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1. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses

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Pan, Hongchao, Peto, Richard, Henao Restrepo, Ana Maria, Preziosi, Marie-Pierre, Sathiyamoorthy, Vasee, Karim, Quarraisha Abdool, Alejandria, Marissa, Hernàndez García, César, Kieny, Marie-Paule, Malekzadeh, Reza, Murthy, Srinivas, Reddy, K. Srinath, Periago, Mirta Roses, Hanna, Pierre Abi, Abutidze, Akaki, Ader, Florence, Al-Bader, Abdullah, Alhasawi, Almonther, Allum, Emma, Al Mawali, Adhra, Alotaibi, Athari, Alvarez- Moreno, Carlos, Appadoo, Sheila, Arts, Derk, Asiri, Abdullah, Aukrust, Pål, Barratt-Due, Andreas, Genetu Bayih, Abebe, Beaumont, Helena, Bellani, Samir, Benassi, Virginia, Bhargava, Balram, Branca, Mattia, Cappel-Porter, Heike, Cerrato, Nery, Cheick Haidara, Fadima, Chow, Ting Soo, Como, Nadia, Eustace, Joe, Gabunia, Tamar, García, Patricia, Godbole, Sheela, Gotuzzo, Eduardo, Griskevicius, Laimonas, Hamra, Rasha, Hassan, Mariam, Hassany, Mohamed, Hutton, David, Irmansyah, Irmansyah, Jancoriene, Ligita, Khamis, Faryal, Kirwan, Jana, Kumar, Suresh, Lennon, Peter, Lopardo, Gustavo, Lydon, Patrick, Magrini, Nicola, Manevska, Suzana, Manuel, Oriol, McGinty, Sybil, Medina, Marco, Mesa Rubio, Maria Lucia, Miranda Montoya, Maria Consuelo, Nel, Jeremy, Nunes, Estevao, Perola, Markus, Portoles, Antonio, Rasmin, Menaldi, Raza, Aun, Rees, Helen, Reges, Paula, Rogers, Chris, Salami, Kolawole, Salvadori, Marina, Sauermann, Mamatha, Sinani, Narvina, Sow, Samba, Sterne, Jonathan AC, Stevanovikj, Milena, Tacconelli, Evelina, Tavares Maltez, Fernando Manuel, Teferi, Mekonnen, Tikkinen, Kari, Trelle, Sven, Tsertsvadze, Tengiz, Zaid, Hala, Røttingen, John-Arne, Swaminathan, Soumya, Ryan, Michael, Gjermeni, Nevila, Meta, Esmeralda, Aguila, Damian, Alonso, Ignacio, Altamirano, Marcos, Alvarez, María, Alzola, Rodrigo, Arce, Veronica, Arribillaga, Patricia, Avila, Rafael, Balbuena, Juan, Barcelona, Laura, Barletta, José, Benedetti, María, Berdiñas, Verónica, Burgui, Julieta, Caimi, Sabrina, Carrillo, Juan, Carrizo, Juan, Castelli, Juan, Cazaux, Alexis, Cervellino, Flavia, Chalco, Angelo, Chediack, Viviana, Cunto, Eleonora, D'Amico, Nicolàs, de Vedia, Lautaro, Delgado, Carolina, Di Pilla, Debora, Díaz, Miguel, Díaz Aguiar, Pablo, Domínguez, Cecilia, Ellero, Leonor, Farina, Javier, Fernàndez, José, Ferreyra, Roxana, Filippi, María, Fogar, Carolina, Frare, Pablo, Giudiche, Celeste, Golikow, Mariana, Gomez, Maria Georgina, Hermida, Laura, Hurtado, Mariano, Jacobo, Mariela, Jaume, Martin, Laplume, Diego, Lescano, María, Lista, Nicolàs, Loiacono, Flavia, López, Ana Belen, Losso, Marcelo, Luna, Cecilia, Lupo, Sergio, Marianelli, Leonardo, Martin, Anabella, Masciottra, Florencia, Mykietiuk, Analía, Orellano, Lorena, Pachioli, Valeria, Padilla, María José, Pallavicini, Cecilia, Patroso, Jazmin, Perez Blanco, Luz, Presas, Jose Louis, Provenzano, Matias, Lavera, Lorena, Reichert, Viviana, Riveros, Florencia, Rodríguez, Alejandra, Rolon, María José, Salvay, Carolina, Simonetta, María, Sisto, Alicia, Themines, Sandra, Tito, Fernando, Toibaro, Javier, Torales, Graciela, Verón, Luciano, Vizzotti, Carla, Egle, Alexander, Greil, Richard, Joannidis, Michael, Altdorfer, Antoine, Belkhir, Leila, Fraipont, Vincent, Hites, Maya, Arruda, Erico, Breda, Giovanni, Colussi, Arthur, Corradi, Miran, Croda, Julio, Duani, Helena, João, Esaú, Machado, Elizabeth, Mello, Fernanda, Miranda Filho, Demócrito, Monteiro, Poliana, Nunes, Ceuci, Pereira Junior, Luiz Carlos, Pinto, Gustavo, Raboni, Sonia, Ramos, Marcelo, Ruffing, Leonardo, Santos, Valdilea, Souza, Tamara, Medeiros, Melissa, Schwarzbold, Alexandre, Ali, Karim, Azher, Tanweer, Bellemare, David, Binnie, Alexandra, Borgia, Sergio, Cavayas, Yiorgos Alexandros, Chagnon, Nicholas, Cheng, Matthew, Cloutier, Eve, Conly, John, Costiniuk, Cecilia, Daneman, Nick, Douglas, James, Downey, Catarina, Duan, Erick, Durand, Medeline, English, Shane, Farjou, George, Fera, Evadiki, Fontela, Patricia, Fowler, Rob, Fralick, Mike, Gamble, David Gregory, Geagea, Anna, Grant, Jennifer, Harrison, Luke, Havey, Thomas, Hoang, Holly, Kelly, Lauren, Keynan, Yoav, Khwaja, Kosar, Klein, Marina, Kolan, Christophe, Kronfli, Nadine, Lamontagne, Francois, Lee, Nelson, Lee, Todd, Lim, Rachel, Lostun, Alexandra, MacIntyre, Erika, Malhamé, Isabelle, Martin-Carrier, Francois, McGuinty, Marlee, Munan, Matthew, O'Neil, Conar, Ovakim, Daniel, Papenburg, Jesse, Parhar, Ken, Parvathy, SeemaNair, Perez-Patrigeon, Santiago, Rishu, Asgar, Rushton, Moira, Scherr, Kim, Schwartz, Kevin, Semret, Makeda, Silverman, Micahel, Singh, Ameeta, Sligl, Wendy, Smith, Stephanie, Somayaji, Ranjani, Tan, Darrell, Tran, Tuong-Vi, Tremblay, Alain, Tsang, Jennifer, Turgeon, Alexis, Vakil, Erik, Weatherald, Jason, Yansouni, Cedric, Zarychanski, Ryan, Aristizabal, Claudia, Bravo, Juan, Caicedo, Monica, Chacón, Julio, Garzón, Diego, Guevara, Fredy, Lozano-Gonzàlez, Silvia, Macareno, Hugo, Montañez-Ayala, Anita, Oñate, Jose, Rojas-Gambasica, Jose, Rosso, Fernando, Saavedra, Carlos, Valderrama, Sandra, Vàquiro-Herrera, Eliana, Varón-Vega, Fabio, Zuluaga, Ivan, Abdel Baki, Amin, Abdelbary, Akram, Abdel-Razek, Wael, Amin, Wagdi, Asem, Noha, Elassal, Gehan, Elshesheny, Marwa, Fathy, Mohamed, Fathy, Naglaa, Fayed, Notaila, Hammam, Ahmed, Hassany, Sahar, Ibrahim, Hamdy, Kamal, Ehab, Masoud, Hossam, Mohamed, Maryam, Mohamed Gouda, Abdullah, Moustafa, Ehab, Okasha, Shaimaa, Rafik, Ahmed, Said, Ahmed, Sedky, Asmaa, Solyman Kabil, Mohamed, Tarek, Sara, Tharwat, Ahmed, Zaky, Samy, Abegaz, Emawayish Tesema, Bekele, Zelalem Mekonnen, Asfaw, Filmona Mekuria, Tegegne, Netsanet Aragaw, Teklemariam, Miheret Fikre, Nigusse, Frehiwot Tamiru, Achalu, Daniel Legesse, Weldegergs, Shewit Tesfagabr, Huluka, Dawit Kebede, Tereda, Addisu Birhanu, Ala-Kokko, Tero, Delany, Jutta, Ekroos, Heikki, Hankkio, Riina, Haukipää, Mia, Hetemäki, Iivo, Holma, Pia, Holmberg, Ville, Horstia, Saana, Jalkanen, Ville, Jämsänen, Toni, Järventie, Juuso, Järvinen, Petrus, Kalliala, Ilkka, Kauma, Heikki, Kilpeläinen, Tuomas, Kreivi, Hanna-Riikka, Kuitunen, Ilari, Lamminmäki, Satu, Mäkinen, Laura, Mäntylä, Jarkko, Mattila, Tiina, Myllärniemi, Marjukka, Niskanen, Joni, Nykänen, Taina, Nyqvist, Miro, Paajanen, Juuso, Partanen, Terhi, Patovirta, Riitta-Liisa, Paukkeri, Erja-Leena, Puusti, Emmi, Renner, Andreas, Reponen, Emma, Risku, Sari, Rosberg, Tuomas, Rutanen, Jarno, Säilä, Petrus, Salonen, Päivi, Sinisalo, Marjatta, Sivenius, Katariina, Tuominen, Susanna, Aboab, Jerone, Alfaiate, Toni, Andrejak, Claire, Andreu, Pascal, Belhadi, Drifa, Benezit, Francois, Botelho-Nevers, Elisabeth, Bouadma, Lila, Bougon, David, Bouiller, Kevin, Bounes, Fanny, Boyer, Alexandre, Bruel, Cédric, Buffet, Alexandre, Burdet, Charles, Cazanave, Charles, Chabertier, Cyrille, Clere-Jehl, Rapahel, Costagliola, Dominique, Courjon, Johan-Victor, Crockett, Flora, Danion, Francois, Dechanet, Aline, Dellamonica, Jean, Delmas, Christelle, Diallo, Alpha, Djossou, Felix, Dubost, Clement, Dupont, Axelle, Epaulard, Olivier, Faure, Emmmanuel, Faure, Karine, Fayol, Antoine, Figueiredo, Samy, Fougerou, Claire, Gaborit, Benjamin, Gaci, Rostane, Gagneux-Brunon, Amandine, Gallien, Sebastien, Garot, D, Goehringer, Francois, Gruson, Didier, Hinschberger, Olivier, Hulot, Jean-Sebastien, Jaureguiberry, Stephane, Jean-Michel, Vanessa, Kerneis, Solen, Kimmoun, Antoine, Klouche, Kada, Lachatre, Marie, Lacombe, Karine, Laine, Fabrice, Lanoix, Jean Philippe, Laribi, Samira, Launay, Odile, Laviolle, Bruno, Le Moing, Vincent, Le Pavec, Jerome, Lebeaux, David, Leroy, Sylvie, Lescure, Xavier, Livrozet, Marine, Makinson, Alain, Malvy, Denis, Marquette, Charles-Hugo, Martin-Blondel, Guillaume, Mayaux, Julien, Mekontso