Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants.

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity against Delta and Omicron SARS-CoV-2 variants in 259 samples from 128 vaccinated individuals. Following Delta breakthrough infection, titers against WT rose 57-fold and 3.1-fold compared with uninfected boosted and unboosted individuals, respectively, versus only a 5.8-fold increase and 3.1-fold decrease for Omicron breakthrough infection. Among immunocompetent, unboosted patients, Delta breakthrough infections induced 10.8-fold higher titers against WT compared with Omicron (p = 0.037). Decreased antibody responses in Omicron breakthrough infections relative to Delta were potentially related to a higher proportion of asymptomatic or mild breakthrough infections (55.0% versus 28.6%, respectively), which exhibited 12.3-fold lower titers against WT compared with moderate to severe infections (p = 0.020). Following either Delta or Omicron breakthrough infection, limited variant-specific cross-neutralizing immunity was observed. These results suggest that Omicron breakthrough infections are less immunogenic than Delta, thus providing reduced protection against reinfection or infection from future variants.

Emerging Pandemic Diseases: How We Got to COVID-19.

Infectious diseases prevalent in humans and animals are caused by pathogens that once emerged from other animal hosts. In addition to these established infections, new infectious diseases periodically emerge. In extreme cases they may cause pandemics such as COVID-19; in other cases, dead-end infections or smaller epidemics result. Established diseases may also re-emerge, for example by extending geographically or by becoming more transmissible or more pathogenic. Disease emergence reflects dynamic balances and imbalances, within complex globally distributed ecosystems comprising humans, animals, pathogens, and the environment. Understanding these variables is a necessary step in controlling future devastating disease emergences.

SARS-CoV-2 in immunocompromised individuals.

Immunocompromised individuals and particularly those with hematologic malignancies are at increased risk for SARS-CoV-2-associated morbidity and mortality due to immunologic deficits that limit prevention, treatment, and clearance of the virus. Understanding the natural history of viral infections in people with impaired immunity due to underlying conditions, immunosuppressive therapy, or a combination thereof has emerged as a critical area of investigation during the COVID-19 pandemic. Studies focused on these individuals have provided key insights into aspects of innate and adaptive immunity underlying both the antiviral immune response and excess inflammation in the setting of COVID-19. This review presents what is known about distinct states of immunologic vulnerability to SARS-CoV-2 and how this information can be harnessed to improve prevention and treatment strategies for immunologically high-risk populations.

Effects on Cancer Prevention from the COVID-19 Pandemic.

The COVID-19 pandemic led to disruption of health services around the world, including cancer services. We carried out a narrative review of the effect of the pandemic on cancer prevention services, including screening. Services were severely affected in the early months of the pandemic, and in some areas are still recovering. Large numbers of additional cancers or additional late-stage cancers have been predicted to arise over the coming years as a result of this disruption. To minimize the effects on cancer outcomes, it is necessary to return as quickly as possible to prepandemic levels of screening and prevention activity or indeed to exceed these levels. The recovery of services should address health inequalities.

COVID-19 precautionary behaviors and vaccine acceptance among older individuals: The role of close kin.

The family plays a central role in shaping health behaviors of its members through social control and support mechanisms. We investigate whether and to what extent close kin (i.e., partner and children) matter for older people in taking on precautionary behaviors (e.g., wearing a mask) and vaccination during the COVID-19 pandemic in Europe. Drawing on data from the Survey of Health, Ageing and Retirement in Europe (SHARE), we combine its Corona Surveys (June to September 2020 and June to August 2021) with pre-COVID information (October 2019 to March 2020). We find that having close kin (especially a partner) is associated with a higher probability of both adopting precautionary behaviors and accepting a COVID-19 vaccine. Results are robust to controlling for other potential drivers of precautionary behaviors and vaccine acceptance and to accounting for coresidence with kin. Our findings suggest that policymakers and practitioners may differently address kinless individuals when promoting public policy measures.

Coupled models of genomic surveillance and evolving pandemics with applications for timely public health interventions.

