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Background: Prior infection with SARS-CoV-2 can provide protection against infection and severe COVID-19. In settings with high pre-existing immunity, vaccine effectiveness (VE) should decrease with higher levels of immunity among unvaccinated individuals. Here, we conducted a systematic review and meta-analysis to understand the influence of prior infection on VE. Methods: We included test-negative design (TND) studies that examined VE against infection or severe disease (hospitalization, ICU admission, or death) for primary vaccination series. To determine the impact of prior infections on VE estimates, we compared studies that excluded or included people with prior COVID-19 infection. We also compared VE estimates by the cumulative incidence of cases before the start of and incidence rates during each study in the study locations, as further measures of prior infections in the community. Findings: We identified 67 studies that met inclusion criteria. Pooled VE among studies that included people with prior COVID-19 infection was lower against infection (pooled VE: 77%; 95% confidence interval (CI): 72%, 81%) and severe disease (pooled VE: 86%; 95% CI: 83%, 89%), compared with studies that excluded people with prior COVID-19 infection (pooled VE against infection: 87%; 95% CI: 85%, 89%; pooled VE against severe disease: 93%; 95% CI: 91%, 95%). There was a negative correlation between the cumulative incidence of cases before the start of the study and VE estimates against infection (spearman correlation ({rho}) = -0.32; 95% CI: -0.45, -0.18) and severe disease ({rho} = -0.49; 95% CI: -0.64, -0.30). There was also a negative correlation between the incidence rates of cases during the study period and VE estimates against infection ({rho} = -0.48; 95% CI: -0.59, -0.34) and severe disease ({rho} = -0.42; 95% CI: -0.58, -0.23). Interpretation: Based on a review of published VE estimates we found clear empirical evidence that higher levels of pre-existing immunity in a population were associated with lower VE estimates. Excluding previously infected individuals from VE studies may result in higher VE estimates with limited generalisability to the wider population. Prior infections should be treated as confounder and effect modificatory when the policies were targeted to whole population or stratified by infection history, respectively.
Subject(s)
COVID-19 , Testicular Neoplasms , DeathABSTRACT
Coronavirus disease 2019 (COVID-19) was caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes human angiotensin converting enzyme 2 (hACE2) as the cellular receptor of its spike glycoprotein (SP) to gain entry into cells. Consequently, we focused on the potential of repurposing clinically available drugs to block the binding of SARS-CoV-2 to hACE2 by utilizing a novel artificial-intelligence drug screening approach. Based on the structure of S-RBD and hACE2, the pharmacophore of SARS-CoV-2-receptor-binding-domain (S-RBD) -hACE2 interface was generated and used to screen a library of FDA-approved drugs. A total of 20 drugs were retrieved as S-RBD-hACE2 inhibitors, of which 16 drugs were identified to bind to S-RBD or hACE2. Notably, tannic acid was validated to interfere with the binding of S-RBD to hACE2, thereby inhibited pseudotyped SARS-CoV-2 entry. Experiments involving competitive inhibition revealed that tannic acid competes with S-RBD and hACE2, whereas molecular docking proved that tannic acid interacts with the essential residues of S-RBD and hACE2. Based on the known antiviral activity and our findings, tannic acid might serve as a promising candidate for preventing and treating SARS-CoV-2 infection.
ABSTRACT
COVID-19 raises attention to epistemological risks related to everyday human activities. Our work quantifies infection transmission risks at different human activity places, including different types of settlements at macro-scale and establishments (restaurants, bars, etc.) at micro-scale, using evidences from COVID-19 in 906 urban areas across four continents. Relatively stable rules of how infection risks are distributed across human settlements and establishments are found. At micro-scale, the infection transmission risks at various establishments differ across countries, but generally, physical activity, entertainment and catering establishments lead to more infections than other activity places. At macro-scale, contrary to common beliefs, we find consistent pattern that transmission does not increase with settlement size and density. When considering interaction between the two scales, there is also consistent pattern that a smaller proportion of infections take place at specific establishments in larger settlements, suggesting that general public spaces such as streets play a greater role in transmission due to longer trips. Though with limitations, our work provides the first steps towards a system of knowledge on the linkage between places, human activities and disease transmission.
