Role of targeted therapies in rheumatic patients on COVID-19 outcomes: Results from the COVIDSER study

Objectives To analyse the effect of targeted therapies, either biological (b) disease-modifying antirheumatic drugs (DMARDs), targeted synthetic (ts) DMARDs and other factors (demographics, comorbidities or COVID-19 symptoms) on the risk of COVID-19 related hospitalisation in patients with inflammatory rheumatic diseases. Methods The COVIDSER study is an observational cohort including 7782 patients with inflammatory rheumatic diseases. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Antirheumatic medication taken immediately prior to infection, demographic characteristics, rheumatic disease diagnosis, comorbidities and COVID-19 symptoms were analysed. Results A total of 426 cases of symptomatic COVID-19 from 1 March 2020 to 13 April 2021 were included in the analyses: 106 (24.9%) were hospitalised and 19 (4.4%) died. In multivariate-adjusted models, bDMARDs and tsDMARDs in combination were not associated with hospitalisation compared with conventional synthetic DMARDs (OR 0.55, 95% CI 0.24 to 1.25 of b/tsDMARDs, p=0.15). Tumour necrosis factor inhibitors (TNF-i) were associated with a reduced likelihood of hospitalisation (OR 0.32, 95% CI 0.12 to 0.82, p=0.018), whereas rituximab showed a tendency to an increased risk of hospitalisation (OR 4.85, 95% CI 0.86 to 27.2). Glucocorticoid use was not associated with hospitalisation (OR 1.69, 95% CI 0.81 to 3.55). A mix of sociodemographic factors, comorbidities and COVID-19 symptoms contribute to patients'' hospitalisation. Conclusions The use of targeted therapies as a group is not associated with COVID-19 severity, except for rituximab, which shows a trend towards an increased risk of hospitalisation, while TNF-i was associated with decreased odds of hospitalisation in patients with rheumatic disease. Other factors like age, male gender, comorbidities and COVID-19 symptoms do play a role.

Search for dark matter produced in association with a hadronically decaying vector boson in pp collisions at sqrt (s) = 13 TeV with the ATLAS detector

A search is presented for dark matter produced in association with a hadronically decaying W or Z boson using 3.2 fb−1 of pp collisions at View the MathML sources=13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet compatible with a W or Z boson and with large missing transverse momentum are analysed. The data are consistent with the Standard Model predictions and are interpreted in terms of both an effective field theory and a simplified model containing dark matter

First measurement of Ωc0 production in pp collisions at s=13 TeV

The inclusive production of the charm–strange baryon 0 c is measured for the first time via its hadronic √ decay into −π+ at midrapidity (|y| <0.5) in proton–proton (pp) collisions at the centre-of-mass energy s =13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 < pT < 12 GeV/c. The pT dependence of the 0 c-baryon production relative to the prompt D0-meson and to the prompt 0 c-baryon production is compared to various models that take different hadronisation mechanisms into consideration. In the measured pT interval, the ratio of the pT-integrated cross sections of 0 c and prompt + c baryons multiplied by the −π+ branching ratio is found to be larger by a factor of about 20 with a significance of about 4σ when compared to e+e− collisions

Elliptic flow of charged particles at midrapidity relative to the spectator plane in Pb–Pb and Xe–Xe collisions

Measurements of the elliptic flow coefficient relative to the collision plane defined by the spectator neutrons v2{ SP} in collisions of Pb ions at center-of-mass energy per nucleon–nucleon pair √ 2.76 TeV and Xe ions at √ sNN = sNN =5.44 TeV are reported. The results are presented for charged particles produced at midrapidity as a function of centrality and transverse momentum for the 5–70% and 0.2–6 GeV/c ranges, respectively. The ratio between v2{ SP} and the elliptic flow coefficient relative to the participant plane v2{4}, estimated using four-particle correlations, deviates by up to 20% from unity depending on centrality. This observation differs strongly from the magnitude of the corresponding eccentricity ratios predicted by the TRENTo and the elliptic power models of initial state fluctuations that are tuned to describe the participant plane anisotropies. The differences can be interpreted as a decorrelation of the neutron spectator plane and the reaction plane because of fragmentation of the remnants from the colliding nuclei, which points to an incompleteness of current models describing the initial state fluctuations. A significant transverse momentum dependence of the ratio v2{ SP}/v2{4} is observed in all but the most central collisions, which may help to understand whether momentum anisotropies at low and intermediate transverse momentum have a common origin in initial state f luctuations. The ratios of v2{ SP} and v2{4} to the corresponding initial state eccentricities for Xe–Xe and Pb–Pb collisions at similar initial entropy density show a difference of (7.0 ±0.9)%with an additional variation of +1.8% when including RHIC data in the TRENTo parameter extraction. These observations provide new experimental constraints for viscous effects in the hydrodynamic modeling of the expanding quark–gluon plasma produced in heavy-ion collisions at the LHC

