Shape-Based Separation of Micro-/Nanoparticles in Liquid Phases

The production of particles with shape-specific properties is reliant upon the separation of micro-/nanoparticles of particular shapes from particle mixtures of similar volumes. However, compared to a large number of size-based particle separation methods, shape-based separation methods have not been adequately explored. We review various up-to-date approaches to shape-based separation of rigid micro-/nanoparticles in liquid phases including size exclusion chromatography, field flow fractionation, deterministic lateral displacement, inertial focusing, electrophoresis, magnetophoresis, self-assembly precipitation, and centrifugation. We discuss separation mechanisms by classifying them as either changes in surface interactions or extensions of size-based separation. The latter includes geometric restrictions and shape-dependent transport properties

Dilepton and Photon Emission Rates from a Hadronic Gas

We analyze the dilepton and photon emission rates from a hadronic gas using chiral reduction formulas and a virial expansion. The emission rates are reduced to pertinent vacuum correlation functions, most of which can be assessed from experiment. Our results indicate that in the low mass region, the dilepton and photon rates are enhanced compared to most of the calculations using chiral Lagrangians. The enhancement is further increased through a finite pion chemical potential. An estimate of the emission rates is also made using Haag's expansion for the electromagnetic current. The relevance of these results to dilepton and photon emission rates in heavy-ion collisions is discussed.Comment: 7 pages, LaTeX using revTeX, 6 figures imbedded in text. Figures slightly changed, text left unchange

Non-equilibrium dynamics of a thermal plasma in a gravitational field

We introduce functional methods to study the non-equilibrium dynamics of a quantum massless scalar field at finite temperature in a gravitational field. We calculate the Close Time Path (CTP) effective action and, using its formal equivalence with the influence functional, derive the noise and dissipation kernels of the quantum open system in terms of quantities in thermodynamical equilibrium. Using this fact, we formally prove the existence of a Fluctuation-Dissipation Relation (FDR) at all temperatures between the quantum fluctuations of the plasma in thermal equilibrium and the energy dissipated by the external gravitational field. What is new is the identification of a stochastic source (noise) term arising from the quantum and thermal fluctuations in the plasma field, and the derivation of a Langevin-type equation which describes the non-equilibrium dynamics of the gravitational field influenced by the plasma. The back reaction of the plasma on the gravitational field is embodied in the FDR. From the CTP effective action the contribution of the quantum scalar field to the thermal graviton polarization tensor can also be derived and it is shown to agree with other techniques, most notably, Linear Response Theory (LRT). We show the connection between the LRT, which is applicable for near-equilibrium conditions and the functional methods used in this work which are useful for fully non-equilibrium conditions.Comment: Final version published in Phys. Rev.