Dessap, Armand, Mentre, France, Mercier, Noemie, Meziani, Ferhat, Molina, Jean Michel, Mootien, Yoganaden, Mourvillier, Bruno, Navellou, Jean Christoph, Noret, M, Peiffer- Smadja, Nathan, Peytavin, Gilles, Pialoux, Gilles, Pilmis, Benoît, Piroth, Lionel, Poindron, Vincent, Poissy, Julien, Pourcher, Valerie, Quenot, Jean Pierre, Raffi, Francois, Reignier, Jean, Richard, Jean Christoph, Robert, Céline, Saillard, Juliette, Sayre, Naomi, Senneville, Eric, Stefan, Francois, Tellier, Marie Capucine, Terzi, Nicolas, Textoris, Julien, Thiery, Guillame, Timsit, Jean Francois, Tolsma, Violaine, Tubiana, Sarah, Wallet, Florent, Yazdanpanah, Yazdan, Zerbib, Yoann, Aguilar, Carlos, Erazo, Laura, Fiallos, Angel, Figueroa, Rosbinda, Flores, Juan Jose, Melendez, Lesddyy, Moncada, Wendy, Abraham, Ooriapadickal Cherian, Acharya, Chetankumar, Aedula, Vinaya Sekhar, Aggarwal, Richa, Agrawal, Nishant, Agrawal, Umang, Agrawal, Abhishekh, Ahmad, Mohammad, Atal, Shubham, Babu, Avinash, Baidya, Dalim Kumar, Balachandran, Amith, Bangar, Rakhee, Bhadade, Rakesh, Bhandari, Sudhir, Bhapal, Meghavi, Bhardwaj, Pankaj, Bhati, Gaurav, Bhatia, Pradeep, Bhatt, Krishnakant, Bingi, Thrilok Chander, Borse, Rohidas, Buch, Vyom, Chand, Dipti, Chandwani, Ashish, Charan, Jaykaran, Chaudhari, Mayur, Chaudhari, Kirti, Chaudhary, Vipul, Chauhan, Nishant, Chikara, Gaurav, Daswani, Bharti, de Souza, Rosemarie, Desai, Chetna, Divakar, Balusamy, Divhare, Sujeet, Dorairajan, Suresh Kumar, Dutt, Naveen, Ethirajan, Therani Rajan, Gamit, Amit, Gamit, Sweta, Garg, Mahendra, Goenka, Ajay, Goenka, Aniket, Guleria, Randeep, Gupta, Paras, Gupta, Nivedita, Gupta, Madhur, Harde, Minal, Ingle, Vaibhav, Iyer, Shivkumar, Jamalapuram, Vaishnavi, Jayanthi, Rangarajan, Joshi, Rajnish, Kadam, Abhijeet, Kalakuntla, Hemanth, Kalikar, Mrunalini, Kalme, Sayali, Kamble, Suchit, Kant, Ravi, Kantharia, Bansari, Kashikar, Arundhati, Kavishvar, Abhay, Kayina, Choro Athipro, Kerkar, Pranali, Khadanga, Sagar, Khandare, Sagar, Kokate, Pranjali, Komathi, Jayavelu, Krishnan, Vijay, Krishnan, Jayasree, Krishnan, Sumitra, Kulur Mukhyaprana, Sudha, Kumarasamy, N, Mahavar, Sunil, Maitra, Souvik, Majumdar, Falguni, Malhotra, Supriya, Mamulwar, Megha, Malini, Padma, Marwah, Vikas, Maurya, Akhilesh, Mehta, Kedar, Mesipogu, Rajarao, Misra, Shobha, Mitra, Sajal, Mittal, Ankit, Mohan, Bharathi, Momin, Mohmmedirfan, Nag, Vijaya, Nagarajan, Ramakrishnan, Nagmani, Kammili, Narlawar, Uday, Natarajan, Gopalakrishnan, Nischal, Neeraj, Ogale, Dhananjay, Palat, Paltial, Panda, Prasan, Panda, Samiran, Pandya, Amee, Parate, Rohit, Paritekar, Arunita, Patel, Parvati, Patel, Chetna, Patel, Sunaina, Patel, Vitan, Patel, Deep, Patel, Harshad, Patil, Girish, Peter, Deepu, Prasad, Durga, Purohit, Vimlesh, Rabindrarajan, Ebenezer, Ranganathan, Lakshmiarasimhan, Rao, Tushara, Rao, Chakradhara, Rathod, Chirag, Raval, Devang, Ray, Avik, Reddy, Kamini, Rege, Sujata, Revathi, Ayyasamy, Roy, Dhara, Saigal, Saurabh, Sane, Suvarna, Sangale, Shashi, Seetharaman, Krishnamoorthy, Selvamuthu, Poongulali, Seshaiah, Kurada Venkata, Shadrach, Benhur, Shah, Jignesh, Shah, Sonal, Sharma, Swati, Sharma, Raman, Sharma, Shrikant, Singh, Krishna, Singh, Anil, Singh, Arjeet, Singhai, Abhishek, Soneja, Manish, Soni, Kapil Dev, Subhan, Thasneem banu, Subramaniam, Sudharshini, Sudarsanam, Thambu David, Sudarsi, Ravindra Kumar, Suleman, Dawood, Suthar, Nilay, Talati, Shriraj, Tambe, Murlidhar, Tejomurtula, Tilak, Tirupakuzhi Vijayaraghavan, Bharatkumar, Trikha, Anjan, Trivedi, Aarti, Udwadia, Zarir, Upadhyay, Kamlesh, Vasava, Ashwin, Vasudevan, Damodaran, Velayudham, Rajendran, Venkatasubramanian, Ramasubramanian, Verma, Mamta, Waghmare, Rakesh, Waikar, Anushka, Wig, Naveet, Afrilia, Annisa Rizky, Amin, Muhammad, Arlinda, Dona, Avrina, Rossa, Bang, Lois, Djaharuddin, Irawaty, Djojo, Aryan, Driyah, Sri Laning, Erastuti, Mila, Fajarwati, Tetra, Harsini, Harsini, Hartantri, Yovita, Herman, Deddy, Isbaniah, Fathiyah, Karyana, Muhammad, Kusuma, Indra, Mahmudji, Harli Amir, Medison, Irvan, Nugroho, Agung, Nurhayati, Nurhayati, Opitasari, Cicih, Pitoyo, Ceva Wicaksono, Pradana, Antonius Arditya, Raharjo, Sofyan Budi, Rahmaini, Ade, Risniati, Yenni, Riyanto, Bambang Sigit, Sajinadiyasa, I Gede Ketut, Sari, Flora Eka, Sitompul, Pompini Agustina, Soedarsono, Soedarsono, Somia, I Ketut Agus, Sugiri, Yani Jane, Sugiyono, Retna Indah, Susanto, Nugroho Harry, Syarif, Armaji Kamaludi, Yulianto, Aris, Afsharian, Mandana, Akhavi Mirab, Atefehsadat, Amini, Fatemeh, Amini, Mahnaz, Ansarin, Khalil, Baba Mahmoodi, Farhang, Baghaei, Parvaneh, Barazandeh, Fateme, Bayani, Masomeh, Dastan, Farzaneh, Ebrahimpour, Soheil, Eghtesad, Sareh, Fallahi, Mohammad Javad, Fallahpoor Golmaee, Fatemeh, Foroghi Ghomi, Seyed Yaser, Ghadir, Mohammad Reza, Gheitani, Mina, Ghiasvand, Fereshteh, Hafizi Lotfabadi, Saied, Hakamifard, Atousa, Hashemi Madani, Shima Sadat, Hormati, Ahmad, Hosseini, Hamed, Janbakhsh, Alireza, Javanian, Mostafa, Joukar, Farahnaz, Kamali, Alireza, Karampour, Amin, Khajavirad, Nasim, Khodabakhshi, Behnaz, Khodadadi, Javad, Khodashahi, Rozita, Kiani Majd, Somaieh, Mahfoozi, Lida, Mahmoodiyeh, Behnam, Mansour-Ghanaei, Fariborz, Mansouri, Feizollah, Mesgarpour, Bita, Mesri, Mehdi, Mikaeili, Haleh, Miladi, Ronak, Moghadami, Mohsen, Mohamadi, Payam, Mohraz, Minoo, Mohseni Afshar, Zeinab, Moogahi, Sasan, Mousavi Anari, Seyed Alireza, Mozaffar, Seyyed Hassan, Mozdourian, Mahnaz, Najafipour, Reza, Najari, Hamidreza, Nazemiyeh, Masoud, Norouzi, Alireza, Pourkazemi, Aydin, Poustchi, Hossein, Saberhosseini, Seyedeh Naeimeh, Saberi, Marzieh, Saber-Moghaddam, Niloufar, Sadeghi, Anahita, Sadeghi Haddad Zavareh, Mahmoud, Sahraian, Mohammad Ali, Salahi, Mehrdad, Salehi, Mohammad Reza, Sarmadian, Hossein, Sayad, Babak, Shirani, Kiana, Shirvani, Maria, Shojaei, Daryanaz, Shokri, Mehran, Siami, Zeinab, Sima, Ali Reza, Soleimani, Alireza, Soltanmohammad, Saedeh, Tabarsi, Payam, Taghizadieh, Ali, Tavassoli, Samaneh, Varnasseri, Mehran, Vaziri, Siavash, Yadyad, Mohammad Jaafar, Yaghoubi, Shoeleh, Yazdanpanah, Yalda, Yousefi, Farid, Zamanian, Mohammad Hossein, Zand, Farid, Zare Hoseinzade, Elham, Bergin, Colm, Cotter, Aoife, de Barra, Eoghan, Jackson, Arthur, Laffey, John, McCarthy, Cormac, Muldoon, Eavan, Sadlier, Corinna, Maguire, Teresa, Angheben, Andrea, Bai, Francesca, Bandera, Alessandra, Barchiesi, Francesco, Bassetti, Matteo, Bisi, Luca, Bonfanti, Paolo, Calò, Federica, Campoli, Caterina, Canovari, Benedetta, Capetti, Amedeo, Castelli, Francesco, Cauda, Roberto, Cingolani, Antonella, Cocco, Nicolò, Coppola, Nicola, Corcione, Silvia, Cremonini, Eleonora, d'Arminio Monforte, Antonella, de Gaetano Donati, Katleen, De Nardo, Pasquale, De Rosa, Francesco Giuseppe, Degioanni, Maria, Della Siega, Paola, Di Bella, Stefano, Drera, Bruno, Focà, Emanuele, Fornabaio, Chiara, Galli, Massimo, Giacomazzi, Donatella, Gori, Andrea, Gustinetti, Giulia, Iannuzzi, Francesca, Kertusha, Blerta, Lamonica, Silvia, Lichtner, Miriam, Lupia, Tommaso, Luzzati, Roberto, Macera, Margherita, Menatti, Elisabetta, Merelli, Maria, Merlini, Esther, Monari, Caterina, Pan, Angelo, Pecori, Davide, Pezzani, Diletta, Riccardi, Niccolò, Rodari, Paola, Roldan, Eugenia, Rovere, Pierangelo, Rusconi, Stefano, Scabini, Silvia, Tascini, Carlo, Viale, Pierluigi, Vincenzi, Marcello, Zuccalà, Paola, Zucchi, Patrizia, Al-Roomi, Moudhi, Al-Sabah, Salman, Schrapp, Kelly, Hassoun, Mahmoud, Matar, Madonna, Dbouni, Oussaima, Yared, Nadine, Saliba, Michele, Farra, Anna, Riachi, Moussa, Zablockiene, Birute, Reuter, Jean, Staub, Therese, Ab Wahab, Suhaila, Chew, Chun Keat, Chua, Hock Hin, Goh, Pik Pin, Lee, Heng Gee, Leong, Chee Loon, Low, Lee Lee, Mak, Wen Yao, Mohamed Gani, Yasmin, Muhamad, Dzawani, Zaidan, Nor Zaila, Ducker, Camilla, Demiri, Ilir, Aballi, Saad, Berg, Åse, Blomberg, Bjørn, Dalgard, Olav, Dyrhol-Riise, Anne