Changing social contact patterns among US workers during the COVID-19 pandemic: April 2020 to December 2021

Non-pharmaceutical interventions minimize social contacts, hence the spread of SARS-CoV-2. We quantified two-day contact patterns among US employees from 2020-2021 during the COVID-19 pandemic. Contacts were defined as face-to-face conversations, involving physical touch or proximity to another individual and were collected using electronic diaries. Mean (standard deviation) contacts reported by 1,456 participants were 2.5 (2.5), 8.2 (7.1), 9.2 (7.1) and 10.1 (9.5) across round 1 (April-June 2020), 2 (November 2020-January 2021), 3 (June-August 2021), and 4 (November-December 2021), respectively. Between round 1 and 2, we report a 3-fold increase in the mean number of contacts reported per participant with no major increases from round 2-4. We modeled SARS-CoV-2 transmission at home, work, and community. The model revealed reduced relative transmission in all settings in round 1. Subsequently, transmission increased at home and in the community but remained very low in work settings. Contact data are important to parameterize models of infection transmission and control.

Did Risk-based or Age-based Vaccine Prioritization for Covid-19 Save More Lives?

ImportanceAll U.S. states provided Covid-19 vaccine access to frontline healthcare workers first, but after that, states varied in whether they gave earlier access to the elderly, versus the vulnerable with comorbidities, or school employees or essential workers, reflecting the underlying scientific and policy uncertainty. ObjectiveTo evaluate if risk-based or age-based prioritization is more effective at reducing reported Covid-19 cases and deaths. DesignA serial cross-sectional study Setting50 U.S. states and Washington D.C. Participants60+ years of age, high-risk individuals, K-12 school employees, and essential workers Main Outcomes and MeasuresHospitalizations and deaths ResultsSeven to nine weeks after 60-year-olds became eligible for a vaccine, there was a statistically significant 40-50% decline in Covid-19 hospitalizations in that state. In contrast, there was no statistically detectable change in hospitalizations in the 7-9 weeks after K-12 employees become eligible for vaccines. Vaccine eligibility of "high-risk adults" and "essential workers" produces effects somewhere in the middle, with reductions in hospitalization of about 25%. There was a large statistically significant decline in death rates (25-38%) 10 to 11 weeks after people aged over 60 became vaccine-eligible. These effects were generally statistically larger than high risk individuals, K-12 school employees, and essential workers. Conclusions and RelevancePanel data analysis of weekly variation in Covid-19 health outcomes reveals that prioritizing adults 60+ years of age is associated with the largest reduction in hospitalizations and Covid-19 cases, followed by vaccines for adults with high-risk comorbidities. Vaccinations extended to K-12 school employees and essential workers is associated with the smallest reductions in hospitalizations and deaths. Key PointsO_ST_ABSQuestionC_ST_ABSDid Risk-based or Age-based Vaccine Prioritization for Covid-19 Save More Lives? FindingsPanel data analysis of weekly variation in Covid-19 health outcomes reveals that prioritizing adults 60+ years of age is associated with the largest reduction in hospitalizations and Covid-19 cases, followed by vaccines for adults with high-risk comorbidities. Vaccinations extended to K-12 school employees and essential workers is associated with the smallest reductions in hospitalizations and deaths. MeaningPrioritizing adults 60+ years of age can lead to a higher estimated reduction in hospitalizations and deaths, followed by a strategy of prioritizing adults with high-risk comorbidities. Our findings add to the limited evidence for the roadmap for prioritizing use of Covid-19 vaccines, and help address uncertainties about the relative effectiveness of different vaccine strategies.

Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose

The emergence of the SARS-CoV-2 Omicron sublineages resulted in drastically increased transmission rates and reduced protection from vaccine-induced immunity. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remains sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed worldwide, particularly in China, and South America. However, whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses and whether these responses vary across age groups remain unknown. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals in central and south America that received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccines. We found that both IgG levels against SARS-CoV-2 spike or RBD, as well as neutralization titers against Omicron sublineages, were substantially reduced in participants that received homologous CoronaVac when compared to heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients older than 50 years of age. In this group, CoronaVac booster induced low virus-specific IgG levels and failed to elevate their neutralization titers against any omicron sublineage. Our results point to significant inefficiency in mounting protective anti-viral humoral immunity in those who were primed with CoronaVac followed by CoronaVac booster, particularly among older adults, urging a heterologous regimen in high-risk populations fully vaccinated with CoronaVac. One Sentence SummaryHomologous CoronaVac boosters do not improve neutralization responses against current VOCs in older adults in contrast to heterologous regimens.

