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ObjectiveThere is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination.MethodsSerological 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.ResultsFollowing 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.ConclusionSARS-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.

We aimed to describe the outcomes of Omicron infection in kidney transplant recipients (KTR), compare the efficacy of the community therapeutic interventions and report the safety profile of molnupiravir.From 142 KTRs diagnosed with COVID-19 infection after Omicron had become the dominant variant in the UK, 116 (78.9%) cases were diagnosed in the community; 47 receiving sotrovimab, 21 molnupiravir and 48 no treatment. 10 (20.8%) non-treated patients were hospitalised following infection, which was significantly higher than the sotrovimab group (2.1%), p=0.0048, but not the molnupiravir treated group (14.3%), p=0.47. The only admission following sotrovimab occurred in a patient infected with BA.2. One patient from the molnupiravir and no-treatment groups required ICU support, and both subsequently died, with one other death in the no-treatment group. No patient receiving sotrovimab died. 6/116 (5.2%) patients required dialysis following their diagnosis; 2 (9.5%) patients receiving molnupiravir and 4 (8.3%) no-treatment. This requirement was significantly higher in the molnupiravir group compared with the sotrovimab treated patients, in whom no patient required dialysis, p=0.035. Both molnupiravir treated patients requiring dialysis had features of systemic thrombotic microangiopathy.Post-vaccination serostatus was available in 110 patients. Seropositive patients were less likely to require hospital admission compared with seronegative patients, 6 (7.0%) and 6 (25.0%) respectively, p=0.023. Seropositive patients were also less likely to require dialysis therapy, p=0.016.In conclusion, sotrovimab treatment in the community was associated with superior patient and transplant outcomes; it’s clinical efficacy against the BA.2 variant requires a rapid review. The treatment benefit of molnupiravir was not evident, and wider safety reporting in transplant patients is needed.

Background Dialysis patients are at risk of severe COVID-19. We managed COVID-19 haemodialysis outpatients in dedicated satellite dialysis units. This provided rare opportunity to study early disease progress in community-based patients. We aimed to (1) understand COVID-19 progression, (2) identify markers of future clinical severity and (3) assess associations between dialysis management strategies and COVID-19 clinical outcomes. Methods We conducted a cohort study of all outpatients managed at a COVID-19 haemodialysis unit. We analysed data recorded as part of providing COVID-19 clinical care. We analysed associations between features at diagnosis and the first 3 consecutive haemodialysis sessions in patients who required future hospital admission, and those who had died at 28 days. Results Isolated outpatient haemodialysis was provided to 106 patients over 8 weeks. No patients received antiviral medication or hydroxychloroquine. 21 patients (20%) were admitted at COVID-19 diagnosis. 29 of 85 patients (34%) were admitted after initial outpatient management. 16 patients (15%) died. By multivariate analysis, non-active transplant list status, use of institutional transport, and increased white cell count associated with future hospitalisation and increased age associated with death. Oxygen saturations progressively decreased over the first 3 dialysis sessions in the cohorts who progressed to future hospital admission or death. Mean ultrafiltration volume of the first three haemodialysis sessions was reduced in the same cohorts. Conclusions Outpatient haemodialysis in patients with COVID-19 is safe for patients and staff. Features at the first 3 dialysis sessions can identify individuals at risk of future hospitalisation and death from COVID-19., Graphical abstract

