Neutralising antibody activity against SARS-CoV-2 variants, including Omicron, in an elderly cohort vaccinated with BNT162b2

SARS-CoV-2 variants threaten the effectiveness of tools we have developed to mitigate against serious COVID-19. This is especially true in clinically vulnerable sections of society including the elderly. Using sera from BNT162b2 (Pfizer-BioNTech) vaccinated individuals aged between 70 and 89 (vaccinated with two doses 3-weeks apart) we examined the neutralising antibody (nAb) response to wildtype SARS-CoV-2. Between 3 and 20-weeks post 2nd dose, nAb titres dropped 4.9-fold to a median titre of 21.3 (ND80) with 21.6% of individuals having no detectable nAbs at the later time point. Experiments examining the neutralisation of twenty-one different SARS-CoV-2 variant spike proteins confirmed a significant potential for antigenic escape, especially for the Omicron (BA.1), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 variants. Interestingly, however, the recently-emerged sub-lineage AY.4.2 was more efficiently neutralised than parental Delta pseudotypes. Combining pseudotype neutralisation with specific receptor binding domain (RBD) ELISAs we confirmed that changes to position 484 in the spike RBD were predominantly responsible for SARS-CoV-2 nAb escape, although the effect of spike mutations is both combinatorial and additive. Lastly, using sera from the same individuals boosted with a 3rd dose of BNT162b2 we showed that high overall levels of neutralising antibody titre can provide significant levels of cross-protection against Omicron. These data provide evidence that SARS-CoV-2 neutralising antibodies wane over time and that antigenically variable SARS-CoV-2 variants are circulating, highlighting the importance of ongoing surveillance and booster programmes. Furthermore, they provide important data to inform risk assessment of new SARS-CoV-2 variants, such as Omicron, as they emerge.

Genome-scale molecular and phylogenetic characterization of Middle Point orbiviruses from Australia

Middle Point orbivirus (MPOV) is an Australian arbovirus, belongs to the Yunnan orbivirus species found in China. First detected and reported from Beatrice Hill, Northern Territory (NT), MPOV has to date, only been exclusively reported from the NT, Australia. Whilst genetic characterization of MPOV has been previously described, only restricted to sequence information for segments 2 and 3 coding core protein VP2 and outer capsid protein VP3, respectively. This study presents for the first time nearly full-length genome sequences of MPOV, which represent 24 isolates collected over a span of more than 20 years from 1997 to 2018. Whilst the majority of isolates were sampled at Beatrice Hill, NT where MPOV is most frequently isolated, this report also describes the first two isolations of MPOV from Queensland (QLD), Australia. One of which is the first non-bovine isolate obtained from the mosquito vector Aedes vittiger. We further compared these MPOV sequences with known sequences of the Yunnan orbivirus and other known orbivirus sequences of mosquito origin found in Australia. The phylogenetic analyses indicate the Australian MPOV sequences are more closely related to each other than other known sequences of Yunnan orbivirus. Furthermore, MPOV sequences are closely related to sequences from the Indonesian isolate JKT-8650. The clustering of Australian sequences in the phylogenetic tree suggests the monophyletic lineage of MPOV circulating in Australia. Further, ongoing surveillance is required to assess the existence and prevalence of this or other yet undetected lineages of MPOV and other orbiviruses in Australia.

Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency

Selenium, a trace element fundamental to human health, is incorporated as the amino acid selenocysteine (Sec) into more than 25 proteins, referred to as selenoproteins. Human mutations in SECISBP2, SEPSECS and TRU-TCA1-1, three genes essential in the selenocysteine incorporation pathway, affect the expression of most if not all selenoproteins. Systemic selenoprotein deficiency results in a complex, multifactorial disorder, reflecting loss of selenoprotein function in specific tissues and/or long-term impaired selenoenzyme-mediated defence against oxidative and endoplasmic reticulum stress. SEPSECS mutations are associated with a predominantly neurological phenotype with progressive cerebello-cerebral atrophy. Selenoprotein deficiency due to SECISBP2 and TRU-TCA1-1 defects are characterized by abnormal circulating thyroid hormones due to lack of Sec-containing deiodinases, low serum selenium levels (low SELENOP, GPX3), with additional features (myopathy due to low SELENON; photosensitivity, hearing loss, increased adipose mass and function due to reduced antioxidant and endoplasmic reticulum stress defence) in SECISBP2 cases. Antioxidant therapy ameliorates oxidative damage in cells and tissues of patients, but its longer term benefits remain undefined. Ongoing surveillance of patients enables ascertainment of additional phenotypes which may provide further insights into the role of selenoproteins in human biological processes.