Distinguishing features of Long COVID identified through immune profiling

SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID1-3. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions1-3; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.

Drivers of COVID-19 policy stringency in 175 countries and territories: COVID-19 cases and deaths, gross domestic products per capita, and health expenditures

ObjectiveTo understand the associations of COVID-19 cases and deaths with policy stringency globally and regionally. MethodsWe modeled the marginal effects of new COVID-19 cases and deaths on policy stringency (scored 0-100) in 175 countries and territories, adjusting for gross domestic product (GDP) per capita and health expenditure (% of GDP). Time periods examined were March-August 2020, September 2020- February 2021, and March-August 2021. ResultsPolicy response to new cases and deaths was faster and more stringent early in the COVID-19 pandemic (March-August 2020) compared to subsequent periods. New deaths were more strongly associated with stringent policies than new cases. In an average week, 1 new death per 100,000 people was associated with a stringency increase of 2.1 units in March-August 2020, 1.3 units in September 2020-February 2021, and 0.7 units in March-August 2021. New deaths in Africa and the Western Pacific were associated with more stringency than in other regions. Higher health expenditure was associated with less stringent policies. GDP per capita did not have consistent patterns of associations with stringency. ConclusionsOur findings demonstrate the need for enhanced mortality surveillance to ensure policy alignment during health emergencies. Countries that invest less of their GDP in health are inclined to enact stringent policies during health emergencies than countries with more significant health expenditure.

Insights into the limited global spread of the immune evasive SARS-CoV-2 variant Mu

SARS-CoV-2 Variants of Concern (VOCs) continue to reshape the trajectory of the COVID-19 pandemic. However, why some VOCs, like Omicron, become globally dominant while the spread of others is limited is not fully understood. To address this question, we investigated the VOC Mu, which was first identified in Colombia in late 2020. Our study demonstrates that, although Mu is less sensitive to neutralization compared to variants that preceded it, it did not spread significantly outside of South and Central America. Additionally, we find evidence that the response to Mu was impeded by reporting delays and gaps in the global genomic surveillance system. Our findings suggest that immune evasion alone was not sufficient to outcompete highly transmissible variants that were circulating concurrently with Mu. Insights into the complex relationship between genomic and epidemiological characteristics of previous variants should inform our response to variants that are likely to emerge in the future.

Prevalence of Chronic Diseases, Depression, and Stress among U.S. Child Care Professionals during the COVID-19 Pandemic

ImportanceThere is no published national research reporting child care professionals physical health, depression, or stress during the COVID-19 pandemic. Given their central role in supporting childrens development, child care professionals overall physical and mental health is important. ObjectivesTo evaluate the prevalence of chronic diseases, depression, and stress levels during the COVID-19 pandemic among U.S. child care professionals. DesignIn this large-scale national survey, data were collected through an online survey from May 22, 2020 to June 8, 2020. We analyzed the association of sociodemographic characteristics with four physical health conditions (asthma, heart disease, diabetes, and obesity), depression, and stress weighted to national representativeness. Sociodemographic characteristics included race, ethnicity, age, gender, medical insurance status, and child care type. SettingCenter- and home-based child care. ParticipantsChild care professionals (n = 81,682) from all U.S. states and the District of Columbia. ResultsMean age was 42.1 years (standard deviation = 14.1); 96.0% (n = 78,725) were female, 2.5% (n = 2,033) were male, and 0.3% (n = 225) were non-binary. For physical health conditions, 14.3% (n = 11,717) reported moderate to severe asthma, 6.5% (n = 5,317) diabetes, 4.9% (n = 3,971) heart disease, and 19.8% (n = 16,207) being obese. Regarding mental health, 45.7% (n = 37,376) screened positive for depression and 66.5% (n = 54,381) reported moderate to high stress levels. Race, ethnicity, and gender disparities were evidenced for physical health conditions of child care professionals, but not for mental health during the pandemic. Conclusions and RelevanceOur findings highlight that child care professionals depression rates during the pandemic were much higher than before the pandemic, and depression, stress and asthma rates were higher than U.S. adult depression rates during the pandemic. Given the essential work child care professionals provide during the pandemic, policy makers and public health officials should consider what can be done to support the physical and mental health of child care professionals. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the prevalence of chronic diseases, depression, and stress among U.S. child care professionals during the COVID-19 pandemic? FindingsIn this survey of 81,682 U.S. child care professionals, 14.3% reported moderate to severe asthma, 6.5% diabetes, 4.9% heart disease, 19.8% being obese, 45.7% screening positive for depression, and 66.5% moderate to high stress levels. MeaningDuring the pandemic, child care professionals reported depression rates much higher than before the pandemic, and asthma, stress, and depression much greater than U.S. adult estimates, highlighting a need for effective supports for the wellbeing of this essential workforce.

