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.
ABSTRACT
Purpose: The response to SARS-CoV-2 may be blunted in transplant recipients, impacting reinfection risk, treatment selection, and vaccine protocols. We quantified antibody response and durability after COVID-19 in solid organ transplant recipients (SOTRs). Methods: SOTRs with PCR-confirmed COVID-19 were recruited through the EMR August 21-October 15, 2020. Participants underwent at-home blood sampling with the TAPTM Blood Collection Device, Second Edition (7SBio, Medford, MA). Serum samples were screened using Elecsys® anti-SARS-CoV-2 immunoassay (Roche), which uses a recombinant protein representing the nucleocapsid antigen. Confirmatory testing was performed using EUROIMMUN anti-SARS-CoV-2 enzyme-linked immuosorbent assay (ELISA) for semi-quantitative detection of IgG antibodies to spike protein (anti-S1-IgG), a likely correlate of neutralizing immunity. Results: Eighteen SOTRs were studied, for whom COVID-19 occurred at a median of 6 years (IQR 2-9) post-transplant. Median age was 56 years (IQR 42-63);56% were female;33% were Black and 11% were Hispanic. Most participants (89%) had experienced COVID-19 symptoms;72% were hospitalized. Among those hospitalized, 15% were admitted to the ICU and 8% were mechanically ventilated. COVID-19 convalescent plasma (CCP) was administered to 3 kidney and 2 lung recipients. At median 98 days (IQR 55-147) after COVID-19 diagnosis, 78% had reactive screening immunoassays (Table 1). Of the four patients with non-reactive immunoassays, 2 were the lung recipients treated with CCP and 1 was the kidney recipient receiving IVIg. Of those who screened positive, anti-S1-IgG was detectable in 83%. SOTRs who received CCP and/or IVIg were less likely to develop anti-S1- IgG and had lower antibody levels. Conclusions: We found antibody levels suggestive of neutralizing immunity in the majority of participants. However, those who were administered CCP and/or IVIg were less likely to mount a durable immune response. This raises the possibility that exogenous antibody preparations may blunt durable antibody formation. We observed a significant association between more severe disease and higher antibody levels. Seropositivity might decline over time;however, we were unable to distinguish between impaired production or rapid decrement. Our findings are important for individuals with compromised immune systems, whether deliberately for conditions like organ transplantation and cancer, or naturally in the elderly, frail, and autoimmune populations.
ABSTRACT
Background: Acute kidney injury (AKI) is common in patients with COVID-19 and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. Methods: We evaluated 19 urinary biomarkers of injury, inflammation, and repair in patients hospitalized with COVID-19 at 2 academic medical centers between April and June 2020. We associated biomarkers with a primary composite outcome of KDIGO stage 3 AKI, requirement for dialysis, or death within 60 days of admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings. Results: Out of 157 patients, 24 (15.3%) experienced the primary outcome. Twofold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR: 1.53;95% CI: 1.33-1.76), monocyte chemoattractant protein (MCP-1) (HR: 1.86;95% CI: 1.48-2.33), and kidney injury molecule-1 (KIM-1) (HR: 2.32;95% CI: 1.69-3.18) were associated with highest risk of the primary outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR 0.52;95% CI: 0.40-0.69). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. Conclusions: Urinary biomarkers are associated with severe kidney complications in patients with COVID-19 and provide valuable information to monitor kidney disease recovery and progression.
ABSTRACT
Background: The performance of serological antibody tests to SARS-CoV-2 infection varies widely and little is known about their performance in Africa. We assessed the performance of CoronaCHEK Lateral Flow Point of Care Tests on samples from Rakai, Uganda and Baltimore, Maryland, USA. Methods: Samples from subjects known to be SARS-CoV-2 PCR+ (Uganda: 50 samples from 50 individuals, and Baltimore: 266 samples from 38 individuals) and samples from pre-pandemic individuals collected prior to 2019 (Uganda: 1077 samples, Baltimore: 580 samples) were analyzed with the CoronaCHEK assay per manufacturers protocol. Sensitivity by duration of infection and specificity among pre-pandemic samples were assessed for the IgM and IgG bands separately and for any reactivity. Poisson regression models were used to calculate prevalence ratios (PR) for factors associated with a false-positive test among pre-pandemic samples. Results: In Baltimore samples, sensitivity for any reactivity increased with duration of infection with 39% (95% CI 30, 49) during 0-7 days since first positive PCR, 86% (95% CI 79, 92) for 8-14 days, and 100% (95% CI 89,100) after 15 days (See Figure). In Uganda, sensitivity was 100% (95% CI 61,100) during 0-7 days, 75% (95%CI 53, 89) for 8-14 days, and 87% (95%CI 55, 97) after 14 days since first positive PCR. Specificity results among pre-pandemic samples from Uganda was 96.5% (95% CI 97.5, 95.2), significantly lower than the 99.3% (95% CI 98.2, 99.8) observed in samples from Baltimore (p<0.01). In Ugandan samples, individuals with a false positive result were more likely to have had a fever more than a month prior to sample acquisition (PR 2.9, 95% CI 1.1, 7.0). Conclusion: Sensitivity of the CoronaCHEK appeared to be significantly higher in Ugandan samples from individuals within their first week of infection compared to their Baltimorean counterparts. By the second week of infection the sensitivity appeared the same between geographic areas. The specificity was significantly lower in Ugandan samples than those from Baltimore. False positive results from pre-pandemic Uganda appear to be correlated with the convalescent disease state, potentially indicative of a highly cross-reactive immune response in these individuals from East Africa.