J/psi production as a function of charged-particle pseudorapidity density in p-Pb collisions at root s(NN)=5.02 TeV

We report measurements of the inclusive J/ψ yield and average transverse momentum as a function of charged-particle pseudorapidity density dNch/dη in p–Pb collisions at sNN=5.02TeV with ALICE at the LHC. The observables are normalised to their corresponding averages in non-single diffractive events. An increase of the normalised J/ψ yield with normalised dNch/dη, measured at mid-rapidity, is observed at mid-rapidity and backward rapidity. At forward rapidity, a saturation of the relative yield is observed for high charged-particle multiplicities. The normalised average transverse momentum at forward and backward rapidities increases with multiplicity at low multiplicities and saturates beyond moderate multiplicities. In addition, the forward-to-backward nuclear modification factor ratio is also reported, showing an increasing suppression of J/ψ production at forward rapidity with respect to backward rapidity for increasing charged-particle multiplicity

Multiplicity dependence of (anti-)deuteron production in pp collisions at root s=7 TeV

none1019siIn this letter, the production of deuterons and anti-deuterons in pp collisions at root s = 7 TeV is studied as a function of the charged-particle multiplicity density at mid-rapidity with the ALICE detector at the LHC. Production yields are measured at mid-rapidity in five multiplicity classes and as a function of the deuteron transverse momentum (p(T)). The measurements are discussed in the context of hadron-coalescence models. The coalescence parameter B-2, extracted from the measured spectra of (anti-)deuteronsand primary (anti-)protons, exhibits no significant p(T)-dependence for p(T) < 3 GeV/c, in agreement with the expectations of a simple coalescence picture. At fixed transverse momentum per nucleon, the B-2 parameter is found to decrease smoothly from low multiplicity pp to Pb-Pb collisions, in qualitative agreement with more elaborate coalescence models. The measured mean transverse momentum of (anti-)deuterons in pp is not reproduced by the Blast-Wave model calculations that simultaneously describe pion, kaon and proton spectra, in contrast to central Pb-Pb collisions. The ratio between the p(T)-integrated yield of deuterons to protons, d/p, is found to increase with the charged-particle multiplicity, as observed in inelastic pp collisions at different centre-of-mass energies. The d/p ratios are reported in a wide range, from the lowest to the highest multiplicity values measured in pp collisions at the LHC. (C) 2019 The Author(s). Published by Elsevier B.VnoneAcharya, S.; Acosta, F. T.; Adamova, D.; Adhya, S. P.; Adler, A.; Adolfsson, J.; Aggarwal, M. M.; Rinella, G. Aglieri; Agnello, M.; Ahammed, Z.; Ahmad, S.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Al-Turany, M.; Alam, S. N.; Albuquerque, D. S. D.; Aleksandrov, D.; Alessandro, B.; Alfanda, H. M.; Alfaro Molina, R.; Ali, B.; Ali, Y.; Alici, A.; Alkin, A.; Alme, J.; Alt, T.; Altenkamper, L.; Altsybeev, I; Anaam, M. N.; Andrei, C.; Andreou, D.; Andrews, H. A.; Andronic, A.; Angeletti, M.; Anguelov, V; Anson, C.; Anticic, T.; Antinori, F.; Antonioli, P.; Anwar, R.; Apadula, N.; Aphecetche, L.; Appelshaeuser, H.; Arcelli, S.; Arnaldi, R.; Arratia, M.; Arsene, I. C.; Arslandok, M.