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Search of the early O3 LIGO data for continuous gravitational waves from the Cassiopeia A and Vela Jr. supernova remnants

partially_open1412sìWe present directed searches for continuous gravitational waves from the neutron stars in the Cassiopeia A (Cas A) and Vela Jr. supernova remnants. We carry out the searches in the LIGO detector data from the first six months of the third Advanced LIGO and Virgo observing run using the weave semicoherent method, which sums matched-filter detection-statistic values over many time segments spanning the observation period. No gravitational wave signal is detected in the search band of 20–976 Hz for assumed source ages greater than 300 years for Cas A and greater than 700 years for Vela Jr. Estimates from simulated continuous wave signals indicate we achieve the most sensitive results to date across the explored parameter space volume, probing to strain magnitudes as low as ∼6.3×10^−26 for Cas A and ∼5.6×10^−26 for Vela Jr. at frequencies near 166 Hz at 95% efficiency.openAbbott, R.; Abbott, T. D.; Acernese, F.; Ackley, K.; Adams, C.; Adhikari, N.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agarwal, D.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Albanesi, S.; Allocca, A.; Altin, P. A.; Amato, A.; Anand, C.; Anand, S.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Andrade, T.; Andres, N.; Andrić, T.; Angelova, S. V.; Ansoldi, S.; Antelis, J. M.; Antier, S.; Appert, S.; Arai, K.; Araya, M. C.; Areeda, J. S.; Arène, M.; Arnaud, N.; Aronson, S. M.; Arun, K. G.; Asali, Y.; Ashton, G.; Assiduo, M.; Aston, S. M.; Astone, P.; Aubin, F.; Austin, C.; Babak, S.; Badaracco, F.; Bader, M. K. M.; Badger, C.; Bae, S.; Baer, A. M.; Bagnasco, S.; Bai, Y.; Baird, J.; Ball, M.; Ballardin, G.; Ballmer, S. W.; Balsamo, A.; Baltus, G.; Banagiri, S.; Bankar, D.; Barayoga, J. C.; Barbieri, C.; Barish, B. C.; Barker, D.; Barneo, P.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Bawaj, M.; Bayley, J. C.; Baylor, A. C.; Bazzan, M.; Bécsy, B.; Bedakihale, V. M.; Bejger, M.; Belahcene, I.; Benedetto, V.; Beniwal, D.; Bennett, T. F.; Bentley, J. D.; BenYaala, M.; Bergamin, F.; Berger, B. K.; Bernuzzi, S.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Beveridge, D.; Bhandare, R.; Bhardwaj, U.; Bhattacharjee, D.; Bhaumik, S.; Bilenko, I. A.; Billingsley, G.; Bini, S.; Birney, R.; Birnholtz, O.; Biscans, S.; Bischi, M.; Biscoveanu, S.; Bisht, A.; Biswas, B.; Bitossi, M.; Bizouard, M.-A.; Blackburn, J. K.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bobba, F.; Bode, N.; Boer, M.; Bogaert, G.; Boldrini, M.; Bonavena, L. D.; Bondu, F.; Bonilla, E.; Bonnand, R.; Booker, P.