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1.
Journal of Clinical Medicine ; 12(2):644, 2023.
Article in English | MDPI | ID: covidwho-2200418

ABSTRACT

Background: There is not much evidence on the prognostic utility of different biological markers in patients with severe COVID-19 living at high altitude. The objective of this study was to determine the predictive value of inflammatory and hematological markers for the risk of mortality at 28 days in patients with severe COVID-19 under invasive mechanical ventilation, living at high altitude and in a low-resource setting. Methods: We performed a retrospective observational study including patients with severe COVID-19, under mechanical ventilation and admitted to the intensive care unit (ICU) located at 2850 m above sea level, between 1 April 2020 and 1 August 2021. Inflammatory (interleukin-6 (IL-6), ferritin, D-dimer, lactate dehydrogenase (LDH)) and hematologic (mean platelet volume (MPV), neutrophil/lymphocyte ratio (NLR), MPV/platelet ratio) markers were evaluated at 24 h and in subsequent controls, and when available at 48 h and 72 h after admission to the ICU. The primary outcome was the association of inflammatory and hematological markers with the risk of mortality at 28 days. Results: We analyzed 223 patients (median age (1st quartile [Q1]-3rd quartile [Q3]) 51 (26-75) years and 70.4% male). Patients with severe COVID-19 and with IL-6 values at 24 h ≥ 11, NLR values at 24 h ≥ 22, and NLR values at 72 h ≥ 14 were 8.3, 3.8, and 3.8 times more likely to die at 28 days, respectively. The SOFA and APACHE-II scores were not able to independently predict mortality. Conclusions: In mechanically ventilated patients with severe COVID-19 and living at high altitude, low-cost and immediately available blood markers such as IL-6 and NLR may predict the severity of the disease in low-resource settings.

2.
Academic Radiology ; 2023.
Article in English | ScienceDirect | ID: covidwho-2175722

ABSTRACT

Background Few reports have studied lung aeration and perfusion in normal lungs, COVID-19 and ARDS from other causes (NC-ARDS) using dual-energy computed tomography pulmonary angiograms (DE-CTPA). Aims To describe lung aeration and blood-volume distribution using DE-CTPAs of patients with NC-ARDS, COVID-19 and controls with a normal DE-CTPA ("healthy lungs”). We hypothesized that each of these conditions have unique ranges of aeration and pulmonary blood volumes. Methods This retrospective, single-center study of DE-CTPAs included patients with COVID-19, NC-ARDS (Berlin criteria) and controls. Patients with macroscopic pulmonary embolism were excluded. The outcomes studied were the (1) lung blood-volume in areas with different aeration levels (normal, ground glass opacities [GGO], consolidated lung) and (2) aeration/blood-volume ratios. Results Included were 20 patients with COVID-19 (10 mild, 10 moderate-severe), 6 with NC-ARDS and 12 healthy-controls. Lung aeration was lowest in patients with severe COVID-19 24%(IQR13%-31%) followed by those with NC-ARDS 40%(IQR21%-46%). Blood-volume in GGO was lowest in patients with COVID-19 [moderate-severe:-28.6(IQR-33.1–23.2);mild: -30.1(IQR-33.3–23.4)] and highest in normal aerated areas in NC-ARDS -37.4(IQR-52.5–30.2-) and moderate-severe COVID-19 -33.5(IQR-44.2–28.5). Median aeration/blood-volume ratio was lowest in severe COVID-19 but some values overlapped with those observed among patients with NC-ARDS. Conclusion Severe COVID-19 disease is associated with low total aerated lung volume and blood-volume in areas with GGO and overall aeration/blood volume ratios, and with high blood volume in normal lung areas. In this hypothesis-generating study, these findings were most pronounced in severe COVID disease. Larger studies are needed to confirm these preliminary findings.

3.
Respiratory Physiology & Neurobiology ; : 104000, 2022.
Article in English | ScienceDirect | ID: covidwho-2132247

ABSTRACT

Coronavirus disease-2019 (COVID-19) may severely affect respiratory function and evolve to life-threatening hypoxia. The clinical experience led to the implementation of standardized protocols assuming similarity to severe acute respiratory syndrome (SARS-CoV-2). Understanding the histopathological and functional patterns is essential to better understand the pathophysiology of COVID-19 and then develop new therapeutic strategies. Epithelial and endothelial cell damage can result from the virus attack, thus leading to immune-mediated response. Pulmonary histopathological findings show the presence of Mallory bodies, alveolar coating cells with nuclear atypia, reactive pneumocytes, reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates, micro-abscesses, microthrombus, hyaline membrane fragments, and emphysema-like lung areas. COVID-19 patients may present different respiratory stages from silent to critical hypoxemia, are associated with the degree of pulmonary parenchymal involvement, thus yielding alteration of ventilation and perfusion relationships. This review aims to: discuss the morphological (histopathological and radiological) and functional findings of COVID-19 compared to acute interstitial pneumonia, acute respiratory distress syndrome (ARDS), and high-altitude pulmonary edema (HAPE), four entities that share common clinical traits, but have peculiar pathophysiological features with potential implications to their clinical management.

4.
Clin Exp Med ; 2022 Nov 13.
Article in English | MEDLINE | ID: covidwho-2116678

ABSTRACT

Patients with severe SARS-CoV-2 infection have an overwhelming inflammatory response characterized by remarkable organs monocyte infiltration. We performed an immunophenotypic analysis on circulating monocytes in 19 COVID-19 patients in comparison with 11 naïve HIV-1 patients and 10 healthy subjects. Reduced frequency of classical monocytes and increased frequency of intermediate monocytes characterized COVID-19 patients with respect to both HIV naïve patients and healthy subjects. Intensity of C-C motif chemokine receptor 2 (CCR2) monocyte expression highly correlated with parameters of kidney dysfunction. Our data indicate that highly activated monocytes of COVID-19 patients may be pathogenically associated with the development of renal disease.

5.
J Clin Monit Comput ; 2022 Oct 25.
Article in English | MEDLINE | ID: covidwho-2084372

ABSTRACT

In severe acute respiratory distress syndrome (ARDS), veno-venous extracorporeal membrane oxygenation (V-V ECMO) has been proposed as a therapeutic strategy to possibly reduce mortality. Transpulmonary thermodilution (TPTD) enables monitoring of the extravascular lung water index (EVLWI) and cardiac preload parameters such as intrathoracic blood volume index (ITBVI) in patients with ARDS, but it is not generally recommended during V-V ECMO. We hypothesized that the amount of extracorporeal blood flow (ECBF) influences the calculation of EVLWI and ITBVI due to recirculation of indicator, which affects the measurement of the mean transit time (MTt), the time between injection and passing of half the indicator, as well as downslope time (DSt), the exponential washout of the indicator. EVLWI and ITBVI were measured in 20 patients with severe ARDS managed with V-V ECMO at ECBF rates from 6 to 4 and 2 l/min with TPTD. MTt and DSt significantly decreased when ECBF was reduced, resulting in a decreased EVLWI (26.1 [22.8-33.8] ml/kg at 6 l/min ECBF vs 22.4 [15.3-31.6] ml/kg at 4 l/min ECBF, p < 0.001; and 13.2 [11.8-18.8] ml/kg at 2 l/min ECBF, p < 0.001) and increased ITBVI (840 [753-1062] ml/m2 at 6 l/min ECBF vs 886 [658-979] ml/m2 at 4 l/min ECBF, p < 0.001; and 955 [817-1140] ml/m2 at 2 l/min ECBF, p < 0.001). In patients with severe ARDS managed with V-V ECMO, increasing ECBF alters the thermodilution curve, resulting in unreliable measurements of EVLWI and ITBVI. German Clinical Trials Register (DRKS00021050). Registered 14/08/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021050.

6.
Front Med (Lausanne) ; 9: 1017257, 2022.
Article in English | MEDLINE | ID: covidwho-2080187

ABSTRACT

Background: Post-COVID-19 Syndrome (PCS) is characterized by residual symptoms following the initial recovery from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The prevalence of PCS is known to be the highest among severe and critical forms of the disease. However, the occurrence and risk factors for PCS after mild or moderate SARS-CoV-2 infection has not been extensively investigated. Methods: Online and offline via both paper or mailed questionnaires distributed among Jordan collected between 1st and 21st August 2021, including a total number of 800 respondents, of whom 495 had previous mild to moderate COVID-19 infection. The Newcastle post-COVID syndrome Follow-up Screening Questionnaire was modified, translated, and used as a standard instrument for data collection regarding psychological, medical, and socio-economic symptoms post-infection. The primary outcome was the prevalence of PCS after mild to moderate COVID-19 in Jordan. Secondary outcome was the identification of PCS risk factors. Results: The most common PCS symptom was mood disturbance followed by fatigue, anxiety, and myalgia. Female gender significantly increased the risk for multiple PCS symptoms. Age < 30 years was found to be an independent risk factor for myalgia (p = 0.001). Conclusion: PCS is highly prevalent among COVID-19 survivors in Jordan, especially in females and patients with comorbidities. Planning physical and mental rehabilitation services is recommended for those patients with PCS symptoms after mild to moderate COVID-19 infection.

7.
Ultraschall Med ; 2021 Nov 03.
Article in English | MEDLINE | ID: covidwho-2077144

ABSTRACT

PURPOSE: The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020. MATERIALS AND METHODS: The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative. RESULTS: 807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0-6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001). CONCLUSION: This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification.

8.
Crit Care ; 26(1): 70, 2022 03 24.
Article in English | MEDLINE | ID: covidwho-2064832

ABSTRACT

BACKGROUND: Excessive inspiratory effort could translate into self-inflicted lung injury, thus worsening clinical outcomes of spontaneously breathing patients with acute respiratory failure (ARF). Although esophageal manometry is a reliable method to estimate the magnitude of inspiratory effort, procedural issues significantly limit its use in daily clinical practice. The aim of this study is to describe the correlation between esophageal pressure swings (ΔPes) and nasal (ΔPnos) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. METHODS: From January 1, 2021, to September 1, 2021, 61 consecutive patients with ARF (83.6% related to COVID-19) admitted to the Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) and candidate to escalation of non-invasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 h after starting NRS. Correlation between ΔPes and ΔPnos served as primary outcome. The effect of ΔPnos measurements on respiratory rate and ΔPes was also assessed. RESULTS: ΔPes and ΔPnos were strongly correlated at admission (R2 = 0.88, p < 0.001) and 24 h apart (R2 = 0.94, p < 0.001). The nasal plug insertion and the mouth closure required for ΔPnos measurement did not result in significant change of respiratory rate and ΔPes. The correlation between measures at 24 h remained significant even after splitting the study population according to the type of NRS (high-flow nasal cannulas [R2 = 0.79, p < 0.001] or non-invasive ventilation [R2 = 0.95, p < 0.001]). CONCLUSIONS: In a cohort of patients with ARF, nasal pressure swings did not alter respiratory mechanics in the short term and were highly correlated with esophageal pressure swings during spontaneous tidal breathing. ΔPnos might warrant further investigation as a measure of inspiratory effort in patients with ARF. TRIAL REGISTRATION: NCT03826797 . Registered October 2016.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Distress Syndrome , Respiratory Insufficiency , Humans , Respiration, Artificial/methods , Respiratory Insufficiency/therapy
9.
Front Med (Lausanne) ; 9: 994900, 2022.
Article in English | MEDLINE | ID: covidwho-2043491

ABSTRACT

Background: Respiratory physiotherapy is reported as safe and feasible in mechanically ventilated patients with severe Coronavirus Disease (COVID-19) admitted to Intensive Care Unit (ICU), but the short-term benefits remain unclear. Methods: We performed a retrospective observational study in four ICUs in Northern Italy. All patients with COVID-19 admitted to ICU and under invasive mechanical ventilation (MV) between March 1st and May 30th, 2020, were enrolled into the study. Overlap weighting based on the propensity score was used to adjust for confounding in the comparison of patients who had or had not been treated by physiotherapists. The primary outcome was the number of days alive and ventilator-free (VFDs). The secondary outcomes were arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F) at ICU discharge, ICU length of stay, ICU and hospital mortality, and survival at 90 days. The trial protocol was registered on clinicaltrials.gov (NCT05067907). Results: A total of 317 patients were included in the analysis. The median VFDs was 18 days [interquartile range (IQR) 10; 24] in patients performing physiotherapy and 21 days (IQR 0; 26) in the group without physiotherapy [incidence rate ratio (IRR) 0.86, 95% confidence interval (CI): 0.78; 0.95]. The chance of 0 VFDs was lower for patients treated by physiotherapists compared to those who were not [odds ratio (OR) = 0.36, 95% CI: 0.18-0.71]. Survival at 90 days was 96.0% in the physiotherapy group and 70.6% in patients not performing physiotherapy [hazard ratio (HR) = 0.14, 95% CI: 0.03-0.71]. Number of VFDs was not associated with body mass index (BMI), sex, or P/F at ICU admission for individuals with at least 1 day off the ventilator. Conclusion: In patients with COVID-19 admitted to ICU during the first pandemic wave and treated by physiotherapists, the number of days alive and free from MV was lower compared to patients who did not perform respiratory physiotherapy. Survival at 90 days in the physiotherapy group was greater compared to no physiotherapy. These findings may be the starting point for further investigation in this setting.

10.
Baruch, Joaquin, Rojek, Amanda, Kartsonaki, Christiana, Vijayaraghavan, Bharath K. T.; Gonçalves, Bronner P.; Pritchard, Mark G.; Merson, Laura, Dunning, Jake, Hall, Matthew, Sigfrid, Louise, Citarella, Barbara W.; Murthy, Srinivas, Yeabah, Trokon O.; Olliaro, Piero, Abbas, Ali, Abdukahil, Sheryl Ann, Abdulkadir, Nurul Najmee, Abe, Ryuzo, Abel, Laurent, Absil, Lara, Acharya, Subhash, Acker, Andrew, Adam, Elisabeth, Adrião, Diana, Al Ageel, Saleh, Ahmed, Shakeel, Ainscough, Kate, Airlangga, Eka, Aisa, Tharwat, Hssain, Ali Ait, Tamlihat, Younes Ait, Akimoto, Takako, Akmal, Ernita, Al Qasim, Eman, Alalqam, Razi, Alberti, Angela, Al‐dabbous, Tala, Alegesan, Senthilkumar, Alegre, Cynthia, Alessi, Marta, Alex, Beatrice, Alexandre, Kévin, Al‐Fares, Abdulrahman, Alfoudri, Huda, Ali, Imran, Ali, Adam, Shah, Naseem Ali, Alidjnou, Kazali Enagnon, Aliudin, Jeffrey, Alkhafajee, Qabas, Allavena, Clotilde, Allou, Nathalie, Altaf, Aneela, Alves, João, Alves, Rita, Alves, João Melo, Amaral, Maria, Amira, Nur, Ampaw, Phoebe, Andini, Roberto, Andréjak, Claire, Angheben, Andrea, Angoulvant, François, Ansart, Séverine, Anthonidass, Sivanesen, Antonelli, Massimo, de Brito, Carlos Alexandre Antunes, Apriyana, Ardiyan, Arabi, Yaseen, Aragao, Irene, Araujo, Carolline, Arcadipane, Antonio, Archambault, Patrick, Arenz, Lukas, Arlet, Jean‐Benoît, Arora, Lovkesh, Arora, Rakesh, Artaud‐Macari, Elise, Aryal, Diptesh, Asensio, Angel, Ashraf, Muhammad, Asif, Namra, Asim, Mohammad, Assie, Jean Baptiste, Asyraf, Amirul, Atique, Anika, Attanyake, A. M. Udara Lakshan, Auchabie, Johann, Aumaitre, Hugues, Auvet, Adrien, Axelsen, Eyvind W.; Azemar, Laurène, Azoulay, Cecile, Bach, Benjamin, Bachelet, Delphine, Badr, Claudine, Bævre‐Jensen, Roar, Baig, Nadia, Baillie, J. Kenneth, Baird, J. Kevin, Bak, Erica, Bakakos, Agamemnon, Bakar, Nazreen Abu, Bal, Andriy, Balakrishnan, Mohanaprasanth, Balan, Valeria, Bani‐Sadr, Firouzé, Barbalho, Renata, Barbosa, Nicholas Yuri, Barclay, Wendy S.; Barnett, Saef Umar, Barnikel, Michaela, Barrasa, Helena, Barrelet, Audrey, Barrigoto, Cleide, Bartoli, Marie, Baruch, Joaquín, Bashir, Mustehan, Basmaci, Romain, Basri, Muhammad Fadhli Hassin, Battaglini, Denise, Bauer, Jules, Rincon, Diego Fernando Bautista, Dow, Denisse Bazan, Beane, Abigail, Bedossa, Alexandra, Bee, Ker Hong, Begum, Husna, Behilill, Sylvie, Beishuizen, Albertus, Beljantsev, Aleksandr, Bellemare, David, Beltrame, Anna, Beltrão, Beatriz Amorim, Beluze, Marine, Benech, Nicolas, Benjiman, Lionel Eric, Benkerrou, Dehbia, Bennett, Suzanne, Bento, Luís, Berdal, Jan‐Erik, Bergeaud, Delphine, Bergin, Hazel, Sobrino, José Luis Bernal, Bertoli, Giulia, Bertolino, Lorenzo, Bessis, Simon, Bevilcaqua, Sybille, Bezulier, Karine, Bhatt, Amar, Bhavsar, Krishna, Bianco, Claudia, Bidin, Farah Nadiah, Singh, Moirangthem Bikram, Humaid, Felwa Bin, Kamarudin, Mohd Nazlin Bin, Bissuel, François, Bitker, Laurent, Bitton, Jonathan, Blanco‐Schweizer, Pablo, Blier, Catherine, Bloos, Frank, Blot, Mathieu, Boccia, Filomena, Bodenes, Laetitia, Bogaarts, Alice, Bogaert, Debby, Boivin, Anne‐Hélène, Bolze, Pierre‐Adrien, Bompart, François, Bonfasius, Aurelius, Borges, Diogo, Borie, Raphaël, Bosse, Hans Martin, Botelho‐Nevers, Elisabeth, Bouadma, Lila, Bouchaud, Olivier, Bouchez, Sabelline, Bouhmani, Dounia, Bouhour, Damien, Bouiller, Kévin, Bouillet, Laurence, Bouisse, Camile, Boureau, Anne‐Sophie, Bourke, John, Bouscambert, Maude, Bousquet, Aurore, Bouziotis, Jason, Boxma, Bianca, Boyer‐Besseyre, Marielle, Boylan, Maria, Bozza, Fernando Augusto, Braconnier, Axelle, Braga, Cynthia, Brandenburger, Timo, Monteiro, Filipa Brás, Brazzi, Luca, Breen, Patrick, Breen, Dorothy, Breen, Patrick, Brickell, Kathy, Browne, Shaunagh, Browne, Alex, Brozzi, Nicolas, Brunvoll, Sonja Hjellegjerde, Brusse‐Keizer, Marjolein, Buchtele, Nina, Buesaquillo, Christian, Bugaeva, Polina, Buisson, Marielle, Buonsenso, Danilo, Burhan, Erlina, Burrell, Aidan, Bustos, Ingrid G.; Butnaru, Denis, Cabie, André, Cabral, Susana, Caceres, Eder, Cadoz, Cyril, Calligy, Kate, Calvache, Jose Andres, Camões, João, Campana, Valentine, Campbell, Paul, Campisi, Josie, Canepa, Cecilia, Cantero, Mireia, Caraux‐Paz, Pauline, Cárcel, Sheila, Cardellino, Chiara Simona, Cardoso, Sofia, Cardoso, Filipe, Cardoso, Filipa, Cardoso, Nelson, Carelli, Simone, Carlier, Nicolas, Carmoi, Thierry, Carney, Gayle, Carqueja, Inês, Carret, Marie‐Christine, Carrier, François Martin, Carroll, Ida, Carson, Gail, Casanova, Maire‐Laure, Cascão, Mariana, Casey, Siobhan, Casimiro, José, Cassandra, Bailey, Castañeda, Silvia, Castanheira, Nidyanara, Castor‐Alexandre, Guylaine, Castrillón, Henry, Castro, Ivo, Catarino, Ana, Catherine, François‐Xavier, Cattaneo, Paolo, Cavalin, Roberta, Cavalli, Giulio Giovanni, Cavayas, Alexandros, Ceccato, Adrian, Cervantes‐Gonzalez, Minerva, Chair, Anissa, Chakveatze, Catherine, Chan, Adrienne, Chand, Meera, Auger, Christelle Chantalat, Chapplain, Jean‐Marc, Chas, Julie, Chatterjee, Allegra, Chaudry, Mobin, Iñiguez, Jonathan Samuel Chávez, Chen, Anjellica, Chen, Yih‐Sharng, Cheng, Matthew Pellan, Cheret, Antoine, Chiarabini, Thibault, Chica, Julian, Chidambaram, Suresh Kumar, Tho, Leong Chin, Chirouze, Catherine, Chiumello, Davide, Cho, Sung‐Min, Cholley, Bernard, Chopin, Marie‐Charlotte, Chow, Ting Soo, Chow, Yock Ping, Chua, Jonathan, Chua, Hiu Jian, Cidade, Jose Pedro, Herreros, José Miguel Cisneros, Citarella, Barbara Wanjiru, Ciullo, Anna, Clarke, Jennifer, Clarke, Emma, Granado, Rolando Claure‐Del, Clohisey, Sara, Cobb, Perren J.; Codan, Cassidy, Cody, Caitriona, Coelho, Alexandra, Coles, Megan, Colin, Gwenhaël, Collins, Michael, Colombo, Sebastiano Maria, Combs, Pamela, Connor, Marie, Conrad, Anne, Contreras, Sofía, Conway, Elaine, Cooke, Graham S.; Copland, Mary, Cordel, Hugues, Corley, Amanda, Cornelis, Sabine, Cornet, Alexander Daniel, Corpuz, Arianne Joy, Cortegiani, Andrea, Corvaisier, Grégory, Costigan, Emma, Couffignal, Camille, Couffin‐Cadiergues, Sandrine, Courtois, Roxane, Cousse, Stéphanie, Cregan, Rachel, Croonen, Sabine, Crowl, Gloria, Crump, Jonathan, Cruz, Claudina, Bermúdez, Juan Luis Cruz, Rojo, Jaime Cruz, Csete, Marc, Cullen, Ailbhe, Cummings, Matthew, Curley, Gerard, Curlier, Elodie, Curran, Colleen, Custodio, Paula, da Silva Filipe, Ana, Da Silveira, Charlene, Dabaliz, Al‐Awwab, Dagens, Andrew, Dahl, John Arne, Dahly, Darren, Dalton, Heidi, Dalton, Jo, Daly, Seamus, Daneman, Nick, Daniel, Corinne, Dankwa, Emmanuelle A.; Dantas, Jorge, D'Aragon, Frédérick, de Loughry, Gillian, de Mendoza, Diego, De Montmollin, Etienne, de Oliveira França, Rafael Freitas, de Pinho Oliveira, Ana Isabel, De Rosa, Rosanna, De Rose, Cristina, de Silva, Thushan, de Vries, Peter, Deacon, Jillian, Dean, David, Debard, Alexa, Debray, Marie‐Pierre, DeCastro, Nathalie, Dechert, William, Deconninck, Lauren, Decours, Romain, Defous, Eve, Delacroix, Isabelle, Delaveuve, Eric, Delavigne, Karen, Delfos, Nathalie M.; Deligiannis, Ionna, Dell'Amore, Andrea, Delmas, Christelle, Delobel, Pierre, Delsing, Corine, Demonchy, Elisa, Denis, Emmanuelle, Deplanque, Dominique, Depuydt, Pieter, Desai, Mehul, Descamps, Diane, Desvallées, Mathilde, Dewayanti, Santi, Dhanger, Pathik, Diallo, Alpha, Diamantis, Sylvain, Dias, André, Diaz, Juan Jose, Diaz, Priscila, Diaz, Rodrigo, Didier, Kévin, Diehl, Jean‐Luc, Dieperink, Wim, Dimet, Jérôme, Dinot, Vincent, Diop, Fara, Diouf, Alphonsine, Dishon, Yael, Djossou, Félix, Docherty, Annemarie B.; Doherty, Helen, Dondorp, Arjen M.; Donnelly, Maria, Donnelly, Christl A.; Donohue, Sean, Donohue, Yoann, Donohue, Chloe, Doran, Peter, Dorival, Céline, D'Ortenzio, Eric, Douglas, James Joshua, Douma, Renee, Dournon, Nathalie, Downer, Triona, Downey, Joanne, Downing, Mark, Drake, Tom, Driscoll, Aoife, Dryden, Murray, Fonseca, Claudio Duarte, Dubee, Vincent, Dubos, François, Ducancelle, Alexandre, Duculan, Toni, Dudman, Susanne, Duggal, Abhijit, Dunand, Paul, Dunning, Jake, Duplaix, Mathilde, Durante‐Mangoni, Emanuele, Durham, Lucian, Dussol, Bertrand, Duthoit, Juliette, Duval, Xavier, Dyrhol‐Riise, Anne Margarita, Ean, Sim Choon, Echeverria‐Villalobos, Marco, Egan, Siobhan, Eggesbø, Linn Margrete, Eira, Carla, El Sanharawi, Mohammed, Elapavaluru, Subbarao, Elharrar, Brigitte, Ellerbroek, Jacobien, Ellingjord‐Dale, Merete, Eloy, Philippine, Elshazly, Tarek, Elyazar, Iqbal, Enderle, Isabelle, Endo, Tomoyuki, Eng, Chan Chee, Engelmann, Ilka, Enouf, Vincent, Epaulard, Olivier, Escher, Martina, Esperatti, Mariano, Esperou, Hélène, Esposito‐Farese, Marina, Estevão, João, Etienne, Manuel, Ettalhaoui, Nadia, Everding, Anna Greti, Evers, Mirjam, Fabre, Marc, Fabre, Isabelle, Faheem, Amna, Fahy, Arabella, Fairfield, Cameron J.; Fakar, Zul, Fareed, Komal, Faria, Pedro, Farooq, Ahmed, Fateena, Hanan, Fatoni, Arie Zainul, Faure, Karine, Favory, Raphaël, Fayed, Mohamed, Feely, Niamh, Feeney, Laura, Fernandes, Jorge, Fernandes, Marília Andreia, Fernandes, Susana, Ferrand, François‐Xavier, Devouge, Eglantine Ferrand, Ferrão, Joana, Ferraz, Mário, Ferreira, Sílvia, Ferreira, Isabel, Ferreira, Benigno, Ferrer‐Roca, Ricard, Ferriere, Nicolas, Ficko, Céline, Figueiredo‐Mello, Claudia, Finlayson, William, Fiorda, Juan, Flament, Thomas, Flateau, Clara, Fletcher, Tom, Florio, Letizia Lucia, Flynn, Deirdre, Foley, Claire, Foley, Jean, Fomin, Victor, Fonseca, Tatiana, Fontela, Patricia, Forsyth, Simon, Foster, Denise, Foti, Giuseppe, Fourn, Erwan, Fowler, Robert A.; Fraher, Marianne, Franch‐Llasat, Diego, Fraser, John F.; Fraser, Christophe, Freire, Marcela Vieira, Ribeiro, Ana Freitas, Friedrich, Caren, Fry, Stéphanie, Fuentes, Nora, Fukuda, Masahiro, Argin, G.; Gaborieau, Valérie, Gaci, Rostane, Gagliardi, Massimo, Gagnard, Jean‐Charles, Gagneux‐Brunon, Amandine, Gaião, Sérgio, Skeie, Linda Gail, Gallagher, Phil, Gamble, Carrol, Gani, Yasmin, Garan, Arthur, Garcia, Rebekha, Barrio, Noelia García, Garcia‐Diaz, Julia, Garcia‐Gallo, Esteban, Garimella, Navya, Garot, Denis, Garrait, Valérie, Gauli, Basanta, Gault, Nathalie, Gavin, Aisling, Gavrylov, Anatoliy, Gaymard, Alexandre, Gebauer, Johannes, Geraud, Eva, Morlaes, Louis Gerbaud, Germano, Nuno, Ghisulal, Praveen Kumar, Ghosn, Jade, Giani, Marco, Gibson, Jess, Gigante, Tristan, Gilg, Morgane, Gilroy, Elaine, Giordano, Guillermo, Girvan, Michelle, Gissot, Valérie, Glikman, Daniel, Glybochko, Petr, Gnall, Eric, Goco, Geraldine, Goehringer, François, Goepel, Siri, Goffard, Jean‐Christophe, Goh, Jin Yi, Golob, Jonathan, Gomez, Kyle, Gómez‐Junyent, Joan, Gominet, Marie, Gonçalves, Bronner P.; Gonzalez, Alicia, Gordon, Patricia, Gorenne, Isabelle, Goubert, Laure, Goujard, Cécile, Goulenok, Tiphaine, Grable, Margarite, Graf, Jeronimo, Grandin, Edward Wilson, Granier, Pascal, Grasselli, Giacomo, Green, Christopher A.; Greene, Courtney, Greenhalf, William, Greffe, Segolène, Grieco, Domenico Luca, Griffee, Matthew, Griffiths, Fiona, Grigoras, Ioana, Groenendijk, Albert, Lordemann, Anja Grosse, Gruner, Heidi, Gu, Yusing, Guedj, Jérémie, Guego, Martin, Guellec, Dewi, Guerguerian, Anne‐Marie, Guerreiro, Daniela, Guery, Romain, Guillaumot, Anne, Guilleminault, Laurent, Guimarães de Castro, Maisa, Guimard, Thomas, Haalboom, Marieke, Haber, Daniel, Habraken, Hannah, Hachemi, Ali, Hackmann, Amy, Hadri, Nadir, Haidri, Fakhir, Hakak, Sheeba, Hall, Adam, Hall, Matthew, Halpin, Sophie, Hameed, Jawad, Hamer, Ansley, Hamers, Raph L.; Hamidfar, Rebecca, Hammarström, Bato, Hammond, Terese, Han, Lim Yuen, Haniffa, Rashan, Hao, Kok Wei, Hardwick, Hayley, Harrison, Ewen M.; Harrison, Janet, Harrison, Samuel Bernard Ekow, Hartman, Alan, Hasan, Mohd Shahnaz, Hashmi, Junaid, Hayat, Muhammad, Hayes, Ailbhe, Hays, Leanne, Heerman, Jan, Heggelund, Lars, Hendry, Ross, Hennessy, Martina, Henriquez‐Trujillo, Aquiles, Hentzien, Maxime, Hernandez‐Montfort, Jaime, Hershey, Andrew, Hesstvedt, Liv, Hidayah, Astarini, Higgins, Eibhilin, Higgins, Dawn, Higgins, Rupert, Hinchion, Rita, Hinton, Samuel, Hiraiwa, Hiroaki, Hirkani, Haider, Hitoto, Hikombo, Ho, Yi Bin, Ho, Antonia, Hoctin, Alexandre, Hoffmann, Isabelle, Hoh, Wei Han, Hoiting, Oscar, Holt, Rebecca, Holter, Jan Cato, Horby, Peter, Horcajada, Juan Pablo, Hoshino, Koji, Houas, Ikram, Hough, Catherine L.; Houltham, Stuart, Hsu, Jimmy Ming‐Yang, Hulot, Jean‐Sébastien, Huo, Stella, Hurd, Abby, Hussain, Iqbal, Ijaz, Samreen, Illes, Hajnal‐Gabriela, Imbert, Patrick, Imran, Mohammad, Sikander, Rana Imran, Imtiaz, Aftab, Inácio, Hugo, Dominguez, Carmen Infante, Ing, Yun Sii, Iosifidis, Elias, Ippolito, Mariachiara, Isgett, Sarah, Isidoro, Tiago, Ismail, Nadiah, Isnard, Margaux, Istre, Mette Stausland, Itai, Junji, Ivulich, Daniel, Jaafar, Danielle, Jaafoura, Salma, Jabot, Julien, Jackson, Clare, Jamieson, Nina, Jaquet, Pierre, Jaud‐Fischer, Coline, Jaureguiberry, Stéphane, Jaworsky, Denise, Jego, Florence, Jelani, Anilawati Mat, Jenum, Synne, Jimbo‐Sotomayor, Ruth, Joe, Ong Yiaw, Jorge García, Ruth N.; Jørgensen, Silje Bakken, Joseph, Cédric, Joseph, Mark, Joshi, Swosti, Jourdain, Mercé, Jouvet, Philippe, Jung, Hanna, Jung, Anna, Juzar, Dafsah, Kafif, Ouifiya, Kaguelidou, Florentia, Kaisbain, Neerusha, Kaleesvran, Thavamany, Kali, Sabina, Kalicinska, Alina, Kalleberg, Karl Trygve, Kalomoiri, Smaragdi, Kamaluddin, Muhammad Aisar Ayadi, Kamaruddin, Zul Amali Che, Kamarudin, Nadiah, Kamineni, Kavita, Kandamby, Darshana Hewa, Kandel, Chris, Kang, Kong Yeow, Kanwal, Darakhshan, Karpayah, Pratap, Kartsonaki, Christiana, Kasugai, Daisuke, Kataria, Anant, Katz, Kevin, Kaur, Aasmine, Kay, Christy, Keane, Hannah, Keating, Seán, Kedia, Pulak, Kelly, Claire, Kelly, Yvelynne, Kelly, Andrea, Kelly, Niamh, Kelly, Aoife, Kelly, Sadie, Kelsey, Maeve, Kennedy, Ryan, Kennon, Kalynn, Kernan, Maeve, Kerroumi, Younes, Keshav, Sharma, Khalid, Imrana, Khalid, Osama, Khalil, Antoine, Khan, Coralie, Khan, Irfan, Khan, Quratul Ain, Khanal, Sushil, Khatak, Abid, Khawaja, Amin, Kherajani, Krish, Kho, Michelle E.; Khoo, Ryan, Khoo, Denisa, Khoo, Saye, Khoso, Nasir, Kiat, Khor How, Kida, Yuri, Kiiza, Peter, Granerud, Beathe Kiland, Kildal, Anders Benjamin, Kim, Jae Burm, Kimmoun, Antoine, Kindgen‐Milles, Detlef, King, Alexander, Kitamura, Nobuya, Kjetland, Eyrun Floerecke Kjetland, Klenerman, Paul, Klont, Rob, Bekken, Gry Kloumann, Knight, Stephen R.; Kobbe, Robin, Kodippily, Chamira, Vasconcelos, Malte Kohns, Koirala, Sabin, Komatsu, Mamoru, Kosgei, Caroline, Kpangon, Arsène, Krawczyk, Karolina, Krishnan, Vinothini, Krishnan, Sudhir, Kruglova, Oksana, Kumar, Ganesh, Kumar, Deepali, Kumar, Mukesh, Vecham, Pavan Kumar, Kuriakose, Dinesh, Kurtzman, Ethan, Kutsogiannis, Demetrios, Kutsyna, Galyna, Kyriakoulis, Konstantinos, Lachatre, Marie, Lacoste, Marie, Laffey, John G.; Lagrange, Marie, Laine, Fabrice, Lairez, Olivier, Lakhey, Sanjay, Lalueza, Antonio, Lambert, Marc, Lamontagne, François, Langelot‐Richard, Marie, Langlois, Vincent, Lantang, Eka Yudha, Lanza, Marina, Laouénan, Cédric, Laribi, Samira, Lariviere, Delphine, Lasry, Stéphane, Lath, Sakshi, Latif, Naveed, Launay, Odile, Laureillard, Didier, Lavie‐Badie, Yoan, Law, Andy, Lawrence, Teresa, Lawrence, Cassie, Le, Minh, Le Bihan, Clément, Le Bris, Cyril, Le Falher, Georges, Le Fevre, Lucie, Le Hingrat, Quentin, Le Maréchal, Marion, Le Mestre, Soizic, Le Moal, Gwenaël, Le Moing, Vincent, Le Nagard, Hervé, Le Turnier, Paul, Leal, Ema, Santos, Marta Leal, Lee, Heng Gee, Lee, Biing Horng, Lee, Yi Lin, Lee, Todd C.; Lee, James, Lee, Jennifer, Lee, Su Hwan, Leeming, Gary, Lefebvre, Laurent, Lefebvre, Bénédicte, Lefèvre, Benjamin, LeGac, Sylvie, Lelievre, Jean‐Daniel, Lellouche, François, Lemaignen, Adrien, Lemee, Véronique, Lemeur, Anthony, Lemmink, Gretchen, Lene, Ha Sha, Lennon, Jenny, León, Rafael, Leone, Marc, Leone, Michela, Lepiller, Quentin, Lescure, François‐Xavier, Lesens, Olivier, Lesouhaitier, Mathieu, Lester‐Grant, Amy, Levy, Yves, Levy, Bruno, Levy‐Marchal, Claire, Lewandowska, Katarzyna, L'Her, Erwan, Bassi, Gianluigi Li, Liang, Janet, Liaquat, Ali, Liegeon, Geoffrey, Lim, Kah Chuan, Lim, Wei Shen, Lima, Chantre, Lina, Lim, Lina, Bruno, Lind, Andreas, Lingad, Maja Katherine, Lingas, Guillaume, Lion‐Daolio, Sylvie, Lissauer, Samantha, Liu, Keibun, Livrozet, Marine, Lizotte, Patricia, Loforte, Antonio, Lolong, Navy, Loon, Leong Chee, Lopes, Diogo, Lopez‐Colon, Dalia, Lopez‐Revilla, Jose W.; Loschner, Anthony L.; Loubet, Paul, Loufti, Bouchra, Louis, Guillame, Lourenco, Silvia, Lovelace‐Macon, Lara, Low, Lee Lee, Lowik, Marije, Loy, Jia Shyi, Lucet, Jean Christophe, Bermejo, Carlos Lumbreras, Luna, Carlos M.; Lungu, Olguta, Luong, Liem, Luque, Nestor, Luton, Dominique, Lwin, Nilar, Lyons, Ruth, Maasikas, Olavi, Mabiala, Oryane, Machado, Moïse, Macheda, Gabriel, Madiha, Hashmi, Maestro de la Calle, Guillermo, Mahieu, Rafael, Mahy, Sophie, Maia, Ana Raquel, Maier, Lars S.; Maillet, Mylène, Maitre, Thomas, Malfertheiner, Maximilian, Malik, Nadia, Mallon, Paddy, Maltez, Fernando, Malvy, Denis, Manda, Victoria, Mandelbrot, Laurent, Manetta, Frank, Mankikian, Julie, Manning, Edmund, Manuel, Aldric, Sant'Ana Malaque, Ceila Maria, Marino, Flávio, Marino, Daniel, Markowicz, Samuel, Maroun Eid, Charbel, Marques, Ana, Marquis, Catherine, Marsh, Brian, Marsh, Laura, Marshal, Megan, Marshall, John, Martelli, Celina Turchi, Martin, Dori‐Ann, Martin, Emily, Martin‐Blondel, Guillaume, Martin‐Loeches, Ignacio, Martinot, Martin, Martin‐Quiros, Alejandro, Martins, João, Martins, Ana, Martins, Nuno, Rego, Caroline Martins, Martucci, Gennaro, Martynenko, Olga, Marwali, Eva Miranda, Marzukie, Marsilla, Maslove, David, Mason, Sabina, Masood, Sobia, Nor, Basri Mat, Matan, Moshe, Mathew, Meghena, Mathieu, Daniel, Mattei, Mathieu, Matulevics, Romans, Maulin, Laurence, Maxwell, Michael, Maynar, Javier, Mazzoni, Thierry, Evoy, Natalie Mc, Sweeney, Lisa Mc, McArthur, Colin, McArthur, Colin, McCarthy, Anne, McCarthy, Aine, McCloskey, Colin, McConnochie, Rachael, McDermott, Sherry, McDonald, Sarah E.; McElroy, Aine, McElwee, Samuel, McEneany, Victoria, McGeer, Allison, McKay, Chris, McKeown, Johnny, McLean, Kenneth A.; McNally, Paul, McNicholas, Bairbre, McPartlan, Elaine, Meaney, Edel, Mear‐Passard, Cécile, Mechlin, Maggie, Meher, Maqsood, Mehkri, Omar, Mele, Ferruccio, Melo, Luis, Memon, Kashif, Mendes, Joao Joao, Menkiti, Ogechukwu, Menon, Kusum, Mentré, France, Mentzer, Alexander J.; Mercier, Noémie, Mercier, Emmanuelle, Merckx, Antoine, Mergeay‐Fabre, Mayka, Mergler, Blake, Merson, Laura, Mesquita, António, Meta, Roberta, Metwally, Osama, Meybeck, Agnès, Meyer, Dan, Meynert, Alison M.; Meysonnier, Vanina, Meziane, Amina, Mezidi, Mehdi, Michelanglei, Céline, Michelet, Isabelle, Mihelis, Efstathia, Mihnovit, Vladislav, Miranda‐Maldonado, Hugo, Misnan, Nor Arisah, Mohamed, Tahira Jamal, Mohamed, Nik Nur Eliza, Moin, Asma, Molina, David, Molinos, Elena, Molloy, Brenda, Mone, Mary, Monteiro, Agostinho, Montes, Claudia, Montrucchio, Giorgia, Moore, Shona C.; Moore, Sarah, Cely, Lina Morales, Moro, Lucia, Morton, Ben, Motherway, Catherine, Motos, Ana, Mouquet, Hugo, Perrot, Clara Mouton, Moyet, Julien, Mudara, Caroline, Mufti, Aisha Kalsoom, Muh, Ng Yong, Muhamad, Dzawani, Mullaert, Jimmy, Müller, Fredrik, Müller, Karl Erik, Munblit, Daniel, Muneeb, Syed, Munir, Nadeem, Munshi, Laveena, Murphy, Aisling, Murphy, Lorna, Murphy, Aisling, Murris, Marlène, Murthy, Srinivas, Musaab, Himed, Muvindi, Himasha, Muyandy, Gugapriyaa, Myrodia, Dimitra Melia, Mohd‐Hanafiah, Farah Nadia, Nagpal, Dave, Nagrebetsky, Alex, Narasimhan, Mangala, Narayanan, Nageswaran, Khan, Rashid Nasim, Nazerali‐Maitland, Alasdair, Neant, Nadège, Neb, Holger, Nekliudov, Nikita, Nelwan, Erni, Neto, Raul, Neumann, Emily, Ng, Pauline Yeung, Ng, Wing Yiu, Nghi, Anthony, Nguyen, Duc, Choileain, Orna Ni, Leathlobhair, Niamh Ni, Nichol, Alistair, Nitayavardhana, Prompak, Nonas, Stephanie, Noordin, Nurul Amani Mohd, Noret, Marion, Norharizam, Nurul Faten Izzati, Norman, Lisa, Notari, Alessandra, Noursadeghi, Mahdad, Nowicka, Karolina, Nowinski, Adam, Nseir, Saad, Nunez, Jose I.; Nurnaningsih, Nurnaningsih, Nusantara, Dwi Utomo, Nyamankolly, Elsa, Nygaard, Anders Benteson, Brien, Fionnuala O.; Callaghan, Annmarie O.; O'Callaghan, Annmarie, Occhipinti, Giovanna, Oconnor, Derbrenn, O'Donnell, Max, Ogston, Tawnya, Ogura, Takayuki, Oh, Tak‐Hyuk, O'Halloran, Sophie, O'Hearn, Katie, Ohshimo, Shinichiro, Oldakowska, Agnieszka, Oliveira, João, Oliveira, Larissa, Olliaro, Piero L.; Ong, Jee Yan, Ong, David S. Y.; Oosthuyzen, Wilna, Opavsky, Anne, Openshaw, Peter, Orakzai, Saijad, Orozco‐Chamorro, Claudia Milena, Ortoleva, Jamel, Osatnik, Javier, O'Shea, Linda, O'Sullivan, Miriam, Othman, Siti Zubaidah, Ouamara, Nadia, Ouissa, Rachida, Oziol, Eric, Pagadoy, Maïder, Pages, Justine, Palacios, Mario, Palacios, Amanda, Palmarini, Massimo, Panarello, Giovanna, Panda, Prasan Kumar, Paneru, Hem, Pang, Lai Hui, Panigada, Mauro, Pansu, Nathalie, Papadopoulos, Aurélie, Parke, Rachael, Parker, Melissa, Parra, Briseida, Pasha, Taha, Pasquier, Jérémie, Pastene, Bruno, Patauner, Fabian, Patel, Drashti, Pathmanathan, Mohan Dass, Patrão, Luís, Patricio, Patricia, Patrier, Juliette, Patterson, Lisa, Pattnaik, Rajyabardhan, Paul, Mical, Paul, Christelle, Paulos, Jorge, Paxton, William A.; Payen, Jean‐François, Peariasamy, Kalaiarasu, Jiménez, Miguel Pedrera, Peek, Giles J.; Peelman, Florent, Peiffer‐Smadja, Nathan, Peigne, Vincent, Pejkovska, Mare, Pelosi, Paolo, Peltan, Ithan D.; Pereira, Rui, Perez, Daniel, Periel, Luis, Perpoint, Thomas, Pesenti, Antonio, Pestre, Vincent, Petrou, Lenka, Petrovic, Michele, Petrov‐Sanchez, Ventzislava, Pettersen, Frank Olav, Peytavin, Gilles, Pharand, Scott, Picard, Walter, Picone, Olivier, de Piero, Maria, Pierobon, Carola, Piersma, Djura, Pimentel, Carlos, Pinto, Raquel, Pires, Catarina, Pironneau, Isabelle, Piroth, Lionel, Pitaloka, Ayodhia, Pius, Riinu, Plantier, Laurent, Png, Hon Shen, Poissy, Julien, Pokeerbux, Ryadh, Pokorska‐Spiewak, Maria, Poli, Sergio, Pollakis, Georgios, Ponscarme, Diane, Popielska, Jolanta, Porto, Diego Bastos, Post, Andra‐Maris, Postma, Douwe F.; Povoa, Pedro, Póvoas, Diana, Powis, Jeff, Prapa, Sofia, Preau, Sébastien, Prebensen, Christian, Preiser, Jean‐Charles, Prinssen, Anton, Pritchard, Mark G.; Priyadarshani, Gamage Dona Dilanthi, Proença, Lucia, Pudota, Sravya, Puéchal, Oriane, Semedi, Bambang Pujo, Pulicken, Mathew, Purcell, Gregory, Quesada, Luisa, Quinones‐Cardona, Vilmaris, González, Víctor Quirós, Quist‐Paulsen, Else, Quraishi, Mohammed, Rabaa, Maia, Rabaud, Christian, Rabindrarajan, Ebenezer, Rafael, Aldo, Rafiq, Marie, Rahardjani, Mutia, Rahman, Rozanah Abd, Rahman, Ahmad Kashfi Haji Ab, Rahutullah, Arsalan, Rainieri, Fernando, Rajahram, Giri Shan, Ramachandran, Pratheema, Ramakrishnan, Nagarajan, Ramli, Ahmad Afiq, Rammaert, Blandine, Ramos, Grazielle Viana, Rana, Asim, Rangappa, Rajavardhan, Ranjan, Ritika, Rapp, Christophe, Rashan, Aasiyah, Rashan, Thalha, Rasheed, Ghulam, Rasmin, Menaldi, Rätsep, Indrek, Rau, Cornelius, Ravi, Tharmini, Raza, Ali, Real, Andre, Rebaudet, Stanislas, Redl, Sarah, Reeve, Brenda, Rehman, Attaur, Reid, Liadain, Reikvam, Dag Henrik, Reis, Renato, Rello, Jordi, Remppis, Jonathan, Remy, Martine, Ren, Hongru, Renk, Hanna, Resseguier, Anne‐Sophie, Revest, Matthieu, Rewa, Oleksa, Reyes, Luis Felipe, Reyes, Tiago, Ribeiro, Maria Ines, Ricchiuto, Antonia, Richardson, David, Richardson, Denise, Richier, Laurent, Ridzuan, Siti Nurul Atikah Ahmad, Riera, Jordi, Rios, Ana L.; Rishu, Asgar, Rispal, Patrick, Risso, Karine, Nuñez, Maria Angelica Rivera, Rizer, Nicholas, Robba, Chiara, Roberto, André, Roberts, Stephanie, Robertson, David L.; Robineau, Olivier, Roche‐Campo, Ferran, Rodari, Paola, Rodeia, Simão, Abreu, Julia Rodriguez, Roessler, Bernhard, Roger, Pierre‐Marie, Roger, Claire, Roilides, Emmanuel, Rojek, Amanda, Romaru, Juliette, Roncon‐Albuquerque, Roberto, Roriz, Mélanie, Rosa‐Calatrava, Manuel, Rose, Michael, Rosenberger, Dorothea, Roslan, Nurul Hidayah Mohammad, Rossanese, Andrea, Rossetti, Matteo, Rossignol, Bénédicte, Rossignol, Patrick, Rousset, Stella, Roy, Carine, Roze, Benoît, Rusmawatiningtyas, Desy, Russell, Clark D.; Ryan, Maria, Ryan, Maeve, Ryckaert, Steffi, Holten, Aleksander Rygh, Saba, Isabela, Sadaf, Sairah, Sadat, Musharaf, Sahraei, Valla, Saint‐Gilles, Maximilien, Sakiyalak, Pranya, Salahuddin, Nawal, Salazar, Leonardo, Saleem, Jodat, Sales, Gabriele, Sallaberry, Stéphane, Salmon Gandonniere, Charlotte, Salvator, Hélène, Sanchez, Olivier, Sanchez‐Miralles, Angel, Sancho‐Shimizu, Vanessa, Sandhu, Gyan, Sandhu, Zulfiqar, Sandrine, Pierre‐François, Sandulescu, Oana, Santos, Marlene, Sarfo‐Mensah, Shirley, Banheiro, Bruno Sarmento, Sarmiento, Iam Claire E.; Sarton, Benjamine, Satya, Ankana, Satyapriya, Sree, Satyawati, Rumaisah, Saviciute, Egle, Savvidou, Parthena, Saw, Yen Tsen, Schaffer, Justin, Schermer, Tjard, Scherpereel, Arnaud, Schneider, Marion, Schroll, Stephan, Schwameis, Michael, Schwartz, Gary, Scott, Janet T.; Scott‐Brown, James, Sedillot, Nicholas, Seitz, Tamara, Selvanayagam, Jaganathan, Selvarajoo, Mageswari, Semaille, Caroline, Semple, Malcolm G.; Senian, Rasidah Bt, Senneville, Eric, Sequeira, Filipa, Sequeira, Tânia, Neto, Ary Serpa, Balazote, Pablo Serrano, Shadowitz, Ellen, Shahidan, Syamin Asyraf, Shamsah, Mohammad, Shankar, Anuraj, Sharjeel, Shaikh, Sharma, Pratima, Shaw, Catherine A.; Shaw, Victoria, Sheharyar, Ashraf, Shetty, Rohan, Shetty, Rajesh Mohan, Shi, Haixia, Shiekh, Mohiuddin, Shime, Nobuaki, Shimizu, Keiki, Shrapnel, Sally, Shrestha, Pramesh Sundar, Shrestha, Shubha Kalyan, Shum, Hoi Ping, Mohammed, Nassima Si, Siang, Ng Yong, Sibiude, Jeanne, Siddiqui, Atif, Sigfrid, Louise, Sillaots, Piret, Silva, Catarina, Silva, Rogério, Silva, Maria Joao, Heng, Benedict Sim Lim, Sin, Wai Ching, Sinatti, Dario, Singh, Punam, Singh, Budha Charan, Sitompul, Pompini Agustina, Sivam, Karisha, Skogen, Vegard, Smith, Sue, Smood, Benjamin, Smyth, Coilin, Smyth, Michelle, Snacken, Morgane, So, Dominic, Soh, Tze Vee, Solberg, Lene Bergendal, Solomon, Joshua, Solomon, Tom, Somers, Emily, Sommet, Agnès, Song, Rima, Song, Myung Jin, Song, Tae, Chia, Jack Song, Sonntagbauer, Michael, Soom, Azlan Mat, Søraas, Arne, Søraas, Camilla Lund, Sotto, Alberto, Soum, Edouard, Sousa, Marta, Sousa, Ana Chora, Uva, Maria Sousa, Souza‐Dantas, Vicente, Sperry, Alexandra, Spinuzza, Elisabetta, Darshana, B. P. Sanka Ruwan Sri, Sriskandan, Shiranee, Stabler, Sarah, Staudinger, Thomas, Stecher, Stephanie‐Susanne, Steinsvik, Trude, Stienstra, Ymkje, Stiksrud, Birgitte, Stolz, Eva, Stone, Amy, Streinu‐Cercel, Adrian, Streinu‐Cercel, Anca, Stuart, David, Stuart, Ami, Subekti, Decy, Suen, Gabriel, Suen, Jacky Y.; Sultana, Asfia, Summers, Charlotte, Supic, Dubravka, Suppiah, Deepashankari, Surovcová, Magdalena, Suwarti, Suwarti, Svistunov, Andrey, Syahrin, Sarah, Syrigos, Konstantinos, Sztajnbok, Jaques, Szuldrzynski, Konstanty, Tabrizi, Shirin, Taccone, Fabio S.; Tagherset, Lysa, Taib, Shahdattul Mawarni, Talarek, Ewa, Taleb, Sara, Talsma, Jelmer, Tamisier, Renaud, Tampubolon, Maria Lawrensia, Tan, Kim Keat, Tan, Yan Chyi, Tanaka, Taku, Tanaka, Hiroyuki, Taniguchi, Hayato, Taqdees, Huda, Taqi, Arshad, Tardivon, Coralie, Tattevin, Pierre, Taufik, M. Azhari, Tawfik, Hassan, Tedder, Richard S.; Tee, Tze Yuan, Teixeira, João, Tejada, Sofia, Tellier, Marie‐Capucine, Teoh, Sze Kye, Teotonio, Vanessa, Téoulé, François, Terpstra, Pleun, Terrier, Olivier, Terzi, Nicolas, Tessier‐Grenier, Hubert, Tey, Adrian, Thabit, Alif Adlan Mohd, Thakur, Anand, Tham, Zhang Duan, Thangavelu, Suvintheran, Thibault, Vincent, Thiberville, Simon‐Djamel, Thill, Benoît, Thirumanickam, Jananee, Thompson, Shaun, Thomson, Emma C.; Thurai, Surain Raaj Thanga, Thwaites, Ryan S.; Tierney, Paul, Tieroshyn, Vadim, Timashev, Peter S.; Timsit, Jean‐François, Vijayaraghavan, Bharath Kumar Tirupakuzhi, Tissot, Noémie, Toh, Jordan Zhien Yang, Toki, Maria, Tonby, Kristian, Tonnii, Sia Loong, Torres, Margarida, Torres, Antoni, Santos‐Olmo, Rosario Maria Torres, Torres‐Zevallos, Hernando, Towers, Michael, Trapani, Tony, Treoux, Théo, Tromeur, Cécile, Trontzas, Ioannis, Trouillon, Tiffany, Truong, Jeanne, Tual, Christelle, Tubiana, Sarah, Tuite, Helen, Turmel, Jean‐Marie, Turtle, Lance C. W.; Tveita, Anders, Twardowski, Pawel, Uchiyama, Makoto, Udayanga, P. G. Ishara, Udy, Andrew, Ullrich, Roman, Uribe, Alberto, Usman, Asad.
Influenza and Other Respiratory Viruses ; 2022.
Article in English | Web of Science | ID: covidwho-2019369

ABSTRACT

Introduction: Case definitions are used to guide clinical practice, surveillance and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the Centers for Disease Control (CDC), European Centre for Disease Prevention and Control (ECDC), World Health Organization (WHO) and UK Health Security Agency (UKHSA) case definitions by age, region and time. Case fatality ratios (CFRs) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test result were excluded. Results: A total of 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe arid Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC) and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years;geographical and time variations were also observed. Estimated CFRs were similar for the patients who met the case definitions. However, when more patients did riot meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions, risking delayed medical care. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.

11.
Expert Opin Investig Drugs ; 31(10): 995-1015, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2008423

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has put a strain on global healthcare systems. Despite admirable efforts to develop rapidly new pharmacotherapies, supportive treatments remain the standard of care. Multiple clinical trials have failed due to design issues, biased patient enrollment, small sample sizes, inadequate control groups, and lack of long-term outcomes monitoring. AREAS COVERED: This narrative review depicts the current situation around failed and success COVID-19 clinical trials and recommendations in hospitalized patients with COVID-19, oversights and streamlining of clinically effective therapeutics. PubMed, EBSCO, Cochrane Library, and WHO and NIH guidelines were searched for relevant literature up to 5 August 2022. EXPERT OPINION: The WHO, NIH, and IDSA have issued recommendations to better clarify which drugs should be used during the different phases of the disease. Given the biases and high heterogeneity of published studies, interpretation of the current literature is difficult. Future clinical trials should be designed to standardize clinical approaches, with appropriate organization, patient selection, addition of control groups, and careful identification of disease phase to reduce heterogeneity and bias and should rely on the integration of scientific societies to promote a consensus on interpretation of the data and recommendations for optimal COVID-19 therapies.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19/drug therapy , Humans , Pandemics , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2
12.
Br J Anaesth ; 129(5): 801-814, 2022 11.
Article in English | MEDLINE | ID: covidwho-2003898

ABSTRACT

BACKGROUND: Survivors of acute respiratory distress syndrome (ARDS) are at risk of long-term comorbidities. This systematic review and meta-analysis evaluated health-related quality of life (HRQoL), and physical and psychological impairments in ARDS survivors from 3 months to 5 yr follow-up after ICU discharge. METHODS: Systematic search of PubMed, AMED, BNI, and CINAHL databases from January 2000 to date. The primary outcome was HRQoL. Secondary outcomes included physical, pulmonary, and cognitive function, mental health, and return to work. A secondary analysis compared classical ARDS with severe acute respiratory syndrome coronavirus disease-2 (SARS-CoV-2) ARDS. RESULTS: Forty-eight papers met inclusion criteria including 11 693 patients; of those 85% (n=9992) had classical ARDS and 14% (n=1632) had SARS-CoV-2 ARDS. The 36-Item Short Form Health Survey (SF-36) physical component summary score mean (95% confidence interval [CI]) was 46 (41-50) at 3 months, 39 (36-41) at 6 months, and 40 (38-43) at 12 months. The SF-36 mental component summary mean score was 53 (48-57) at 3 months, 45 (40-50) at 6 months, and 44 (42-47) at 12 months. SF-36 values were lower than those found in the normal population up to 5 yr. The predictive distance walked in 6 min was 57% (45-69), 63% (56-69), and 66% (62-70) at 3, 6, and 12 months, respectively. Classical ARDS and SARS-CoV-2 ARDS showed no difference in HRQoL and physical function; however, patients with classical ARDS had higher incidence of anxiety and depression (P<0.001). CONCLUSION: ARDS survivors can experience reduced HRQoL and physical and mental health impairment. These symptoms might not recover completely up to 5 yr after ICU discharge. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42021296506.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Quality of Life/psychology , SARS-CoV-2 , COVID-19/complications , Survivors/psychology
13.
Front Med (Lausanne) ; 9: 930217, 2022.
Article in English | MEDLINE | ID: covidwho-1987507

ABSTRACT

Introduction: Neurological manifestations and complications in coronavirus disease-2019 (COVID-19) patients are frequent. Prior studies suggested a possible association between neurological complications and fatal outcome, as well as the existence of potential modifiable risk factors associated to their occurrence. Therefore, more information is needed regarding the incidence and type of neurological complications, risk factors, and associated outcomes in COVID-19. Methods: This is a pre-planned secondary analysis of the international multicenter observational study of the COVID-19 Critical Care Consortium (which collected data both retrospectively and prospectively from the beginning of COVID-19 pandemic) with the aim to describe neurological complications in critically ill COVID-19 patients and to assess the associated risk factors, and outcomes. Adult patients with confirmed COVID-19, admitted to Intensive Care Unit (ICU) will be considered for this analysis. Data collected in the COVID-19 Critical Care Consortium study includes patients' pre-admission characteristics, comorbidities, severity status, and type and severity of neurological complications. In-hospital mortality and neurological outcome were collected at discharge from ICU, and at 28-days. Ethics and Dissemination: The COVID-19 Critical Care Consortium main study and its amendments have been approved by the Regional Ethics Committee of participating sites. No further approval is required for this secondary analysis. Trial Registration Number: ACTRN12620000421932.

14.
Expert Opin Emerg Drugs ; 27(2): 187-209, 2022 06.
Article in English | MEDLINE | ID: covidwho-1965653

ABSTRACT

INTRODUCTION: Ventilatory management and general supportive care of acute respiratory distress syndrome (ARDS) in the adult population have led to significant clinical improvements, but morbidity and mortality remain high. Pharmacologic strategies acting on the coagulation cascade, inflammation, oxidative stress, and endothelial cell injury have been targeted in the last decade for patients with ARDS, but only a few of these have shown potential benefits with a meaningful clinical response and improved patient outcomes. The lack of availability of specific pharmacologic treatments for ARDS can be attributed to its complex pathophysiology, different risk factors, huge heterogeneity, and difficult classification into specific biological phenotypes and genotypes. AREAS COVERED: In this narrative review, we briefly discuss the relevance and current advances in pharmacologic treatments for ARDS in adults and the need for the development of new pharmacological strategies. EXPERT OPINION: Identification of ARDS phenotypes, risk factors, heterogeneity, and pathophysiology may help to design clinical trials personalized according to ARDS-specific features, thus hopefully decreasing the rate of failed clinical pharmacologic trials. This concept is still under clinical investigation and needs further development.


Subject(s)
Respiratory Distress Syndrome , Clinical Trials, Phase II as Topic , Humans , Inflammation , Respiratory Distress Syndrome/drug therapy , Risk Factors
15.
Br J Anaesth ; 129(5): 679-692, 2022 11.
Article in English | MEDLINE | ID: covidwho-1966391

ABSTRACT

BACKGROUND: We performed a systematic review of mechanically ventilated patients with COVID-19, which analysed the effect of tracheostomy timing and technique (surgical vs percutaneous) on mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS), decannulation from tracheostomy, duration of mechanical ventilation, and complications. METHODS: Four databases were screened between January 1, 2020 and January 10, 2022 (PubMed, Embase, Scopus, and Cochrane). Papers were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Population or Problem, Intervention or exposure, Comparison, and Outcome (PICO) guidelines. Meta-analysis and meta-regression for main outcomes were performed. RESULTS: The search yielded 9024 potentially relevant studies, of which 47 (n=5268 patients) were included. High levels of between-study heterogeneity were observed across study outcomes. The pooled mean tracheostomy timing was 16.5 days (95% confidence interval [CI]: 14.7-18.4; I2=99.6%). Pooled mortality was 22.1% (95% CI: 18.7-25.5; I2=89.0%). Meta-regression did not show significant associations between mortality and tracheostomy timing, mechanical ventilation duration, time to decannulation, and tracheostomy technique. Pooled mean estimates for ICU and hospital LOS were 29.6 (95% CI: 24.0-35.2; I2=98.6%) and 38.8 (95% CI: 32.1-45.6; I2=95.7%) days, both associated with mechanical ventilation duration (coefficient 0.8 [95% CI: 0.2-1.4], P=0.02 and 0.9 [95% CI: 0.4-1.4], P=0.01, respectively) but not tracheostomy timing. Data were insufficient to assess tracheostomy technique on LOS. Duration of mechanical ventilation was 23.4 days (95% CI: 19.2-27.7; I2=99.3%), not associated with tracheostomy timing. Data were insufficient to assess the effect of tracheostomy technique on mechanical ventilation duration. Time to decannulation was 23.8 days (95% CI: 19.7-27.8; I2=98.7%), not influenced by tracheostomy timing or technique. The most common complications were stoma infection, ulcers or necrosis, and bleeding. CONCLUSIONS: In patients with COVID-19 requiring tracheostomy, the timing and technique of tracheostomy did not clearly impact on patient outcomes. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021272220.


Subject(s)
COVID-19 , Critical Illness , Humans , Critical Illness/therapy , Time Factors , Tracheostomy/methods , Respiration, Artificial/methods , Length of Stay
16.
Infect Dis Ther ; 11(5): 1779-1791, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1966201

ABSTRACT

Systemic or pulmonary reactivations of herpes simplex virus 1 (HSV-1) have been reported in critically ill patients with COVID-19, posing a dilemma for clinicians in terms of their diagnostic and clinical relevance. Prevalence of HSV-1 reactivation may be as high as > 40% in this population, but with large heterogeneity across studies, likely reflecting the different samples and/or cut-offs for defining reactivation. There is frequently agreement on the clinical significance of HSV-1 reactivation in the presence of severe manifestations clearly attributable to the virus. However, the clinical implications of HSV-1 reactivations in the absence of manifest signs and symptoms remain controversial. Our review aims at providing immunological background and at reviewing clinical findings on HSV-1 reactivations in critically ill patients with COVID-19.

17.
Front Immunol ; 13: 857573, 2022.
Article in English | MEDLINE | ID: covidwho-1933647

ABSTRACT

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes a wide spectrum of clinical manifestations, with progression to multiorgan failure in the most severe cases. Several biomarkers can be altered in coronavirus disease 2019 (COVID-19), and they can be associated with diagnosis, prognosis, and outcomes. The most used biomarkers in COVID-19 include several proinflammatory cytokines, neuron-specific enolase (NSE), lactate dehydrogenase (LDH), aspartate transaminase (AST), neutrophil count, neutrophils-to-lymphocytes ratio, troponins, creatine kinase (MB), myoglobin, D-dimer, brain natriuretic peptide (BNP), and its N-terminal pro-hormone (NT-proBNP). Some of these biomarkers can be readily used to predict disease severity, hospitalization, intensive care unit (ICU) admission, and mortality, while others, such as metabolomic and proteomic analysis, have not yet translated to clinical practice. This narrative review aims to identify laboratory biomarkers that have shown significant diagnostic and prognostic value for risk stratification in COVID-19 and discuss the possible clinical application of novel analytic strategies, like metabolomics and proteomics. Future research should focus on identifying a limited but essential number of laboratory biomarkers to easily predict prognosis and outcome in severe COVID-19.


Subject(s)
COVID-19 , Biomarkers , COVID-19/diagnosis , Humans , Prognosis , Proteomics , SARS-CoV-2
19.
Crit Care ; 25(1): 236, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1854835

ABSTRACT

Infectious diseases may affect brain function and cause encephalopathy even when the pathogen does not directly infect the central nervous system, known as infectious disease-associated encephalopathy. The systemic inflammatory process may result in neuroinflammation, with glial cell activation and increased levels of cytokines, reduced neurotrophic factors, blood-brain barrier dysfunction, neurotransmitter metabolism imbalances, and neurotoxicity, and behavioral and cognitive impairments often occur in the late course. Even though infectious disease-associated encephalopathies may cause devastating neurologic and cognitive deficits, the concept of infectious disease-associated encephalopathies is still under-investigated; knowledge of the underlying mechanisms, which may be distinct from those of encephalopathies of non-infectious cause, is still limited. In this review, we focus on the pathophysiology of encephalopathies associated with peripheral (sepsis, malaria, influenza, and COVID-19), emerging therapeutic strategies, and the role of neuroinflammation.


Subject(s)
Brain Diseases/immunology , COVID-19/complications , Cytokines/immunology , Influenza, Human/complications , Malaria/complications , Sepsis/complications , Blood-Brain Barrier/immunology , Brain Diseases/prevention & control , COVID-19/immunology , Humans , Influenza, Human/immunology , Malaria/immunology , Sepsis/immunology
20.
J Clin Med ; 11(10)2022 May 11.
Article in English | MEDLINE | ID: covidwho-1847369

ABSTRACT

INTRODUCTION: The aim was to investigate the impact of different ventilator strategies (non-invasive ventilation (NIV); invasive MV with tracheal tube (TT) and with tracheostomy (TS) on outcomes (mortality and intensive care unit (ICU) length of stay) in patients with COVID-19. We also assessed the impact of timing of percutaneous tracheostomy and other risk factors on mortality. METHODS: The retrospective cohort included 868 patients with severe COVID-19. Demographics, MV parameters and duration, and ICU mortality were collected. RESULTS: MV was provided in 530 (61.1%) patients, divided into three groups: NIV (n = 139), TT (n = 313), and TS (n = 78). Prevalence of tracheostomy was 14.7%, and ICU mortality was 90.4%, 60.2%, and 30.2% in TT, TS, and NIV groups, respectively (p < 0.001). Tracheostomy increased the chances of survival and being discharged from ICU (OR 6.3, p < 0.001) despite prolonging ICU stay compared to the TT group (22.2 days vs. 10.7 days, p < 0.001) without differences in survival rates between early and late tracheostomy. Patients who only received invasive MV had higher odds of survival compared to those receiving NIV in ICU prior to invasive MV (OR 2.7, p = 0.001). The odds of death increased with age (OR 1.032, p < 0.001), obesity (1.58, p = 0.041), chronic renal disease (1.57, p = 0.019), sepsis (2.8, p < 0.001), acute kidney injury (1.7, p = 0.049), multiple organ dysfunction (3.2, p < 0.001), and ARDS (3.3, p < 0.001). CONCLUSIONS: Percutaneous tracheostomy compared to MV via TT significantly increased survival and the rate of discharge from ICU, without differences between early or late tracheostomy.

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