Serological responses to COVID-19 booster vaccine in England

Importance: There are limited data on immune responses after COVID-19 vaccine boosters in individuals receiving primary immunisation with BNT162b2 (Pfizer-BioNTech) or AZD1222 (AstraZeneca) Objective: To assess SARS-CoV-2 antibody responses before and after booster vaccination with BNT162b2 in adults receiving two BNT162b2 or AZD1222 vaccine doses at least 6 months previously, as part of the United Kingdom national immunisation schedule Design: Prospective, cohort study Setting: London, England Participants: 750 immunocompetent adults aged ≥50 years Interventions: A single dose of BNT162b2 administered at least six months after primary immunisation with two doses of BNT162b2 given <30 days apart (BNT162b2-control) or ≥30 days apart (BNT162b2-extended) compared to AZD1222 given ≥30 days apart (AZD1222-extended) Main Outcome and Measures: SARS-CoV-2 spike protein antibody geometric mean titres (GMTs) before and 2-4 weeks after booster Results: Of 750 participants, 626 provided serum samples for up to 38 weeks after their second vaccine dose. Antibody GMTs peaked at 2-4 weeks after the second dose, before declining by 68% at 36-38 weeks after dose 2 for BNT162b2-control participants, 85% at 24-29 weeks for BNT162b2-extended participants and 78% at 24-29 weeks for AZD1222-extended participants. Antibody GMTs was highest in BNT162b2-extended participants (942 [95%CI, 797-1113]) than AZD1222-extended (183 [124-268]) participants at 24-29 weeks or BNT162b2-control participants at 36-38 weeks (208; 95%CI, 150-289). At 2-4 weeks after booster, GMTs were significantly higher than after primary vaccination in all three groups: 18,104 (95%CI, 13,911-23,560; n=47) in BNT162b2-control (76.3-fold), 13,980 (11,902-16,421; n=118) in BNT162b2-extended (15.9-fold) and 10,799 (8,510-13,704; n=43) in AZD1222-extended (57.2-fold) participants. BNT162b2-control participants (median:262 days) had a longer interval between primary and booster doses than BNT162b2-extended or AZD1222-extended (both median:186 days) participants. Conclusions and Relevance: We observed rapid serological responses to boosting with BNT162b2, irrespective of vaccine type or schedule used for primary immunisation, with higher post-booster responses with longer interval between primary immunisation and boosting. Boosters will not only provide additional protection for those at highest risk of severe COVID-19 but also prevent infection and, therefore, interrupt transmission, thereby reducing infections rates in the population. Ongoing surveillance will be important for monitoring the duration of protection after the booster.

Achieving integrated self-directed Cancer aftercare (ASICA) for melanoma: how a digital intervention to support total skin self-examination was used by people treated for cutaneous melanoma

Background Melanoma incidence has quadrupled since 1970 and melanoma is now the second most common cancer in individuals under 50. Targeted immunotherapies for melanoma now potentially enable long-term remission even in advanced melanoma, but these melanoma survivors require ongoing surveillance, with implications for NHS resources and significant social and psychological consequences for patients. Total skin self-examination (TSSE) can detect recurrence earlier and improve clinical outcomes but is underperformed in the UK. To support survivors, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) intervention was developed to prompt and improve TSSE performance, with subsequent reporting of concerns and submission of skin photos to a Dermatology Nurse Practitioner (DNP). ASICA was delivered as a randomized pilot trial. Methods This paper reports on process evaluation. Data on participants’ demographics and the concerns they reported during the trial were tabulated and displayed using Microsoft Excel and SPSS. We explored which participants used ASICA, and how frequently, to report any skin concerns. We also determined how the interactions had worked in terms of quality of skin photographs submitted, clinical assessments made by the DNP, and the assessments and decisions made for each concern. Finally, we explored significant events occurring during the trial. Data on participants’ demographics and the concerns they reported during the trial were tabulated and displayed using SPSS. A semi-structured interview was undertaken with the DNP to gain perspective on the range of concerns presented and how they were resolved. Results Of 121 recruited melanoma patients receiving ASICA for 12 months, 69 participants submitted a total of 123 reports detailing 189 separate skin-related concerns and including 188 skin photographs. Where participants fully complied with follow-up by the DNP, concerns were usually resolved remotely, but 19 (10.1%) were seen at a secondary care clinic and 14 (7.4%) referred to their GP. 49 (25.9%) of concerns were not completely resolved due to partial non-compliance with DNP follow-up. Conclusion Melanoma patients randomized to the ASICA intervention were able to report skin-related concerns that could be resolved remotely through interaction with a DNP. Feasibility issues highlighted by ASICA will support further development and optimization of this digital tool. Trial registration Clinical Trials.gov, NCT03328247. Registered on 1 November 2017

