRs and to develop an evidence-based multidisciplinary approach for caring for these patients beyond the acute phase. (Table Presented).

16.
Taiwan Journal of Public Health ; 41(1):96-104, 2022.
Article in Chinese | Scopus | ID: covidwho-2025280

ABSTRACT

Objectives: This study aimed to examine the relationship between family income loss and child health during the COVID-19 pandemic. Methods: Data for the analysis were obtained from the Taiwan Birth Cohort Study, a nationally representative sample of babies born in 2005, and 18, 024 caregivers participated in the survey as their children aged 15. In analysis, we first conducted descriptive analyses to test the correlation between socioeconomic variables and family income loss. We next assessed whether there was a gradient relationship between family income loss and child health using Cochran-Armitage trend test. Finally, multiple logistic regression was used to estimate the relationship between family income loss and child health. Results: Our findings indicated that (1) lower socioeconomic families were at a greater risk of suffering income loss during COVID-19;(2) children in the families experiencing a more severe loss of income had worse health, but the gradient relationship was not significant for those in higher income families;and (3) significantly higher risk of fair/poor health of children was found in the severe (OR: 1.3, 95% CI 1.2-1.5) and mild (OR: 1.2, 95% CI 1.1-1.3) income loss groups than in the no income loss group after adjustment for socioeconomic variables. Conclusions: Family income loss due to COVID-19 was significantly associated with child health inequality. To avoid widening the health gap, children in families experiencing financial impacts during the COVID-19 pandemic should be protected and supported, particularly those in lower socioeconomic groups. © 2022 Chinese Public Health Association of Taiwan. All rights reserved.

17.
Annals of the Rheumatic Diseases ; 81:369-370, 2022.
Article in English | EMBASE | ID: covidwho-2009092

ABSTRACT

Background: An attenuated humoral response to SARS-CoV-2 vaccination has been observed in some patients with rheumatic and musculoskeletal diseases (RMD) (1). We sought to identify clinical factors associated with poor humoral response following primary (two-dose mRNA or single adenoviral vector dose) SARS-COV-2 vaccination in patients with RMD on immunosuppression. Objectives: To identify clinical predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination in RMD patients on immunosuppression. Methods: We included patients ≥18 years old with RMD on immunosuppres-sion who received either two-dose mRNA or single dose Janssen/Johnson and Johnson (J&J) vaccination. Demographics, diagnoses, and therapeutic regimens were collected via participant report;those with prior COVID-19 infection were excluded. One month after vaccination, participants underwent SARS-CoV-2 antibody testing on the semi-quantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which measures antibody to the SARS-CoV-2 S-recep-tor binding domain (RBD) protein (ceiling >250U/mL later expanded to >2500U/mL). Associations were evaluated using Fisher's exact and Wilcoxon rank sum tests. Logistic regression analyses were performed to evaluate for clinical factors associated with antibody response. We adapted survival methods to address right-truncation of titers;this methodology was used to calculate medians. Participants provided informed consent electronically and the study was approved by the local Institutional Review Board. Results: We studied 1138 RMD participants on immunosuppression;most were female (93%) and white (91%) (Table 1). One-hundred and ffteen (10%) had anti-RBD response in the negative range at a median (IQR) of 29 days (28-34) following completion of vaccine series. A greater proportion of participants with negative response were non-white, received J&J vaccine, reported use of myco-phenolate, rituximab, or glucocorticoids. Antibody response differed by immuno-suppressive regimen, with those receiving rituximab having poorest response (Figure 1). Use of mycophenolate (aOR 9.92, p=0.001), rituximab (aOR 56.99, p=0.001), glucocorticoids (aOR 2.99, p=0.001) or receipt of J&J (aOR 3.13, p=0.039) were associated with negative antibody response. Conclusion: Use of mycophenolate, glucocorticoids, rituximab and receipt of J&J vaccine were the strongest predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination;these data support use of an additional primary dose in RMD patients.

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