Recent Submissions

  • COVID-19 and Solid Organ Transplantation: A Review Article.

    Azzi, Yorg; Bartash, Rachel; Scalea, Joseph; Loarte-Campos, Pablo; Akalin, Enver (Wolters Kluwer Health, 2021-01)
    The coronavirus pandemic has significantly impacted solid organ transplantation (SOT). Early in the outbreak period, transplant societies recommended suspending living kidney transplant programs in communities with widespread transmission to avoid exposing recipients to increased risk of immunosuppression, while recommendations were made to reserve deceased-donor kidney transplantation for likely life-saving indications. SOT recipients may be at high risk from COVID-19 disease due to chronic immunosuppressive treatment and other medical comorbidities. Mortality rates reported between 13 to over 30% in SOT recipients. In addition to high rates of complications and mortality attributable to COVID-19 infections, the pandemic has also led to additional complexities in transplantation including new questions regarding screening of donors and recipients, decision making to accept a patient for kidney transplant or wait after pandemic. The clinical implications of COVID-19 infection may also differ depending on the type of the transplanted organ and recipient comorbidities which further impacts decisions on continuing transplantation during the pandemic. Transplant activity during a pandemic should be tailored with careful selection of both donors and recipients. Furthermore, while tremendous strides have been made in treatment strategies and vaccinations, the impact of these in transplant recipients may be attenuated in the setting of their immunosuppression. In this review, we aim to summarize several aspects of COVID-19 in transplantation, including the immune response to SARS-CoV-2, SARS-CoV-2 diagnostics, clinical outcomes in SOT recipients, and end-stage kidney disease patients, transplant activity during the pandemic, and treatment options for COVID-19 disease.
  • Clinical strategies for optimizing infusion center care through a pandemic

    Hanna, Kirollos S; Segal, Eve M; Barlow, Ashley; Barlow, Brooke (SAGE Publications Inc., 2020-09-25)
    The national pandemic resulting from the novel coronavirus, COVID-19, has made the delivery of care for patients with cancer a challenge. There are competing risks of mortality from cancer versus serious complications and higher risk of death from COVID-19 in immunocompromised hosts. Furthermore, compounding these concerns is the inadequate supply of personal protective equipment, decreased hospital capacity, and paucity of effective treatments or vaccines to date for COVID-19. Guidance measures and recommendations have been published by national organizations aiming to facilitate the delivery of care in a safe and effective manner, many of which, are permanently adoptable interventions. Given the critical importance to continue chemotherapy, there remains additional interventions to further enhance patient safety while conserving healthcare resources such as adjustments in medication administration, reduction in laboratory or drug monitoring, and home delivery of specialty infusions. In this manuscript, we outline how to implement these actionable interventions of chemotherapy and supportive care delivery to further enhance the current precautionary measures while maintaining safe and effective patient care. Coupled with current published standards, these strategies can help alleviate the numerous challenges associated with this pandemic. © The Author(s) 2020.
  • Proton-Coupled Conformational Activation of SARS Coronavirus Main Proteases and Opportunity for Designing Small-Molecule Broad-Spectrum Targeted Covalent Inhibitors.

    Verma, Neha; Henderson, Jack A; Shen, Jana (American Chemical Society, 2020-12-15)
    The SARS coronavirus 2 (SARS-CoV-2) main protease (Mpro) is an attractive broad-spectrum antiviral drug target. Despite the enormous progress in structure elucidation, the Mpro's structure-function relationship remains poorly understood. Recently, a peptidomimetic inhibitor has entered clinical trial; however, small-molecule orally available antiviral drugs have yet to be developed. Intrigued by a long-standing controversy regarding the existence of an inactive state, we explored the proton-coupled dynamics of the Mpros of SARS-CoV-2 and the closely related SARS-CoV using a newly developed continuous constant pH molecular dynamics (MD) method and microsecond fixed-charge all-atom MD simulations. Our data supports a general base mechanism for Mpro's proteolytic function. The simulations revealed that protonation of His172 alters a conserved interaction network that upholds the oxyanion loop, leading to a partial collapse of the conserved S1 pocket, consistent with the first and controversial crystal structure of SARS-CoV Mpro determined at pH 6. Interestingly, a natural flavonoid binds SARS-CoV-2 Mpro in the close proximity to a conserved cysteine (Cys44), which is hyper-reactive according to the CpHMD titration. This finding offers an exciting new opportunity for small-molecule targeted covalent inhibitor design. Our work represents a first step toward the mechanistic understanding of the proton-coupled structure-dynamics-function relationship of CoV Mpros; the proposed strategy of designing small-molecule covalent inhibitors may help accelerate the development of orally available broad-spectrum antiviral drugs to stop the current pandemic and prevent future outbreaks.
  • Incidence of symptomatic venous thromboembolism following hospitalization for coronavirus disease 2019: Prospective results from a multi-center study.