Ma, Eiken, Ragnhild, Ernst, Gernot, Hannula, Ranula, Haugli, Metter, Heggelund, Lars, Hoel, Hedda, Hoff, Dag Arne Lihaug, Holten, Aleksander Rygh, Johannessen, Asgeir, Kåsine, Trine, Kildal, Anders Benjamin, Kittang, Bård Reikvam, Nezvalova-Henriksen, Katerina, Olsen, Inge Christoffer, Olsen, Roy Bjørkolt, Skei, Nina Vibeche, Skudal, Hilde, Tholin, Birgitte, Thoresen, Lars, Trøseid, Marius, Tveita, Anders, Vinge, Leif, Ystrøm, Carl Magnus, Al Jahdhami, Issa, AlNaamani, Khalid, Al Balushi, Zakariya, Pandak, Nenad, Abbas, Salma, Akhtar, Nasim, Azam, Sumeyya, Begum, Dilshad, Hassan, Sadia, Herekar, Fivzia, Khan, Shahzaib, Khan, Ejaz Ahmed, Mahmood, Syed Faisal, Nasir, Nosheen, Rahim, Anum, Sarfaraz, Samreen, Shaikh, Qurat-ul-Ain, Sultan, Faisal, Walayat, Usman, Agurto-Lescano, Erika Cecilia, Alcantara-Díaz, Andrés Martín, Alva-Correa, Ana María, Alvarado-Moreno, José Gustavo, Ángeles-Padilla, Bethsabé, Arbañil-Huamàn, Hugo César, Ávila-Reyes, Pool Christopher, Azañero-Haro, Johan Alexander, Barreto-Rocchetti, Luis Guillermo, Benitez-Peche, Jorge Marko A., Bernal-Màlaga, Karla Hortencia, Cabrera-Portillo, Liliana Norma, Carazas-Chavarry, Reynaldo Javier, Càrcamo, Paloma Mariana, Casimiro-Porras, Indira Catalina, Castillo-Espinoza, Jhuliana, Chacaltana-Huarcaya, Jesús Norberto, Cornejo-Valdivia, Carla Raquel, Cruz-Chereque, Augusto, Del-Aguila-Torres, Keith Cayetano Marcelino, Díaz-Chipana, Erika, Flores-Valdez, Neil, Franco-Vàsquez, Rosanna Andrea, Gallegos-López, Roxana Consuelo, Gastiaburú-Rodriguez, Dauma Yesenia, Gianella-Malca, Gonzalo Ernesto, Gomero-Lopez, Andrés Alonso, Hercilla-Vàsquez, Luis Enrique, Hueda-Zavaleta, Miguel Ángel, Ibarcena-Llerena, Claudia Vanessa, Iberico-Barrera, Carlos Alberto, Inquilla-Castillo, Miguel Angel, Juàrez-Eyzaguirre, Jesus Alberto, Laca-Barrera, Manuel, León-Jiménez, Franco, Luna-Wilson, Carla Vanessa, Màlaga, German, Marin, Ricardo, Mejía-Cordero, Fernando, Mendoza-Laredo, Juan Arturo, Meregildo-Rodríguez, Edinson Dante, Miranda-Manrique, Gonzalo Francisco, Olivera-Chaupis, Marco, Ortega-Monasterios, Fatima Josefina, Otazú-Ybàñez, Jimmy Pedro, Paredes-Moreno, María Angélica, Peña-Mayorga, Claudia Ximena, Peña-Vàsquez, Olivia del Carmen, Peña-Villalobos, Alejandro, Ponce, Oscar J, Ponte-Fernandez, Katherin Estefania, Pro, Jose, Quispe-Nolazco, César Miguel, Ramos-Samanez, Manuel Efrain, Rojas-Murrugarra, Kory Mirtha, Samanez-Pérez, Jorge Mauro, Sànchez-Carrillo, Halbert Chrostian, Sànchez-Garavito, Epifanio, Sànchez-Sevillano, Ricardo Manuel, Sandoval-Manrique, Hernan, Santos-Revilla, Gabriela, Silva-Ramos, Julio Antonio, Solano-Ico, Manuel Alberto, Soto, Alonso, Sotomayor-Woolcott, Giannilu Michelle, Tapia-Orihuela, Ruben Kevin Arnold, Terrazas-Obregón, Carmen Sara, Terrones-Levano, Victor Francisco, Ticona-Huaroto, Cesar Eduardo, Torres-Ninapayta, Walter, Torres-Ruiz, Oscar Martin, Ugarte-Mercado, Dario, Vargas-Anahua, Orlando José, Vàsquez-Becerra, Ruben Dario, Vàsquez-Cerro, José Gabriel, Villegas-Chiroque, Miguel, Williams, Anna Larson, Yauri-Lazo, Randi Mauricio, Abad, Cybele Lara, Andales-Bacolcol, Silverose Ann, Arcegono, Marlon, Arches, Jamie, Astudillo, Mary Grace, Aventura, Emily, Awing, Arlyn, Bala, Mishelle Vonnabie, Bello, Jia An, Blanco, Peter, Benedicto, Jubert, Buno, Susana, Cabrera, Justine, Cajulao, Thea Pamela, Caoili, Janice, Casiple-Amsua, Lina, Catambing, Victor, Chin, Inofel, Chua, Ma. Bernadette, Chua, Mitzi Marie, Climacosa, Fresthel Monica, David-Wang, Aileen, De los Reyes, Virginia, Europa, Gilly May, Fernandez, Lenora, Francisco, Jorge, Garcia, Gerard, Garcia, Jemelyn, Gler, Maria Tarcela, Isidro, Marie Grace Dawn, Javier, Rozelle Jade, Kwek, Marion, Lansang, Mary Ann, Lee, Aileen, Li, Kingbherly, Llanes, Mark Ramon Victor, Llorin, Ryan, Macadato, Omar Khayyam, Malundo, Anna Flor, Mercado, Maria Elizabeth, Mujeres, Mercedes, Nepomuceno, Marisse, Ngo-Sanchez, Katha, Orden, Mary Claire, Pablo-Villamor, Maria Philina, Paez, Ruel Dionisio, Palmes, Patricio, Panaligan, Marion, Quinivista-Yoon, Jenny Mae, Ramos, Mary Shiela Ariola, Ramos -Penalosa, Christine, Reyes, Sheila Marie, Roa, Kathryn, Roman, Arthur Dessi, Rosario, Minette Claire, Roxas, Evalyn, Santos, Lourdes Ella Gonzales, Soldevilla, Helmar, Solante, Rontgene, Suaco, Jane, Tagarda, Daisy, Tang, Issa Rufina, Te, Bob, Teo, Dennis, Tibayan, Christopher John, Villalobos, Ralph Elvi, Ymbong, Duane Richard, Zabat, Gelza Mae, Batkova, Stepanka, Cardoso, Orlando, Garrote, Ana-Raquel, Lino, Sara, Manata, Maria-José, Pinheiro, Helder, Póvoas, Diana, Ramirez, Freddy, Seixas, Diana, Naji, Assem, Al Gethamy, M Al, AL-Mulaify, Mohammed Sami, Al Maghraby, Reem, Alrajhi, A, Al Sharidi, Aynaa, Alotaibi, Naif, AlShaharani, F, Barry, Mazin, Ghonem, Leen, Khalel, Anas, Kharaba, Ayman Mohammed, Alabdan, Lulwah, AlAbdullah, Mohammed Sharaf, Al Shabib, Abdullah, Bengu, Simangele, Bennet, Jacklyn, Dubula, Thozama, Howell, Pauline, Janse van Vuuren, Cloete, Kalla, Ismail, Lifson, Aimee, Maasdorp, Shaun, Magua, Nombulelo, Maluleke, Vongani, Mbhele, Nokuphiwa, Mdladla, Nathi, Mendelson, Mark, Menezes, Colin, Mwelase, Thando, Nchabeleng, Maphoshane, Palanee-Phillips, Thesla, Parker, Victoria, Rassool, Mohammed, Reeder, Paul, Sossen, Bianca, Steyn, Dewald, Tsitsi, Merika, van Blydenstein, Sarah Alex, Venter, Michelle, Van Vuuren, Janse, Venturas, Jacquie, Abad Pérez, Daniel, Abenza, Maria José, Alarcón-Payer, Carolina, Armero Garrigos, Eva, Arribas, Jose Ramon, Ascaso, Ana, Berenguer, Juan, Cabello-Clotet, Noemí, Chamorro Tojeiro, Sandra, Cuenca-Acevedo, Rafael, de la Calle, Fernando, Del Toro, Maria Dolores, Díaz Pollàn, Beatriz, Diez, Cristina, Esquillor-Rodrigo, María José, Estrada, Vicente, Fanciulli, Chiara, Fanjul, Francisco, Fernàndez de Orueta, Lucía, Ferre, Adrian, Ferreira Pasos, Eva Maria, Gainzarain-Arana, Juan-Carlos, Garcia, Felipe, García Deltoro, Miguel, Goikoetxea Agirre, Ane Josune, Gómez Barquero, Julia, Gomez-Huelgas, Ricardo, Gonzàlez Moraleja, Julio, Guijarro, Carlos, Gutierrez, Felix, Guzmàn, Jesús, Ibarguren, Maialen, Iribarren, Jose Antonio, Jerusalem, Koen, Juan Arribas, Arturo, Lalueza, A, Leone, Antonio, Lopez Azkarreta, Iñigo, Lozano-Martin, Daniel, Lucendo, Alfredo J, Luengo López, Mariella, Martín Oterino, JA, Masa, JF, Merino, Esperanza, Monge-Maillo, Begoña, Moran-Rodríguez, Miguel-Angel, Muñez Rubio, Elena, Muñoz Sanchez, Josefa, Nuñez Orantos, Maria Jose, Nuño, Enrique, Ortiz-De-Zarate-Ibarra, Zuriñe, Pagàn-Muñoz, Bàrbara, Paño-Pardo, José Ramón, Peñaranda, Maria, Pérez Chica, Gerardo, Pérez Fernàndez, AM, Pérez-López, Carmen, Polo San Ricardo, Victor, Portu-Zapirain, Joseba, Puchades, Francesco, Rivas Paterna, Ana Belen, Rodríguez Vidigal, Francisco F, Rodríguez-Baño, Jesus, Ruiz-Seco, Pilar, Ryan, Pablo, Saez-De-Adana, Ester, Salas, Rosario, Salavert Lletí, Miguel, Sandoval, Raquel, Toyas-Miazza, Carla, Valencia, Jorge, Vargas, Emilio, Velasco, Maria, Von Wichmann, Miguel Angel, Bosshard, Andreas, Calmy, Alexandra, Castro, Tiago, Cavassini, Matthias, Clerc, Olivier, Conen, Anna, Desbaillets, Nicolas, Desgranges, Florian, Duss, Francois, Emonet, Stephane, Erard, Veronique, Eyer, Myriam, Fayet-Mello, Aurélie, Flammer, Yvonne, Friedl, Andrée, Fulchini, Rosamaria, Furrer, Hansjakob, Garin, Nicolas, Gastberger, Salome, Greiner, Michael, Haefliger, David, Haubitz, Sebastian, Hoffmann, Matthias, Isenring, Egon, Jakopp, Barbara, Lampert, Markus, Marinosci, Annalisa, Martin, Yvonne, Petignat, Pierre-Auguste, Piso, Rein Jan, Prendki, Virginie, Rutishauser, Jonas, Schaefer, Elisabeth, Schmiedel, Yvonne, Schwery, Stefan, Stavropoulou, Elisavet, Stoeckle, Marcel, Suttels, Veronique, Thurnher, Maria Christine, van den Bogaart, Lorena, West, Emily, Wiegand, Jan, and Wiggli, Benedikt

