Household transmission of SARS-CoV-2 during the Omicron wave in Shanghai, China：a case-ascertained study (preprint)

Since late 2021, the highly transmissible SARS-CoV-2 Omicron variant has driven a new surge of infections across the world. We used a case-ascertained study to determine the features of household transmission of SARS-CoV-2 Omicron variant in Shanghai, China. We collected detailed information on 323 pediatric cases and their 951 household members, all received consecutively intensive RT-PCR testing. We estimated the transmission parameters. Both secondary infection attack rates (SARI) and secondary clinical attack rates (SARC) among adult household contacts were computed, through which the transmission heterogeneities in infectivity and susceptibility were characterized and the vaccine effectiveness were estimated. The mean incubation period and serial interval of Omicron variant were estimated to be 4.6±2.1 days and 3.9±3.7 days. The overall SARI and SARC among adult household contacts were 77.11% (95% confidence interval [CI]: 73.58%-80.63%) and 67.03% (63.09%-70.98%). We found higher household susceptibility in females, while infectivity was not significantly different in primary cases by age, sex, vaccination status and clinical severity. Full vaccination and booster vaccination of inactivated vaccines were 14.8% (5.8%-22.9%) and 18.9% (9.0%-27.7%) effective against Omicron infection and 21.5% (10.4%-31.2%) and 24.3% (12.3%-34.7%) effective against symptomatic disease. Overall, we found high household transmission during the Omicron wave in Shanghai due to asymptomatic and pre-symptomatic transmission in the context of city-wide lockdown, indicating the importance of early detection and timely isolation of SARS-CoV-2 infections and quarantine of close contacts. Marginal effectiveness of inactivated vaccines against Omicron infection poses great challenge for prevention and control of the SARS-CoV-2 Omicron variant.

Household transmission of SARS-CoV-2 during the Omicron wave in Shanghai, China:a case-ascertained study (preprint)

Background Since late 2021, the highly transmissible SARS-CoV-2 Omicron variant has driven a new surge of infections across the world. We used a case-ascertained study to determine the features of household transmission of SARS-CoV-2 Omicron variant in Shanghai, China. Methods We collected detailed information on 323 pediatric cases and their 951 household members in April 2022 during the Omicron outbreak. All household members received consecutively intensive RT-PCR testing for SARS-CoV-2 and routine symptom monitoring within 14 days after exposure to a confirmed case. We described the characteristics of study participants and estimated the transmission parameters. Both secondary infection attack rates (SAR I ) and secondary clinical attack rates (SAR C ) among adult household contacts were computed, through which the transmission heterogeneities in infectivity and susceptibility were characterized and the vaccine effectiveness were estimated. Results We estimated the mean incubation period of SARS-CoV-2 Omicron variant to be 4.6 (median: 4.4, IQR: 3.1-6.0) days and the mean serial interval to be 3.9 (median:4.0, IQR: 1.4-6.5) days. The overall SAR I and SAR C among adult household contacts were 77.11% (95% confidence interval [CI]: 73.58%-80.63%) and 67.03% (63.09%-70.98%). We found higher household susceptibility in females, while infectivity was not significantly different in primary cases by age, sex, vaccination status and clinical severity. The estimated VEs of full vaccination was 14.8% (95% CI: 5.8%-22.9%) against Omicron infection and 21.5% (95% CI: 10.4%-31.2%) against symptomatic disease. The booster vaccination was 18.9% (95% CI: 9.0%-27.7%) and 24.3% (95% CI: 12.3%-34.7%) effective against infection and symptomatic disease, respectively. Conclusions We found high household transmission during the Omicron wave in Shanghai due to asymptomatic and pre-symptomatic transmission in the context of city-wide lockdown, indicating the importance of early detection and timely isolation of SARS-CoV-2 infections and quarantine of close contacts. Marginal effectiveness of inactivated vaccines against Omicron infection poses great challenge for prevention and control of the SARS-CoV-2 Omicron variant.

Expenditure Responsibility Assignment and High-Quality Equity of Compulsory Education—Empirical Analysis Based on OECD Countries

Education for sustainable development poses high challenges to governments and public finance. Compared with OECD countries, China’s local governments bear too much expenditure responsibilities with respect to compulsory education, which theoretically affects the high-quality equity of compulsory education. Through empirical analysis using cross-country data with the panel spatial model, it is found that the proportion of central government expenditure and the government’s educational effort both have a steady and negative impact on the regional variable coefficient of compulsory education completion rate. Unitary or federal regime does not have a significant impact on the result. This paper suggests establishing a sharing financing system among all levels of government. According to the minimum standard guarantee principle of basic public services, the central government, which has the strongest fiscal capacity, should establish the national standard and take the responsibility on coordinating and balancing education service among regions and promoting the inter-regional equity. Local governments are encouraged to provide education services above national standard in accordance with their fiscal capacities.