Disease surveillance systems provide early warnings of disease outbreaks before they become public health emergencies. However, pandemics containment would be challenging due to the complex immunity landscape created by multiple variants. Genomic surveillance is critical for detecting novel variants with diverse characteristics and importation/emergence times. Yet, a systematic study incorporating genomic monitoring, situation assessment, and intervention strategies is lacking in the literature. We formulate an integrated computational modeling framework to study a realistic course of action based on sequencing, analysis, and response. We study the effects of the second variant's importation time, its infectiousness advantage and, its cross-infection on the novel variant's detection time, and the resulting intervention scenarios to contain epidemics driven by two-variants dynamics. Our results illustrate the limitation in the intervention's effectiveness due to the variants' competing dynamics and provide the following insights: i) There is a set of importation times that yields the worst detection time for the second variant, which depends on the first variant's basic reproductive number; ii) When the second variant is imported relatively early with respect to the first variant, the cross-infection level does not impact the detection time of the second variant. We found that depending on the target metric, the best outcomes are attained under different interventions' regimes. Our results emphasize the importance of sustained enforcement of Non-Pharmaceutical Interventions on preventing epidemic resurgence due to importation/emergence of novel variants. We also discuss how our methods can be used to study when a novel variant emerges within a population.

Reminders, but not monetary incentives, increase COVID-19 booster uptake.

Despite substantially decreasing the risk of hospitalization and death from COVID-19, COVID-19 booster vaccination rates remain low around the world. A key question for public health agencies is how to increase booster vaccination rates, particularly among high-risk groups. We conducted a large preregistered randomized controlled trial (with 57,893 study subjects) in a county health system in northern California to test the impact of personal reminder messages and small financial incentives of $25 on booster vaccination rates. We found that reminders increased booster vaccination rates within 2 wk by 0.86 percentage points (P = 0.000) or nearly 33% off the control mean of 2.65%. Monetary incentives had no additional impact on vaccination rates. The results highlight the potential of low-cost targeted messages, but not small financial incentives, to increase booster vaccination rates.

Digital public health interventions at scale: The impact of social media advertising on beliefs and outcomes related to COVID vaccines.

Public health organizations increasingly use social media advertising campaigns in pursuit of public health goals. In this paper, we evaluate the impact of about $40 million of social media advertisements that were run and experimentally tested on Facebook and Instagram, aimed at increasing COVID-19 vaccination rates in the first year of the vaccine roll-out. The 819 randomized experiments in our sample were run by 174 different public health organizations and collectively reached 2.1 billion individuals in 15 languages. We find that these campaigns are, on average, effective at influencing self-reported beliefs-shifting opinions close to 1% at baseline with a cost per influenced person of about $3.41. Combining this result with an estimate of the relationship between survey outcomes and vaccination rates derived from observational data yields an estimated cost per additional vaccination of about $5.68. There is further evidence that campaigns are especially effective at influencing users' knowledge of how to get vaccines. Our results represent, to the best of our knowledge, the largest set of online public health interventions analyzed to date.

Immunogenicity and efficacy of Ad26.COV2.S: An adenoviral vector-based COVID-19 vaccine.

Since its emergence in late 2019, the coronavirus disease 2019 (COVID-19) pandemic has caused substantial morbidity and mortality. Despite the availability of efficacious vaccines, new variants with reduced sensitivity to vaccine-induced protection are a troubling new reality. The Ad26.COV2.S vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding a full-length, membrane-bound severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation. This review discusses the immunogenicity and efficacy of Ad26.COV2.S as a single-dose primary vaccination and as a homologous or heterologous booster vaccination. Ad26.COV2.S elicits broad humoral and cellular immune responses, which are associated with protective efficacy/effectiveness against SARS-CoV-2 infection, moderate to severe/critical COVID-19, and COVID-19-related hospitalization and death, including against emerging SARS-CoV-2 variants. The humoral immune responses elicited by Ad26.COV2.S vaccination are durable, continue to increase for at least 2-3 months postvaccination, and involve a range of functional antibodies. Ad26.COV2.S given as a heterologous booster to mRNA vaccine-primed individuals markedly increases humoral and cellular immune responses. The use of Ad26.COV2.S as primary vaccination and as part of booster regimens is supporting the ongoing efforts to control and mitigate the COVID-19 pandemic.

Hyperimmune Globulins in COVID-19.

