COVID-19 differentiated measures for unvaccinated individuals: The need for clear goals and strong justifications.

Numerous countries and jurisdictions have implemented differential COVID-19 public health restrictions based on individual vaccination status to mitigate the public health risks posed by unvaccinated individuals. Although it is scientifically and ethically justifiable to introduce such vaccination-based differentiated measures as a risk-based approach to resume high-risk activities in an ongoing pandemic, their justification is weakened by lack of clarity on their intended goals and the specific risks or potential harms they intend to mitigate. Furthermore, the criteria for the removal of differentiated measures may not be clear, which raises the possibility of shifting goalposts without clear justification and with potential for unfairly discriminatory consequences. This paper seeks to clarify the ethical justification of COVID-19 vaccination-based differentiated measures based on a public health risk-based approach, with focus on their deployment in domestic settings. We argue that such measures should be consistent with the principal goal of COVID-19 vaccination programmes, which is to reduce the incidence of severely ill patients and associated healthcare burdens so as to protect a health system. We provide some considerations for the removal of vaccination-based differentiated measures based on this goal.

Adolescent girls' recommendations for the design of a human papillomavirus vaccination program in Sindh, Pakistan: a qualitative study.

PURPOSE: Vaccination of adolescent girls against human papillomavirus (HPV) significantly reduces the incidence of cervical cancer. HPV vaccines are available in Pakistan but plans to develop HPV vaccination program are at a nascent stage. We conducted a formative study to explore adolescent girls' knowledge and perspectives on HPV and cervical cancer and collect their recommendations for implementing an HPV vaccination program in their community. METHODS: Using qualitative exploratory study design, we conducted four focus group discussions (FGDs) with 12 adolescent girls per group in District West, Karachi. We recruited unmarried girls aged 16-19 years from schools and community settings between May-December 2020. Data analysis was done using NVivo. RESULTS: Overall, participants displayed a positive attitude toward HPV vaccine. However, they were unfamiliar with basic concepts related to female reproductive health. Female relatives were indicated as girls' preferred point of contact for discussions on HPV and cervical cancer, but fathers were portrayed as decision-making authority on vaccination. Participants indicated vaccine hesitancy among parents may affect HPV vaccination uptake. Girls suggested individual household visits and community-based camps as strategies for successful implementation of HPV vaccination program. A solid foundation of trust between girls' families, program managers, and other stakeholders emerged as a key asset for the program's success. CONCLUSION: Adolescent girls' suggestions of informing key decision-makers in the family (particularly fathers) of the benefits of HPV vaccination, establishing trust with vaccine providers, and increasing accessibility of vaccinations should be explored for successful implementation of an HPV vaccination program in Pakistan.

Public acceptability of COVID-19 control measures in Singapore, Hong Kong, and Malaysia: A cross-sectional survey.

BACKGROUND: Several countries have implemented control measures to limit SARS-CoV-2 spread, including digital contact tracing, digital monitoring of quarantined individuals, and testing of travelers. These raise ethical issues around privacy, personal freedoms, and equity. However, little is known regarding public acceptability of these measures. METHODS: In December 2020, we conducted a survey among 3635 respondents in Singapore, Hong Kong, and Malaysia to understand public perceptions on the acceptability of COVID-19 control measures. FINDINGS: Hong Kong respondents were much less supportive of digital contact tracing and monitoring devices than those in Malaysia and Singapore. Around three-quarters of Hong Kong respondents perceived digital contact tracing as an unreasonable restriction of individual freedom; <20% trusted that there were adequate local provisions preventing these data being used for other purposes. This was the opposite in Singapore, where nearly 3/4 of respondents agreed that there were adequate data protection rules locally. In contrast, only a minority of Hong Kong respondents viewed mandatory testing and vaccination for travelers as unreasonable infringements of privacy or freedom. Less than 2/3 of respondents in all territories were willing to be vaccinated against COVID-19, with a quarter of respondents undecided. However, support for differential travel restrictions for vaccinated and unvaccinated individuals was high in all settings. INTERPRETATION: Our findings highlight the importance of sociopolitical context in public perception of public health measures and emphasize the need to continually monitor public attitudes toward such measures to inform implementation and communication strategies.

A country-specific model of COVID-19 vaccination coverage needed for herd immunity in adult only or population wide vaccination programme.