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badala, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Baldisseri, A.; Ball, M.; Baral, R. C.; Barbera, R.; Barioglio, L.; Barnafoldi, G. G.; Barnby, L. S.; Barret, V; Bartalini, P.; Barth, K.; Bartsch, E.; Bastid, N.; Basu, S.; Batigne, G.; Batyunya, B.; Batzing, P. C.; Bauri, D.; Bazo Alba, J. L.; Bearden, I. G.; Bedda, C.; Behera, N. K.; Belikov, I; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Beltran, L. G. E.; Belyaev, V; Bencedi, G.; Beole, S.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhatt, H.; Bhattacharjee, B.; Bianchi, A.; Bianchi, L.; Bianchi, N.; Bielcik, J.; Bielcikova, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Blair, J. T.; Blau, D.; Blume, C.; Boca, G.; Bock, F.; Bogdanov, A.; Boldizsar, L.; Bolozdynya, A.; Bombara, M.; Bonomi, G.; Bonora, M.; Borel, H.; Borissov, A.; Borri, M.; Botta, E.; Bourjau, C.; Bratrud, L.; Braun-Munzinger, P.; Bregant, M.; Broker, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Buckland, M. D.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buhler, P.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Caffarri, D.; Caines, H.; Caliva, A.; Calvo Villar, E.; Camacho, R. S.; Camerini, P.; Capon, A. A.; Carnesecchi, F.; Castellanos, J. Castillo; Castro, A. J.; Casula, E. A. R.; Sanchez, C. Ceballos; Chakraborty, P.; Chandra, S.; Chang, B.; Chang, W.; Chapeland, S.; Chartier, M.; Chattopadhyay, S.; Chauvin, A.; Cheshkov, C.; Cheynis, B.; Barroso, V. Chibante; Chinellato, D. D.; Cho, S.; Chochula, P.; Chowdhury, T.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Concas, M.; Balbastre, G. Conesa; del Valle, Z. Conesa; Contin, G.; Contreras, J. G.; Cormier, T. M.; Morales, Y. Corrales; Cortese, P.; Cosentino, M. R.; Costa, F.; Costanza, S.; Crkovska, J.; Crochet, P.; Cuautle, E.; Cunqueiro, L.; Dabrowski, D.; Dahms, T.; Dainese, A.; Damas, F. P. A.; Dani, S.; Danisch, M. C.; Danu, A.; Das, D.; Das, I; Das, S.; Dash, A.; Dash, S.; Dashi, A.; De, S.; De Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; De Souza, R. D.; Degenhardt, H. F.; Deisting, A.; Deloff, A.; Delsanto, S.; Dhankher, P.; Di Bari, D.; Di Mauro, A.; Diaz, R. A.; Dietel, T.; Dillenseger, P.; Ding, Y.; Divia, R.; Djuvsland, O.; Dobrin, A.; Domenicis Gimenez, D.; Doenigus, B.; Dordic, O.; Dubey, A. K.; Dubla, A.; Dudi, S.; Duggal, A. K.; Dukhishyam, M.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Engel, H.; Epple, E.; Erazmus, B.; Erhardt, F.; Erokhin, A.; Ersdal, M. R.; Espagnon, B.; Eulisse, G.; Eum, J.; Evans, D.; Evdokimov, S.; Fabbietti, L.; Faggin, M.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Fernandez Tellez, A.; Ferrero, A.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiorenza, G.; Flor, F.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francisco, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Girard, M. Fusco; Gaardhoje, J. J.; Gagliardi, M.; Gago, A. M.; Gajdosova, K.; Galvan, C. D.; Ganoti, P.; Garabatos, C.; Garcia-Solis, E.; Garg, K.; Gargiulo, C.; Garner, K.; Gasik, P.; Gauger, E. F.; Gay Ducati, M. B.; Germain, M.; Ghosh, J.; Ghosh, P.; Ghosh, S. K.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Glaessel, P.; Gomez Coral, D. M.; Ramirez, A. Gomez; Gonzalez, V; Gonzalez-Zamora, P.; Gorbunov, S.; Gorlich, L.; Gotovac, S.; Grabski, V; Graczykowski, L. K.; Graham, K. L.; Greiner, L.; Grelli, A.; Grigoras, C.; Grigoriev, V; Grigoryan, A.; Grigoryan, S.; Gronefeld, J. M.; Grosa, F.; Grosse-Oetringhaus, J. F.; Grosso, R.; Guernane, R.; Guerzoni, B.; Guittiere, M.