Published
2022
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3. Circulating markers of extracellular matrix remodelling in severe COVID‐19 patients.

Author

Murphy, Sarah Louise, Halvorsen, Bente, Holter, Jan Cato, Huse, Camilla, Tveita, Anders, Trøseid, Marius, Hoel, Hedda, Kildal, Anders Benjamin, Holten, Aleksander Rygh, Lerum, Tøri Vigeland, Skjønsberg, Ole Henning, Michelsen, Annika E, Aaløkken, Trond M, Tonby, Kristian, Lind, Andreas, Dudman, Susanne, Granerud, Beathe Kiland, Heggelund, Lars, Bøe, Simen, and Dyrholt‐Riise, Anne Ma

Subjects
COVID-19, EXTRACELLULAR matrix, CALCIUM-binding proteins, MATRIX metalloproteinases, INTENSIVE care units, PULMONARY fibrosis
Abstract

Background: Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID‐19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID‐19, we examined circulating levels of mediators involved in various aspects of these processes in COVID‐19 patients. Methods: Serial blood samples were obtained from two cohorts of hospitalised COVID‐19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3‐month follow‐up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60‐day total mortality and pulmonary pathology after 3‐months. We also evaluated the direct effect of inactivated SARS‐CoV‐2 on the release of the different ECM mediators in relevant cell lines. Results: Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium‐binding protein A12 and YKL‐40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3‐months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) in vitro after exposure to inactivated SARS‐CoV‐2 suggesting a direct link between these mediators and the causal agent of COVID‐19. Conclusion: Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL‐40 in the pathogenesis of severe COVID‐19. [ABSTRACT FROM AUTHOR]

Published
2023
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4. Elevated Levels of Interleukin-1β and Interleukin-10 Are Associated With Faster Lung Function Decline in People With Well-Treated Human Immunodeficiency Virus

Author

Thudium, Rebekka F, primary, Arentoft, Nicoline S, additional, Hoel, Hedda, additional, Afzal, Shoaib, additional, von Stemann, Jakob H, additional, Forman, Julie L, additional, Wilcke, Jon T, additional, Benfield, Thomas, additional, Trøseid, Marius, additional, Borges, Álvaro H, additional, Ostrowski, Sisse R, additional, Vestbo, Jørgen, additional, Kunisaki, Ken M, additional, Jensen, Jens-Ulrik S, additional, and Nielsen, Susanne D, additional

Published
2023
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5. DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients

Author

Olsen, Maria Belland, primary, Huse, Camilla, additional, Sousa, Mirta Mittelstedt Leal de, additional, Murphy, Sarah Louise, additional, Sarno, Antonio, additional, Obermann, Tobias Sebastian, additional, Yang, Kuan, additional, Holter, Jan Cato, additional, Jørgensen, Marte Jøntvedt, additional, Christensen, Erik Egeland, additional, Wang, Wei, additional, Ji, Ping, additional, Heggelund, Lars, additional, Hoel, Hedda, additional, Dyrhol-Riise, Anne Margarita, additional, Gregersen, Ida, additional, Aukrust, Pål, additional, Bjørås, Magnar, additional, Halvorsen, Bente, additional, and Dahl, Tuva Børresdatter, additional

Published
2022
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6. CXCL16 associates with adverse outcome and cardiac involvement in hospitalized patients with Covid-19

Author

Gregersen, Ida, primary, Ueland, Thor, additional, Holter, Jan Cato, additional, Olsen, Maria Belland, additional, Michelsen, Annika E, additional, Murphy, Sarah L, additional, Tveita, Anders Aune, additional, Henriksen, Katerina Nezvalova, additional, Hoel, Hedda, additional, Nordberg, Lena Bugge, additional, Holten, Aleksander Rygh, additional, Edvardsen, Thor, additional, Yang, Kuan, additional, Heggelund, Lars, additional, Trøseid, Marius, additional, Müller, Fredrik, additional, Kildal, Anders Benjamin, additional, Dyrhol-Riise, Anne Ma, additional, Barratt-Due, Andreas, additional, Dahl, Tuva B, additional, Aukrust, Pål, additional, and Halvorsen, Bente, additional

Published
2022
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7. Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies

Author

Trøseid, Marius, Dahl, Tuva Børresdatter, Holter, Jan Cato, Kildal, Anders Benjamin, Murphy, Sarah Louise Mikalsen, Yang, Kuan, Quiles Jimenez, Ana Maria Teresa, Heggelund, Lars, Muller, Karl Erik, Tveita, Anders Aune, Michelsen, Annika Elisabet, Bøe, Simen, Holten, Aleksander Rygh, Hoel, Hedda Benedicte, Mathiessen, Alexander, Aaløkken, Trond Mogens, Fevang, Børre, Granerud, Beathe Kiland, Tonby, Kristian, Nezvalova-Henriksen, Katerina, Lerum, Tøri Vigeland, Müller, Fredrik, Skjønsberg, Ole Henning, Barratt-Due, Andreas, Riise, Anne Margarita Dyrhol, Aukrust, Pål, Halvorsen, Bente Evy, and Ueland, Thor

Subjects
Cohort Studies, SARS-CoV-2, T-Lymphocytes, Internal Medicine, COVID-19, Humans, Lymphocyte Activation
Abstract

Background - T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. Objectives - To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19. Methods - Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID-19 (n = 414) were analyzed for soluble (s) markers of T-cell activation (sCD25) and exhaustion (sTim-3) during hospitalization and follow-up. Results - Both markers were strongly associated with acute respiratory failure, but only sTim-3 was independently associated with 60-day mortality. Levels of sTim-3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months. Conclusion - Our findings suggest prolonged T-cell exhaustion is an important immunological sequela, potentially related to long-term outcomes after severe COVID-19.