We present a country specific method to calculate the COVID-19 vaccination coverage needed for herd immunity by considering age structure, age group-specific contact patterns, relative infectivity and susceptibility of children to adults, vaccination effectiveness and seroprevalence prior to vaccination. We find that across all six countries, vaccination of adults age 60 and above has little impact on Reff and this is could be due to the smaller number of contacts between this age group and the rest of the population according to the contact matrices used. If R0 is above 6, herd immunity by vaccine alone is unattainable for most countries either if vaccination is only available for adults or that vaccine effectiveness is lower at 65% against symptomatic infections. In this situation, additional control measures, booster shots, if they improve protection against infection, or the extension of vaccination to children, are required. For a highly transmissible variant with R0 up to 8, herd immunity is possible for all countries and for all four scenarios of varying relative infectivity and susceptibility of children compared to adults, if vaccine effectiveness is very high at 95% against symptomatic infections and that high vaccination coverage is achieved for both adults and children. In addition, we show that the effective reproduction number will vary between countries even if the same proportion of the population is vaccinated, depending on the demographics, the contact rates and the previous pre-vaccination seroprevalence in the country. This therefore means that care must be taken in extrapolating population level impacts of certain vaccine coverages from one country to another.

Contrasting SARS-CoV-2 epidemics in Singapore: cohort studies in migrant workers and the general population.

IMPORTANCE: Since January 2020, Singapore has implemented comprehensive measures to suppress SARS-CoV-2. Despite this, the country has experienced contrasting epidemics, with limited transmission in the community and explosive outbreaks in migrant worker dormitories. OBJECTIVE: To estimate SARS-CoV-2 infection incidence among migrant workers and the general population in Singapore. DESIGN: Prospective serological cohort studies. SETTING: Two cohort studies - in a migrant worker dormitory and in the general population in Singapore. PARTICIPANTS: 478 residents of a SARS-CoV-2-affected migrant worker dormitory were followed up between May and July 2020, with blood samples collected on recruitment and after 2 and 6 weeks. In addition, 937 community-dwelling adult Singapore residents, for whom pre-pandemic sera were available, were recruited. These individuals also provided a serum sample on recruitment in November/December 2020. EXPOSURE: Exposure to SARS-CoV-2 in a densely populated migrant worker dormitory and in the general population. MAIN OUTCOMES AND MEASURES: The main outcome measures were the incidences of SARS-CoV-2 infection in migrant workers and in the general population, as determined by the detection of neutralizing antibodies against SARS-CoV-2, and adjusting for assay sensitivity and specificity using a Bayesian modeling framework. RESULTS: No evidence of community SARS-CoV-2 exposure was found in Singapore prior to September 2019. It was estimated that < 2 per 1000 adult residents in the community were infected with SARS-CoV-2 in 2020 (cumulative seroprevalence: 0.16%; 95% CrI: 0.008-0.72%). Comparison with comprehensive national case notification data suggested that around 1 in 4 infections in the general population were associated with symptoms. In contrast, in the migrant worker cohort, almost two-thirds had been infected by July 2020 (cumulative seroprevalence: 63.8%; 95% CrI: 57.9-70.3%); no symptoms were reported in almost all of these infections. CONCLUSIONS AND RELEVANCE: Our findings demonstrate that SARS-CoV-2 suppression is possible with strict and rapid implementation of border restrictions, case isolation, contact tracing, quarantining, and social-distancing measures. However, the risk of large-scale epidemics in densely populated environments requires specific consideration in preparedness planning. Prioritization of these settings in vaccination strategies should minimize the risk of future resurgences and potential spillover of transmission to the wider community.

Immunity certification for COVID-19: ethical considerations.

Restrictive measures imposed because of the coronavirus disease 2019 (COVID-19) pandemic have resulted in severe social, economic and health effects. Some countries have considered the use of immunity certification as a strategy to relax these measures for people who have recovered from the infection by issuing these individuals a document, commonly called an immunity passport. This document certifies them as having protective immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes COVID-19. The World Health Organization has advised against the implementation of immunity certification at present because of uncertainty about whether long-term immunity truly exists for those who have recovered from COVID-19 and concerns over the reliability of the proposed serological test method for determining immunity. Immunity certification can only be considered if scientific thresholds for assuring immunity are met, whether based on antibodies or other criteria. However, even if immunity certification became well supported by science, it has many ethical issues in terms of different restrictions on individual liberties and its implementation process. We examine the main considerations for the ethical acceptability of immunity certification to exempt individuals from restrictive measures during the COVID-19 pandemic. As well as needing to meet robust scientific criteria, the ethical acceptability of immunity certification depends on its uses and policy objectives and the measures in place to reduce potential harms, and prevent disproportionate burdens on non-certified individuals and violation of individual liberties and rights.