    Rashidi, Farid; Barco, Stefano; Kamangar, Farin; Heresi, Gustavo A; Emadi, Ashkan; Kaymaz, Cihangir; Jansa, Pavel; Reis, Abilio; Rashidi, Arash; Taghizadieh, Ali; et al. (Elsevier Ltd., 2021-01)
    Background: Thrombosis and pulmonary embolism appear to be major causes of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients. However, few studies have focused on the incidence of venous thromboembolism (VTE) after hospitalization for COVID-19. Methods: In this multi-center study, we followed 1529 COVID-19 patients for at least 45 days after hospital discharge, who underwent routine telephone follow-up. In case of signs or symptoms of pulmonary embolism (PE) or deep vein thrombosis (DVT), they were invited for an in-hospital visit with a pulmonologist. The primary outcome was symptomatic VTE within 45 days of hospital discharge. Results: Of 1529 COVID-19 patients discharged from hospital, a total of 228 (14.9%) reported potential signs or symptoms of PE or DVT and were seen for an in-hospital visit. Of these, 13 and 12 received Doppler ultrasounds or pulmonary CT angiography, respectively, of whom only one patient was diagnosed with symptomatic PE. Of 51 (3.3%) patients who died after discharge, two deaths were attributed to VTE corresponding to a 45-day cumulative rate of symptomatic VTE of 0.2% (95%CI 0.1%–0.6%; n = 3). There was no evidence of acute respiratory distress syndrome (ARDS) in these patients. Other deaths after hospital discharge included myocardial infarction (n = 13), heart failure (n = 9), and stroke (n = 9). Conclusions: We did not observe a high rate of symptomatic VTE in COVID-19 patients after hospital discharge. Routine extended thromboprophylaxis after hospitalization for COVID-19 may not have a net clinical benefit. Randomized trials may be warranted.
  • Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults

    Anderson, Evan J; Rouphael, Nadine G; Widge, Alicia T; Jackson, Lisa A; Roberts, Paul C; Makhene, Mamodikoe; Chappell, James D; Denison, Mark R; Stevens, Laura J; Pruijssers, Andrea J; et al. (Massachusetts Medical Society, 2020-09-29)
    BACKGROUND Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. METHODS We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. RESULTS Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti-S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. CONCLUSIONS In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial.
  • The SKI complex is a broad-spectrum, host-directed antiviral drug target for coronaviruses, influenza, and filoviruses.

    Weston, Stuart; Baracco, Lauren; Keller, Chloe; Matthews, Krystal; McGrath, Marisa E; Logue, James; Liang, Janie; Dyall, Julie; Holbrook, Michael R; Hensley, Lisa E; et al. (National Academy of Sciences, 2020-11-12)
    The SARS-CoV-2 pandemic has made it clear that we have a desperate need for antivirals. We present work that the mammalian SKI complex is a broad-spectrum, host-directed, antiviral drug target. Yeast suppressor screening was utilized to find a functional genetic interaction between proteins from influenza A virus (IAV) and Middle East respiratory syndrome coronavirus (MERS-CoV) with eukaryotic proteins that may be potential host factors involved in replication. This screening identified the SKI complex as a potential host factor for both viruses. In mammalian systems siRNA-mediated knockdown of SKI genes inhibited replication of IAV and MERS-CoV. In silico modeling and database screening identified a binding pocket on the SKI complex and compounds predicted to bind. Experimental assays of those compounds identified three chemical structures that were antiviral against IAV and MERS-CoV along with the filoviruses Ebola and Marburg and two further coronaviruses, SARS-CoV and SARS-CoV-2. The mechanism of antiviral activity is through inhibition of viral RNA production. This work defines the mammalian SKI complex as a broad-spectrum antiviral drug target and identifies lead compounds for further development.
  • Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

