Lack of seroresponse to SARS-CoV-2 booster vaccines given early post-transplant in patients primed pre-transplantation.

SARS-CoV-2 vaccines are recommended pre-transplantation, however, waning immunity and evolving variants mandate booster doses. Currently there no data to inform the optimal timing of booster doses post-transplant, in patients primed pre-transplant. We investigated serial serological samples in 204 transplant recipients who received 2 or 3 SARS-CoV-2 vaccines pre-transplant. Spike protein antibody concentrations, [anti-S], were measured on the day of transplantation and following booster doses post-transplant. In infection-naïve patients, post-booster [anti-S] did not change when V3 (1st booster) was given at 116(78-150) days post-transplant, falling from 122(32-574) to 111(34-682) BAU/ml, p=0.78. Similarly, in infection-experienced patients, [anti-S] on Day-0 and post-V3 were 1090(133-3667) and 2207(650-5618) BAU/ml respectively, p=0.26. In patients remaining infection-naïve, [anti-S] increased post-V4 (as 2nd booster) when given at 226(208-295) days post-transplant, rising from 97(34-1074) to 5134(229-5680) BAU/ml, p=0.0016. Whilst in patients who had 3 vaccines pre-transplant, who received V4 (as 1st booster) at 82(49-101) days post-transplant, [anti-S] did not change, falling from 981(396-2666) to 871(242-2092) BAU/ml, p=0.62. Overall, infection pre-transplant and [anti-S] at the time of transplantation predicted post-transplant infection risk. As [Anti-S] fail to respond to SARS-CoV-2 booster vaccines given early post-transplant, passive immunity may be beneficial to protect patients during this period.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study.

Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.

Comparison of immunogenicity and clinical effectiveness between BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines in people with end-stage kidney disease receiving haemodialysis: A prospective, observational cohort study.

Background: People with end-stage kidney disease, including people on haemodialysis, are susceptible to greater COVID-19 related morbidity and mortality. This study compares the immunogenicity and clinical effectiveness of BNT162B2 versus ChAdOx1 in haemodialysis patients. Methods: In this observational cohort study, 1021 patients were followed-up from time of vaccination until December 2021. All patients underwent weekly RT-PCR screening. Patients were assessed for nucleocapsid(anti-NP) and spike(anti-S) antibodies at timepoints after second(V2) and third(V3) vaccinations. 191 patients were investigated for T-cell responses. Vaccine effectiveness (VE) for prevention of infection, hospitalisation and mortality was evaluated using the formula VE=(1-adjustedHR)x100. Findings: 45.7% (467/1021) had evidence of prior infection. There was no difference in the proportion of infection-naïve patients who seroconverted by vaccine type, but median anti-S antibody titres were higher post-BNT162b2 compared with ChAdOx1; 462(152-1171) and 78(20-213) BAU/ml respectively, p<0.001.  Concomitant immunosuppressant use was a risk factor for non-response, OR 0.12[95% CI 0.05-0.25] p<0.001.  Post-V3 (all BNT162b2), median anti-S antibody titres remained higher in those receiving BNT162b2 versus ChAdOx1 as primary doses; 2756(187-1246) and 1250(439-2635) BAU/ml respectively, p=0.003.Anti-S antibodies waned over time. Hierarchical levels of anti-S post-V2 predicted risk of infection; patients with no/low anti-S being at highest risk. VE for preventing infection, hospitalisation and death was 53% (95% CI 6-75), 77% (95% CI 30-92) and 93% (95% CI 59-99) respectively, with no difference seen by vaccine type. Interpretation: Serum anti-S concentrations predict risk of breakthrough infection. Anti-S responses vary dependent upon clinical features, infection history and vaccine type. Monitoring of serological responses may enable individualised approaches to vaccine boosters in at risk populations. Funding: National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London.

Immune responses following 3rd and 4th doses of heterologous and homologous COVID-19 vaccines in kidney transplant recipients.

Background: Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3rd- (V3) and 4th- (V4) doses of heterologous and homologous vaccines in a kidney transplant population. Methods: We undertook a single centre cohort study of 724 kidney transplant recipients prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their first dose of vaccine. Findings: 586/724 (80.9%) patients were infection-naïve post-V3; 141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001; immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001.Post-V4, 45/239 (18.8%) infection-naïve patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type. Interpretation: A significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection. As such alternative strategies are required to provide protection to this vulnerable group. Funding: MW/PK received study support from Oxford Immunotec.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study [version 2;peer review: 2 approved]

Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited;the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124;95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62;95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.