Subject(s)
COVID-19ABSTRACT
The SARS-CoV-2 Omicron variant exhibits striking immune evasion and is spreading globally at an unprecedented speed. Understanding the underlying structural basis of the high transmissibility and greatly enhanced immune evasion of Omicron is of high importance. Here through cryo-EM analysis, we present both the closed and open states of the Omicron spike, which appear more compact than the counterparts of the G614 strain, potentially related to the Omicron substitution induced enhanced protomer-protomer and S1-S2 interactions. The closed state showing dominant population may indicate a conformational masking mechanism of immune evasion for Omicron spike. Moreover, we capture two states for the Omicron S/ACE2 complex with S binding one or two ACE2s, revealing that the substitutions on the Omicron RBM result in new salt bridges/H-bonds and more favorable electrostatic surface properties, together strengthened interaction with ACE2, in line with the higher ACE2 affinity of the Omicron relative to the G614 strain. Furthermore, we determine cryo-EM structures of the Omicron S/S3H3 Fab, an antibody able to cross-neutralize major variants of concern including Omicron, elucidating the structural basis for S3H3-mediated broad-spectrum neutralization. Our findings shed new lights on the high transmissibility and immune evasion of the Omicron variant and may also inform design of broadly effective vaccines against emerging variants.
ABSTRACT
Places are fundamental factors in the spread of epidemics, as they are where people agglomerate and interact. This paper explores how different types of places--activity spaces at micro-level and human settlements at macro-level--impact the transmission of infections using evidences from COVID-19. We examine eleven types of activity spaces and find heterogeneous impacts across countries, yet we also find that non-essential activity spaces tend to have larger impacts than essential ones. Contrary to common beliefs, settlement size and density are not positively associated with reproduction numbers. Further, the impacts of closing activity spaces vary with settlement types and are consistently lower in larger settlements in all sample countries, suggesting more complex pattern of virus transmission in large settlements. This work takes first steps in systematically evaluating the epistemological risks of places at multiple scales, which contributes to knowledge in urban resilience, health and livability. TeaserActivity spaces and human settlement characteristics impact the spread of epidemics in multiple ways and should be considered in policy making.
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COVID-19ABSTRACT
The pandemic of coronavirus disease 2019 (COVID-19) resulted in a stringent lockdown in China to reduce the infection rate. We adopted a machine learning technique to analyze the air quality impacts of the COVID-19 lockdown from January to April 2020 for six megacities with different lockdown durations. Compared with the scenario without lockdowns, we estimated that the lockdown reduced ambient NO2 concentrations by 36–53% during the most restrictive periods, which involved Level-1 public health emergency response control actions. Several cities lifted the Level-1 control actions during February and March, and the avoided NO2 concentrations subsequently dropped below 10% in late April. Traffic analysis during the same periods in Beijing and Chengdu confirmed that traffic emission changes were a major factor in the substantial NO2 reduction, but they were also associated with increased O3 concentrations. The lockdown also reduced PM2.5 concentrations, although heavy pollution episodes occurred on certain days due to the enhanced formation of secondary aerosols in association with the increased atmospheric oxidizing capacity. We also observed that the changes in air pollution levels decreased as the lockdown was gradually eased in various cities.
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Development of effective strategies to detect, treat, or prevent COVID-19 requires a robust understanding of natural immunity to SARS-CoV-2, including the cellular response mediated by T cells. We used an unbiased, genome-wide screening technology to comprehensively identify the specific epitopes in SARS-CoV-2 that are recognized by the memory CD8+ T cells of 25 COVID-19 convalescent patients. For each of six HLA types examined, patient T cells recognized 3–8 immunodominant epitopes that are broadly shared among patients, and single-cell sequencing revealed common structural features of TCRs recognizing these epitopes. We detected minimal cross-reactivity to the endemic coronaviruses that cause the common cold, arguing that pre-existing immunity to other coronaviruses does not significantly shape CD8+ T cell responses to SARS-CoV-2. Notably, only 3 of the 29 immunodominant epitopes we identified reside in the Spike protein, highlighting the need for second-generation vaccines that recapitulate natural CD8+ T cell immunity to SARS-CoV-2.Funding: This work was supported by TScan Therapeutics, a privately-owned biotechnology company.Ethical Approval: The study was conducted in accordance with the Declaration of Helsinki (1996), approved by the Atlantic Health System Institutional Review Board and the Ochsner Clinic Foundation Institutional Review Board and registered at clinicaltrials.gov (# NCT04397900).