BackgroundSolid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. Emerging evidence suggests at least equivalent immunogenicity of heterologous compared with homologous vaccine regimens in the general population. In this study, we report on immune responses to 3rd dose BNT162b2 vaccines in transplant recipients either primed with ChAdOx1 or BNT162b2.Methods700 kidney transplant recipients were prospectively screened for serological responses (median time of 33 (21-52) days) following 3 primary doses of a SARS-CoV2 vaccine. All vaccine doses were received post-transplant, and all 3rd doses were BNT162b2. All participants had serological testing performed post-2nd vaccination at a median time of 34 (IQR 26-46) days following the 2nd inoculation, and at least once prior to their 1st dose of vaccine.Results366/700 (52.3%) participants were primed with BNT162b2, whilst 334/700 (47.7) had received ChAdOx1. Overall, 139/700 (19.9%) participants had evidence of prior infection. Of 561 infection naïve participants, 263 (46.9%) had no detectable anti-S following 2-doses of vaccine (V2). 134 (23.9%) participants remained seronegative post 3rd vaccine (V3); 54/291 (18.6%) and 79/270 (29.3%) of participants receiving BNT162b2 and ChAdOx1 respectively, p=0.0029. Median anti-S concentrations were significantly higher post-V3 in patients who had received BNT162b2 compared with ChAdOx1, at 612 (27-234) versus 122 (7.1-1111) BAU/ml respectively, pCellular responses were investigated in 30 infection naïve participants at a median time of 35 (24-46) days post-V3. Eighteen of 30 (60.0%) participants had undetectable T-cell responses. There were neither qualitative or quantitative differences in T-cell responses between those patients who received BNT162b2 or ChAdOx1 as their first 2-doses, with 10/16 (62.5%) and 8/14 (57.1%) respectively having undetectable T-cell responses, p=0.77.ConclusionA significant proportion of transplant recipients remain seronegative following 3 doses of SARS-CoV-2 vaccines, with anti-S concentrations lower in patients receiving heterologous versus homologous vaccinations.

BackgroundEmerging data suggest a reduction in SARS-CoV-2 vaccine effectiveness against Omicron SARS-CoV-2 infection. There is also evidence to show that Omicron is less pathogenic than previous variants. For clinically vulnerable populations, a less pathogenic variant may still have significant impact on morbidity and mortality. Herein we assess the clinical impact of Omicron infection, and vaccine effectiveness, in an in-centre haemodialysis (IC-HD) population.MethodsOne thousand, one hundred and twenty-one IC-HD patients were included in the analysis, all patients underwent weekly screening for SARS-CoV-2 infection via RT-PCR testing between 1st December 2021 and 16th January 2022. Screening for infection via weekly RT-PCR testing and 3-monthly serological assessment started prior to the vaccine roll out in 2020.ResultsOmicron infection was diagnosed in 145/1121 (12.9%) patients over the study period, equating to an infection rate of 3.1 per 1000 patient days. Vaccine effectiveness (VE) against Omicron infection in patients who had received a booster vaccine was 58 (23-75)%, p=0.002; VE was seen in patients who received either ChAdOx1, VE of 47(2-70)%, p=0.034, or BNT162b2, VE of 66 (36-81)%, p=0.0005, as their first two doses. No protection against infection was seen in patients who were partially vaccinated (2-doses), p=0.83. Prior infection was associated with reduced likelihood of Omicron infection, HR 0.69 (0.50-0.96), p=0.0289. Four (2.8%) patients died within 28 days of infection diagnosis, with no excess mortality was seen in patients with infection.Conclusion3-doses of SARS-CoV-2 vaccines are required in ICHD to provide protection against Omicron infection.

BackgroundLateral flow immunoassays (LFIAs) have the potential to deliver 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 SARS-CoV-2 vaccine.MethodsThis is a prospective diagnostic accuracy study.SettingSampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Laboratory analyses were performed across Imperial College London sites and university facilities.ParticipantsTwo cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following SARS-CoV-2 vaccine booster, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination, and 21 day follow up. A total of 186 paired samples were collected.InterventionsDuring the participants visit, capillary 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 were detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA.Main outcome measuresThe accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay.ResultsUsing the threshold value for positivity on serological testing of ≥7.10 BAU/ml, the overall performance of the test produces an estimate of sensitivity of 91.94% (95% CI 85.67% to 96.06%) and specificity of 93.55% (95% CI 84.30% to 98.21%) using the Abbott assay as reference standard.ConclusionsFortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveys, but does not meet criteria for individual testing.

BackgroundAttenuated immune responses to mRNA SARS-CoV-2 vaccines have been reported in solid organ transplant recipients. Most studies have assessed serological responses alone, and there is limited immunological data on vector-based vaccines in this population. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in a cohort of kidney transplant patients, assessing both serological and cellular responses.Methods920 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=490) or ChAdOx1 (n=430). 106 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group.ResultsAnti-S was detected in 569 (61.8%) patients. Seroconversion rates in infection-naïve patients who received BNT162b2 were higher compared with ChAdOx1, at 269/410 (65.6%) and 156/358 (43.6%) respectively, p1st year post-transplant and receiving BNT162b2 was associated with seroconversion.Only 28/106 (26.4%) of patients had detectable T-cell responses. There was no difference in detection between infection-naïve patients who received BNT162b2, 7/40 (17.5%), versus ChAdOx1, 2/39 (5.1%), p=0.15. There was also no difference in patients with prior infection who received BNT162b2, 8/11 (72.7%), compared with ChAdOx1, 11/16 (68.8%), p=0.83.ConclusionsEnhanced humoral responses were seen with BNT162b2 compared with ChAdOx1 in kidney transplant patients. T-cell responses to both vaccines were markedly attenuated. Clinical efficacy data is still required but immunogenicity data suggests weakened responses to both vaccines in transplant patients, with ChAdOx1 less immunogenic compared with BNT162b2.