Les restrictions imposées dans le cadre de la lutte contre la pandémie de maladie à coronavirus 2019 (COVID-19) ont eu de lourdes conséquences économiques, sociales et sanitaires. Certains pays ont envisagé la mise en place d'une stratégie visant à alléger ces restrictions pour les individus guéris en leur octroyant un document communément appelé «passeport d'immunité¼. Ce document atteste qu'ils ont développé une immunité protectrice contre le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2), le virus à l'origine de la COVID-19. L'Organisation mondiale de la Santé a déconseillé l'usage du certificat d'immunité pour l'instant, car l'incertitude demeure quant à l'existence réelle d'une immunité à long terme pour ceux qui se sont remis de la COVID-19. En outre, la fiabilité des tests sérologiques censés déterminer si l'individu est immunisé n'est pas avérée. Un tel certificat ne peut être instauré que si les seuils scientifiques en matière d'immunité sont respectés, qu'ils soient fondés sur les anticorps ou sur d'autres critères. Néanmoins, même si le certificat d'immunité est désormais bien accepté par la science, il s'accompagne de nombreuses questions d'ordre éthique en ce qui concerne la limitation des libertés individuelles et la mise en œuvre. Dans le présent document, nous examinons les principales considérations à prendre en compte pour garantir l'acceptabilité éthique du certificat d'immunité visant à lever les mesures de restriction pour certaines personnes durant la pandémie de COVID-19. Cette acceptabilité éthique dépend non seulement de son degré de conformité à des critères scientifiques stricts, mais aussi de son usage, des objectifs politiques ainsi que des mesures mises en place pour atténuer les préjudices potentiels et éviter d'imposer une charge disproportionnée sur les individus dépourvus de certificat, ou de bafouer les droits et libertés de tout un chacun.

Las medidas restrictivas impuestas a causa de la pandemia de la enfermedad coronavirus de 2019 (COVID-19) han tenido graves efectos sociales, económicos y sanitarios. Algunos países han considerado la posibilidad de utilizar la certificación de inmunidad como estrategia para flexibilizar dichas medidas para las personas que se han recuperado de la infección mediante la expedición a dichas personas de un documento, comúnmente denominado pasaporte de inmunidad. Este documento certifica que han desarrollado inmunidad protectora contra el coronavirus-2 del síndrome respiratorio agudo severo (SARS-CoV-2), el virus que causa la COVID-19. La Organización Mundial de la Salud ha desaconsejado la aplicación de la certificación de la inmunidad en la actualidad debido a la incertidumbre sobre si existe realmente una inmunidad a largo plazo para quienes se han recuperado de la COVID-19 y a las preocupaciones sobre la fiabilidad del método de prueba serológica propuesto para determinar la inmunidad. La certificación de la inmunidad solo puede considerarse si se cumplen los umbrales científicos para asegurar la inmunidad, ya sea que se basen en anticuerpos o en otros criterios. Sin embargo, incluso si la certificación de la inmunidad llegara a estar bien respaldada por la ciencia, tiene muchas cuestiones éticas en cuanto a las diferentes restricciones de las libertades individuales y su proceso de aplicación. Examinamos las principales consideraciones sobre la aceptabilidad ética de la certificación de la inmunidad para eximir a los individuos de las medidas restrictivas durante la pandemia de la COVID-19. Además de necesitar cumplir criterios científicos sólidos, la aceptabilidad ética de la certificación de inmunidad depende de sus usos y objetivos de política y de las medidas que se apliquen para reducir los posibles daños y evitar que se impongan cargas desproporcionadas a las personas que no cuenten con dicha certificación y se violen las libertades y derechos individuales.

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection.

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2-specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2-specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1ß) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2-infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.