The COVID-19 pandemic, resulting from the emergence of the novel coronavirus SARS-CoV-2, posed unprecedented challenges to global health systems as no proven therapy was available. Initially, COVID-19 convalescent plasma (CCP) from recovered COVID-19 patients showed promise as a therapeutic option. However, the efficacy of this approach was closely correlated with the neutralizing antibody titer in the administered plasma and thus effectiveness was not always guaranteed. In response, hyperimmune immunoglobulins (hIG) derived from CCP obtained by apheresis from recovered or vaccinated individuals emerged as a potential alternative. hIG were purified through stringent chromatographic processing from CCP units and displayed varying results in clinical trials, although it seems likely that they improved outcomes compared to placebo or CCP at day 28, particularly in unvaccinated patients. The variability in the effect of hIG likely stems from factors such as the timing of outcome assessment, the administered dose of hIG, the patients' immunological background, and the matching between the variant infecting patients and the neutralization ability of the immunoglobulin batch, which depended on the timing of the CCP collection. Despite logistical challenges and high production costs, hIG showcase advantages over CCP, offering versatility in administration routes and eliminating the need for blood matching, thus facilitating administration in the community, and allowing for variant-specific preparations. hIG appear to be of particular importance in the treatment of immunocompromised patients and patients with persistent COVID-19, although studies in these populations are lacking. Non-human alternatives, such as equine-derived hIG and recombinant hIG, may provide a solution to the logistical challenges of large-scale hIG preparation. Further study is needed to explore these avenues. Establishing the infrastructure for large-scale hIG production independent of plasma donations emerges as a strategic approach for future pandemics, justifying exploration and promotion by health authorities.

Immunogenicity, clinical efficacy and safety of additional second COVID-19 booster vaccines against Omicron and its subvariants: A systematic review.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 is a new variant of concern (VOC) and an emerging subvariant that exhibits heightened infectivity, transmissibility, and immune evasion, escalating the incidence of moderate to severe coronavirus disease 2019 (COVID-19). It resists monoclonal antibodies and diminishes vaccine efficacy. Notably, new sublineages have outpaced earlier predominant sublineages. Although the primary vaccination series and initial boosters were robust against previous VOCs, their efficacy waned against Omicron and its subvariants. In this systematic review, we assessed real-world evidence on the immunogenicity, clinical efficacy, and safety of a second booster or fourth COVID-19 vaccine dose against the Omicron VOC and its subvariants. A comprehensive literature search was conducted in Medline/PubMed, Google Scholar, bioRxiv, and medRxiv, and relevant studies published between 2022 and 30 May 2023 were reviewed. We found a total of 40 relevant articles focusing on a second booster dose for COVID-19, including clinical trials and observational studies, involving 3,972,856 patients. The results consistently revealed that an additional second booster dose restored and prolonged waning immunity, activating both humoral and cellular responses against Omicron and its subvariants. A second booster treatment correlated with enduring protection against COVID-19, notably preventing substantial symptomatic disease and mortality associated with severe Omicron infection. Both monovalent messenger RNA (mRNA) and nonmRNA vaccines demonstrated similar efficacy and safety, with bivalent mRNA vaccines exhibiting broader protection against emerging subvariants of Omicron. The safety profiles of second booster were favourable with only mild systemic and local symptoms reported in some recipients. In conclusion, this systematic review underscores the additional COVID-19 vaccine boosters, particularly with bivalent or multivalent mRNA vaccines, for countering the highly infectious emerging subvariants of Omicron.

Azvudine versus Paxlovid in COVID-19: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to compare the effectiveness and safety of azvudine versus nirmatrelvir/ritonavir (Paxlovid) in treating coronavirus disease 2019 (COVID-19). The researchers conducted searches on PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar until January 2024. The Cochrane risk of bias tool was utilised to evaluate the quality of the included studies, and data analysis was performed using Comprehensive Meta-Analysis software. Thirteen studies, including 4949 patients, were analysed. The meta-analysis results showed no significant difference between the azvudine and Paxlovid groups in terms of mortality rate (odds rate [OR] = 0.84, 95% confidence interval [CI]: 0.59-1.21), negative polymerase chain reaction (PCR) conversion time (standard mean difference [SMD] = 1.52, 95% CI: -1.07-4.11), and hospital stay (SMD = -0.39, 95% CI: -1.12-0.33). However, a significant difference was observed between the two groups in terms of intensive care unit admission (OR = 0.42, 95% CI: 0.23-0.75) and the need for mechanical ventilation (OR = 0.61, 95% CI: 0.44-0.86) in favour of azvudine. The incidence of adverse events in the azvudine group was significantly lower (OR = 0.66, 95% CI: 0.43-0.99). The certainty of evidence was rated as low and moderate. Azvudine and Paxlovid demonstrated similar effectiveness in reducing mortality rates, negative PCR conversion time and hospital stay. However, azvudine showed better effectiveness in improving other outcomes. Regarding the level of certainty of evidence, further research is needed to validate or challenge these results.