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, N.; Bose, S.; Bossilkov, V.; Boudart, V.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Bramley, A.; Branch, A.; Branchesi, M.; Brau, J. E.; Breschi, M.; Briant, T.; Briggs, J. H.; Brillet, A.; Brinkmann, M.; Brockill, P.; Brooks, A. F.; Brooks, J.; Brown, D. D.; Brunett, S.; Bruno, G.; Bruntz, R.; Bryant, J.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buscicchio, R.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Bustillo, J. Calderón; Callaghan, J. D.; Callister, T. A.; Calloni, E.; Cameron, J.; Camp, J. B.; Canepa, M.; Canevarolo, S.; Cannavacciuolo, M.; Cannon, K. C.; Cao, H.; Capote, E.; Carapella, G.; Carbognani, F.; Carlin, J. B.; Carney, M. F.; Carpinelli, M.; Carrillo, G.; Carullo, G.; Carver, T. L.; Diaz, J. Casanueva; Casentini, C.; Castaldi, G.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Ceasar, M.; Cella, G.; Cerdá-Durán, P.; Cesarini, E.; Chaibi, W.; Chakravarti, K.; Subrahmanya, S. Chalathadka; Champion, E.; Chan, C.-H.; Chan, C.; Chan, C. L.; Chan, K.; Chandra, K.; Chanial, P.; Chao, S.; Charlton, P.; Chase, E. A.; Chassande-Mottin, E.; Chatterjee, C.; Chatterjee, Debarati; Chatterjee, Deep; Chaturvedi, M.; Chaty, S.; Chen, H. Y.; Chen, J.; Chen, X.; Chen, Y.; Chen, Z.; Cheng, H.; Cheong, C. K.; Cheung, H. Y.; Chia, H. Y.; Chiadini, F.; Chiarini, G.; Chierici, R.; Chincarini, A.; Chiofalo, M. L.; Chiummo, A.; Cho, G.; Cho, H. S.; Choudhary, R. K.; Choudhary, S.; Christensen, N.; Chu, Q.; Chua, S.; Chung, K. W.; Ciani, G.; Ciecielag, P.; Cieślar, M.; Cifaldi, M.; Ciobanu, A. A.; Ciolfi, R.; Cipriano, F.; Cirone, A.; Clara, F.; Clark, E. N.; Clark, J. A.; Clarke, L.; Clearwater, P.; Clesse, S.; Cleva, F.; Coccia, E.; Codazzo, E.; Cohadon, P.-F.; Cohen, D. E.; Cohen, L.; Colleoni, M.; Collette, C. G.; Colombo, A.; Colpi, M.; Compton, C. M.; Constancio, M.; Conti, L.; Cooper, S. J.; Corban, P.; Corbitt, T. R.; Cordero-Carrión, I.; Corezzi, S.; Corley, K. R.; Cornish, N.; Corre, D.; Corsi, A.; Cortese, S.; Costa, C. A.; Cotesta, R.; Coughlin, M. W.; Coulon, J.-P.; Countryman, S. T.; Cousins, B.; Couvares, P.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Creighton, J. D. E.; Creighton, T. D.; Criswell, A. W.; Croquette, M.; Crowder, S. G.; Cudell, J. R.; Cullen, T. J.; Cumming, A.; Cummings, R.; Cunningham, L.; Cuoco, E.; Curyło, M.; Dabadie, P.; Canton, T. Dal; Dall’Osso, S.; Dálya, G.; Dana, A.; DaneshgaranBajastani, L. M.; D’Angelo, B.; Danilishin, S.; D’Antonio, S.; Danzmann, K.; Darsow-Fromm, C.; Dasgupta, A.; Datrier, L. E. H.; Datta, S.; Dattilo, V.; Dave, I.; Davier, M.; Davies, G. S.; Davis, D.; Davis, M. C.; Daw, E. J.; Dean, R.; DeBra, D.; Deenadayalan, M.; Degallaix, J.; De Laurentis, M.; Deléglise, S.; Del Favero, V.; De Lillo, F.; De Lillo, N.; Del Pozzo, W.; DeMarchi, L. M.; De Matteis, F.; D’Emilio, V.; Demos, N.; Dent, T.; Depasse, A.; De Pietri, R.; De Rosa, R.; De Rossi, C.; DeSalvo, R.; De Simone, R.; Dhurandhar, S.; Díaz, M. C.; Diaz-Ortiz, M.; Didio, N. A.; Dietrich, T.; Di Fiore, L.; Di Fronzo, C.; Di Giorgio, C.; Di Giovanni, F.; Di Giovanni, M.; Di Girolamo, T.; Di Lieto, A.; Ding, B.; Di Pace, S.; Di Palma, I.; Di Renzo, F.; Divakarla, A. K.; Dmitriev, A.; Doctor, Z.; D’Onofrio, L.