Population anxiety and positive behaviour change during the COVID-19 epidemic: Cross-sectional surveys in Singapore, China and Italy.

BACKGROUND: On 31 December 2019, an epidemic of pneumonia of unknown aetiology was first reported in the city of Wuhan, Hubei Province, People's Republic of China. A rapidly progressing epidemic of COVID-19 ensued within China, with multiple exportations to other countries. We aimed to measure perceptions and responses towards COVID-19 in three countries to understand how population-level anxiety can be mitigated in the early phases of a pandemic. METHODS: Between February and March 2020, we conducted online surveys in Singapore, China and Italy with a total of 4505 respondents to measure respondents' knowledge, perceptions, anxiety and behaviours towards the COVID-19 epidemic, and identified factors associated with lower anxiety and more positive behavioural responses. RESULTS: Respondents reported high awareness of COVID-19 and its accompanying symptoms, comparable information-seeking habits and similarly high levels of information sufficiency, adherence to and acceptance of public health control measures. Higher self-efficacy was associated with lower anxiety levels in all three countries, while willingness to comply with restrictive measures and greater information sufficiency were associated with more positive behavioural changes to reduce spread of infection. CONCLUSION: Population-level anxiety and behavioural responses to an outbreak can be influenced by information provided. This should be used to inform future outbreak preparedness plans, taking into account the importance of increasing population-level self-efficacy and information sufficiency to reduce anxiety and promote positive behavioural changes.

Family Presence for Patients and Separated Relatives During COVID-19: Physical, Virtual, and Surrogate.

During an outbreak or pandemic involving a novel disease such as COVID-19, infected persons may need to undergo strict medical isolation and be separated from their families for public health reasons. Such a practice raises various ethical questions, the characteristics of which are heightened by uncertainties such as mode of transmission and increasingly scarce healthcare resources. For example, under what circumstances should non-infected parents be allowed to stay with their infected children in an isolation facility? This paper will examine ethical issues with three modes of "family presence" or "being there or with" a separated family member during the current COVID-19 pandemic: physical, virtual, and surrogate. Physical visits, stays, or care by family members in isolation facilities are usually prohibited, discouraged, or limited to exceptional circumstances. Virtual presence for isolated patients is often recommended and used to enable communication. When visits are disallowed, frontline workers sometimes act as surrogate family for patients, such as performing bedside vigils for dying patients. Drawing on lessons from past outbreaks such as the 2002-2003 SARS epidemic and the recent Ebola epidemic in West Africa, we consider the ethical management of these modes of family presence and argue for the promotion of physical presence under some conditions.

COVID-19 vaccine development: Time to consider SARS-CoV-2 challenge studies?

While a human challenge study holds the prospect of accelerating the development of a vaccine for the coronavirus SARS-CoV-2, it may be opposed due to risks of harm to participants and researchers. Given the increasing number of human deaths and severe disruption to lives worldwide, we argue that a SARS-CoV-2 challenge study is ethically justifiable as its social value substantially outweighs the risks. Such a study should therefore be seriously considered as part of the global research response towards the COVID-19 pandemic. In this paper, we contribute to the debate by addressing the misperception that a challenge study for the coronavirus would lower scientific and ethical standards for vaccine research and development, and examine how it could be ethically conducted. We also set out information that needs to be disclosed to prospective participants to obtain their consent.

Ethical Implementation of Immunity Passports During the COVID-19 Pandemic.

A number of countries are planning the use of "immunity passports" as a way to ease restrictive measures and allow infected and recovered people to return to work during the COVID-19 pandemic. This paper brings together key scientific uncertainties regarding the use of serological tests to assure immune status and a public health ethics perspective to inform key considerations in the ethical implementation of immunity passport policies. Ill-conceived policies have the potential to cause severe unintended harms that could result in greater inequity, the stigmatization of certain sectors of society, and heightened risks and unequal treatment of individuals due to erroneous test results. Immunity passports could, however, be used to achieve collective benefits and benefits for specific populations besides facilitating economic recovery. We conclude that sector-based policies that prioritize access to testing based on societal need are likely to be fairer and logistically more feasible, while minimizing stigma and reducing incentives for fraud. Clear guidelines need to be set out for which sectors of society should be prioritized for testing, and rigorous mechanisms should be in place to validate test results and identify cases of reinfection.

Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity.

Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.