BackgroundLimited data exists on the immunogenicity of vector-based SARS-CoV-2 vaccines in patients with kidney disease. Given their use in over 180 countries, such data is of upmost importance to inform policy on optimal vaccination strategies. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in patients receiving haemodialysis.Methods1021 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=523) or ChAdOx1 (n=498). 191 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group.ResultsAnti-S was detected in 936 (91.2%) of patients post-vaccination. There was no difference in seroconversion rates between infection-naïve patients who received BNT162b2, 248/281 (88.3%), compared with ChAdOx1, 227/272 (83.5%), p=0.11. Anti-S concentrations were higher following BNT162b, 462(152-1171) BAU/ml, compared with ChAdOx-1 79(20-213) BAU/ml, pOnly 73 (38.2%) of patients had detectable T-cell responses post-vaccination, with no proportional difference between infection-naïve patients who received BNT162b2, 2/19 (10.5%), versus ChAdOx1, 15/75 (20.0%), p=0.34. There were no quantitative differences in T-cell responses in infection-naïve patients, with a median 2(0-16) SFU/106PBMCs and 10(4-28) SFU/106PBMCs in those receiving BNT162b2 and ChAdOx1 respectively, p=0.35. These responses were significantly weaker compared with healthy controls.ConclusionsEnhanced immunogenicity was seen with BNT162b2 compared with ChAdOx1, driven by superior humoral responses, with attenuated T-cell responses to both vaccines. Comparative data on clinical efficacy is now required.Significance StatementLimited data exist on the immunogenicity of vector-based SARS-CoV-2 vaccines in patients with kidney disease. Given their use in over 180 countries worldwide, such data are of upmost importance to inform policy on optimal vaccination strategies. This study compares the immunogenicity of BNT162b2 (n=523) against the adenovirus vector vaccine, ChAdOx1 (n=498), in 1021 haemodialysis patients. In infection-naïve patients, overall seroconversion rates were comparable, however, spike protein antibody concentrations were significantly higher following BNT162b2. No difference in T-cell responses was seen, however, all naïve patients had weaker responses compared with healthy controls. Equivalent attenuated cellular responses to both vaccines, with greater humoral responses to BNT162b2, suggests BNT162b2 has superior immunogenicity in this patient population, with data on clinical efficacy required.

Flood poses significant risk to society. In many regions flood remains an uninsured peril, which means national governments, donor organizations, charities, and tax payers can end up funding the economic losses. One of the challenges the re/insurance industry faces is not having the necessary tools available with global coverage to quantify flood risk, especially in low income regions where data are often sparse. Traditional reinsurers and providers of alternative risk transfer or primary insurance rely heavily on catastrophe models to understand and manage flood risk. For high income territories with established re/insurance markets such as Europe, United States, and Japan, there are several flood models available, ranging from simple deterministic to more sophisticated probabilistic solutions. How can we increase flood risk modeling capabilities to not only include the most vulnerable populations but also supply a broader array of tools, such as quantifying the physical impacts of climate change on extreme events? This chapter discusses how Earth Observation (EO) data provides instrumental input for a number of applications, from validating and benchmarking flood solutions to estimating the exposed risks in vulnerable regions, responding to catastrophe events in real time, and increasing resilience. While EO technology is constantly evolving, challenges in the re/insurance industry remain around real-time accessibility, value-added applications, consistent global solutions such as high-resolution digital terrain models, and how to stay abreast of the wealth of data sources and portals available. Relevant industry partnerships are one way forward, and community activities such as Global Flood Risk Monitoring (GFRM), the Willis Research Network, the Lighthill Risk Network, and Oasis will be discussed.