Comparison of infectious SARS-CoV-2 from the nasopharynx of vaccinated and unvaccinated individuals

The frequency of SARS-CoV-2 breakthrough infections in fully vaccinated individuals increased with the emergence of the Delta variant, particularly with longer time from vaccine completion. However, whether breakthrough infections lead to onward transmission remains unclear. Here, we conducted a study involving 125 patients comprised of 72 vaccinated and 53 unvaccinated individuals, to assess the levels of infectious virus in vaccinated and unvaccinated individuals. Quantitative plaque assays showed no significant differences in the titers of virus between these cohorts. However, the proportion of nasopharyngeal samples with culturable virus was lower in the vaccinated patients relative to unvaccinated patients (21% vs. 40%). Finally, time-to-event analysis with Kaplan-Myer curves revealed that protection from culturable infectious virus waned significantly starting at 5 months after completing a 2-dose regimen of mRNA vaccines. These results have important implications in timing of booster dose to prevent onward transmission from breakthrough cases.

Immunogenicity of heterologous BNT162b2 booster in fully vaccinated individuals with CoronaVac against SARS-CoV-2 variants Delta and Omicron: the Dominican Republic Experience

The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and by its numerous spike mutations with potential to evade neutralizing antibodies elicited by COVID-19 vaccines. The Dominican Republic was among the first countries in recommending the administration of a third dose COVID-19 vaccine to address potential waning immunity and reduced effectiveness against variants. Here, we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants that had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that heterologous CoronaVac prime followed by BNT162b2 booster regimen induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and Delta variant, resembling the titers obtained after two doses of mRNA vaccines. While neutralization of Omicron was undetectable in participants that had received a two-dose regimen of CoronaVac vaccine, BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron, compared to two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 6.3-fold and 2.7-fold for Omicron compared to ancestral and Delta variant, respectively. Surprisingly, previous SARS-CoV-2 infection did not affect the neutralizing titers for Omicron in participants that received the heterologous regimen. Our findings have immediate implications for multiples countries that previously used a two-dose regimen of CoronaVac and reinforce the notion that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.

Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity in uninfected and previously infected individuals

The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1-6. We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained higher antibody titers than uninfected individuals post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain than previously infected individuals 7 days after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination in the time-points analysed. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2) or with E484K (without N501Y/T). While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity.

Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 160 million infections and more than 3 million deaths worldwide. While effective vaccines are currently being deployed, the adaptive immune determinants which promote viral clearance and confer protection remain poorly defined. Using mouse models of SARS-CoV-2, we demonstrate that both humoral and cellular adaptive immunity contributes to viral clearance in the setting of primary infection. Furthermore, we find that either convalescent mice, or mice that receive mRNA vaccination are protected from both homologous infection and infection with a variant of concern, B.1.351. Additionally, we find this protection to be largely mediated by antibody response and not cellular immunity. These results highlight the in vivo protective capacity of antibodies generated to both vaccine and natural infection. One-Sentence SummaryDefining the roles of humoral and cellular adaptive immunity in viral clearance and protection from SARS-CoV-2 and a variant of concern.

