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1. Deploying vaccine distribution sites for improved accessibility and equity to support pandemic response

   https://doi.org/10.1007/s10458-023-09614-9  

   Li, George; Li, Ann; Marathe, Madhav; Srinivasan, Aravind; Tsepenekas, Leonidas; Vullikanti, Anil (August 2023, Autonomous Agents and Multi-Agent Systems)

   In response to COVID-19, many countries have mandated social distancing and banned large group gatherings in order to slow down the spread of SARS-CoV-2. These social interventions along with vaccines remain the best way forward to reduce the spread of SARS CoV-2. In order to increase vaccine accessibility, states such as Virginia have deployed mobile vaccination centers to distribute vaccines across the state. When choosing where to place these sites, there are two important factors to take into account: accessibility and equity. We formulate a combinatorial problem that captures these factors and then develop efficient algorithms with theoretical guarantees on both of these aspects. Furthermore, we study the inherent hardness of the problem, and demonstrate strong impossibility results. Finally, we run computational experiments on real-world data to show the efficacy of our methods. 

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2. Endemicity Is Not a Victory: The Unmitigated Downside Risks of Widespread SARS-CoV-2 Transmission

   https://doi.org/10.3390/covid2120121  

   Stoddard, Madison; Novokhodko, Alexander; Sarkar, Sharanya; Van Egeren, Debra; White, Laura F.; Hochberg, Natasha S.; Rogers, Michael S.; Zetter, Bruce; Joseph-McCarthy, Diane; Chakravarty, Arijit (December 2022, COVID)

   The strategy of relying solely on current SARS-CoV-2 vaccines to halt SARS-CoV-2 transmission has proven infeasible. In response, many public-health authorities have advocated for using vaccines to limit mortality while permitting unchecked SARS-CoV-2 spread (“learning to live with the disease”). The feasibility of this strategy critically depends on the infection fatality rate (IFR) of SARS-CoV-2. An expectation exists that the IFR will decrease due to selection against virulence. In this work, we perform a viral fitness estimation to examine the basis for this expectation. Our findings suggest large increases in virulence for SARS-CoV-2 would result in minimal loss of transmissibility, implying that the IFR may vary freely under neutral evolutionary drift. We use an SEIRS model framework to examine the effect of hypothetical changes in the IFR on steady-state death tolls under COVID-19 endemicity. Our modeling suggests that endemic SARS-CoV-2 implies vast transmission resulting in yearly US COVID-19 death tolls numbering in the hundreds of thousands under many plausible scenarios, with even modest increases in the IFR leading to unsustainable mortality burdens. Our findings highlight the importance of enacting a concerted strategy and continued development of biomedical interventions to suppress SARS-CoV-2 transmission and slow its evolution. 

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3. Dynamic SARS-CoV-2 emergence algorithm for rationally-designed logical next-generation vaccines

   https://doi.org/10.1038/s42003-022-04030-3  

   Maison, David P.; Ching, Lauren L.; Cleveland, Sean B.; Tseng, Alanna C.; Nakano, Eileen; Shikuma, Cecilia M.; Nerurkar, Vivek R. (December 2022, Communications Biology)

   Abstract SARS-CoV-2 worldwide spread and evolution has resulted in variants containing mutations resulting in immune evasive epitopes that decrease vaccine efficacy. We acquired SARS-CoV-2 positive clinical samples and compared the worldwide emerged spike mutations from Variants of Concern/Interest, and developed an algorithm for monitoring the evolution of SARS-CoV-2 in the context of vaccines and monoclonal antibodies. The algorithm partitions logarithmic-transformed prevalence data monthly and Pearson’s correlation determines exponential emergence of amino acid substitutions (AAS) and lineages. The SARS-CoV-2 genome evaluation indicated 49 mutations, with 44 resulting in AAS. Nine of the ten most worldwide prevalent (>70%) spike protein changes have Pearson’s coefficient r  > 0.9. The tenth, D614G, has a prevalence >99% and r -value of 0.67. The resulting algorithm is based on the patterns these ten substitutions elucidated. The strong positive correlation of the emerged spike protein changes and algorithmic predictive value can be harnessed in designing vaccines with relevant immunogenic epitopes. Monitoring, next-generation vaccine design, and mAb clinical efficacy must keep up with SARS-CoV-2 evolution, as the virus is predicted to remain endemic. 

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4. Host Immune Response Driving SARS-CoV-2 Evolution

   https://doi.org/10.3390/v12101095  

   Wang, Rui; Hozumi, Yuta; Zheng, Yong-Hui; Yin, Changchuan; Wei, Guo-Wei (October 2020, Viruses)

   null (Ed.)

   The transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance in controlling and combating the coronavirus disease 2019 (COVID-19) pandemic. Currently, over 15,000 SARS-CoV-2 single mutations have been recorded, which have a great impact on the development of diagnostics, vaccines, antibody therapies, and drugs. However, little is known about SARS-CoV-2’s evolutionary characteristics and general trend. In this work, we present a comprehensive genotyping analysis of existing SARS-CoV-2 mutations. We reveal that host immune response via APOBEC and ADAR gene editing gives rise to near 65% of recorded mutations. Additionally, we show that children under age five and the elderly may be at high risk from COVID-19 because of their overreaction to the viral infection. Moreover, we uncover that populations of Oceania and Africa react significantly more intensively to SARS-CoV-2 infection than those of Europe and Asia, which may explain why African Americans were shown to be at increased risk of dying from COVID-19, in addition to their high risk of COVID-19 infection caused by systemic health and social inequities. Finally, our study indicates that for two viral genome sequences of the same origin, their evolution order may be determined from the ratio of mutation type, C > T over T > C. 

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5. Biology and Pathogenesis of SARS-CoV-2: Understandings for Therapeutic Developments against COVID-19

   https://doi.org/10.3390/pathogens10091218  

   Sharma, Homa Nath; Latimore, Charity O.; Matthews, Qiana L. (September 2021, Pathogens)

   Coronaviruses are positive sense, single-stranded, enveloped, and non-segmented RNA viruses that belong to the Coronaviridae family within the order Nidovirales and suborder Coronavirinae. Two Alphacoronavirus strains: HCoV-229E and HCoV-NL63 and five Betacoronaviruses: HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2 have so far been recognized as Human Coronaviruses (HCoVs). Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is currently the greatest concern for humanity. Despite the overflow of research on SARS-CoV-2 and other HCoVs published every week, existing knowledge in this area is insufficient for the complete understanding of the viruses and the diseases caused by them. This review is based on the analysis of 210 published works, and it attempts to cover the basic biology of coronaviruses, including the genetic characteristics, life cycle, and host-pathogen interaction, pathogenesis, the antiviral drugs, and vaccines against HCoVs, especially focusing on SARS-CoV-2. Furthermore, we will briefly discuss the potential link between extracellular vesicles (EVs) and SARS-CoV-2/COVID-19 pathophysiology. 

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