Diet quality and risk and severity of COVID-19: a prospective cohort study (preprint)

Objective: Poor metabolic health and certain lifestyle factors have been associated with risk and severity of coronavirus disease 2019 (COVID-19), but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its intersection with socioeconomic deprivation. Design: We used data from 592,571 participants of the smartphone-based COVID Symptom Study. Diet quality was assessed using a healthful plant-based diet score, which emphasizes healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalization with oxygen support, respectively. Results: Over 3,886,274 person-months of follow-up, 31,815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR, 0.91; 95% CI, 0.88-0.94) and severe COVID-19 (HR, 0.59; 95% CI, 0.47-0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate for lowest vs highest quartile of diet score was 22.5 (95% CI, 18.8-26.3) and 40.8 (95% CI, 31.7-49.8; 10,000 person-months) among persons living in areas with low and high deprivation, respectively. Conclusions: A dietary pattern characterized by healthy plant-based foods was associated with lower risk and severity of COVID-19. These association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.

Aspirin and NSAID use and the risk of COVID-19 (preprint)

Early reports raised concern that use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19). Users of the COVID Symptom Study smartphone application reported use of aspirin and other NSAIDs between March 24 and May 8, 2020. Users were queried daily about symptoms, COVID-19 testing, and healthcare seeking behavior. Cox proportional hazards regression was used to determine the risk of COVID-19 among according to aspirin or non-aspirin NSAID users. Among 2,736,091 individuals in the U.S., U.K., and Sweden, we documented 8,966 incident reports of a positive COVID-19 test over 60,817,043 person-days of follow-up. Compared to non-users and after stratifying by age, sex, country, day of study entry, and race/ethnicity, non-aspirin NSAID use was associated with a modest risk for testing COVID-19 positive (HR 1.23 [1.09, 1.32]), but no significant association was observed among aspirin users (HR 1.13 [0.92, 1.38]). After adjustment for lifestyle factors, comorbidities and baseline symptoms, any NSAID use was not associated with risk (HR 1.02 [0.94, 1.10]). Results were similar for those seeking healthcare for COVID-19 and were not substantially different according to lifestyle and sociodemographic factors or after accounting for propensity to receive testing. Our results do not support an association of NSAID use, including aspirin, with COVID-19 infection. Previous reports of a potential association may be due to higher rates of comorbidities or use of NSAIDs to treat symptoms associated with COVID-19. One Sentence Summary NSAID use is not associated with COVID-19 risk.

Racial and ethnic differences in COVID-19 vaccine hesitancy and uptake (preprint)

Background Racial and ethnic minorities have been disproportionately impacted by COVID-19. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy and limited access may result in disparities in uptake. Methods We performed a cohort study among U.S. and U.K. participants in the smartphone-based COVID Symptom Study (March 24, 2020-February 16, 2021). We used logistic regression to estimate odds ratios (ORs) of COVID-19 vaccine hesitancy (unsure/not willing) and receipt. Results In the U.S. ( n =87,388), compared to White non-Hispanic participants, the multivariable ORs of vaccine hesitancy were 3.15 (95% CI: 2.86 to 3.47) for Black participants, 1.42 (1.28 to 1.58) for Hispanic participants, 1.34 (1.18 to 1.52) for Asian participants, and 2.02 (1.70 to 2.39) for participants reporting more than one race/other. In the U.K. ( n =1,254,294), racial and ethnic minorities had similarly elevated hesitancy: compared to White participants, their corresponding ORs were 2.84 (95% CI: 2.69 to 2.99) for Black participants, 1.66 (1.57 to 1.76) for South Asian participants, 1.84 (1.70 to 1.98) for Middle East/East Asian participants, and 1.48 (1.39 to 1.57) for participants reporting more than one race/other. Among U.S. participants, the OR of vaccine receipt was 0.71 (0.64 to 0.79) for Black participants, a disparity that persisted among individuals who specifically endorsed a willingness to obtain a vaccine. In contrast, disparities in uptake were not observed in the U.K. Conclusions COVID-19 vaccine hesitancy was greater among racial and ethnic minorities, and Black participants living in the U.S. were less likely to receive a vaccine than White participants. Lower uptake among Black participants in the U.S. during the initial vaccine rollout is attributable to both hesitancy and disparities in access.