    Gordon, David E; Hiatt, Joseph; Bouhaddou, Mehdi; Rezelj, Veronica V; Ulferts, Svenja; Braberg, Hannes; Jureka, Alexander S; Obernier, Kirsten; Guo, Jeffrey Z; Batra, Jyoti; et al. (American Association for the Advancement of Science, 2020-12-04)
    The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.
  • Remdesivir: a pendulum in a pandemic

    Schwartz, Ilan S; Heil, Emily L; McCreary, Erin K (BMJ Publishing Group, 2020-11-24)
  • Legal and ethical implications of wastewater monitoring of SARS-CoV-2 for COVID-19 surveillance.

    Gable, Lance; Ram, Natalie; Ram, Jeffrey L (Oxford University Press, 2020-06-24)
    Scientists have observed that molecular markers for COVID-19 can be detected in wastewater of infected communities both during an outbreak and, in some cases, before the first case is confirmed. The Centers for Disease Control and Prevention and other government entities are considering whether to add community surveillance through wastewater monitoring to assist in tracking disease prevalence and guiding public health responses to the COVID-19 pandemic. This scientific breakthrough may lead to many useful potential applications for tracking disease, intensifying testing, initiating social distancing or quarantines, and even lifting restrictions once a cessation of infection is detected and confirmed. Yet, new technologies developed in response to a public health crisis may raise difficult legal and ethical questions about how such technologies may impact both the public health and civil liberties of the population. This paper describes recent scientific evidence regarding COVID-19 detection in wastewater, identifying public health benefits that may result from this breakthrough, as well as the limitations of existing data. The paper then assesses the legal and ethical implications of implementing policy based on positive sewage signals. It concludes that the first step to implementing legal and ethical wastewater monitoring is to develop scientific understanding. Even if reliability and efficacy are established, limits on sample and data collection, use, and sharing must also be considered to prevent undermining privacy and autonomy in order to implement these public health strategies consistent with legal and ethical considerations.
  • Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID-19.

    Adams, Christopher D; Altshuler, Jerry; Barlow, Brooke L; Dixit, Deepali; Droege, Christopher A; Effendi, Muhammad K; Heavner, Mojdeh S; Johnston, Jackie P; Kiskaddon, Amy L; Lemieux, Diana G; et al. (Pharmacotherapy Publications Inc., 2020-10-17)
    Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short- and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.
  • A Case-Control Study of the 2019 Influenza Vaccine and Incidence of COVID-19 Among Healthcare Workers.

    Massoudi, Nilofar; Mohit, Babak (2020-11-26)
    Purpose: The influenza vaccine is essential in reducing the influenza burden, especially among healthcare workers (HCW). Experimental studies suggest both coronaviruses and influenza viruses engage with the angiotensin-converting enzyme 2 (ACE 2) and tetraspanin antibodies, and that ACE 2 tetraspanin antibodies in turn may inhibit both coronavirus and low-pathogenicity influenza A viruses (LP IAV) infections. This study aims to investigate the potential clinical association between receiving the 2019 influenza vaccine and the incidence of COVID-19 among HCW. Methods: We designed a case–control study within a hospital setting in Iran when it became a center for treating COVID-19 patients. We collected data and calculated relevant incidence and associative measures among HCW who had received the 2019 influenza vaccine as compared to HCW who had not received the vaccine. Results: Our total sample size was 261 HCW. Of 80 COVID-19 incident cases, three cases had received the influenza vaccine, while 87 of 181 controls had received the vaccine. The odds ratio (OR) and confidence interval (CI) of being vaccinated were 0.04 (95% CI: 0.01 to 0.14) among COVID-19 cases as compared to controls. Conclusions: Significant findings suggest that the 2019 influenza vaccine may have a protective association against COVID-19 among HCW.
  • Rapid, Ultrasensitive, and Quantitative Detection of SARS-CoV-2 Using Antisense Oligonucleotides Directed Electrochemical Biosensor Chip.

