Backgrounds:

HCMV-specific cell-mediated immunity (CMI) is essential in the control of viral replication to prevent end-organ HCMV disease. HCMV-specific interferon gamma release assays, such as HCMV-ELISPOT and HCMV-QuantiFERON, have been used to measure HCMV-specific CMI. In pregnant women, the role of HCMV-specific CMI in controlling viral replication and transmission to the foetus have not been fully investigated. We aimed to perform serial HCMV-ELISPOT and HCMV-QuantiFERON measurements in HCMV-seropositive women during pregnancy.

Methods

HCMV-seropositive pregnant women receiving antenatal care at a tertiary hospital in London (UK) were enrolled. Blood samples were collected at three time-points in pregnancy and a fourth time-point after delivery, and HCMV-ELISPOT and HCMV-QuantiFERON assays were performed on these samples. HCMV-ELISPOT was recorded as responsive or non-responsive, as a spot count, and as specific spot counts to IE-1 and pp65 antigens. HCMV-QuantiFERON was recorded as positive or negative.

Results:

From 67 HCMV-seropositive pregnant women, 105 blood samples were tested with both assays. All women had a responsive HCMV-ELISPOT result on at least one time-point, and 70% (47/67) of women had a positive HCMV-QuantiFERON result on at least one time-point. The two assays showed no overall agreement (Cohen’s Kappa 0.032), although the overall mean HCMV-ELISPOT spot counts to IE-1 and pp65 antigens were higher when HCMV-QuantiFERON was positive than when it was negative (Figure 1).

Conclusions/Learning Points:

In this cohort, the HCMV-ELISPOT assay was more likely than the HCMV-QuantiFERON assay to detect HCMV-specific CMI in HCMV-seropositive pregnant women. This may have implications for optimal CMI monitoring in this important population.

Backgrounds:

Neonatal herpes simplex virus (HSV) infection is a rare but dangerous condition. A recent study suggests that the UK incidence may have increased since the last national surveillance study in 2007. Rising numbers of cases may support the wider use of empirical treatment. Postnatal transmission is thought to account for ~10% of cases. More information about this disease is required to inform future prevention and treatment strategies.

Methods

Analysis of questionnaires completed for the current British Paediatric Surveillance Unit neonatal HSV study was conducted. Semi-anonymised patient identifiers allow removal of duplicate cases. The study was extended from 25 months to 30 months to capture additional data on changing trends during the COVID-19 pandemic. Interim results are reported here.

Results:

228 cases were notified July 19 - Dec 2021. 159 questionnaires were completed and basic data on 111 cases was available after duplications and incomplete records were removed. 29.7% were premature, 26.1% died. Full data analysed on the first 80 cases (July 19-April 21) show: 27.0% were premature, 26.9% had disseminated disease and mortality was 71.0% in disseminated disease. 23.8% of babies with disseminated disease had no fever at presentation. Treatment was delayed by more than one day in 60%. Case notifications reduced during UK lockdown periods.

Conclusions/Learning Points:

UK incidence of neonatal HSV disease has increased since the last BPSU study. Mortality remains high and presenting features are non-specific. Absence of fever at presentation demonstrates that HSV should not only be considered in febrile infants. Falling numbers of reported cases during periods of social distancing and strict public hygiene measures may highlight the importance of postnatal transmission. Follow-up focusing on disease recurrence and long-term complications at 12 and 24 months is ongoing.

Backgrounds:

Few data are published on immune responses against SARS-CoV-2 induced by COVID-19 vaccines in people under the age of 18 years compared with adults.

Methods:

COV006 is a phase 1/2, single-blind, randomised controlled trial of ChAdOx1 nCoV-19 (ChAd) in children and adolescents aged 6-17 years in the UK. Participants were randomised 4:1:4:1 to receive two doses of ChAd or control (capsular group B meningococcal) vaccine (4:1), 28 days (short-interval) or 84 days (long-interval) apart. The primary outcome was safety and tolerability, with immunogenicity in the baseline-seronegative participants as the secondary outcome. Due to the restrictions in the use of ChAd introduced during the study, only participants aged 12-17 years randomised to the short-interval were vaccinated as planned (D28). The remaining participants received their second dose at D112.

Results:

Of 262 participants, 211 and 51 were randomised to the ChAd and control arms, respectively. No serious adverse events related to ChAd administration were recorded. Solicited adverse reactions were reported more frequently after the first dose compared with the second dose, across all age and interval groups.

In participants aged 12-17 years, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at D28 post-second dose were higher in the long-interval arm (geometric mean ratios (GMR): 1.70, 95%CI: 1.27-2.26 and 1.99, 95%CI: 1.39-2.86, respectively) than after a short-interval.

Humoral responses were higher in participants aged 6-11 years than those aged 12-17 years (GMR: 1.48, 95%CI: 1.07-2.07 and 2.96, 95%CI: 1.89-4.62 for anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres, respectively). Cellular responses peaked after a first dose of ChAd across all age and interval groups.

Conclusions/Learning Points:

ChAdOx1 nCoV-19 is well-tolerated and immunogenic in children aged 6-17 years. No safety concerns were raised in this trial.