Effects of High Temperature on COVID‐19 Deaths in U.S. Counties

The United States of America (USA) was afflicted by extreme heat in the summer of 2021 and some states experienced a record‐hot or top‐10 hottest summer. Meanwhile, the United States was also one of the countries impacted most by the coronavirus disease 2019 (COVID‐19) pandemic. Growing numbers of studies have revealed that meteorological factors such as temperature may influence the number of confirmed COVID‐19 cases and deaths. However, the associations between temperature and COVID‐19 severity differ in various study areas and periods, especially in periods of high temperatures. Here we choose 119 US counties with large counts of COVID‐19 deaths during the summer of 2021 to examine the relationship between COVID‐19 deaths and temperature by applying a two‐stage epidemiological analytical approach. We also calculate the years of life lost (YLL) owing to COVID‐19 and the corresponding values attributable to high temperature exposure. The daily mean temperature is approximately positively correlated with COVID‐19 deaths nationwide, with a relative risk of 1.108 (95% confidence interval: 1.046, 1.173) in the 90th percentile of the mean temperature distribution compared with the median temperature. In addition, 0.02 YLL per COVID‐19 death attributable to high temperature are estimated at the national level, and distinct spatial variability from −0.10 to 0.08 years is observed in different states. Our results provide new evidence on the relationship between high temperature and COVID‐19 deaths, which might help us to understand the underlying modulation of the COVID‐19 pandemic by meteorological variables and to develop epidemic policy response strategies. Key Points This study explores the relationship between COVID‐19 deaths and temperature by applying a two‐stage epidemiological analytical approach during the summer of 2021 in the Unites States The daily mean temperature is approximately positively correlated with COVID‐19 deaths nationwide, with different shapes of temperature–mortality curves noted at the regional level Evaluation of temperature‐mortality relationship is important in controlling COVID‐19 severity

Effects of High Temperature on COVID-19 Deaths in U.S. Counties.

The United States of America (USA) was afflicted by extreme heat in the summer of 2021 and some states experienced a record-hot or top-10 hottest summer. Meanwhile, the United States was also one of the countries impacted most by the coronavirus disease 2019 (COVID-19) pandemic. Growing numbers of studies have revealed that meteorological factors such as temperature may influence the number of confirmed COVID-19 cases and deaths. However, the associations between temperature and COVID-19 severity differ in various study areas and periods, especially in periods of high temperatures. Here we choose 119 US counties with large counts of COVID-19 deaths during the summer of 2021 to examine the relationship between COVID-19 deaths and temperature by applying a two-stage epidemiological analytical approach. We also calculate the years of life lost (YLL) owing to COVID-19 and the corresponding values attributable to high temperature exposure. The daily mean temperature is approximately positively correlated with COVID-19 deaths nationwide, with a relative risk of 1.108 (95% confidence interval: 1.046, 1.173) in the 90th percentile of the mean temperature distribution compared with the median temperature. In addition, 0.02 YLL per COVID-19 death attributable to high temperature are estimated at the national level, and distinct spatial variability from -0.10 to 0.08 years is observed in different states. Our results provide new evidence on the relationship between high temperature and COVID-19 deaths, which might help us to understand the underlying modulation of the COVID-19 pandemic by meteorological variables and to develop epidemic policy response strategies.

Neutralizing Potency of Prototype and Omicron RBD mRNA Vaccines Against Omicron Variant

The newly emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains more than 30 mutations on the spike protein, 15 of which are located within the receptor binding domain (RBD). Consequently, Omicron is able to extensively escape existing neutralizing antibodies and may therefore compromise the efficacy of current vaccines based on the original strain, highlighting the importance and urgency of developing effective vaccines against Omicron. Here we report the rapid generation and evaluation of an mRNA vaccine candidate specific to Omicron, and explore the feasibility of heterologous immunization with WT and Omicron RBD vaccines. This mRNA vaccine encodes the RBD of Omicron (designated as RBD-O) and is formulated with lipid nanoparticle. Two doses of the RBD-O mRNA vaccine efficiently induce neutralizing antibodies in mice;however, the antisera are effective only on the Omicron variant but not on the wildtype and Delta strains, indicating a narrow neutralization spectrum. It is noted that the neutralization profile of the RBD-O mRNA vaccine is opposite to that observed for the mRNA vaccine expressing the wildtype RBD (RBD-WT). Importantly, booster with RBD-O mRNA vaccine after two doses of RBD-WT mRNA vaccine can significantly increase neutralization titers against Omicron. Additionally, an obvious increase in IFN-γ, IL-2, and TNF-α-expressing RBD-specific CD4+ T cell responses was observed after immunization with the RBD-WT and/or RBD-O mRNA vaccine. Together, our work demonstrates the feasibility and potency of an RBD-based mRNA vaccine specific to Omicron, providing important information for further development of heterologous immunization program or bivalent/multivalent SARS-CoV-2 vaccines with broad-spectrum efficacy.

