Response to Vaccination Against SARS-CoV-2 in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Renal Involvement.

BACKGROUND: Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) present with multisystem disease including renal impairment. The treatment for AAV involves a high burden of immunosuppression. Patients with renal involvement are treated especially intensively. As a result, we identified these patients as being potentially at high risk of failure to seroconvert to COVID-19 vaccination. METHODS: We collected data on seroconversion response rates to COVID-19 vaccination in a multi-ethnic cohort of patients with AAV and renal involvement treated at a busy tertiary nephrology centre as part of a retrospective review of patient notes. Blood samples were taken following vaccination with either Pfizer or Astra-Zeneca COVID-19 vaccines and median fluorescence intensity was measured using the validated MULTICOV-Ab Magnetic LuminexⓇ Assay. We also evaluated whether seroconversion was affected by immunosuppression regimen. RESULTS: 81 patients were included. The mean age was 62, and there were 49 (60%) females. 55 patients had a blood test after the first dose; 46 after the second dose. Patients were in remission with a median BVAS of 0 (IQR 2). Seroconversion after the first dose with either vaccine was 35/55 (63.6%). After the second it was 38/46 (82.6%). Subgroup analyses revealed a trend to impaired seroconversion in non-white versus white patients (77.8 vs. 81.7% (p = 0.69) after the first dose of vaccine and in those treated with Rituximab in the last 12 months (73.3 vs. 87.1%, p = 0.41). CONCLUSIONS: These data offer real-world evidence of lower seroconversion in response to vaccination with one dose in patients with AAV and renal involvement than the general UK population. After two doses, seroconversion is in line with national data. These data provide a rationale for hospital-led identification of patients most at risk of COVID-19 and underscore the importance of local connexions between hospitals and their communities. These data provide further support for targeting booster vaccination programmes to vulnerable patient cohorts. They add to the growing evidence of reduced seroconversion in response to vaccination in patients with renal disease of any cause.

A missed opportunity: birth registration coverage is lagging behind Bacillus Calmette-Guérin (BCG) immunization coverage and maternal health services utilization in low- and lower middle-income countries.

BACKGROUND: Civil registration and vital statistics (CRVS) systems lay the foundation for good governance by increasing the effectiveness and delivery of public services, providing vital statistics for the planning and monitoring of national development, and protecting fundamental human rights. Birth registration provides legal rights and facilitates access to essential public services such as health care and education. However, more than 110 low- and middle-income countries (LMICs) have deficient CRVS systems, and national birth registration rates continue to fall behind childhood immunization rates. Using Demographic and Health Survey (DHS) and Multiple Indicator Cluster Survey (MICS) data in 72 LMICs, the objectives are to (a) explore the status of birth registration, routine childhood immunization, and maternal health services utilization; (b) analyze indicators of birth registration, routine childhood immunization, and maternal health services utilization; and (c) identify missed opportunities for strengthening birth registration systems in countries with strong childhood immunization and maternal health services by measuring the absolute differences between the birth registration rates and these childhood and maternal health service indicators. METHODS: We constructed a database using DHS and MICS data from 2000 to 2017, containing information on birth registration, immunization coverage, and maternal health service indicators. Seventy-three countries including 34 low-income countries and 38 lower middle-income countries were included in this exploratory analysis. RESULTS: Among the 14 countries with disparity between birth registration and BCG vaccination of more than 50%, nine were from sub-Saharan Africa (Tanzania, Uganda, Gambia, Mozambique, Djibouti, Eswatini, Zambia, Democratic Republic of Congo, Ghana), two were from South Asia (Bangladesh, Nepal), one from East Asia and the Pacific (Vanuatu) one from Latin America and the Caribbean (Bolivia), and one from Europe and Central Asia (Moldova). Countries with a 50% or above absolute difference between birth registration and antenatal care coverage include Democratic Republic of Congo, Gambia, Mozambique, Nepal, Tanzania, and Uganda, in low-income countries. Among lower middle-income countries, this includes Eswatini, Ghana, Moldova, Timor-Leste, Vanuatu, and Zambia. Countries with a 50% or above absolute difference between birth registration and facility delivery care coverage include Democratic Republic of Congo, Djibouti, Moldova, and Zambia. CONCLUSION: The gap between birth registration and immunization coverage in low- and lower middle-income countries suggests the potential for leveraging immunization programs to increase birth registration rates. Engaging health providers during the antenatal, delivery, and postpartum periods to increase birth registration may be a useful strategy in countries with access to skilled providers.

Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination.

BACKGROUND: The timing of host cytokine responses to influenza vaccination is poorly understood. OBJECTIVES: We examined serum cytokine kinetics following inactivated trivalent influenza vaccine (TIV) to better understand potential relationships between markers of inflammation and TIV-related side effects. PATIENTS/METHODS: Twenty healthy adult subjects received TIV. Cytokines/chemokines were assessed in intervals from 3 hours to 14 days. Antibody titers were measured at baseline and Day 14. RESULTS: Serum cytokine responses to TIV were evident as early as 3 hours post-immunization. Compared to baseline, IFN-γ and IP-10 were significantly elevated 7 hours after TIV administration. Both remained elevated and peaked between 16 and 24 hours before returning to baseline by 44 hours post-vaccination. Although IL-8 levels were variable between subjects during the first 24 hours after TIV, by 44 hours, IL-8 was significantly lower compared to baseline. Interestingly, IL-8 levels remained significantly lower for up to 2 weeks after receiving TIV. Fifteen of 20 subjects reported mild adverse events. The one subject who reported moderate myalgias and injection site pain after vaccination displayed a distinctive, early cytokine response profile which included IL-6, IL-2, IL-8, IP-10, MCP-1, TNF-α, TARC, and MCP-4. CONCLUSIONS: Serum cytokines changed rapidly following TIV and generally peaked at 24 hours. Trivalent influenza vaccine-induced reductions in IL-8 occurred later (44 hours) and were sustained for 2 weeks. An outlier response coincided with the only moderate side effects to the vaccine. These data suggest that early cytokine/chemokine responses may provide additional insight into the pathogenesis of adverse events and immune reactivity to vaccination.