Published
2022

8. High circulating levels of the homeostatic chemokines CCL19 and CCL21 predict mortality and disease severity in Covid-19

Author

Tveita, Anders, Murphy, Sarah Louise, Holter, Jan Cato, Kildal, Anders Benjamin, Michelsen, Annika E, Lerum, Tøri Vigeland, Kaarbø, Mari, Heggelund, Lars, Holten, Aleksander Rygh, Finbråten, Ane-Kristine, Müller, Karl Erik, Mathiessen, Alexander, Bøe, Simen, Fevang, Børre, Granerud, Beathe Kiland, Tonby, Kristian, Lind, Andreas, Dudman, Susanne Gjeruldsen, Henriksen, Katerina Nezvalova, Müller, Fredrik, Skjønsberg, Ole Henning, Trøseid, Marius, Barratt-Due, Andreas, Dyrhol-Riise, Anne Ma, Aukrust, Pål, Halvorsen, Bente, Dahl, Tuva Børresdatter, Ueland, Thor, Austad, Cathrine, Bogen, Mette, Hermann, Anne, Opsand, Hanne, Steinsvik, Trude, Woll, Bjørn Martin, Christensen, Erik Egeland, Eftestøl, Kristin, Hesstvedt, Liv, Jenum, Synne, Jørgensen, Marthe Jøntvedt, Landaas, Elisabeth Toverud, Nur, Sarah, Ormaasen, Vidar, Pettersen, Frank Olav, Quist-Paulsen, Else, Reikvam, Dag Henrik, Røstad, Kjerstin, Skeie, Linda, Steffensen, Anne Katrine, Stiksrud, Birgitte, Gravrok, Berit, Skogen, Vegard, Tylden, Garth Daryl, Andersen, Jan Terje, Kolderup, Anette, Kåsine, Trine, Lund-Johansen, Fridtjof, Olsen, Inge Christoffer, Skåra, Karoline Hansen, Tran, Trung, Fladeby, Cathrine, Holberg-Petersen, Mona, Johal, Simreen Kaur, Vaage, Eline Brenno, Aballi, Saad, Brynhildsen, Jorunn, Ghanima, Waleed, Halstensen, Anne Marie, Berg, Åse, Blomberg, Bjørn, Kvåle, Reidar, Langeland, Nina, Mohn, Kristin Greve Isdahl, Dalgard, Olav, Eiken, Ragnhild, Molvik, Richard Alexander, Ystrøm, Carl Magnus, Ernst, Gernot, Thoresen, Lars, Gustad, Lise Tuset, Saxhaug, Lars Mølgaard, Skei, Nina Vibeche, Hannula, Raisa, Haugli, Mette, Olsen, Roy Bjørkholt, Hoel, Hedda, Hoff, Dag Arne Lihaug, Johannessen, Asgeir, Åsheim-Hansen, Bjørn, Kittang, Bård Reikvam, Le, Lan Ai Kieu, Manotheepan, Ravinea, Nordberg, Lena Bugge, Rasmussen, Hans Schmidt, Stenvik, Grethe-Elisabeth, Thorkildsen, Ruth Foseide, Vinge, Leif Erik, Mielnik, Pawel, Skudal, Hilde, and Tholin, Birgitte

Subjects
Inflammation, Receptors, CCR7, Infectious Diseases, Chemokine CCL21, SARS-CoV-2, Patient Acuity, Humans, Chemokine CCL19, COVID-19, Immunology and Allergy, Chemokines
Abstract

Background Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 patients. Methods Serial blood samples were obtained from patients hospitalized with COVID-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and 3-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms. Results A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the 3-month follow-up. Conclusions Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in COVID-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in COVID-19. Clinical Trials Registration NCT04321616 and NCT04381819.

Published
2022

9. Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations

Author

Vestad, Beate, Ueland, Thor, Lerum, Tøri Vigeland, Dahl, Tuva Børresdatter, Holm, Kristian, Barratt-Due, Andreas, Kåsine, Trine, Dyrhol-Riise, Anne Ma, Stiksrud, Birgitte, Tonby, Kristian, Hoel, Hedda, Olsen, Inge Christoffer, Henriksen, Katerina N., Tveita, Anders Aune, Manotheepan, Ravinea, Haugli, Mette, Eiken, Ragnhild, Berg, Åse, Halvorsen, Bente, Lekva, Tove, Ranheim, Trine, Michelsen, Annika Elisabeth, Kildal, Anders Benjamin, Johannessen, Asgeir, Thoresen, Lars, Skudal, Hilde Kristin, Kittang, Bård Reiakvam, Olsen, Roy Bjørkholt, Ystrøm, Carl Magnus, Skei, Nina Vibeche, Hannula, Raisa, Aballi, Saad, Kvåle, Reidar, Skjønsberg, Ole Henning, Aukrust, Pål, Hov, Johannes Espolin Roksund, and Trøseid, Marius

Subjects
Inflammation, Clinical Trials as Topic, SARS-CoV-2, Post-Acute COVID-19 Syndrome, RNA, Ribosomal, 16S, Internal Medicine, COVID-19, Humans, microbiome, Gastrointestinal Microbiome, pulmonary function
Abstract

Background - Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. Methods - Plasma was collected during hospital admission and after 3 months from the NOR-Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene. Results - Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2/fiO2 (P/F ratio)

Published
2022

10. Gut microbiota alterations in patients with persistent respiratory dysfunction three months after severe COVID-19

Author

Vestad, Beate, primary, Ueland, Thor, additional, Lerum, Tøri Vigeland, additional, Børresdatter Dahl, Tuva, additional, Holm, Kristian, additional, Barratt-Due, Andreas, additional, Kåsine, Trine, additional, Dyrhol-Riise, Anne Ma, additional, Stiksrud, Birgitte, additional, Tonby, Kristian, additional, Hoel, Hedda, additional, Olsen, Inge Christoffer, additional, Henriksen, Katerina Nezvalova, additional, Tveita, Anders, additional, Manotheepan, Ravinea, additional, Haugli, Mette, additional, Eiken, Ragnhild, additional, Berg, Åse, additional, Halvorsen, Bente, additional, Lekva, Tove, additional, Ranheim, Trine, additional, Michelsen, Annika Elisabeth, additional, Kildal, Anders Benjamin, additional, Johannessen, Asgeir, additional, Thoresen, Lars, additional, Skudal, Hilde, additional, Kittang, Bård Reiakvam, additional, Bjørkholt Olsen, Roy, additional, Ystrøm, Carl Magnus, additional, Skei, Nina Vibeche, additional, Hannula, Raisa, additional, Aballi, Saad, additional, Kvåle, Reidar, additional, Skjønsberg, Ole Henning, additional, Aukrust, Pål, additional, Hov, Johannes Roksund, additional, and Trøseid, Marius, additional

Published
2021
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11. Potential role of plasma extracellular vesicles in microbial translocation and cardiovascular risk in people living with HIV and type 2 diabetes

Author

Vestad, Beate, primary, Nyman, Tuula Anneli, additional, Hove-Skovsgaard, Malene, additional, Stensland, Maria, additional, Hoel, Hedda, additional, Trøseid, Anne-Marie Siebke, additional, Aspelin, Trude, additional, Aass, Hans Christian Dalsbotten, additional, Puhka, Maija, additional, Hov, Johannes Roksund, additional, Nielsen, Susanne Dam, additional, Øvstebø, Reidun, additional, and Trøseid, Marius, additional

Published
2021
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12. Inflammasome activation, gut microbiota and comorbidities in HIV and COVID-19

Author

Hoel, Hedda Benedicte

Abstract

Despite antiretroviral treatment people with HIV still have a lower life expectancy and increased risk of non-communicable comorbidities such as cardiovascular diseases. Several mechanisms including chronic immune activation, inflammation and traditional risk factors contribute, but exact mechanisms remain elusive. Altered gut microbiota is seen in many diseases including HIV, and lately also COVID-19. Tryptophan metabolism through the kynurenine pathway is of importance in the interplay between microbiota and the immune system. Inflammasome activation is central in the atherogenic pathogenesis, and leads to the release of the proinflammatory cytokines IL-1 and IL-18. These cytokines are tightly regulated, and markers of this activation can be analyzed in plasma. This thesis aimed to elucidate mechanisms related to microbiota, inflammasome activation and cardiovascular involvement in the RNA viral diseases HIV and Covid-19. The main findings were that patients that had both HIV and Type 2 diabetes had a reduced gut microbial diversity, higher levels of inflammation and a higher Kynurenine/Tryptophan ratio. Also, tryptophan metabolism was associated with endothelial dysfunction. Furthermore, in a nested case control study, markers of IL-1 activity predicted myocardial infarction in HIV patients up to 10 years before the insult, suggesting the IL-1 system could be an important target for preventive intervention. In Covid-19 disease respiratory symptoms are most common, but the gut and heart is also affected. In a longitudinal observational study of hospitalized patients with COVID-19, those with cardiac involvement had higher levels of LPS binding Protein and IL-18 suggesting a gut-heart axis in Covid-19, possibly involving inflammasome activation, but further studies are needed.