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Gupta, R.; Guzman, I. B.; Haake, R.; Habib, M. K.; Hadjidakis, C.; Hamagaki, H.; Hamar, G.; Hamid, M.; Hamon, J. C.; Hannigan, R.; Haque, M. R.; Harlenderova, A.; Harris, J. W.; Harton, A.; Hassan, H.; Hatzifotiadou, D.; Hauer, P.; Hayashi, S.; Heckel, S. T.; Hellbaer, E.; Helstrup, H.; Herghelegiu, A.; Hernandez, E. G.; Herrera Corral, G.; Herrmann, F.; Hetland, K. F.; Hilden, T. E.; Hillemanns, H.; Hills, C.; Hippolyte, B.; Hohlweger, B.; Horak, D.; Hornung, S.; Hosokawa, R.; Hota, J.; Hristov, P.; Huang, C.; Hughes, C.; Huhn, P.; Humanic, T. J.; Hushnud, H.; Husova, L. A.; Hussain, N.; Hussain, T.; Hutter, D.; Hwang, D. S.; Iddon, J. P.; Ilkaev, R.; Inaba, M.; Ippolitov, M.; Islam, M. S.; Ivanov, M.; Ivanov, V; Izucheev, V; Jacak, B.; Jacazio, N.; Jacobs, P. M.; Jadhav, M. B.; Jadlovska, S.; Jadlovsky, J.; Jaelani, S.; Jahnke, C.; Jakubowska, M. J.; Janik, M. A.; Jercic, M.; Jevons, O.; Bustamante, R. T. Jimenez; Jin, M.; Jones, P. G.; Jusko, A.; Kalinak, P.; Kalweit, A.; Kang, J. H.; Kaplin, V; Kar, S.; Uysal, A. Karasu; Karavichev, O.; Karavicheva, T.; Karczmarczyk, P.; Karpechev, E.; Kebschull, U.; Keidel, R.; Keil, M.; Ketzer, B.; Khabanova, Z.; Khan, A. M.; Khan, S.; Khan, S. A.; Khanzadeev, A.; Kharlov, Y.; Khatun, A.; Khuntia, A.; Kielbowicz, M. M.; Kileng, B.; Kim, B.; Kim, D.; Kim, D. J.; Kim, E. J.; Kim, H.; Kim, J. S.; Kim, J.; Kim, M.; Kim, S.; Kim, T.; Kindra, K.; Kirsch, S.; Kisel, I; Kiselev, S.; Kisiel, A.; Klay, J. L.; Klein, C.; Klein, J.; Klein, S.; Klein-Boesing, C.; Klewin, S.; Kluge, A.; Knichel, M. L.; Knospe, A. G.; Kobdaj, C.; Kofarago, M.; Koehler, M. K.; Kollegger, T.; Kondratyeva, N.; Kondratyuk, E.; Konopka, P. J.; Konyushikhin, M.; Koska, L.; Kovalenko, O.; Kovalenko, V; Kowalski, M.; Kralik, I; Kravcakova, A.; Kreis, L.; Krivda, M.; Krizek, F.; Krueger, M.; Kryshen, E.; Krzewicki, M.; Kubera, A. M.; Kucera, V; Kuhn, C.; Kuijer, P. G.; Kumar, L.; Kumar, S.; Kundu, S.; Kurashvili, P.; Kurepin, A.; Kurepin, A. B.; Kushpil, S.; Kvapil, J.; Kweon, M. J.; Kwon, Y.; La Pointe, S. L.; La Rocca, P.; Lai, Y. S.; Langoy, R.; Lapidus, K.; Lardeux, A.; Larionov, P.; Laudi, E.; Lavicka, R.; Lazareva, T.; Lea, R.; Leardini, L.; Lee, S.; Lehas, F.; Lehner, S.; Lehrbach, J.; Lemmon, R. C.; Leon Monzon, I; Levai, P.; Li, X.; Li, X. L.; Lien, J.; Lietava, R.; Lim, B.; Lindal, S.; Lindenstruth, V; Lindsay, S. W.; Lippmann, C.; Lisa, M. A.; Litichevskyi, V; Liu, A.; Ljunggren, H. M.; Llope, W. J.; Lodato, D. F.; Loginov, V; Loizides, C.; Loncar, P.; Lopez, X.; Lopez Torres, E.; Luettig, P.; Luhder, J. R.; Lunardon, M.; Luparello, G.; Lupi, M.; Maevskaya, A.; Mager, M.; Mahmood, S. M.; Mahmoud, T.; Maire, A.; Majka, R. D.; Malaev, M.; Malik, Q. W.; Malinina, L.; Mal'Kevich, D.; Malzacher, P.; Mamonov, A.; Manko, V; Manso, F.; Manzari, V; Mao, Y.; Marchisone, M.; Mares, J.; Margagliotti, G., V; Margotti, A.; Margutti, J.; Marin, A.; Markert, C.; Marquard, M.; Martin, N. A.; Martinengo, P.; Martinez, J. L.; Martinez, M., I; Garcia, G. Martinez; Pedreira, M. Martinez; Masciocchi, S.; Masera, M.; Masoni, A.; Massacrier, L.; Masson, E.; Mastroserio, A.; Mathis, A. M.; Matuoka, P. F. T.; Matyja, A.; Mayer, C.; Mazzilli, M.; Mazzoni, M. A.; Meddi, F.; Melikyan, Y.; Menchaca-Rocha, A.; Meninno, E.; Meres, M.; Mhlanga, S.; Miake, Y.; Micheletti, L.; Mieskolainen, M. M.; Mihaylov, D. L.; Mikhaylov, K.; Mischke, A.; Mishra, A. N.; Miskowiec, D.; Mitra, J.; Mitu, C. M.; Mohammadi, N.; Mohanty, A. P.; Mohanty, B.; Khan, M. Mohisin; Mondal, M. M.; Mordasini, C.; De