Vaccine effects on COVID-19 infection with bivalent boosting by age group.

This paper examines time-series vaccine effectiveness on COVID-19 infection with/without a bivalent booster dose by 6 age groups such as 18-29, 30-49, 50-64, 65-79, 80+, and all_ages respectively. CDC's COVID data on rates of COVID-19 cases and deaths by updated (bivalent) booster status was used in this study. This result concludes that there is no difference between vaccines with or without a bivalent booster dose for preventing COVID-19 infection in 6 age groups 18-29, 30-49, 50-64, 65-79, 80+, and all_ages. Vaccination is effective in two age groups of 65-79 and 80+ for preventing COVID-19 infection. However, vaccine effectiveness against COVID-19 infection has not been confirmed in the 18-29 and 30-49 age groups.

Pandemic fatigue fueled political discontent during the COVID-19 pandemic.

Health authorities have highlighted "pandemic fatigue" as a psychological consequence of the COVID-19 pandemic and warned that "fatigue" could demotivate compliance with health-related policies and mandates. Yet, fatigue from following the policies of authorities may have consequences far beyond the health domain. Theories from the social sciences have raised that real and perceived costs of policies can also drive sentiments of discontent with the entire political establishment. Integrating theories from the health and social sciences, we ask how pandemic fatigue (i.e., perceived inability to "keep up" with restrictions) developed over the pandemic and whether it fueled political discontent. Utilizing longitudinal and panel surveys collected from September 2020 to July 2021 in eight Western countries (N = 49,116), we analyze: 1) fatigue over time at the country level, 2) associations between pandemic fatigue and discontent, and 3) the effect of pandemic fatigue on political discontent using panel data. Pandemic fatigue significantly increased with time and the severity of interventions but also decreased with COVID-19 deaths. When triggered, fatigue elicited a broad range of discontent, including protest support and conspiratorial thinking. The results demonstrate the significant societal impact of the pandemic beyond the domain of health and raise concerns about the stability of democratic societies, which were already strained by strife prior to the pandemic.

The effect of masks on cognitive performance.

The use of face masks has been a key response to the COVID-19 pandemic in almost every country. However, despite widespread use of masks in classrooms and offices around the world, almost nothing is known about their effects on cognitive performance. Using a natural experiment, I show that mandatory mask wearing has a negative causal effect on the cognitive performance of competitive chess players. I analyzed the quality of almost 3 million chess moves played by 8,531 individuals (ages 5-98 y) in 18 countries before and during the pandemic. Wearing a mask decreased the quality of players' decisions-a measure of their cognitive performance-by approximately one-third of an SD. However, the disruptive effect of masks is relatively short-lived, gradually weakening such that there is no measurable disadvantage from wearing a mask after roughly 4 h of play. The mask effect is driven by a large, negative effect for experts, with minimal change in performance at lower levels, and is stronger in high-incentive competitions. I provide support for a distraction mechanism whereby masks interfere with performance when working memory load is high.

Masks as a moral symbol: Masks reduce wearers' deviant behavior in China during COVID-19.

Since the outbreak of COVID-19, mask wearing has become a global phenomenon. How do masks influence wearers' behavior in everyday life? We examine the effect of masks on wearers' deviant behavior in China, where mask wearing is mostly a public-health issue rather than a political issue. Drawing on behavioral ethics research, we test two competing hypotheses: (a) masks disinhibit wearers' deviant behavior by increasing their sense of anonymity and (b) masks are a moral symbol that reduces wearers' deviant behavior by heightening their moral awareness. The latter hypothesis was consistently supported by 10 studies (including direct replications) using mixed methods (e.g., traffic camera recording analysis, observational field studies, experiments, and natural field experiment) and different measures of deviant behavior (e.g., running a red light, bike parking in no-parking zones, cheating for money, and deviant behavior in the library). Our research (n = 68,243) is among the first to uncover the psychological and behavioral consequences of mask wearing beyond its health benefits.