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Drago, M.; Driggers, J. C.; Drori, Y.; Ducoin, J.-G.; Dupej, P.; Durante, O.; D’Urso, D.; Duverne, P.-A.; Dwyer, S. E.; Eassa, C.; Easter, P. J.; Ebersold, M.; Eckhardt, T.; Eddolls, G.; Edelman, B.; Edo, T. B.; Edy, O.; Effler, A.; Eichholz, J.; Eikenberry, S. S.; Eisenmann, M.; Eisenstein, R. A.; Ejlli, A.; Engelby, E.; Errico, L.; Essick, R. C.; Estellés, H.; Estevez, D.; Etienne, Z.; Etzel, T.; Evans, M.; Evans, T. M.; Ewing, B. E.; Fafone, V.; Fair, H.; Fairhurst, S.; Farah, A. M.; Farinon, S.; Farr, B.; Farr, W. M.; Farrow, N. W.; Fauchon-Jones, E. J.; Favaro, G.; Favata, M.; Fays, M.; Fazio, M.; Feicht, J.; Fejer, M. M.; Fenyvesi, E.; Ferguson, D. L.; Fernandez-Galiana, A.; Ferrante, I.; Ferreira, T. A.; Fidecaro, F.; Figura, P.; Fiori, I.; Fishbach, M.; Fisher, R. P.; Fittipaldi, R.; Fiumara, V.; Flaminio, R.; Floden, E.; Fong, H.; Font, J. A.; Fornal, B.; Forsyth, P. W. F.; Franke, A.; Frasca, S.; Frasconi, F.; Frederick, C.; Freed, J. P.; Frei, Z.; Freise, A.; Frey, R.; Fritschel, P.; Frolov, V. V.; Fronzé, G. G.; Fulda, P.; Fyffe, M.; Gabbard, H. A.; Gadre, B. U.; Gair, J. R.; Gais, J.; Galaudage, S.; Gamba, R.; Ganapathy, D.; Ganguly, A.; Gaonkar, S. G.; Garaventa, B.; García-Núñez, C.; García-Quirós, C.; Garufi, F.; Gateley, B.; Gaudio, S.; Gayathri, V.; Gemme, G.; Gennai, A.; George, J.; Gerberding, O.; Gergely, L.; Gewecke, P.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, Shaon; Ghosh, Shrobana; Giacomazzo, B.; Giacoppo, L.; Giaime, J. A.; Giardina, K. D.; Gibson, D. R.; Gier, C.; Giesler, M.; Giri, P.; Gissi, F.; Glanzer, J.; Gleckl, A. E.; Godwin, P.; Goetz, E.; Goetz, R.; Gohlke, N.; Goncharov, B.; González, G.; Gopakumar, A.; Gosselin, M.; Gouaty, R.; Gould, D. W.; Grace, B.; Grado, A.; Granata, M.; Granata, V.; Grant, A.; Gras, S.; Grassia, P.; Gray, C.; Gray, R.; Greco, G.; Green, A. C.; Green, R.; Gretarsson, A. M.; Gretarsson, E. M.; Griffith, D.; Griffiths, W.; Griggs, H. L.; Grignani, G.; Grimaldi, A.; Grimm, S. J.; Grote, H.; Grunewald, S.; Gruning, P.; Guerra, D.; Guidi, Gianluca; Guimaraes, A. R.; Guixé, G.; Gulati, H. K.; Guo, H.-K.; Guo, Y.; Gupta, Anchal; Gupta, Anuradha; Gupta, P.; Gustafson, E. K.; Gustafson, R.; Guzman, F.; Haegel, L.; Halim, O.; Hall, E. D.; Hamilton, E. Z.; Hammond, G.; Haney, M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hannuksela, O.; Hansen, H.; Hansen, T. J.; Hanson, J.; Harder, T.; Hardwick, T.; Haris, K.; Harms, J.; Harry, G. M.; Harry, I. W.; Hartwig, D.; Haskell, B.; Hasskew, R. K.; Haster, C.