    Alafeef, Maha; Dighe, Ketan; Moitra, Parikshit; Pan, Dipanjan (American Chemical Society, 2020-10-20)
    A large-scale diagnosis of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is essential to downregulate its spread within as well as across communities and mitigate the current outbreak of the pandemic novel coronavirus disease 2019 (COVID-19). Herein, we report the development of a rapid (less than 5 min), low-cost, easy-to-implement, and quantitative paper-based electrochemical sensor chip to enable the digital detection of SARS-CoV-2 genetic material. The biosensor uses gold nanoparticles (AuNPs), capped with highly specific antisense oligonucleotides (ssDNA) targeting viral nucleocapsid phosphoprotein (N-gene). The sensing probes are immobilized on a paper-based electrochemical platform to yield a nucleic-acid-testing device with a readout that can be recorded with a simple hand-held reader. The biosensor chip has been tested using samples collected from Vero cells infected with SARS-CoV-2 virus and clinical samples. The sensor provides a significant improvement in output signal only in the presence of its target-SARS-CoV-2 RNA-within less than 5 min of incubation time, with a sensitivity of 231 (copies μL-1)-1 and limit of detection of 6.9 copies/μL without the need for any further amplification. The sensor chip performance has been tested using clinical samples from 22 COVID-19 positive patients and 26 healthy asymptomatic subjects confirmed using the FDA-approved RT-PCR COVID-19 diagnostic kit. The sensor successfully distinguishes the positive COVID-19 samples from the negative ones with almost 100% accuracy, sensitivity, and specificity and exhibits an insignificant change in output signal for the samples lacking a SARS-CoV-2 viral target segment (e.g., SARS-CoV, MERS-CoV, or negative COVID-19 samples collected from healthy subjects). The feasibility of the sensor even during the genomic mutation of the virus is also ensured from the design of the ssDNA-conjugated AuNPs that simultaneously target two separate regions of the same SARS-CoV-2 N-gene.
  • An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.

    Jackson, Lisa A; Anderson, Evan J; Rouphael, Nadine G; Roberts, Paul C; Makhene, Mamodikoe; Coler, Rhea N; McCullough, Michele P; Chappell, James D; Denison, Mark R; Stevens, Laura J; et al. (Massachusetts Medical Society, 2020-07-14)
    BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. METHODS We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. RESULTS After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events. CONCLUSIONS The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.
  • SARS-CoV-2 and nervous system: From pathogenesis to clinical manifestation.

    Keyhanian, Kiandokht; Umeton, Raffaella Pizzolato; Mohit, Babak; Davoudi, Vahid; Hajighasemi, Fatemeh; Ghasemi, Mehdi (Elsevier Ltd., 2020-11-07)
    Since the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a growing body of evidence indicates that besides common COVID-19 symptoms, patients may develop various neurological manifestations affecting both the central and peripheral nervous systems as well as skeletal muscles. These manifestations can occur prior, during and even after the onset of COVID-19 general symptoms. In this Review, we discuss the possible neuroimmunological mechanisms underlying the nervous system and skeletal muscle involvement, and viral triggered neuroimmunological conditions associated with SARS-CoV-2, as well as therapeutic approaches that have been considered for these specific complications worldwide
  • Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients

    Thomas, Tiffany; Stefanoni, Davide; Dzieciatkowska, Monika; Issaian, Aaron; Nemkov, Travis; Hill, Ryan C; Francis, Richard O; Hudson, Krystalyn E; Buehler, Paul W; Zimring, James C; et al. (American Chemical Society, 2020-10-26)
    The SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which is primarily characterized by shortness of breath, persistent dry cough, and fever. Because they transport oxygen, red blood cells (RBCs) may play a role in the severity of hypoxemia in COVID-19 patients. The present study combines state-of-the-art metabolomics, proteomics, and lipidomics approaches to investigate the impact of COVID-19 on RBCs from 23 healthy subjects and 29 molecularly diagnosed COVID-19 patients. RBCs from COVID-19 patients had increased levels of glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also observed, in particular, short- and medium-chain saturated fatty acids, acyl-carnitines, and sphingolipids. Nonetheless, there were no alterations of clinical hematological parameters, such as RBC count, hematocrit, or mean corpuscular hemoglobin concentration, with only minor increases in mean corpuscular volume. Taken together, these results suggest a significant impact of SARS-CoV-2 infection on RBC structural membrane homeostasis at the protein and lipid levels. Increases in RBC glycolytic metabolites are consistent with a theoretically improved capacity of hemoglobin to off-load oxygen as a function of allosteric modulation by high-energy phosphate compounds, perhaps to counteract COVID-19-induced hypoxia. Conversely, because the N-terminus of AE1 stabilizes deoxyhemoglobin and finely tunes oxygen off-loading and metabolic rewiring toward the hexose monophosphate shunt, RBCs from COVID-19 patients may be less capable of responding to environmental variations in hemoglobin oxygen saturation/oxidant stress when traveling from the lungs to peripheral capillaries and vice versa.
  • Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection

    Rathnasinghe, Raveen; Strohmeier, Shirin; Amanat, Fatima; Gillespie, Virginia L; Krammer, Florian; García-Sastre, Adolfo; Coughlan, Lynda; Schotsaert, Michael; Uccellini, Melissa B (Springer Nature, 2020-11-06)
    Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2) [1-3]. Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection. The K18-hACE2 model provides a stringent model for testing vaccines and antivirals, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.
  • Successful transfer of anti-SARS-CoV-2 immunity using convalescent plasma in an MM patient with hypogammaglobulinemia and COVID-19

    Luetkens, Tim; Metcalf, Ryan; Planelles, Vicente; Zheng, Yue; Larragoite, Erin T; Spivak, Emily S; Spivak, Adam M; Steinbach, Mary; Blaylock, Robert C; Avila, Stephanie V; et al. (American Society of Hematology, 2020-10-08)
  • Mobile device data reveal the dynamics in a positive relationship between human mobility and COVID-19 infections

    Xiong, Chenfeng; Hu, Songhua; Yang, Mofeng; Luo, Weiyu; Zhang, Lei (National Academy of Sciences, 2020-10-15)
    Accurately estimating human mobility and gauging its relationship with virus transmission is critical for the control of COVID-19 spreading. Using mobile device location data of over 100 million monthly active samples, we compute origin-destination travel demand and aggregate mobility inflow at each US county from March 1 to June 9, 2020. Then, we quantify the change of mobility inflow across the nation and statistically model the time-varying relationship between inflow and the infections. We find that external travel to other counties decreased by 35% soon after the nation entered the emergency situation, but recovered rapidly during the partial reopening phase. Moreover, our simultaneous equations analysis highlights the dynamics in a positive relationship between mobility inflow and the number of infections during the COVID-19 onset. This relationship is found to be increasingly stronger in partially reopened regions. Our study provides a quick reference and timely data availability for researchers and decision makers to understand the national mobility trends before and during the pandemic. The modeling results can be used to predict mobility and transmissions risks and integrated with epidemics models to further assess the public health outcomes.
  • NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge.

    Guebre-Xabier, Mimi; Patel, Nita; Tian, Jing-Hui; Zhou, Bin; Maciejewski, Sonia; Lam, Kristal; Portnoff, Alyse D; Massare, Michael J; Frieman, Matthew B; Piedra, Pedro A; et al. (Elsevier Ltd., 2020-10-23)
    There is an urgent need for a safe and protective vaccine to control the global spread of SARS-CoV-2 and prevent COVID-19. Here, we report the immunogenicity and protective efficacy of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length SARS-CoV-2 spike (S) glycoprotein stabilized in the prefusion conformation. Cynomolgus macaques (Macaca fascicularis) immunized with NVX-CoV2373 and the saponin-based Matrix-M™ adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. Following intranasal and intratracheal challenge with SARS-CoV-2, immunized macaques were protected against upper and lower infection and pulmonary disease. These results support ongoing phase 1/2 clinical studies of the safety and immunogenicity of NVX-CoV2327 vaccine (NCT04368988).
  • COVID-19: What do we know?

    Marshall, Steve; Duryea, Michael; Huang, Greg; Kadioglu, Onur; Mah, James; Palomo, Juan Martin; Rossouw, Emile; Stappert, Dina; Stewart, Kelton; Tufekci, Eser (Mosby Inc., 2020-09-21)

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