What Is the Willingness to Receive Vaccination Against COVID-19 Among the Elderly in Italy? Data From the PASSI d'Argento Surveillance System

Introduction: Italy was one of the earliest countries to experience a severe COVID-19 epidemic and vaccinating the elderly, who constitute 23% of the population and have experienced the highest mortality rates, is a top priority. Estimating prevalences and understanding risk factors for COVID-19 vaccine hesitancy or refusal are important for development of targeted interventions.Methods: We used data from a specially developed COVID-19 module of PASSI D'Argento, an ongoing surveillance system of residents 65+ years of age to measure the prevalence and identify risk factors for hesitancy and refusal to receive the COVID-19 vaccine. We calculated multinomial regression relative risk ratios to examine the association between demographic characteristics, health status, COVID-19 attitudes and experiences and likely vaccine hesitancy and refusal.Results: Of the 1876 respondents, 55% reported they would accept vaccination and 16% would likely refuse; the remaining 29% were categorized as hesitant. Compared with the acceptance group, we identified several risk factors in common between the hesitancy group and the refusal group, including not having received vaccination against influenza during the previous flu season (hesitancy: RRR = 2.0; 95% CI 1.4–2.9; refusal: RRR = 12.1; 95%CI 7.6–19.4) and lower risk of having had a death from COVID-19 among family or friends (hesitancy: RRR = 4.8; 95%CI 2.0–11.4; refusal: RRR = 15.4; 95%CI 3.7–64.5). The hesitancy group was significantly more likely being worried and they did not know if consequences of the disease would be serious for them.Conclusion: Our findings show the importance of establishing and maintaining active contact between the preventive services, primary care providers and the population because trust is difficult to establish during an emergency like the COVID-19 pandemic. Italian public health is based on a capillary network of general practitioners and having them reach out to their patients who have not previously received influenza vaccine may be a useful strategy for targeting efforts to further encourage uptake of COVID-19 vaccination.

1209. The Evolving Nature of Syndromic Surveillance During the COVID-19 Pandemic in Massachusetts

Background We developed a syndromic algorithm for COVID-19 like illness (CLI) to provide supplementary surveillance data on COVID-19 activity. Methods The CLI algorithm was developed using the Electronic Medical Record Support for Public Health platform (esphealth.org) and data from five clinical practice groups in Massachusetts that collectively care for 25% of the state’s population. Signs and symptoms of CLI were identified using ICD-10 diagnosis codes and measured temperature. The algorithm originally included three categories: Category 1 required codes for coronavirus infection and lower respiratory tract infections (LRTI); Category 2 required an LRTI-related diagnosis and fever; Category 3 required an upper or lower RTI and fever. The three categories mirrored statewide laboratory-confirmed case trends during spring and summer 2020 but did not detect the increase in late fall. We hypothesized this was due to the requirements for fever and LRTI. Therefore, we added three new categories defined by milder symptoms without fever: Category 4 requires LRTI-related diagnoses only; Category 5 requires upper or lower RTI or olfactory/taste disorders; and Category 6 requires at least one sign of CLI not identified by another category. Results The six-category algorithm detected the initial surge in April 2020, the summer lull, and the second surge in late fall (see figure). Category 1 cases were not identified until mid-March, which coincides with the first laboratory-confirmed cases in Massachusetts. Categories 2 and 3, which required fever, were prominent during the initial surge but declined over time. Category 5, the broadest category, declined during February and March 2020, likely capturing the end of the influenza season, and successfully detected the spring surge and fall resurgence. Weekly number of COVID-19 like illnesses by category, February 2, 2020 through May 8, 2021 Conclusion A syndromic definition that included mild upper RTI and olfactory/taste disorders, with or without fever or LRTI, mirrored changes in laboratory-confirmed COVID-19 cases better than definitions that required fever and LRTI. This suggests a shift in medically attended care and/or coding practices during initial vs subsequent surges of COVID-19, and the importance of using a broad definition of CLI for ongoing surveillance. Disclosures Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author)