Cluster‐Enhanced Ensemble Learning for Mapping Global Monthly Surface Ozone From 2003 to 2019

Surface ozone is damaging to human health and crop yields. When evaluating global air pollution risk, gridded datasets with high accuracy are desired to reflect the local variations in air pollution concentrations. Here, a cluster‐enhanced ensemble machine learning method was used to develop a new 0.5‐degree monthly surface ozone data set during 2003–2019 by combining numerous informative variables. The overall accuracy of our data set is 91.5% (90.8% for space and 92.3% for time). Historically, populations in South Asia, North Africa and Middle‐East, and High‐income North America are exposed to the highest ozone concentrations. Globally, the population weighted ozone concentration in the peak season is 47.07 ppbv. Our results highlight that ozone pollution is intensifying in some regions, and implicate air quality management is crucial to secure human health from air pollution. Plain Language Summary: Surface ozone is one of the most hazardous air pollutants to human health and plants. However, estimation of global surface ozone is still limited. Here, by using state‐of‐the‐art machine learning techniques, we fuse satellite, chemical transport model outputs, atmospheric reanalyses, and emission data with surface observations to construct a full coverage and long‐time period surface ozone data set. We demonstrate that surface population weighted ozone concentration in North America and Europe has decreased from 2003 to 2019, while ozone pollution in East Asia has intensified during 2016–2019. We also show at least 37% of the world's population is exposed to ozone greater than the World Health Organization's interim target one of 50 ppbv (MDA8) in the peak season. Our results could help identify the key regions for improving global air quality and offers an insightful data set for human health assessments and air quality management. Key Points: A cluster‐enhanced ensemble machine learning method can predict global surface ozone with high accuracyPopulations in South Asia, North Africa and Middle‐East, and High‐income North America are exposed to the highest MDA8 during 2003–2019At least 37% of world's population is exposed to greater than 50 ppbv MDA8 in peak seasons [ FROM AUTHOR] Copyright of Geophysical Research Letters is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein.

The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs and defining their epitopes. Here, we isolate 9 neutralizing mouse MAbs raised against the spike protein of a SARS-CoV-2 prototype strain and evaluate their neutralizing potency towards a panel of variants, including B.1.1.7, B.1.351, B.1.617.1, and B.1.617.2. By using a combination of biochemical, virological, and cryo-EM structural analyses, we identify three types of cross-variant neutralizing MAbs, represented by S5D2, S5G2, and S3H3, respectively, and further define their epitopes. S5D2 binds the top lateral edge of the receptor-binding motif within the receptor-binding domain (RBD) with a binding footprint centred around the loop477-489, and efficiently neutralizes all variant pseudoviruses, but the potency against B.1.617.2 was observed to decrease significantly. S5G2 targets the highly conserved RBD core region and exhibits comparable neutralization towards the variant panel. S3H3 binds a previously unreported epitope located within the evolutionarily stable SD1 region and is able to near equally neutralize all of the variants tested. Our work thus defines three distinct cross-variant neutralizing sites on the SARS-CoV-2 spike protein, providing guidance for design and development of broadly effective vaccines and MAb-based therapies.

Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection.

Massive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here the preclinical development of yeast-produced receptor-binding domain (RBD)-based recombinant protein SARS-CoV-2 vaccines. We found that monomeric RBD of SARS-CoV-2 could be efficiently produced as a secreted protein from transformed Pichia pastoris (P. pastoris) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level of neutralizing antibodies in mice. We further designed and expressed a genetically linked dimeric RBD protein in yeast. The engineered dimeric RBD was more potent than the monomeric RBD in inducing long-lasting neutralizing antibodies. Mice immunized with either monomeric RBD or dimeric RBD were effectively protected from live SARS-CoV-2 virus challenge even at 18 weeks after the last vaccine dose. Importantly, we found that the antisera raised against the RBD of a single SARS-CoV-2 prototype strain could effectively neutralize the two predominant circulating variants B.1.1.7 and B.1.351, implying broad-spectrum protective potential of the RBD-based vaccines. Our data demonstrate that yeast-derived RBD-based recombinant SARS-CoV-2 vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of SARS-CoV-2 vaccines to achieve global immunization.

Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate.

NO x Emission Changes Over China During the COVID-19 Epidemic Inferred From Surface NO2 Observations.

The COVID-19 epidemic has substantially limited human activities and affected anthropogenic emissions. In this work, daily NO x emissions are inferred using a regional data assimilation system and hourly surface NO2 measurement over China. The results show that because of the coronavirus outbreak, NO x emissions across the whole mainland China dropped sharply after 31 January, began to rise slightly in certain areas after 10 February, and gradually recover across the country after 20 February. Compared with the emissions before the outbreak, NO x emissions fell by more than 60% and ~30% in many large cities and most small to medium cities, respectively. Overall, NO x emissions were reduced by 36% over China, which were mainly contributed by transportation. Evaluations show that the inverted changes over eastern China are credible, whereas those in western China might be underestimated. These findings are of great significance for exploring the reduction potential of NO x emissions in China.

Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.

Global air quality change during the COVID-19 pandemic: Regionally different ozone pollution responses: COVID-19疫情期间全球空气质量变化:臭氧响应的区域间差异

The explosive spread of the 2019 novel coronavirus (COVID-19) provides a unique chance to rethink the relationship between human activity and air pollution. Though related studies have revealed substantial reductions in primary emissions, obvious differences do exist in the responses of secondary pollutants, like ozone (O3) pollution. However, the regional disparities of O3 responses and their causes have still not been fully investigated. To better elucidate the interrelationship between anthropogenic emissions, chemical production, and meteorological conditions, O3 responses caused by lockdowns over different regions were comprehensively explored at a global scale. Observational signals of air-quality change were derived from multi-year surface measurements and satellite retrievals. With similar substantial drops in nitrogen dioxide (NO2), ozone shows rising signals in most areas of both East Asia and Europe, even up to ∼14 ppb, while a non-negligible declining signal exists in North America, by about 2–4 ppb. Furthermore, the drivers behind the different O3 responses are discussed based on meteorological analysis and O3 sensitivity diagnosis. On the one hand, O3 responses to NO2 declines can be affected by the primary dependence on its precursors. On the other hand, it is also highly dependent on meteorological factors, especially temperature. Our study further highlights the great importance of taking into consideration both the regional disparities and synergistic effects of precursor reductions and meteorological influence for scientific mitigation of O3 pollution. 摘要: 疫情期间全球各地一次排放大幅削减, 而臭氧等二次污染的响应则存在着区域间差异.结合地面和卫星观测发现, 同在氮氧化物大幅下降的情况下,臭氧在东亚和欧洲呈现出可达14ppb的上升信号, 而北美则下降为主 (约2-4ppb) .我们结合气象分析和臭氧敏感性进一步讨论了臭氧响应差异性的原因, 一方面受臭氧与前体物间关系的影响;另一方面来自于气象, 尤其是温度.研究明晰了人为排放,化学和气象三者的内在关联, 强调了在臭氧控制过程中考虑前体物削减和气象条件协同的重要性.

Enhanced secondary pollution offset reduction of primary emissions during COVID-19 lockdown in China.

To control the spread of the 2019 novel coronavirus (COVID-19), China imposed nationwide restrictions on the movement of its population (lockdown) after the Chinese New Year of 2020, leading to large reductions in economic activities and associated emissions. Despite such large decreases in primary pollution, there were nonetheless several periods of heavy haze pollution in eastern China, raising questions about the well-established relationship between human activities and air quality. Here, using comprehensive measurements and modeling, we show that the haze during the COVID lockdown was driven by enhancements of secondary pollution. In particular, large decreases in NOx emissions from transportation increased ozone and nighttime NO3 radical formation, and these increases in atmospheric oxidizing capacity in turn facilitated the formation of secondary particulate matter. Our results, afforded by the tragic natural experiment of the COVID-19 pandemic, indicate that haze mitigation depends upon a coordinated and balanced strategy for controlling multiple pollutants.