Subject(s)
COVID-19ABSTRACT
Development of effective strategies to detect, treat, or prevent COVID-19 requires a robust understanding of the natural immune response to SARS-CoV-2, including the cellular response mediated by T cells. We used an unbiased, genome-wide screening technology, termed T-Scan, to identify specific epitopes in SARS-CoV-2 that are recognized by the memory CD8+ T cells of 25 COVID-19 convalescent patients, focusing on epitopes presented by the six most prevalent HLA types: A*02:01, A*01:01, A*03:01, A*11:01, A*24:02, and B*07:02. For each HLA type, the patients T cells recognized 3-8 immunodominant epitopes that are broadly shared among patients. Remarkably, 94% of screened patients had T cells that recognized at least one of the three most dominant epitopes for a given HLA, and 53% of patients had T cells that recognized all three. Subsequent validation studies in 18 additional A*02:01 patients confirmed the presence of memory CD8+ T cells specific for the top six A*02:01 epitopes, and single-cell sequencing revealed that patients often have many different T cell clones targeting each epitope, but that the same T cell receptor V regions are predominantly used to recognize these epitopes, even across patients. In total, we identified 29 shared epitopes across the six HLA types studied. T cells that target most of these epitopes (27 of 29) do not cross-react with the endemic coronaviruses that cause the common cold, and the epitopes do not occur in regions with high mutational variation. Notably, only 3 of the 29 epitopes reside in the spike protein, highlighting the need to design new classes of vaccines that recapitulate natural CD8+ T cell responses to SARS-CoV-2.
Subject(s)
COVID-19ABSTRACT
The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-Å and 3.8-Å-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding.Competing Interest StatementThe authors have declared no competing interest.View Full Text
ABSTRACT
Background:Public health measures including social isolationare essential forCOVID-19 control,but also increase the risk of depression. This study examined the influencing and moderating factors on socially isolated people’s depressive symptoms. Methods: Data were collected from people in mandatory home or centralizedsocial isolation in Shenzhen, China from February 28 to March 6 in 2020. We assessed their perceived COVID-19risk, perceived tone of media coverage, perceived quality of people-oriented public health services, and depressive symptoms.Three stepwise multiple regressions were performed to examine the moderating effects controlling age, gender, education, monthly income, socially isolated venue,time spent on COVID-related news, and online social support.Results:We examined data from 340 people. 57.6% men, averaged age at 35.5 years old (SD = 8.37), 55.6% held bachelor’s degree or above.Overall, people in social isolation reported a moderate level ofdepressive symptoms (M =1.24, SD = 0.4). The perceived susceptibility of being infected was relatively low (M = 1.36, SD = 0.54), and the perceived tone of media coverage was mainly positive (M = 1.97, SD = 1.05). In terms of perceived quality of public health services, 3.2% (n = 11) participants reported low-level, 49.1% (n = 167) medium-level, and 47.6 (n =162) high-level quality ofpeople-oriented services. Perceived riskwas significantly associated with depression (β= .12, p< 0.01), and perceived tone of media coverage was negatively associated with depression (β= -.05, p< 0.01).The quality of people-centered public health service moderated the association between perceived riskand depressive symptoms(β= -.15, p< 0.05), and the relationship between perceived tone of media coverage and depressive symptoms(β= .01, p< 0.01).Conclusions:This studyfound thatpeople-oriented public health servicesreduced the effect of risk perception and media tone on depressive symptoms among COVID-19 socially isolated people, suggesting a critical role for frontline public health workers in protecting public mental health.