African Swine Fever Re-Emerging in Estonia: The Role of Seropositive Wild Boar from an Epidemiological Perspective

African swine fever (ASF) emerged in Estonia in 2014. From February 2019 to August 2020, no pigs or wild boar tested positive for ASF virus (ASFV), only ASFV-specific antibodies could be detected in shot wild boar. However, ASF recently re-emerged in wild boar. We tested three hypotheses that might explain the current situation: (i) ASFV may have been present throughout, but at a prevalence below the detection limit; (ii) seropositive wild boar may have remained infectious (i.e., virus-carriers) and kept the epidemic going; or (iii) ASF was gone for 1.5 years, but was recently re-introduced. Using Estonian surveillance data, the sensitivity of the surveillance system and the confidence in freedom from ASF were estimated. Furthermore, the detection probability was determined and cluster analyses were performed to investigate the role of serological positive wild boar. The results suggest that the surveillance system was not able to detect virus circulation at a design prevalence below 1%. With respect to the confidence in freedom from ASF, the results indicate that circulating virus should have been detected over time, if the prevalence was ≥2%. However, the decreasing wild boar population density and ongoing surveillance activities made ASFV circulation at a low prevalence unlikely. Cluster analyses provided no evidence for a significant accumulation of serologically positive wild boar in temporal connection to the re-emergence of ASFV. Further targeted research, such as long-term experimental studies and molecular epidemiology, is necessary to improve our knowledge on the epidemiology of ASF and to control the disease more effectively.

IQOS marketing strategies in the USA before and after US FDA modified risk tobacco product authorisation

IntroductionGiven that the US Food and Drug Administration (FDA) authorised reduced exposure messaging to be used in IQOS marketing, we examined: (1) IQOS ad content; (2) advertising media channels and (3) changes in advertising efforts over time.MethodsWe conducted a mixed-methods study regarding IQOS ad content (headlines, themes, images), ad occurrence characteristics (including content, media channels and adspend) in the USA from August 2019 to April 2021 using Numerator advertising/marketing data.ResultsAcross 24 unique ads and 591 occurrences (84.6% online, 8.0% print, 7.4% mobile), there was $4 902 110 total adspend (98.9% allocated to print). Across unique ads, occurrences and adspend, prominent themes included ‘real tobacco’ (45.8%, 47.4%, 30.1%, respectively), less odour/ash (29.2%, 21.0%, 29.9%) and switching from cigarettes (25.0%, 19.5%, 69.4%), and images mainly featured the product alone (58.2%, 61.4%, 99.5%) or with women (25.0%, 19.1%, 0.3%). Per occurrences and adspend, the most prominent media channel themes (eg, magazine/website topics) were technology (19.3%, 10.6%), women’s fashion (18.1%, 26.2%), weather/news (9.0%, 15.3%) and entertainment/pop culture/gaming (8.5%, 23.1%). Ad themes appearing only post-FDA authorisation included switching from traditional cigarettes, same-day/home-delivery, convenience (eg, use indoors), reduced exposure to some dangerous substances, science/research and distinction from e-cigarettes. Overall adspend per occurrence increased postauthorisation (p=0.016); the highest adspend per unique ad (69.3% of total) focused on ads featuring reduced exposure.ConclusionsRegulatory efforts must be informed by ongoing surveillance of IQOS marketing efforts and its impacts, particularly how specific consumer subgroups (eg, tobacco non-users, women, young people) are impacted by marketing exposure.

Pioneering Secondary Recovery Strategies in a Complex Geological Environment and Challenging Reservoirs Located in Offshore Sarawak

The Balingian province is located offshore Sarawak, comprising of at least 7 oil fields with its regional geology consisting of a combination of deltaic & shoreface system. Though consisting of clastic reservoirs, the fields are highly sophisticated in terms of reservoir compartmentalization, hence uncertainties in fluid contacts, differing depletion strategies and varying production performance per well. As the regional production has gone into brownfield stage, the challenge is to determine the most suitable secondary recovery method to prolong field life. The subsurface & feasibility studies conducted produced mixed results between application of water & gas injection, giving recovery factors between 30 to 40%, and implementation so much depending on source of water & gas and cost benefit analyses. The application of IOR across Balingian province are executed in pilot mode across all fields. While the pilots are still continuing, this paper is to share the methodology, recovery factors and process of the regional study and some results from the ongoing surveillance post-execution, and the wayforward.