Prosocial nudges and visual indicators increase social distancing, but authoritative nudges do not.

Social distancing reduces the transmission of COVID-19 and other airborne diseases. To test different ways to increase social distancing, we conducted a field experiment at a major US airport using a system that presented color-coded visual indicators on crowdedness. We complemented those visual indicators with nudges commonly used to increase COVID-19-preventive behaviors. Analyzing data from 57,146 travelers, we find that visual indicators and nudges significantly affected social distancing. Introducing visual indicators increased the share of travelers practicing social distancing, and this positive effect was enhanced by introducing nudges focused on personal benefits ("protect yourself") and public benefits ("protect others"). Conversely, an authoritative nudge referencing the Centers for Disease Control and Prevention ("don't break CDC COVID-19 guidelines") did not change social distancing behavior. Our results demonstrate that visual indicators and informed nudges can boost social distancing and potentially curb the spread of contagious diseases.

Politicians polarize and experts depolarize public support for COVID-19 management policies across countries.

Political polarization impeded public support for policies to reduce the spread of COVID-19, much as polarization hinders responses to other contemporary challenges. Unlike previous theory and research that focused on the United States, the present research examined the effects of political elite cues and affective polarization on support for policies to manage the COVID-19 pandemic in seven countries (n = 12,955): Brazil, Israel, Italy, South Korea, Sweden, the United Kingdom, and the United States. Across countries, cues from political elites polarized public attitudes toward COVID-19 policies. Liberal and conservative respondents supported policies proposed by ingroup politicians and parties more than the same policies from outgroup politicians and parties. Respondents disliked, distrusted, and felt cold toward outgroup political elites, whereas they liked, trusted, and felt warm toward both ingroup political elites and nonpartisan experts. This affective polarization was correlated with policy support. These findings imply that policies from bipartisan coalitions and nonpartisan experts would be less polarizing, enjoying broader public support. Indeed, across countries, policies from bipartisan coalitions and experts were more widely supported. A follow-up experiment replicated these findings among US respondents considering international vaccine distribution policies. The polarizing effects of partisan elites and affective polarization emerged across nations that vary in cultures, ideologies, and political systems. Contrary to some propositions, the United States was not exceptionally polarized. Rather, these results suggest that polarizing processes emerged simply from categorizing people into political ingroups and outgroups. Political elites drive polarization globally, but nonpartisan experts can help resolve the conflicts that arise from it.

A global experiment on motivating social distancing during the COVID-19 pandemic.

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one's core values) or behavioral intentions. Results supported hypothesized associations between people's existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.

Determining containment policy impacts on public sentiment during the pandemic using social media data.

Stringent containment and closure policies have been widely implemented by governments to prevent the transmission of COVID-19. Yet, such policies have significant impacts on people's emotions and mental well-being. Here, we study the effects of pandemic containment policies on public sentiment in Singapore. We computed daily sentiment values scaled from −1 to 1, using high-frequency data of ∼240,000 posts from highly followed public Facebook groups during January to November 2020. The lockdown in April saw a 0.1 unit rise in daily average sentiment, followed by a 0.2 unit increase with partially lifting of lockdown in June, and a 0.15 unit fall after further easing of restrictions in August. Regarding the impacts of specific containment measures, a 0.13 unit fall in sentiment was associated with travel restrictions, whereas a 0.18 unit rise was related to introducing a facial covering policy at the start of the pandemic. A 0.15 unit fall in sentiment was linked to restrictions on public events, post lock-down. Virus infection, wearing masks, salary, and jobs were the chief concerns found in the posts. A 2 unit increase in these concerns occurred even when some restrictions were eased in August 2020. During pandemics, monitoring public sentiment and concerns through social media supports policymakers in multiple ways. First, the method given here is a near real-time scalable solution to study policy impacts. Second, it aids in data-driven and evidence-based revision of existing policies and implementation of similar policies in the future. Third, it identifies public concerns following policy changes, addressing which can increase trust in governments and improve public sentiment.