Real World Effectiveness of COVID-19 mRNA Vaccines against Hospitalizations and Deaths in the United States

The authors have withdrawn this manuscript because they are continuing to review the analytical methods utilized in this iteration of the work and, as of yet, do not have adequate confidence in their reproducibility. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

COVID-19 Vaccine Acceptance and Hesitancy in Low and Middle Income Countries, and Implications for Messaging

We analyze COVID-19 vaccine acceptance across 15 survey samples covering ten low- and middle-income countries (LMICs) in Asia, Africa, and South America, Russia (an upper-middle-income country), and the United States, using survey responses from 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in LMIC samples (80% on average) compared to the United States (65%) and Russia (30%). Vaccine acceptance was primarily explained by an interest in personal protection against COVID-19, while concern about side effects was the most commonly expressed reason for reluctance. Health workers were the most trusted sources of information about COVID-19 vaccines. Our findings suggest that prioritizing vaccine distribution to LMICs should yield high returns in promoting global immunization coverage, and that vaccination campaigns in these countries should focus on translating acceptance into uptake. Messaging highlighting vaccine efficacy and safety, delivered by healthcare workers, may be most effective in addressing remaining hesitancy.

Beliefs about Mask Efficacy and the Effect of Social Norms on Mask Wearing Intentions for COVID-19 Risk Reduction

In the absence of widespread vaccination for COVID-19, governments and public health officials have advocated for the public to wear masks during the pandemic. The decision to wear a mask in public is likely affected by both beliefs about its efficacy and the prevalence of the behavior. Greater mask use in the community may encourage others to follow this norm, but it also creates an incentive for individuals to free ride on the protection afforded to them by others. We report the results of two vignette-based experiments conducted in the United States and Italy to examine the causal relationship between beliefs, social norms, and reported intentions to engage in mask promoting behavior. We find that providing factual information about how masks protect others increases the likelihood that someone would wear a mask or encourage others to do so in the United States, but not in Italy. There is no effect of providing information about how masks protect the wearer in either country. Additionally, greater mask use increases intentions to wear a mask and encourage someone else to wear theirs properly in both the United States and Italy. Thus, community mask use may be self-reinforcing.

National interest may require distributing COVID-19 vaccines to other countries

As the clinical trials for COVID-19 vaccine progress, understanding how to distribute the initially scarce doses is of paramount importance and a quantitative analysis of the trade-offs involved in domestic-only versus cooperative distribution is still missing. In this study we use a network Susceptible-Infected-Removed (SIR) model to show under which circumstances it is in a countrys self-interest to ensure other countries can also obtain a COVID-19 vaccine rather than focusing only on vaccination of their own residents. In particular, we focus our analysis on the USs decision and estimate the internal burden of COVID-19 disease under different scenarios about vaccine cooperation. We show that in scenarios in which the US has reached the threshold for domestic herd immunity, the US may find it optimal to donate doses to other countries with lower vaccination coverage, as this would allow for a sharp reduction in the inflow of infected individuals from abroad.

Social contact patterns among employees in 3 U.S. companies during early phases of the COVID-19 pandemic, April to June 2020.

2.ImportanceDevising control strategies against diseases such as COVID-19 require understanding of contextual social mixing and contact patterns. There has been no standardized multi-site social contact study conducted in workplace settings in the United States that can be used to broadly inform pandemic preparedness policy in these settings. ObjectiveThe study aimed to characterize the patterns of social contacts and mixing across workplace environments, including on-site or when teleworking. DesignThis was a cross-sectional non-probability survey that used standardized social contact diaries to collect data. Employees were requested to record their physical and non-physical contacts in a diary over two consecutive days, documented at the end of each day. Employees from each company were enrolled through email and electronic diaries sent as individual links. Data were collected from April to June 2020. SettingTwo multinational consulting companies and one university administrative department, all located in Georgia, USA. ParticipantsEmployees opted into the study by accepting the invitation on a link sent via email. Main OutcomeThe outcome was median number of contacts per person per day. This was stratified by day of data collection, age, sex, race and ethnicity. ResultsOf 3,835 employees approached, 357 (9.3%) completed the first day of contact diary of which 304 completed both days of contact diary. There was a median of 2 contacts (IQR: 1-4, range: 0-21) per respondent on both day one and two. The majority (55%) of contacts involved conversation only, occurred at home (64%), and cumulatively lasted more than 4 hours (38%). Most contacts were repeated, and within same age groups, though participants aged 30-59 years reported substantial inter-generational mixing with children. ConclusionParticipating employees in 3 surveyed workplaces reported few contacts, similar to studies from the UK and China when shelter-in-place orders were in effect during the pandemic. Many contacts were repeated which may limit the spread of infection. Future rounds are planned to assess changes in contact patterns when employees resume work in the office after the lockdown due to COVID-19 pandemic.