Association of social distancing and masking with risk of COVID-19 (preprint)

Given the continued burden of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) disease (COVID-19) across the U.S., there is a high unmet need for data to inform decision-making regarding social distancing and universal masking. We examined the association of community-level social distancing measures and individual masking with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported masking was associated with a 63% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. In the current environment of relaxed social distancing mandates and practices, universal masking may be particularly important in mitigating risk of infection.

SARS-CoV-2 (COVID-19) infection in pregnant women: characterization of symptoms and syndromes predictive of disease and severity through real-time, remote participatory epidemiology. (preprint)

Background: From the beginning of COVID-19 pandemic, pregnant women have been considered at greater risk of severe morbidity and mortality. However, data on hospitalized pregnant women show that the symptom profile and risk factors for severe disease are similar to those among women who are not pregnant, although preterm birth, Cesarean delivery, and stillbirth may be more frequent and vertical transmission is possible. Limited data are available for the cohort of pregnant women that gave rise to these hospitalized cases, hindering our ability to quantify risk of COVID-19 sequelae for pregnant women in the community. Objective: To test the hypothesis that pregnant women in community differ in their COVID-19 symptoms profile and disease severity compared to non-pregnant women. This was assessed in two community-based cohorts of women aged 18-44 years in the United Kingdom, Sweden and the United States of America. Study design: This observational study used prospectively collected longitudinal (smartphone application interface) and cross-sectional (web-based survey) data. Participants in the discovery cohort were drawn from 400,750 UK, Sweden and US women (79 pregnant who tested positive) who self-reported symptoms and events longitudinally via their smartphone, and a replication cohort drawn from 1,344,966 USA women (162 pregnant who tested positive) cross-sectional self-reports samples from the social media active user base. The study compared frequencies of symptoms and events, including self-reported SARS-CoV-2 testing and differences between pregnant and non-pregnant women who were hospitalized and those who recovered in the community. Multivariable regression was used to investigate disease severity and comorbidity effects. Results: Pregnant and non-pregnant women positive for SARS-CoV-2 infection drawn from these community cohorts were not different with respect to COVID-19-related severity. Pregnant women were more likely to have received SARS-CoV-2 testing than non-pregnant, despite reporting fewer clinical symptoms. Pre-existing lung disease was most closely associated with the severity of symptoms in pregnant hospitalized women. Heart and kidney diseases and diabetes were additional factors of increased risk. The most frequent symptoms among all non-hospitalized women were anosmia [63% in pregnant, 92% in non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant women who were hospitalized. Gastrointestinal symptoms, including nausea and vomiting, were different among pregnant and non-pregnant women who developed severe outcomes. Conclusions: Although pregnancy is widely considered a risk factor for SARS-CoV-2 infection and outcomes, and was associated with higher propensity for testing, the profile of symptom characteristics and severity in our community-based cohorts were comparable to those observed among non-pregnant women, except for the gastrointestinal symptoms. Consistent with observations in non-pregnant populations, comorbidities such as lung disease and diabetes were associated with an increased risk of more severe SARS-CoV-2 infection during pregnancy. Pregnant women with pre-existing conditions require careful monitoring for the evolution of their symptoms during SARS-CoV-2 infection.

Racial and ethnic determinants of Covid-19 risk (preprint)

BackgroundRacial and ethnic minorities have disproportionately high hospitalization rates and mortality related to the novel coronavirus disease 2019 (Covid-19). There are comparatively scant data on race and ethnicity as determinants of infection risk. MethodsWe used a smartphone application (beginning March 24, 2020 in the United Kingdom [U.K.] and March 29, 2020 in the United States [U.S.]) to recruit 2,414,601 participants who reported their race/ethnicity through May 25, 2020 and employed logistic regression to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for a positive Covid-19 test among racial and ethnic groups. ResultsWe documented 8,858 self-reported cases of Covid-19 among 2,259,841 non-Hispanic white; 79 among 9,615 Hispanic; 186 among 18,176 Black; 598 among 63,316 Asian; and 347 among 63,653 other racial minority participants. Compared with non-Hispanic white participants, the risk for a positive Covid-19 test was increased across racial minorities (aORs ranging from 1.24 to 3.51). After adjustment for socioeconomic indices and Covid-19 exposure risk factors, the associations (aOR [95% CI]) were attenuated but remained significant for Hispanic (1.58 [1.24-2.02]) and Black participants (2.56 [1.93-3.39]) in the U.S. and South Asian (1.52 [1.38-1.67]) and Middle Eastern participants (1.56 [1.25-1.95]) in the U.K. A higher risk of Covid-19 and seeking or receiving treatment was also observed for several racial/ethnic minority subgroups. ConclusionsOur results demonstrate an increase in Covid-19 risk among racial and ethnic minorities not completely explained by other risk factors for Covid-19, comorbidities, and sociodemographic characteristics. Further research investigating these disparities are needed to inform public health measures.

Symptom clusters in Covid19: A potential clinical prediction tool from the COVID Symptom study app (preprint)

As no one symptom can predict disease severity or the need for dedicated medical support in COVID-19, we asked if documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study Smartphone application, yielding six distinct symptom presentations. Clustering was validated on an independent replication dataset between May 1- May 28th, 2020. Using the first 5 days of symptom logging, the ROC-AUC of need for respiratory support was 78.8%, substantially outperforming personal characteristics alone (ROC-AUC 69.5%). Such an approach could be used to monitor at-risk patients and predict medical resource requirements days before they are required.

Risk of symptomatic Covid-19 among frontline healthcare workers (preprint)

BackgroundData for frontline healthcare workers (HCWs) and risk of SARS-CoV-2 infection are limited and whether personal protective equipment (PPE) mitigates this risk is unknown. We evaluated risk for COVID-19 among frontline HCWs compared to the general community and the influence of PPE. MethodsWe performed a prospective cohort study of the general community, including frontline HCWs, who reported information through the COVID Symptom Study smartphone application beginning on March 24 (United Kingdom, U.K.) and March 29 (United States, U.S.) through April 23, 2020. We used Cox proportional hazards modeling to estimate multivariate-adjusted hazard ratios (aHRs) of a positive COVID-19 test. FindingsAmong 2,035,395 community individuals and 99,795 frontline HCWs, we documented 5,545 incident reports of a positive COVID-19 test over 34,435,272 person-days. Compared with the general community, frontline HCWs had an aHR of 11{middle dot}6 (95% CI: 10{middle dot}9 to 12{middle dot}3) for reporting a positive test. The corresponding aHR was 3{middle dot}40 (95% CI: 3{middle dot}37 to 3{middle dot}43) using an inverse probability weighted Cox model adjusting for the likelihood of receiving a test. A symptom-based classifier of predicted COVID-19 yielded similar risk estimates. Compared with HCWs reporting adequate PPE, the aHRs for reporting a positive test were 1{middle dot}46 (95% CI: 1{middle dot}21 to 1{middle dot}76) for those reporting PPE reuse and 1{middle dot}31 (95% CI: 1{middle dot}10 to 1{middle dot}56) for reporting inadequate PPE. Compared with HCWs reporting adequate PPE who did not care for COVID-19 patients, HCWs caring for patients with documented COVID-19 had aHRs for a positive test of 4{middle dot}83 (95% CI: 3{middle dot}99 to 5{middle dot}85) if they had adequate PPE, 5{middle dot}06 (95% CI: 3{middle dot}90 to 6{middle dot}57) for reused PPE, and 5{middle dot}91 (95% CI: 4{middle dot}53 to 7{middle dot}71) for inadequate PPE. InterpretationFrontline HCWs had a significantly increased risk of COVID-19 infection, highest among HCWs who reused PPE or had inadequate access to PPE. However, adequate supplies of PPE did not completely mitigate high-risk exposures. FundingZoe Global Ltd., Wellcome Trust, EPSRC, NIHR, UK Research and Innovation, Alzheimers Society, NIH, NIOSH, Massachusetts Consortium on Pathogen Readiness RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSThe prolonged course of the coronavirus disease 2019 (COVID-19) pandemic, coupled with sustained challenges supplying adequate personal protective equipment (PPE) for frontline healthcare workers (HCW), have strained global healthcare systems in an unprecedented fashion. Despite growing awareness of this problem, there are few data to inform policy makers on the risk of COVID-19 among HCWs and the impact of PPE on their disease burden. Prior reports of HCW infections are based on cross sectional data with limited individual-level information on risk factors for infection. A PubMed search for articles published between January 1, 2020 and May 5, 2020 using the terms "covid-19", "healthcare workers", and "personal protective equipment," yielded no population-scale investigations exploring this topic. Added value of this studyIn a prospective study of 2,135,190 individuals, frontline HCWs may have up to a 12-fold increased risk of reporting a positive COVID-19 test. Compared with those who reported adequate availability of PPE, frontline HCWs with inadequate PPE had a 31% increase in risk. However, adequate availability of PPE did not completely reduce risk among HCWs caring for COVID-19 patients. Implications of all the available evidenceBeyond ensuring adequate availability of PPE, additional efforts to protect HCWs from COVID-19 are needed, particularly as lockdown is lifted in many regions of the world.