Godoy, D. A. Moreira; Moreno, L. A. P.; Moretto, S.; Morreale, A.; Morsch, A.; Mrnjavac, T.; Muccifora, V; Mudnic, E.; Muehlheim, D.; Muhuri, S.; Mukherjee, M.; Mulligan, J. D.; Munhoz, M. G.; Muenning, K.; Munzer, R. H.; Murakami, H.; Murray, S.; Musa, L.; Musinsky, J.; Myers, C. J.; Myrcha, J. W.; Naik, B.; Nair, R.; Nandi, B. K.; Nania, R.; Nappi, E.; Naru, M. U.; Nassirpour, A. F.; Natal da Luz, H.; Nattrass, C.; Navarro, S. R.; Nayak, K.; Nayak, R.; Nayak, T. K.; Nazarenko, S.; De Oliveira, R. A. Negrao; Nellen, L.; Nesbo, S., V; Neskovic, G.; Ng, F.; Nielsen, B. S.; Nikolaev, S.; Nikulin, S.; Nikulin, V; Noferini, F.; Nomokonov, P.; Nooren, G.; Noris, J. C. C.; Norman, J.; Nyanin, A.; Nystrand, J.; Ogino, M.; Ohlson, A.; Oleniacz, J.; Oliveira Da Silva, A. C.; Oliver, M. H.; Onderwaater, J.; Oppedisano, C.; Orava, R.; Ortiz Velasquez, A.; Oskarsson, A.; Otwinowski, J.; Oyama, K.; Pachmayer, Y.; Pacik, V; Pagano, D.; Paic, G.; Palni, P.; Pan, J.; Pandey, A. K.; Panebianco, S.; Papikyan, V; Pareek, P.; Park, J.; Parkkila, J. E.; Parmar, S.; Passfeld, A.; Pathak, S. P.; Patra, R. N.; Paul, B.; Pei, H.; Peitzmann, T.; Peng, X.; Pereira, L. G.; Da Costa, H. Pereira; Peresunko, D.; Perez, G. M.; Lezama, E. Perez; Peskov, V; Pestov, Y.; Petracek, V; Petrovici, M.; Pezzi, R. P.; Piano, S.; Pikna, M.; Pillot, P.; Pimentel, L. O. D. L.; Pinazza, O.; Pinsky, L.; Pisano, S.; Piyarathna, D. B.; Ploskon, M.; Planinic, M.; Pliquett, F.; Pluta, J.; Pochybova, S.; Podesta-Lerma, P. L. M.; Poghosyan, M. G.; Polichtchouk, B.; Poljak, N.; Poonsawat, W.; Pop, A.; Poppenborg, H.; Porteboeuf-Houssais, S.; Pozdniakov, V; Prasad, S. K.; Preghenella, R.; Prino, F.; Pruneau, C. A.; Pshenichnov, I; Puccio, M.; Punin, V; Puranapanda, K.; Putschke, J.; Quishpe, R. E.; Ragoni, S.; Raha, S.; Rajput, S.; Rak, J.; Rakotozafindrabe, A.; Ramello, L.; Rami, F.; Raniwala, R.; Raniwala, S.; Rasanen, S. S.; Rascanu, B. T.; Rath, R.; Ratza, V; Ravasenga, I; Read, K. F.; Redlich, K.; Rehman, A.; Reichelt, P.; Reidt, F.; Ren, X.; Renfordt, R.; Reshetin, A.; Revol, J-P; Reygers, K.; Riabov, V; Richert, T.; Richter, M.; Riedler, P.; Riegler, W.; Riggi, F.; Ristea, C.; Rode, S. P.; Rodriguez Cahuantzi, M.; Roed, K.; Rogalev, R.; Rogochaya, E.; Rohr, D.; Rohrich, D.; Rokita, P. S.; Ronchetti, F.; Rosas, E. D.; Roslon, K.; Rosnet, P.; Rossi, A.; Rotondi, A.; Roukoutakis, F.; Roy, A.; Roy, P.; Rueda, O., V; Rui, R.; Rumyantsev, B.; Rustamov, A.; Ryabinkin, E.; Ryabov, Y.; Rybicki, A.; Saarinen, S.; Sadhu, S.; Sadovsky, S.; Safarik, K.; Saha, S. K.; Sahoo, B.; Sahoo, P.; Sahoo, R.; Sahoo, S.; Sahu, P. K.; Saini, J.; Sakai, S.; Sambyal, S.; Samsonov, V; Sandoval, A.; Sarkar, A.; Sarkar, D.; Sarkar, N.; Sarma, P.; Sarti, V. M.; Sas, M. H. P.; Scapparone, E.; Schaefer, B.; Schambach, J.; Scheid, H. S.; Schiaua, C.; Schicker, R.; Schmah, A.; Schmidt, C.; Schmidt, H. R.; Schmidt, M. O.; Schmidt, M.; Schmidt, N., V; Schmier, A. R.; Schukraft, J.; Schutz, Y.; Schwarz, K.; Schweda, K.; Scioli, G.; Scomparin, E.; Sefcik, M.; Seger, J. E.; Sekiguchi, Y.; Sekihata, D.; Selyuzhenkov, I; Senyukov, S.; Serradilla, E.; Sett, P.; Sevcenco, A.; Shabanov, A.; Shabetai, A.; Shahoyan, R.; Shaikh, W.; Shangaraev, A.; Sharma, A.; Sharma, M.; Sharma, N.; Sheikh, A., I; Shigaki, K.; Shimomura, M.; Shirinkin, S.; Shou, Q.; Sibiriak, Y.; Siddhanta, S.; Siemiarczuk, T.; Silvermyr, D.; Simatovic, G.; Simonetti, G.; Singh, R.; Singhal, V; Sinha, T.; Sitar, B.; Sitta, M.; Skaali, T. B.; Slupecki, M.; Smirnov, N.; Snellings, R. J. M.; Snellman, T. 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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 hospitalization2,3,4 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

Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche

Cell competition is a short-range cell-cell interaction leading to the proliferation of winner cells at the expense of losers, although either cell type shows normal growth in homotypic environments. Drosophila Myc (dMyc; Dm - FlyBase) is a potent inducer of cell competition in wing epithelia, but its role in the ovary germline stem cell niche is unknown. Here, we show that germline stem cells (GSCs) with relative lower levels of dMyc are replaced by GSCs with higher levels of dMyc. By contrast, dMyc-overexpressing GSCs outcompete wild-type stem cells without affecting total stem cell numbers. We also provide evidence for a naturally occurring cell competition border formed by high dMyc-expressing stem cells and low dMyc-expressing progeny, which may facilitate the concentration of the niche-provided self-renewal factor BMP/Dpp in metabolically active high dMyc stem cells. Genetic manipulations that impose uniform dMyc levels across the germline produce an extended Dpp signaling domain and cause uncoordinated differentiation events. We propose that dMyc-induced competition plays a dual role in regulating optimal stem cell pools and sharp differentiation boundaries, but is potentially harmful in the case of emerging dmyc duplications that facilitate niche occupancy by pre-cancerous stem cells. Moreover, competitive interactions among stem cells may be relevant for the successful application of stem cell therapies in humans.Research was funded by the Swiss National Science Foundation to C.R., the Ministry of Science and Innovation to J.F.P., the Ramon y Cajal program and by JGL Caja Madrid, the autonomous community of Madrid and FMMA awards to E.M.Peer Reviewe