COVID-19 in rural Africa: Food access disruptions, food insecurity and coping strategies in Kenya, Namibia, and Tanzania.

This study assesses the extent of COVID-19-related food insecurity in Kenya, Tanzania, and Namibia. Using the Household Food Insecurity Access Scale, we measure food insecurity in various dimensions and document several food access disruptions associated with the COVID-19 pandemic between April and July 2020. Furthermore, we assess the association of COVID-19 countermeasures with the adoption of various strategies in line with the coping strategies index. We rely on a unique phone survey that followed households who participated in an earlier field-based survey. First, through Ordinary Least-Squares and Probit regressions, we show a strong and statistically significant association between COVID-19 countermeasures and food access disruptions and food insecurity in each of the three countries. We then use a multivariate probit regression model to understand the use of the various coping strategies, including reducing food intake, increasing food search, and relying more on less nutritious foods. We provide evidence on the complementarities and trade-offs in using these coping strategies. COVID-19 and related lockdown measures coincided with a deleterious increase in food insecurity in rural Africa.

Postvaccination COVID-19 infection is associated with reduced mortality in patients with cirrhosis.

BACKGROUND AND AIMS: Patients develop breakthrough COVID-19 infection despite vaccination. The aim of this study was to identify outcomes in patients with cirrhosis who developed postvaccination COVID-19. METHODS: We performed a retrospective cohort study among US veterans with cirrhosis and postvaccination or unvaccinated COVID-19. Patients were considered fully vaccinated if COVID-19 was diagnosed 14 days after the second dose of either the Pfizer BNT162b2, the Moderna 1273-mRNA, or the single-dose Janssen Ad.26.COV2.S vaccines and partially vaccinated if COVID-19 was diagnosed 7 days after the first dose of any vaccine but prior to full vaccination. We investigated the association of postvaccination COVID-19 with mortality. RESULTS: We identified 3242 unvaccinated and 254 postvaccination COVID-19 patients with cirrhosis (82 after full and 172 after partial vaccination). In a multivariable analysis of a 1:2 propensity-matched cohort including vaccinated (n = 254) and unvaccinated (n = 508) participants, postvaccination COVID-19 was associated with reduced risk of death (adjusted HR [aHR], 0.21; 95% CI, 0.11-0.42). The reduction was observed after both full (aHR, 0.22; 95% CI, 0.08-0.63) and partial (aHR, 0.19; 95% CI, 0.07-0.54) vaccination, following the 1273-mRNA (aHR, 0.12; 95% CI 0.04-0.37) and BNT162b2 (aHR, 0.27; 95% CI, 0.10-0.71) vaccines and among patients with compensated (aHR, 0.19; 95% CI, 0.08-0.45) and decompensated (aHR, 0.27; 95% CI, 0.08-0.90) cirrhosis. Findings were consistent in a sensitivity analysis restricted to participants who developed COVID-19 after vaccine availability. CONCLUSIONS: Though patients with cirrhosis can develop breakthrough COVID-19 after full or partial vaccination, these infections are associated with reduced mortality.

Health Status, Persistent Symptoms, and Effort Intolerance One Year After Acute COVID-19 Infection.

BACKGROUND: The long-term prevalence and risk factors for post-acute COVID-19 sequelae (PASC) are not well described and may have important implications for unvaccinated populations and policy makers. OBJECTIVE: To assess health status, persistent symptoms, and effort tolerance approximately 1 year after COVID-19 infection DESIGN: Retrospective observational cohort study using surveys and clinical data PARTICIPANTS: Survey respondents who were survivors of acute COVID-19 infection requiring Emergency Department presentation or hospitalization between March 3 and May 15, 2020. MAIN MEASURE(S): Self-reported health status, persistent symptoms, and effort tolerance KEY RESULTS: The 530 respondents (median time between hospital presentation and survey 332 days [IQR 325-344]) had mean age 59.2±16.3 years, 44.5% were female and 70.8% were non-White. Of these, 41.5% reported worse health compared to a year prior, 44.2% reported persistent symptoms, 36.2% reported limitations in lifting/carrying groceries, 35.5% reported limitations climbing one flight of stairs, 38.1% reported limitations bending/kneeling/stooping, and 22.1% reported limitations walking one block. Even those without high-risk comorbid conditions and those seen only in the Emergency Department (but not hospitalized) experienced significant deterioration in health, persistent symptoms, and limitations in effort tolerance. Women (adjusted relative risk ratio [aRRR] 1.26, 95% CI 1.01-1.56), those requiring mechanical ventilation (aRRR 1.48, 1.02-2.14), and people with HIV (aRRR 1.75, 1.14-2.69) were significantly more likely to report persistent symptoms. Age and other risk factors for more severe COVID-19 illness were not associated with increased risk of PASC. CONCLUSIONS: PASC may be extraordinarily common 1 year after COVID-19, and these symptoms are sufficiently severe to impact the daily exercise tolerance of patients. PASC symptoms are broadly distributed, are not limited to one specific patient group, and appear to be unrelated to age. These data have implications for vaccine hesitant individuals, policy makers, and physicians managing the emerging longer-term yet unknown impact of the COVID-19 pandemic.

Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression.

OBJECTIVE: There is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination. METHODS: Serological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases. RESULTS: Following first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy. CONCLUSION: SARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.

Thirty-Day Post-Discharge Outcomes Following COVID-19 Infection.

BACKGROUND: The clinical course of COVID-19 includes multiple disease phases. Data describing post-hospital discharge outcomes may provide insight into disease course. Studies describing post-hospitalization outcomes of adults following COVID-19 infection are limited to electronic medical record review, which may underestimate the incidence of outcomes. OBJECTIVE: To determine 30-day post-hospitalization outcomes following COVID-19 infection. DESIGN: Retrospective cohort study SETTING: Quaternary referral hospital and community hospital in New York City. PARTICIPANTS: COVID-19 infected patients discharged alive from the emergency department (ED) or hospital between March 3 and May 15, 2020. MEASUREMENT: Outcomes included return to an ED, re-hospitalization, and mortality within 30 days of hospital discharge. RESULTS: Thirty-day follow-up data were successfully collected on 94.6% of eligible patients. Among 1344 patients, 16.5% returned to an ED, 9.8% were re-hospitalized, and 2.4% died. Among patients who returned to the ED, 50.0% (108/216) went to a different hospital from the hospital of the index presentation, and 61.1% (132/216) of those who returned were re-hospitalized. In Cox models adjusted for variables selected using the lasso method, age (HR 1.01 per year [95% CI 1.00-1.02]), diabetes (1.54 [1.06-2.23]), and the need for inpatient dialysis (3.78 [2.23-6.43]) during the index presentation were independently associated with a higher re-hospitalization rate. Older age (HR 1.08 [1.05-1.11]) and Asian race (2.89 [1.27-6.61]) were significantly associated with mortality. CONCLUSIONS: Among patients discharged alive following their index presentation for COVID-19, risk for returning to a hospital within 30 days of discharge was substantial. These patients merit close post-discharge follow-up to optimize outcomes.

Resuming Deceased Donor Kidney Transplantation in the COVID-19 Era: What Do Patients Want?

BACKGROUND: The rapidly evolving novel coronavirus 2019 (COVID-19) pandemic bought many kidney transplant (KT) programs to a halt. Integral to resuming KT activity is understanding the perspectives of potential transplant candidates during this highly dynamic time. METHODS: From June 1 to July 7, 2020, a telephone survey of KT candidates on the deceased donor waiting list at Imperial College Renal and Transplant Centre in West London was conducted. The survey captured ongoing COVID-19 exposure risks and patients' views on waitlist (WL) reactivation and undergoing transplantation. RESULTS: Two hundred seven responses were received. Of the respondents, 180 patients (87%) were happy to be reactivated onto the WL; with 141 patients (68%) willing to give consent to transplantation currently, while 53 patients (26%) felt unsure, and 13 patients (6%) would decline a KT. The vast majority of patients had no concerns. In the responses from those who were uncertain or who would decline a KT, concerns about COVID-19 infection and the need for reassurance from transplant units dominated. Universally patients wanted more information about COVID-19 infection risk with KT and the precautions being taken to reduce this risk. CONCLUSIONS: The majority of surveyed patients are in favor of reactivation and receiving a KT despite the ongoing COVID-19 pandemic. Reactivation of candidates cannot be assumed and should take an individualized approach, incorporating clinical risk with patient perspectives. Improved communication with KT candidates is highly requested.