The live attenuated chimeric vaccine rWN/DEN4Δ30 is well-tolerated and immunogenic in healthy flavivirus-naïve adult volunteers.

WNV has become the leading vector-borne cause of meningoencephalitis in the United States. Although the majority of WNV infections result in asymptomatic illness, approximately 20% of infections result in West Nile fever and 1% in West Nile neuroinvasive disease (WNND), which causes encephalitis, meningitis, or flaccid paralysis. The elderly are at particular risk for WNND, with more than half the cases occurring in persons older than sixty years of age. There is no licensed treatment for WNND, nor is there any licensed vaccine for humans for the prevention of WNV infection. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a recombinant live attenuated WNV vaccine based on chimerization of the wild-type WNV NY99 genome with that of the live attenuated DENV-4 candidate vaccine rDEN4Δ30. The genes encoding the prM and envelope proteins of DENV-4 were replaced with those of WNV NY99 and the resultant virus was designated rWN/DEN4Δ30. The vaccine was evaluated in healthy flavivirus-naïve adult volunteers age 18-50 years in two separate studies, both of which are reported here. The first study evaluated 10³ or 104 PFU of the vaccine given as a single dose; the second study evaluated 105 PFU of the vaccine given as two doses 6 months apart. The vaccine was well-tolerated and immunogenic at all three doses, inducing seroconversion to WNV NY99 in 74% (10³ PFU), 75% (104 PFU), and 55% (105 PFU) of subjects after a single dose. A second 105 PFU dose of rWN/DEN4Δ30 given 6 months after the first dose increased the seroconversion rate 89%. Based on the encouraging results from these studies, further evaluation of the candidate vaccine in adults older than 50 years of age is planned.

Calcium scoring in patients with a history of Kawasaki disease.

OBJECTIVES: The goal of this study was to assess coronary artery calcification in patients ≥10 years or age with a history of Kawasaki disease (KD). BACKGROUND: Patients with a history of KD and coronary artery aneurysms are at risk for late morbidity from coronary artery events. It is unknown whether patients with KD with acutely normal or transiently dilated coronary arteries also have increased risk of late coronary artery complications. Coronary calcium scoring using noncontrast computed tomography is a well-established tool for risk-stratifying patients with atherosclerotic coronary artery disease, but there are limited data on its role in evaluating patients with a history of KD. METHODS: We performed coronary artery calcium (CAC) volume scoring using a low radiation dose computed tomography protocol on 70 patients (median age 20.0 years) with a remote history of KD (median interval from acute KD to imaging 14.8 years). Forty-four (63%) patients had no history of coronary dilation, 12 (17%) had a history of transient dilation, and 14 (20%) had coronary aneurysms. RESULTS: All of the patients with normal coronary artery internal diameter during the acute phase of KD and 11 of 12 patients with transient dilation had CAC scores of zero. Coronary calcification was observed in 10 of the 14 patients with coronary aneurysms, with the degree of calcification ranging from mild to severe and occurring years after the patients' acute KD. CONCLUSIONS: Coronary calcification was not observed in patients with a history of KD and normal coronary arteries during the acute phase. Therefore, CAC scanning may be a useful tool to screen patients with a remote history of KD or suspected KD and unknown coronary artery status. Coronary calcification, which may be severe, occurs late in patients with coronary aneurysms. The pathophysiology and clinical implications of coronary calcification in patients with aneurysms are currently unknown and warrant further study.

Kinetics of DNA and RNA Hybridization in Serum and Serum-SDS.

Cancer is recognized as a serious health challenge both in the United States and throughout the world. While early detection and diagnosis of cancer leads to decreased mortality rates, current screening methods require significant time and costly equipment. Recently, increased levels of certain micro-ribonucleic acids (miRNAs) in the blood have been linked to the presence of cancer. While blood-based biomarkers have been used for years in cancer detection, studies analyzing trace amounts of miRNAs in blood and serum samples are just beginning. Recent developments in deoxyribonucleic acid (DNA) nanotechnology and DNA computing have shown that it is possible to construct nucleic-acid-based chemical networks that accept miRNAs as inputs, perform Boolean logic functions on those inputs, and generate as an output a large number of DNA strands that can readily be detected. Since miRNAs occur in blood in low abundance, these networks would allow for amplification without using polymerase chain reaction. In this study, we report initial progress in the development of a DNA-based cross-catalytic network engineered to amplify specific cancer-related miRNAs. Subcomponents of the DNA network were tested individually, and their operation in serum, as well as a mixture of serum with sodium dodecyl sulfate, is demonstrated. Preliminary simulations of the full cross-catalytic network indicate successful operation.