Modeling Dynamic Network Strategies for SARS-CoV-2 Control on a Cruise Ship

SARS-CoV-2 outbreaks have occurred on several nautical vessels, driven by the high-density contact networks on these ships. Optimal strategies for prevention and control that account for realistic contact networks are needed. We developed a network-based transmission model for SARS-CoV-2 on the Diamond Princess outbreak to characterize transmission dynamics and to estimate the epidemiological impact of outbreak control and prevention measures. This model represented the dynamic multi-layer network structure of passenger-passenger, passengercrew, and crew-crew contacts, both before and after the large-scale network lockdown imposed on the ship in response to the disease outbreak. Model scenarios evaluated variations in the timing of the network lockdown, reduction in contact intensity within the sub-networks, and diagnosis-based case isolation on outbreak prevention. We found that only extreme restrictions in contact patterns during network lockdown and idealistic clinical response scenarios could avert a major COVID-19 outbreak. Contact network changes associated with adequate outbreak prevention were the restriction of passengers to their cabins, with limited passenger-crew contacts. Clinical response strategies required for outbreak prevention included early mass screening with an ideal PCR test (100% sensitivity) and immediate case isolation upon diagnosis. Public health restrictions on optional leisure activities like these should be considered until longer-term effective solutions such as a COVID-19 vaccine become widely available.

COVID-19 Risk Perception Among U.S. Adults: Changes from February to May 2020

The COVID-19 pandemic continues to detrimentally impact the United States. Using a survey, we collected demographic and COVID-19 risk perception, behavior, knowledge, and attitude data from 672 adults across the U.S. in May 2020. These variables were compared with the results from a survey in February 2020. Participants who were older (55+ years; M = 6.3, SD = 2.0), identified as Native American/Alaska Native (M = 6.8, SD = 1.0) or Asian (M = 6.0, SD = 2.0), and those who had contracted (M = 6.8, SD = 2.0) or knew someone who had contracted COVID-19 (M = 6.2, SD = 1.7) reported higher perceived risk. Health behaviors, such as physical distancing, have shown to impact infectious disease trajectories. As the U.S. reopens its economy, public health officials and politicians must formulate culturally appropriate and evidence-based messaging and policies, based on the publics COVID-19 risk perceptions, to encourage preventive behaviors.

Newborn dried blood spots for serological surveys of COVID-19

As COVID-19 continues to spread across the globe, the need for inexpensive, large-scale prevalence surveillance testing increases. We present a method for testing newborn dried blood spots (DBS) for anti-SARS-COV-2 IgG antibodies, and demonstrate its applicability as an easily accessible proxy for measuring maternal seroprevalence.

Host response-based screening to identify undiagnosed cases of COVID-19and expand testing capacity

The COVID-19 pandemic has created unprecedented challenges in diagnostic testing. At the beginning of the epidemic, a confluence of factors resulted in delayed deployment of PCR-based diagnostic tests, resulting in lack of testing of individuals with symptoms of the disease. Although these tests are now more widely available, it is estimated that a three- to ten-fold increase in testing capacity will be required to ensure adequate surveillance as communities reopen1. In response to these challenges, we evaluated potential roles of host response-based screening in the diagnosis of COVID-19. Previous work from our group showed that the nasopharyngeal (NP) level of CXCL10, a protein produced as part of the host response to viral infection, is a sensitive predictor of respiratory virus infection across a wide spectrum of viruses2. Here, we show that NP CXCL10 is elevated during SARS-CoV-2 infection and use a CXCL10-based screening strategy to identify four undiagnosed cases of COVID-19 in Connecticut in early March. In a second set of samples tested at the Yale New Haven Hospital, we show that NP CXCL10 had excellent performance as a rule-out test (NPV 0.99, 95% C.I. 0.985-0.997). Our results demonstrate how biomarker-based screening could be used to leverage existing PCR testing capacity to rapidly enable widespread testing for COVID-19. One Sentence SummaryWe describe a host-response based screening strategy to identify undiagnosed cases of COVID-19 and to expand capacity for PCR-based testing.