-J.; Haughian, K.; Hayes, F. J.; Healy, J.; Heidmann, A.; Heidt, A.; Heintze, M. C.; Heinze, J.; Heinzel, J.; Heitmann, H.; Hellman, F.; Hello, P.; Helmling-Cornell, A. F.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennes, E.; Hennig, J.; Hennig, M. H.; Hernandez, A. G.; Vivanco, F. Hernandez; Heurs, M.; Hild, S.; Hill, P.; Hines, A. S.; Hochheim, S.; Hofman, D.; Hohmann, J. N.; Holcomb, D. G.; Holland, N. A.; Hollows, I. J.; Holmes, Z. J.; Holt, K.; Holz, D. E.; Hopkins, P.; Hough, J.; Hourihane, S.; Howell, E. J.; Hoy, C. G.; Hoyland, D.; Hreibi, A.; Hsu, Y.; Huang, Y.; Hübner, M. T.; Huddart, A. D.; Hughey, B.; Hui, V.; Husa, S.; Huttner, S. H.; Huxford, R.; Huynh-Dinh, T.; Idzkowski, B.; Iess, A.; Ingram, C.; Isi, M.; Isleif, K.; Iyer, B. R.; JaberianHamedan, V.; Jacqmin, T.; Jadhav, S. J.; Jadhav, S. P.; James, A. L.; Jan, A. Z.; Jani, K.; Janquart, J.; Janssens, K.; Janthalur, N. N.; Jaranowski, P.; Jariwala, D.; Jaume, R.; Jenkins, A. C.; Jenner, K.; Jeunon, M.; Jia, W.; Johns, G. R.; Jones, A. W.; Jones, D. I.; Jones, J. D.; Jones, P.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Juste, V.; Kalaghatgi, C. V.; Kalogera, V.; Kamai, B.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kao, Y.; Kapadia, S. J.; Kapasi, D. P.; Karat, S.; Karathanasis, C.; Karki, S.; Kashyap, R.; Kasprzack, M.; Kastaun, W.; Katsanevas, S.; Katsavounidis, E.; Katzman, W.; Kaur, T.; Kawabe, K.; Kéfélian, F.; Keitel, D.; Key, J. S.; Khadka, S.; Khalili, F. Y.; Khan, S.; Khazanov, E. A.; Khetan, N.; Khursheed, M.; Kijbunchoo, N.; Kim, C.; Kim, J. C.; Kim, K.; Kim, W. S.; Kim, Y.-M.; Kimball, C.; Kinley-Hanlon, M.; Kirchhoff, R.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Knee, A. M.; Knowles, T. D.; Knyazev, E.; Koch, P.; Koekoek, G.; Koley, S.; Kolitsidou, P.; Kolstein, M.; Komori, K.; Kondrashov, V.; Kontos, A.; Koper, N.; Korobko, M.; Kovalam, M.; Kozak, D. B.; Kringel, V.; Krishnendu, N. V.; Królak, A.; Kuehn, G.; Kuei, F.; Kuijer, P.; Kumar, A.; Kumar, P.; Kumar, Rahul; Kumar, Rakesh; Kuns, K.; Kuwahara, S.; Lagabbe, P.; Laghi, D.; Lalande, E.; Lam, T. L.; Lamberts, A.; Landry, M.; Lane, B. B.; Lang, R. N.; Lange, J.; Lantz, B.; La Rosa, I.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lecoeuche, Y. K.; Lee, H. M.; Lee, H. W.; Lee, J.; Lee, K.; Lehmann, J.; Lemaître, A.; Leroy, N.; Letendre, N.; Levesque, C.; Levin, Y.; Leviton, J. N.; Leyde, K.; Li, A. K. Y.; Li, B.; Li, J.; Li, T. G. F.; Li, X.; Linde, F.; Linker, S. D.; Linley, J. N.; Littenberg, T. B.; Liu, J.; Liu, K.; Liu, X.; Llamas, F.; Llorens-Monteagudo, M.; Lo, R. K. L.; Lockwood, A.; London, L. T.; Longo, A.; Lopez, D.; Portilla, M. Lopez; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lott, T. P.; Lough, J. D.; Lousto, C. O.; Lovelace, G.; Lucaccioni, J. F.; Lück, H.; Lumaca, D.; Lundgren, A. P.; Lynam, J. E.; Macas, R.; MacInnis, M.; Macleod, D. M.; MacMillan, I. A. O.; Macquet, A.; Hernandez, I. Magaña; Magazzù, C.; Magee, R. M.; Maggiore, R.; Magnozzi, M.; Mahesh, S.; Majorana, E.; Makarem, C.; Maksimovic, I.; Maliakal, S.; Malik, A.; Man, N.; Mandic, V.; Mangano, V.; Mango, J. L.; Mansell, G. L.; Manske, M.; Mantovani, M.; Mapelli, M.; Marchesoni, F.; Marion, F.; Mark, Z.; Márka, S.; Márka, Z.; Markakis, C.; Markosyan, A. S.; Markowitz, A.; Maros, E.; Marquina, A.; Marsat, S.; Martelli, F.; Martin, I. W.; Martin, R. M.; Martinez, M.; Martinez, V. A.; Martinez, V.; Martinovic, K.; Martynov, D. V.; Marx, E. J.; Masalehdan, H.; Mason, K.; Massera, E.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matas, A.; Mateu-Lucena, M.; Matichard, F.; Matiushechkina, M.; Mavalvala, N.; McCann, J. J.; McCarthy, R.; McClelland, D. E.; McClincy, P. K.; McCormick, S.; McCuller, L.; McGhee, G. I.; McGuire, S. C.; McIsaac, C.; McIver, J.; McRae, T.; McWilliams, S. T.; Meacher, D.; Mehmet, M.; Mehta, A. K.; Meijer, Q.; Melatos, A.; Melchor, D. A.; Mendell, G.; Menendez-Vazquez, A.; Menoni, C. S.; Mercer, R. A.; Mereni, L.; Merfeld, K.; Merilh, E. L.; Merritt, J. D.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Meyers, P. M.; Meylahn, F.; Mhaske, A.; Miani, A.; Miao, H.; Michaloliakos, I.; Michel, C.; Middleton, H.; Milano, L.; Miller, A.; Miller, A. L.; Miller, B.; Millhouse, M.; Mills, J. C.; Milotti, E.; Minazzoli, O.; Minenkov, Y.; Mir, Ll. M.; Miravet-Tenés, M.; Mishra, C.; Mishra, T.; Mistry, T.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Mo, Geoffrey; Moguel, E.; Mogushi, K.; Mohapatra, S. R. P.; Mohite, S. R.; Molina, I.; Molina-Ruiz, M.; Mondin, M.; Montani, M.; Moore, C. J.; Moraru, D.; Morawski, F.; More, A.; Moreno, C.; Moreno, G.; Morisaki, S.; Mours, B.; Mow-Lowry, C. M.; Mozzon, S.; Muciaccia, F.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, Soma; Mukherjee, Subroto; Mukherjee, Suvodip; Mukund, N.; Mullavey, A.; Munch, J.; Muñiz, E. A.; Murray, P. G.; Musenich, R.; Muusse, S.; Nadji, S. L.; Nagar, A.; Napolano, V.; Nardecchia, I.; Naticchioni, L.; Nayak, B.; Nayak, R. K.; Neil, B. F.; Neilson, J.; Nelemans, G.; Nelson, T. J. N.; Nery, M.; Neubauer, P.; Neunzert, A.; Ng, K. Y.; Ng, S. W. S.; Nguyen, C.; Nguyen, P.; Nguyen, T.; Nichols, S. A.; Nissanke, S.; Nitoglia, E.; Nocera, F.; Norman, M.; North, C.; Nuttall, L. K.; Oberling, J.; O’Brien, B. D.; O’Dell, J.; Oelker, E.; Oganesyan, G.; Oh, J. J.; Oh, S. H.; Ohme, F.; Ohta, H.; Okada, M. A.; Olivetto, C.; Oram, R.; O’Reilly, B.; Ormiston, R. G.; Ormsby, N. D.; Ortega, L. F.; O’Shaughnessy, R.; O’Shea, E.; Ossokine, S.; Osthelder, C.; Ottaway, D. J.; Overmier, H.; Pace, A. E.; Pagano, G.; Page, M. A.; Pagliaroli, G.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pan, H.; Panda, P. K.; Pang, P. T. H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Panther, F. H.; Paoletti, F.; Paoli, A.; Paolone, A.; Park, H.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patel, M.; Pathak, M.; Patricelli, B.; Patron, A. S.; Paul, S.; Payne, E.; 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The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice