Geographic Variations in Human Mobility Patterns during the First Six Months of the COVID-19 Pandemic in California

Human mobility influenced the spread of the COVID-19 virus, as revealed by the high spatiotemporal granularity location service data gathered from smart devices. We conducted time series clustering analysis to delineate the relationships between human mobility patterns (HMPs) and their social determinants in California (CA) using aggregated smart device tracking data from SafeGraph. We first identified four types of temporal patterns for five human mobility indicator changes by applying dynamic-time-warping self-organizing map clustering methods. We then performed an analysis of variance and linear discriminant analysis on the HMPs with 17 social, economic, and demographic variables. Asians, children under five, adults over 65, and individuals living below the poverty line were found to be among the top contributors to the HMPs, including the HMP with a significant increase in the median home dwelling time and the HMP with emerging weekly patterns in full-time and part-time work devices. Our findings show that the CA shelter-in-place policy had varying impacts on HMPs, with socially disadvantaged places showing less compliance. The HMPs may help practitioners to anticipate the efficacy of non-pharmaceutical interventions on cases and deaths in pandemics.

Independent associations of short- and long-term air pollution exposure with COVID-19 mortality among Californians.

The growing literature demonstrating air pollution associations on COVID-19 mortality contains studies predominantly examining long-term exposure, with few on short-term exposure, and rarely both together to estimate independent associations. Because mechanisms by which air pollution may impact COVID-19 mortality risk function over timescales ranging from years to days, and given correlation among exposure time windows, consideration of both short- and long-term exposure is of importance. We assessed the independent associations between COVID-19 mortality rates with short- and long-term air pollution exposure by modeling both concurrently. Using California death certificate data COVID-19-related deaths were identified, and decedent residential information used to assess short- (4-week mean) and long-term (6-year mean) exposure to particulate matter <2.5µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3). Negative binomial mixed models were fitted on weekly census tract COVID-19 mortality adjusting for potential confounders with random effects for county and census tract and an offset for population. Data were evaluated separately for two time periods March 16, 2020-October 18, 2020 and October 19, 2020-April 25, 2021, representing the Spring/Summer surges and Winter surge. Independent positive associations with COVID-19 mortality were observed for short- and long-term PM2.5 in both study periods, with strongest associations observed in the first study period: COVID-19 mortality rate ratio for a 2-µg/m3 increase in long-term PM2.5 was 1.13 (95%CI:1.09,1.17) and for a 4.7-µg/m3 increase in short-term PM2.5 was 1.05 (95%CI:1.02,1.08). Statistically significant positive associations were seen for both short- and long-term NO2 in study period 1, but short-term NO2 was not statistically significant in study period 2. Results for long-term O3 indicate positive associations, however, only marginal significance is achieved in study period 1. These findings support an adverse effect of long-term PM2.5 and NO2 exposure on COVID-19 mortality risk, independent of short-term exposure, and a possible independent effect of short-term PM2.5.

Crystal Structures of Bat and Human Coronavirus ORF8 Protein Ig-Like Domain Provide Insights Into the Diversity of Immune Responses.

ORF8 is a viral immunoglobulin-like (Ig-like) domain protein encoded by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome. It tends to evolve rapidly and interfere with immune responses. However, the structural characteristics of various coronavirus ORF8 proteins and their subsequent effects on biological functions remain unclear. Herein, we determined the crystal structures of SARS-CoV-2 ORF8 (S84) (one of the epidemic isoforms) and the bat coronavirus RaTG13 ORF8 variant at 1.62 Å and 1.76 Å resolution, respectively. Comparison of these ORF8 proteins demonstrates that the 62-77 residues in Ig-like domain of coronavirus ORF8 adopt different conformations. Combined with mutagenesis assays, the residue Cys20 of ORF8 is responsible for forming the covalent disulfide-linked dimer in crystal packing and in vitro biochemical conditions. Furthermore, immune cell-binding assays indicate that various ORF8 (SARS-CoV-2 ORF8 (L84), ORF8 (S84), and RaTG13 ORF8) proteins have different interaction capabilities with human CD14+ monocytes in human peripheral blood. These results provide new insights into the specific characteristics of various coronavirus ORF8 and suggest that ORF8 variants may influence disease-related immune responses.

Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.

The emerging new lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have marked a new phase of coronavirus disease 2019 (COVID-19). Understanding the recognition mechanisms of potent neutralizing monoclonal antibodies (NAbs) against the spike protein is pivotal for developing new vaccines and antibody drugs. Here, we isolated several monoclonal antibodies (MAbs) against the SARS-CoV-2 spike protein receptor-binding domain (S-RBD) from the B cell receptor repertoires of a SARS-CoV-2 convalescent. Among these MAbs, the antibody nCoV617 demonstrates the most potent neutralizing activity against authentic SARS-CoV-2 infection, as well as prophylactic and therapeutic efficacies against the human angiotensin-converting enzyme 2 (ACE2) transgenic mouse model in vivo. The crystal structure of S-RBD in complex with nCoV617 reveals that nCoV617 mainly binds to the back of the "ridge" of RBD and shares limited binding residues with ACE2. Under the background of the S-trimer model, it potentially binds to both "up" and "down" conformations of S-RBD. In vitro mutagenesis assays show that mutant residues found in the emerging new lineage B.1.1.7 of SARS-CoV-2 do not affect nCoV617 binding to the S-RBD. These results provide a new human-sourced neutralizing antibody against the S-RBD and assist vaccine development. IMPORTANCE COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It contains a variety of dominant neutralizing epitopes and is an important antigen for the development of new coronavirus antibodies. The significance of our research lies in the determination of new epitopes, the discovery of antibodies against RBD, and the evaluation of the antibodies' neutralizing effect. The identified antibodies here may be drug candidates for the development of clinical interventions for SARS-CoV-2.

Long-term air pollution and COVID-19 mortality rates in California: Findings from the Spring/Summer and Winter surges of COVID-19.

A growing number of studies report associations between air pollution and COVID-19 mortality. Most were ecological studies at the county or regional level which disregard important local variability and relied on data from only the first few months of the pandemic. Using COVID-19 deaths identified from death certificates in California, we evaluated whether long-term ambient air pollution was related to weekly COVID-19 mortality at the census tract-level during the first ∼12 months of the pandemic. Weekly COVID-19 mortality for each census tract was calculated based on geocoded death certificate data. Annual average concentrations of ambient particulate matter <2.5 µm (PM2.5) and <10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) over 2014-2019 were assessed for all census tracts using inverse distance-squared weighting based on data from the ambient air quality monitoring system. Negative binomial mixed models related weekly census tract COVID-19 mortality counts to a natural cubic spline for calendar week. We included adjustments for potential confounders (census tract demographic and socioeconomic factors), random effects for census tract and county, and an offset for census tract population. Data were analyzed as two study periods: Spring/Summer (March 16-October 18, 2020) and Winter (October 19, 2020-March 7, 2021). Mean (standard deviation) concentrations were 10.3 (2.1) µg/m3 for PM2.5, 25.5 (7.1) µg/m3 for PM10, 11.3 (4.0) ppb for NO2, and 42.8 (6.9) ppb for O3. For Spring/Summer, adjusted rate ratios per standard deviation increase were 1.13 (95% confidence interval: 1.09, 1.17) for PM2.5, 1.16 (1.11, 1.21) for PM10, 1.06 (1.02, 1.10) for NO2, and 1.09 (1.04, 1.14) for O3. Associations were replicated in Winter, although they were attenuated for PM2.5 and PM10. Study findings support a relation between long-term ambient air pollution exposure and COVID-19 mortality. Communities with historically high pollution levels might be at higher risk of COVID-19 mortality.

COVID-19 mortality in California based on death certificates: disproportionate impacts across racial/ethnic groups and nativity.

PURPOSE: To examine characteristics of coronavirus disease 2019 (COVID-19) decedents in California (CA) and evaluate for disproportionate mortality across race/ethnicity and ethnicity/nativity. METHODS: COVID-19 deaths were identified from death certificates. Age-adjusted mortality rate ratios (MRR) were compared across race/ethnicity. Proportionate mortality rates (PMR) were compared across race/ethnicity and by ethnicity/nativity. RESULTS: We identified 10,200 COVID-19 deaths in CA occurring February 1 through July 31, 2020. The most frequently observed characteristics among decedents were age 65 years or above, male, Hispanic, foreign-born, and educational attainment of High School or below. MRR indicated elevated COVID-19 morality rates among Asian/Pacific Islander, Black, and Hispanic groups compared with the White group, with Black and Hispanic groups having the highest MRR at 2.75 (95%CI: 2.54-2.97) and 4.18 (95%CI: 3.99-4.37), respectively. Disparities were larger at younger ages. Similar results were observed with PMR, and patterns of age-racial/ethnic disparities remained in analyses stratified by education. Elevated PMR were observed in all ethnicity/nativity groups, especially foreign-born Hispanic individuals, relative to U.S.-born non-Hispanic individuals. These were generally larger at younger ages and persisted after stratifying by education. CONCLUSIONS: Differential COVID-19 mortality was observed in California across racial/ethnic groups and by ethnicity/nativity groups with evidence of greater disparities among younger age groups. Identifying COVID-19 disparities is an initial step toward mitigating disease impacts in vulnerable communities.