Published
2021

13. Independent Associations of Tumor Necrosis Factor-Alpha and Interleukin-1 Beta With Radiographic Emphysema in People Living With HIV

Author

Thudium, Rebekka F., primary, Ringheim, Hedda, additional, Ronit, Andreas, additional, Hoel, Hedda, additional, Benfield, Thomas, additional, Mocroft, Amanda, additional, Gerstoft, Jan, additional, Trøseid, Marius, additional, Borges, Álvaro H., additional, Ostrowski, Sisse R., additional, Vestbo, Jørgen, additional, and Nielsen, Susanne D., additional

Published
2021
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14. Evaluation of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 Patients: Results from the NOR-Solidarity Randomised Trial

Author

Barratt-Due, Andreas, primary, Olsen, Inge Christoffer, additional, Henriksen, Katerina Nezvalova, additional, Kåsine, Trine, additional, Lund-Johansen, Fridtjof, additional, Hoel, Hedda, additional, Holten, Aleksander Rygh, additional, Tveita, Anders, additional, Mathiessen, Alexander, additional, Haugli, Mette, additional, Eiken, Ragnhild, additional, Kildal, Anders Benjamin, additional, Berg, Åse, additional, Johannessen, Asgeir, additional, Heggelund, Lars, additional, Dahl, Tuva Børresdatter, additional, Skåra, Karoline Hansen, additional, Mielnik, Pawel, additional, Le, Lan Ai Kieu, additional, Thoresen, Lars, additional, Ernst, Gernot, additional, Hoff, Dag Arne Lihaug, additional, Skudal, Hilde, additional, Kittang, Bård Reiakvam, additional, Olsen, Roy Bjørkholt, additional, Tholin, Birgitte, additional, Ystrøm, Carl Magnus, additional, Skei, Nina Vibeche, additional, Tran, Trung, additional, Dudman, Susanne, additional, Andersen, Jan Terje, additional, Hannula, Raisa, additional, Dalgard, Olav, additional, Finbråten, Ane-Kristine, additional, Tonby, Kristian, additional, Blomberg, Bjørn, additional, Aballi, Saad, additional, Fladeby, Cathrine, additional, Steffensen, Anne, additional, Müller, Fredrik, additional, Dyrhol-Riise, Anne Ma, additional, Trøseid, Marius, additional, and Aukrust, Pål, additional

Published
2021
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15. Independent Association of Interleukin 6 With Low Dynamic Lung Function and Airflow Limitation in Well-Treated People With Human Immunodeficiency Virus

Author

Thudium, Rebekka F, primary, Knudsen, Andreas D, additional, Von Stemann, Jakob Hjorth, additional, Hove-Skovsgaard, Malene, additional, Hoel, Hedda, additional, Mocroft, Amanda, additional, Reekie, Joanne, additional, Ronit, Andreas, additional, Gerstoft, Jan, additional, Vestbo, Jørgen, additional, Trøseid, Marius, additional, Borges, Álvaro H, additional, Ostrowski, Sisse R, additional, and Nielsen, Susanne D, additional

Published
2020
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16. Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection

Author

Hoel, Hedda, primary, Ueland, Thor, additional, Hove-Skovsgaard, Malene, additional, Hartling, Hans Jakob, additional, Gelpi, Marco, additional, Benfield, Thomas, additional, Ullum, Henrik, additional, Michelsen, Annika E, additional, Aukrust, Pål, additional, Nielsen, Susanne Dam, additional, and Trøseid, Marius, additional

Published
2020
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17. Impact of Human Immunodeficiency Virus–Related Gut Microbiota Alterations on Metabolic Comorbid Conditions

Author

Gelpi, Marco, primary, Vestad, Beate, additional, Hansen, Simen Hyll, additional, Holm, Kristian, additional, Drivsholm, Ninna, additional, Goetz, Alexandra, additional, Kirkby, Nicolai Søren, additional, Lindegaard, Birgitte, additional, Lebech, Anne-Mette, additional, Hoel, Hedda, additional, Michelsen, Annika E, additional, Ueland, Thor, additional, Gerstoft, Jan, additional, Lundgren, Jens, additional, Hov, Johannes Roksund, additional, Nielsen, Susanne Dam, additional, and Trøseid, Marius, additional

Published
2020
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18. Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial.

Author

Barratt-Due, Andreas, Olsen, Inge Christoffer, Nezvalova-Henriksen, Katerina, Kåsine, Trine, Lund-Johansen, Fridtjof, Hoel, Hedda, Holten, Aleksander Rygh, Tveita, Anders, Mathiessen, Alexander, Haugli, Mette, Eiken, Ragnhild, Kildal, Anders Benjamin, Berg, Åse, Johannessen, Asgeir, Heggelund, Lars, Dahl, Tuva Børresdatter, Skåra, Karoline Hansen, Mielnik, Pawel, Le, Lan Ai Kieu, and Thoresen, Lars

Subjects
REMDESIVIR, COVID-19, MEDICAL research, HYDROXYCHLOROQUINE, SARS-CoV-2
Abstract

Background: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known.Objective: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx.Design: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616).Setting: 23 hospitals in Norway.Patients: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection.Intervention: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87).Measurements: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables.Results: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance.Limitation: The trial had no placebo group.Conclusion: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19.Primary Funding Source: National Clinical Therapy Research in the Specialist Health Services, Norway. [ABSTRACT FROM AUTHOR]

Published
2021
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19. Independent Association of Interleukin 6 With Low Dynamic Lung Function and Airflow Limitation in Well-Treated People With Human Immunodeficiency Virus.

Author

Thudium, Rebekka F, Knudsen, Andreas D, Stemann, Jakob Hjorth Von, Hove-Skovsgaard, Malene, Hoel, Hedda, Mocroft, Amanda, Reekie, Joanne, Ronit, Andreas, Gerstoft, Jan, Vestbo, Jørgen, Trøseid, Marius, Borges, Álvaro H, Ostrowski, Sisse R, Nielsen, Susanne D, and Von Stemann, Jakob Hjorth

Subjects
HIV, TUMOR necrosis factors, VITAL capacity (Respiration), AIR flow, HIV infections, HIV infection complications, INTERLEUKINS, CYTOKINES, RESEARCH, LUNG diseases, LUNGS, RESEARCH methodology, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies
Abstract

Background: Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH.Methods: We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices.Results: PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (-212 mL [95% confidence interval, -308 to -116 mL]), lower forced vital capacity (-208 mL [-322 to -93 mL]), and airflow limitation (aOR, 2.62 [1.58-4.36]) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005).Conclusion: IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases. [ABSTRACT FROM AUTHOR]

Published
2021
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20. Soluble Markers of Interleukin 1 Activation as Predictors of First-Time Myocardial Infarction in HIV-Infected Individuals

Author

Hoel, Hedda, primary, Ueland, Thor, additional, Knudsen, Andreas, additional, Kjær, Andreas, additional, Michelsen, Annika E, additional, Sagen, Ellen Lund, additional, Halvorsen, Bente, additional, Yndestad, Arne, additional, Nielsen, Susanne Dam, additional, Aukrust, Pål, additional, Lebech, Anne-Mette, additional, and Trøseid, Marius, additional

Published
2019
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21. Neutrophil count predicts clinical outcome in hospitalized COVID‐19 patients: Results from the NOR‐Solidarity trial.

Author

Kåsine, Trine, Dyrhol‐Riise, Anne Ma, Barratt‐Due, Andreas, Kildal, Anders Benjamin, Olsen, Inge Christoffer, Nezvalova‐Henriksen, Katerina, Lund‐Johansen, Fridtjof, Hoel, Hedda, Holten, Aleksander Rygh, Tveita, Anders, Mathiessen, Alexander, Haugli, Mette, Eiken, Ragnhild, Berg, Åse, Johannessen, Asgeir, Heggelund, Lars, Dahl, Tuva Børresdatter, Halvorsen, Bente, Mielnik, Pawel, and Le, Lan Ai Kieu

Subjects
COVID-19, HOSPITAL patients, NEUTROPHILS, TREATMENT effectiveness, LEUKOCYTE count
Abstract

To the Editor: Despite numerous studies on SARS-CoV-2-induced inflammation, we still lack markers for rapid disease progression with admission to intensive care unit (ICU) or respiratory failure (RF). Both ferritin, reflecting macrophage activation, and LDH, as a general marker of cell damage, correlate with severe disease manifestations and/or unfavourable outcome in COVID-19 patients [7,8]. Neutrophil count predicts clinical outcome in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial. [Extracted from the article]

Published
2022
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22. Soluble Markers of Interleukin 1 Activation as Predictors of First-Time Myocardial Infarction in HIV-Infected Individuals.

Author

Hoel, Hedda, Ueland, Thor, Knudsen, Andreas, Kjær, Andreas, Michelsen, Annika E, Sagen, Ellen Lund, Halvorsen, Bente, Yndestad, Arne, Nielsen, Susanne Dam, Aukrust, Pål, Lebech, Anne-Mette, and Trøseid, Marius

Subjects
*HIV, *CARDIOVASCULAR diseases, *HIV infection complications, *THERAPEUTIC use of monoclonal antibodies, *PROTEINS, *HIV infections, *ANTI-HIV agents, *RESEARCH, *RESEARCH methodology, *INTERLEUKIN-1, *MYOCARDIAL infarction, *CASE-control method, *MONOCLONAL antibodies, *PROGNOSIS, *RNA, *EVALUATION research, *MEDICAL cooperation, *COMPARATIVE studies, *CHEMICAL inhibitors
Abstract

People with human immunodeficiency virus (HIV) infection (PWH) have an increased risk of cardiovascular disease (CVD), compared with the general population. In a nested case-control study of 55 PWH with first-time myocardial infarction (MI; cases) and 182 PWH with no CVD (controls), we measured soluble markers of interleukin 1 (IL-1) activation at 4 different time points before the case's MI. Cases had higher levels of IL-1 receptor antagonist (IL-1Ra) at all time points leading up to first-time MI, and higher levels of IL-1Ra were associated with an approximately 1.5-fold increased risk of MI, supporting the rationale to target IL-1 activation to reduce cardiovascular risk in PWH. [ABSTRACT FROM AUTHOR]

Published
2020
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23. Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction

Author

Hoel, Hedda, primary, Hove-Skovsgaard, Malene, additional, Hov, Johannes R., additional, Gaardbo, Julie Christine, additional, Holm, Kristian, additional, Kummen, Martin, additional, Rudi, Knut, additional, Nwosu, Felix, additional, Valeur, Jørgen, additional, Gelpi, Marco, additional, Seljeflot, Ingebjørg, additional, Ueland, Per Magne, additional, Gerstoft, Jan, additional, Ullum, Henrik, additional, Aukrust, Pål, additional, Nielsen, Susanne Dam, additional, and Trøseid, Marius, additional

Published
2018
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26. Prevalence of hepatitis B & hepatitis C virus infections in potential blood donors in rural Vietnam

Author

Le, Viet, Nguyen, Thi Ngoc Lan, Ty, Phung Xuan, Bjørkvoll, Bjørn, Hoel, Hedda B, Gutteberg, Tore Jarl, Husebekk, Anne, Larsen, Stig, Skjerve, Eystein, and Husum, Hans

Subjects
hepatitis C virus, hepatitis B surface antigen, occult hepatitis B infection, HBsAg, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, Vietnam, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, virus diseases, Original Article, safe blood transfusion, hepatitis B core antibody, Anti-HBc, blood donor screening
Abstract

This article is part of Viet Le's doctoral thesis which is available in Munin at http://hdl.handle.net/10037/6970 Safe blood and blood products should be offered to all patients in need for blood transfusion. The objectives of the present study were to establish prevalence estimates for hepatitis B and hepatitis C virus infections as a foundation for safe blood transfusion in rural Vietnam, and to check the accuracy of the laboratory analysis used for hepatitis testing of blood donors in Vietnam. A cross-sectional study was conducted in two rural communities in Quang Tri, Vietnam. A total of 1,200 blood samples collected from potential blood donors were tested by an enzyme immunoassay technique (EIA) for detection of hepatitis surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and antibodies to hepatitis C antigen (anti-HCV). The EIA test outcome was validated by a chemiluminescent micro particle immunoassay technique (CMIA). Results: The prevalence of HBsAg and anti-HBc in the study population was 11.4 per cent (95% CI 9.6 - 13.2) and 51.7 per cent (95% CI 48.8 - 54.5), respectively, the prevalences being higher in males than females. The prevalence of anti-HCV was 0.17 per cent. The test agreement between the EIA and CMIA techniques was high both for HBsAg detection (κ = 0.91; 95% CI: 0.83 - 0.99) and for anti-HBc detection (κ = 0.89; 95% CI 0.81 - 0.97). Compared to CMIA results, the positive and negative predictive values of the EIA tests were found to be 94.9 per cent (95% CI 87.5 - 98.6) and 97.5 per cent (95% CI 86.8 - 99.9) for HBsAg, and 92.4 per cent (95% CI 84.2 - 97.2) and 100 per cent (95% CI 91.2 - 100) for anti-HBc. Interpretation & conclusions: The study shows that hepatitis B virus infection is endemic in rural areas of Vietnam and that almost half of the population is or has been infected. Hepatitis C infection is rare, but false negative test results cannot be ruled out. Also, the results indicate that the EIA performance in blood donor screening in Vietnam may be sub-optimal, missing 2.5 per cent of hepatitis B virus carriers and falsely excluding more than 7 per cent of blood donors. As the prevalence of hepatitis B infection is high, occult hepatitis B infection may represent a threat to safe blood transfusion. Therefore, nucleic acid amplification testing for HBV should be considered for blood donor screening in Vietnam.

Published
2012

29. Microbiota-Dependent Marker TMAO Is Elevated in Silent Ischemia but Is Not Associated With First-Time Myocardial Infarction in HIV Infection

Author

Haissman, Judith M., primary, Knudsen, Andreas, additional, Hoel, Hedda, additional, Kjær, Andreas, additional, Kristoffersen, Ulrik S., additional, Berge, Rolf K., additional, Katzenstein, Terese L., additional, Svardal, Asbjørn, additional, Ueland, Thor, additional, Aukrust, Pål, additional, Lebech, Anne-Mette, additional, Nielsen, Susanne D., additional, and Trøseid, Marius, additional

Published
2016
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30. Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19

Author

Barratt-Due, Andreas, Olsen, Inge Christoffer, Nezvalova-Henriksen, Katerina, Kåsine, Trine, Lund-Johansen, Fridtjof, Hoel, Hedda, Holten, Aleksander Rygh, Tveita, Anders, Mathiessen, Alexander, Haugli, Mette, Eiken, Ragnhild, Kildal, Anders Benjamin, Berg, Åse, Johannessen, Asgeir, Heggelund, Lars, Dahl, Tuva Børresdatter, Skåra, Karoline Hansen, Mielnik, Pawel, Le, Lan Ai Kieu, Thoresen, Lars, Ernst, Gernot, Hoff, Dag Arne Lihaug, Skudal, Hilde, Kittang, Bård Reiakvam, Olsen, Roy Bjørkholt, Tholin, Birgitte, Ystrøm, Carl Magnus, Skei, Nina Vibeche, Tran, Trung, Dudman, Susanne, Andersen, Jan Terje, Hannula, Raisa, Dalgard, Olav, Finbråten, Ane-Kristine, Tonby, Kristian, Blomberg, Bjorn, Aballi, Saad, Fladeby, Cathrine, Steffensen, Anne, Müller, Fredrik, Dyrhol-Riise, Anne Ma, Trøseid, Marius, and Aukrust, Pål

Subjects
Inflammation, Male, Alanine, Norway, SARS-CoV-2, viruses, COVID-19, Oropharynx, Standard of Care, Middle Aged, Viral Load, Antibodies, Viral, Antiviral Agents, Severity of Illness Index, Adenosine Monophosphate, COVID-19 Drug Treatment, Treatment Outcome, Cause of Death, Humans, Female, Hospital Mortality, Respiratory Insufficiency, Biomarkers, Original Research, Hydroxychloroquine
Abstract

In an add-on study of the WHO Solidarity trial, Norwegian investigators examined the effect of remdesivir and hydroxychloroquine on the degree of clinical respiratory failure, on SARS-CoV-2 viral load in the oropharynx, and on levels of inflammatory variables in plasma or serum., Visual Abstract. Remdesivir and Hydroxychloroquine: Effects on SARS-CoV-2 Clearance. In an add-on study of the WHO Solidarity trial, Norwegian investigators examined the effect of remdesivir and hydroxychloroquine on the degree of clinical respiratory failure, on SARS-CoV-2 viral load in the oropharynx, and on levels of inflammatory variables in plasma or serum. Visual Abstract. Remdesivir and Hydroxychloroquine: Effects on SARS-CoV-2 Clearance. In an add-on study of the WHO Solidarity trial, Norwegian investigators examined the effect of remdesivir and hydroxychloroquine on the degree of clinical respiratory failure, on SARS-CoV-2 viral load in the oropharynx, and on levels of inflammatory variables in plasma or serum., Background: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. Objective: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. Design: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616) Setting: 23 hospitals in Norway. Patients: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. Intervention: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). Measurements: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. Results: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. Limitation: The trial had no placebo group. Conclusion: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. Primary Funding Source: National Clinical Therapy Research in the Specialist Health Services, Norway.

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31. Chronic HIV Infection Increases Monocyte NLRP3 Inflammasome-Dependent IL-1α and IL-1β Release.

Author

Hoel H, Dahl TB, Yang K, Skeie LG, Michelsen AE, Ueland T, Damås JK, Dyrhol-Riise AM, Fevang B, Yndestad A, Aukrust P, Trøseid M, and Sandanger Ø

Subjects
Humans, Male, Female, Adult, Middle Aged, Nuclear Proteins metabolism, Nuclear Proteins genetics, Phosphoproteins metabolism, Chronic Disease, Viral Load, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Monocytes metabolism, Monocytes immunology, HIV Infections immunology, HIV Infections virology, HIV Infections metabolism, Interleukin-1beta metabolism, Inflammasomes metabolism, Interleukin-1alpha metabolism
Abstract

Antiretroviral treatment (ART) has converted HIV from a lethal disease to a chronic condition, yet co-morbidities persist. Incomplete immune recovery and chronic immune activation, especially in the gut mucosa, contribute to these complications. Inflammasomes, multi-protein complexes activated by innate immune receptors, appear to play a role in these inflammatory responses. In particular, preliminary data indicate the involvement of IFI16 and NLRP3 inflammasomes in chronic HIV infection. This study explores inflammasome function in monocytes from people with HIV (PWH); 22 ART-treated with suppressed viremia and 17 untreated PWH were compared to 33 HIV-negative donors. Monocytes were primed with LPS and inflammasomes activated with ATP in vitro. IFI16 and NLRP3 mRNA expression were examined in a subset of donors. IFI16 and NLRP3 expression in unstimulated monocytes correlated negatively with CD4 T cell counts in untreated PWH. For IFI16, there was also a positive correlation with viral load. Monocytes from untreated PWH exhibit increased release of IL-1α, IL-1β, and TNF compared to treated PWH and HIV-negative donors. However, circulating monocytes in PWH are not pre-primed for inflammasome activation in vivo. The findings suggest a link between IFI16, NLRP3, and HIV progression, emphasizing their potential role in comorbidities such as cardiovascular disease. The study provides insights into inflammasome regulation in HIV pathogenesis and its implications for therapeutic interventions., Competing Interests: The authors declare no conflicts of interest.

Published
2024
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32. Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies.

Author

Trøseid M, Dahl TB, Holter JC, Kildal AB, Murphy SL, Yang K, Quiles-Jiménez A, Heggelund L, Müller KE, Tveita A, Michelsen AE, Bøe S, Holten AR, Hoel H, Mathiessen A, Aaløkken TM, Fevang B, Granerud BK, Tonby K, Henriksen KN, Lerum TV, Müller F, Skjønsberg OH, Barratt-Due A, Dyrhol-Riise AM, Aukrust P, Halvorsen B, and Ueland T

Subjects
Cohort Studies, Humans, Lymphocyte Activation, SARS-CoV-2, T-Lymphocytes, COVID-19
Abstract

Background: T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown., Objectives: To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19., Methods: Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID-19 (n = 414) were analyzed for soluble (s) markers of T-cell activation (sCD25) and exhaustion (sTim-3) during hospitalization and follow-up., Results: Both markers were strongly associated with acute respiratory failure, but only sTim-3 was independently associated with 60-day mortality. Levels of sTim-3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months., Conclusion: Our findings suggest prolonged T-cell exhaustion is an important immunological sequela, potentially related to long-term outcomes after severe COVID-19., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Published
2022
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33. Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations.

Author

Vestad B, Ueland T, Lerum TV, Dahl TB, Holm K, Barratt-Due A, Kåsine T, Dyrhol-Riise AM, Stiksrud B, Tonby K, Hoel H, Olsen IC, Henriksen KN, Tveita A, Manotheepan R, Haugli M, Eiken R, Berg Å, Halvorsen B, Lekva T, Ranheim T, Michelsen AE, Kildal AB, Johannessen A, Thoresen L, Skudal H, Kittang BR, Olsen RB, Ystrøm CM, Skei NV, Hannula R, Aballi S, Kvåle R, Skjønsberg OH, Aukrust P, Hov JR, and Trøseid M

Subjects
Clinical Trials as Topic, Humans, Inflammation, RNA, Ribosomal, 16S genetics, SARS-CoV-2, Post-Acute COVID-19 Syndrome, COVID-19 complications, Gastrointestinal Microbiome
Abstract

Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown., Methods: Plasma was collected during hospital admission and after 3 months from the NOR-Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DL CO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene., Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DL CO below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO 2 /fiO 2 (P/F ratio) <26.6 kPa. LBP levels remained elevated during and after hospitalization and were associated with low-grade inflammation and respiratory dysfunction after 3 months., Conclusion: Respiratory dysfunction after COVID-19 is associated with altered gut microbiota and persistently elevated LBP levels. Our results should be regarded as hypothesis generating, pointing to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID., (© 2022 The Association for the Publication of the Journal of Internal Medicine.)

Published
2022
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34. Microbiota-Dependent Marker TMAO Is Elevated in Silent Ischemia but Is Not Associated With First-Time Myocardial Infarction in HIV Infection.

Author

Haissman JM, Knudsen A, Hoel H, Kjær A, Kristoffersen US, Berge RK, Katzenstein TL, Svardal A, Ueland T, Aukrust P, Lebech AM, Nielsen SD, and Trøseid M

Subjects
Adolescent, Adult, Aged, Biomarkers metabolism, Case-Control Studies, Cohort Studies, Coronary Artery Disease complications, Coronary Artery Disease microbiology, Cross-Sectional Studies, Female, HIV Infections microbiology, Humans, Ischemia microbiology, Male, Middle Aged, Myocardial Infarction microbiology, Plaque, Atherosclerotic complications, Plaque, Atherosclerotic microbiology, Risk Factors, Young Adult, HIV Infections complications, Ischemia complications, Methylamines metabolism, Microbiota, Myocardial Infarction complications
Abstract

Objectives: HIV infection is associated with increased risk of coronary heart disease beyond that explained by traditional risk factors, and altered gut microbiota has been proposed as a potential trigger. Trimethylamine-N-oxide (TMAO) is a proatherogenic substance formed in the liver from trimethylamine, exclusively generated by gut microbiota from dietary phosphatidylcholine. We aimed to investigate whether TMAO is associated with subclinical and clinical coronary heart disease in HIV infection., Methods: Two previously described cohorts were examined as follows: (1) cross-sectional cohort of HIV-infected persons and uninfected controls with known atherosclerotic plaque burden as assessed by myocardial perfusion scintigraphy, coronary artery calcium score, and intima-media thickness and (2) nested case-control study of HIV-infected persons with first-time myocardial infarction (MI) compared with HIV-infected persons without MI, assessed at 4 time points from before initiation of antiretroviral therapy (ART) to last sample before the case's MI (median: 51, range: 0-239 days)., Results: There was no difference in plasma TMAO when comparing HIV-infected persons and uninfected controls. TMAO was elevated in HIV-infected persons with myocardial perfusion defects but was not associated with coronary artery calcium score, intima media thickness, or Framingham risk score. In the nested case control study, plasma TMAO was not associated with first-time MI. However, TMAO increased after ART introduction and was associated with the use of protease inhibitors in both cohorts., Conclusions: TMAO was elevated in HIV-infected persons with myocardial perfusion defects, but was not associated with first-time MI. Our data question TMAO as a useful biomarker of cardiovascular risk in HIV infection, at least in ART-treated individuals.

Published
2016
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35. Prevalence of hepatitis B & hepatitis C virus infections in potential blood donors in rural Vietnam.

Author

Viet L, Lan NT, Ty PX, Björkvoll B, Hoel H, Gutteberg T, Husebekk A, Larsen S, Skjerve E, and Husum H

Subjects
Cross-Sectional Studies, Female, Hepatitis Antigens blood, Humans, Immunoenzyme Techniques, Luminescent Measurements methods, Male, Prevalence, Sex Factors, Vietnam epidemiology, Blood Donors statistics & numerical data, Hepatitis B epidemiology, Hepatitis C epidemiology, Rural Health statistics & numerical data
Abstract

Background & Objectives: Safe blood and blood products should be offered to all patients in need for blood transfusion. The objectives of the present study were to establish prevalence estimates for hepatitis B and hepatitis C virus infections as a foundation for safe blood transfusion in rural Vietnam, and to check the accuracy of the laboratory analysis used for hepatitis testing of blood donors in Vietnam., Methods: A cross-sectional study was conducted in two rural communities in Quang Tri, Vietnam. A total of 1,200 blood samples collected from potential blood donors were tested by an enzyme immunoassay technique (EIA) for detection of hepatitis surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and antibodies to hepatitis C antigen (anti-HCV). The EIA test outcome was validated by a chemiluminescent micro particle immunoassay technique (CMIA)., Results: The prevalence of HBsAg and anti-HBc in the study population was 11.4 per cent (95% CI 9.6 - 13.2) and 51.7 per cent (95% CI 48.8 - 54.5), respectively, the prevalences being higher in males than females. The prevalence of anti-HCV was 0.17 per cent. The test agreement between the EIA and CMIA techniques was high both for HBsAg detection (κ = 0.91; 95% CI: 0.83 - 0.99) and for anti-HBc detection (κ = 0.89; 95% CI 0.81 - 0.97). Compared to CMIA results, the positive and negative predictive values of the EIA tests were found to be 94.9 per cent (95% CI 87.5 - 98.6) and 97.5 per cent (95% CI 86.8 - 99.9) for HBsAg, and 92.4 per cent (95% CI 84.2 - 97.2) and 100 per cent (95% CI 91.2 - 100) for anti-HBc., Interpretation & Conclusions: The study shows that hepatitis B virus infection is endemic in rural areas of Vietnam and that almost half of the population is or has been infected. Hepatitis C infection is rare, but false negative test results cannot be ruled out. Also, the results indicate that the EIA performance in blood donor screening in Vietnam may be sub-optimal, missing 2.5 per cent of hepatitis B virus carriers and falsely excluding more than 7 per cent of blood donors. As the prevalence of hepatitis B infection is high, occult hepatitis B infection may represent a threat to safe blood transfusion. Therefore, nucleic acid amplification testing for HBV should be considered for blood donor screening in Vietnam.

Published
2012

36. Screening test accuracy among potential blood donors of HBsAg, anti-HBc and anti-HCV to detect hepatitis B and C virus infection in rural Cambodia and Vietnam.

Author

Bjoerkvoll B, Viet L, Ol HS, Lan NT, Sothy S, Hoel H, Gutteberg T, Husebekk A, Larsen S, and Husum H

Subjects
Adult, Cambodia epidemiology, Confidence Intervals, Cross-Sectional Studies, Female, Hepatitis B blood, Hepatitis C blood, Humans, Immunoassay methods, Male, Prevalence, Rural Population, Sensitivity and Specificity, Vietnam epidemiology, Blood Donors, Hepatitis B epidemiology, Hepatitis B Core Antigens blood, Hepatitis B Surface Antigens blood, Hepatitis C epidemiology, Hepatitis C Antibodies blood, Mass Screening methods
Abstract

The aim of this study was to determine the accuracy of rapid tests for HBsAg, anti-HBc and anti-HCV in rural Cambodia and Vietnam to detect hepatitis B and C. In a cross-sectional epidemiological study of two populations of 1,200 potential blood donors in rural Cambodia and Vietnam the prevalence rates of HBsAg, anti-HBc and anti-HCV as established by enzyme immunoassay (EIA) tests were compared to rapid test outcomes. The EIA reference test results were validated by Architect Chemiluminescent Microparticle Immunoassay (CMIA) technique. The actual rapid test demonstrated high specificity for all three test categories as claimed by the manufacturer. The test sensitivity observed was significantly lower than that claimed by the manufacturer: 86.5% for HBsAg, 86.6% for anti-HBc, and 76.4% for anti-HCV. There were large and significant variations in test performance between the two countries, especially for HBsAg detection. The low sensitivity of the actual rapid tests for HBsAg, anti-HBc and anti-HCV make them useless for blood donor screening in rural Southeast Asia. Rapid tests may be useful screening tools in blood transfusion services in low-resource settings, but tests should be carefully validated locally before being used for screening purposes since test performance varies by location.

Published
2010

37. Prevalence of hepatitis B and hepatitis C virus infections in potential blood donors in rural Cambodia.

Author

Ol HS, Bjoerkvoll B, Sothy S, Van Heng Y, Hoel H, Husebekk A, Gutteberg T, Larsen S, and Husum H

Subjects
Adolescent, Adult, Cambodia epidemiology, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Hepatitis B Surface Antigens blood, Hepatitis C Antibodies blood, Humans, Male, Middle Aged, Prevalence, Sensitivity and Specificity, Young Adult, Blood Donors statistics & numerical data, Hepatitis B epidemiology, Hepatitis C epidemiology, Rural Population statistics & numerical data
Abstract

The aims of the present study were to provide accurate prevalence of acute and occult hepatis B infection and hepatis C infection among potential blood donors in Cambodia and to study the accuracy of ELISA tests used for blood donor screening. A cross-sectional study was performed on samples collected from potential volunteer blood donors (n = 1,200) in two districts in rural Cambodia. The samples were tested using the ELISA technique for HBsAg, anti-HBc, and anti-HCV at a local blood bank. To validate the ELISA outcomes, a subset (n = 319) was analyzed by Automated Chemiluminescent Microparticle Immunoassay Technique (CMIA) at the University Hospital North Norway. The overall prevalence of the HBsAg positives was 7.7% (95% CI 6.2-9.3); the prevalence of anti-HBc positive samples was 58.6% (95% CI 55.8-61.4), and the prevalence of anti-HCV positive samples was 14.7% (95% CI 12.7-16.7). The prevalence rate of samples being both HBsAg positive and anti-HBc positive was 7.3% (95% CI 5.9 - 9.0), and the prevalence rate of HBsAg negative and anti-HBc positive samples was 51.2% (95% CI 48.4 - 54.1). The overall agreement between the ELISA and the CMIA test results was very high both for HBsAg and anti-HBc (kappa 0.93), and high for anti-HCV measurements (kappa 0.83). However, the false-negative rate for the ELISA anti-HCV test was as high as 15% (95% CI 6 - 30).

Published
2009

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