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1.
Intensive Care Med ; 47(9): 1024-1027, 2021 09.
Article in English | MEDLINE | ID: covidwho-1813638
2.
Bradbury, Charlotte A. M. D. PhD, Lawler, Patrick R. M. D. M. P. H.; Stanworth, Simon J. M. D.; McVerry, Bryan J. M. D.; McQuilten, Zoe PhD, Higgins, Alisa M. PhD, Mouncey, Paul R. MSc, Al-Beidh, Farah PhD, Rowan, Kathryn M. PhD, Berry, Lindsay R. PhD, Lorenzi, Elizabeth PhD, Zarychanski, Ryan M. D. MSc, Arabi, Yaseen M. M. D.; Annane, Djillali M. D. PhD, Beane, Abi PhD, van Bentum-Puijk, Wilma MSc, Bhimani, Zahra M. P. H.; Bihari, Shailesh PhD, M Bonten, Marc J. M. D. PhD, Brunkhorst, Frank M. M. D. PhD, Buzgau, Adrian MSc, Buxton, Meredith PhD, Carrier, Marc M. D. MSc, Cheng, Allen C. Mbbs PhD, Cove, Matthew Mbbs, Detry, Michelle A. PhD, Estcourt, Lise J. MBBCh PhD, Fitzgerald, Mark PhD, Girard, Timothy D. M. D. Msci, Goligher, Ewan C. M. D. PhD, Goossens, Herman PhD, Haniffa, Rashan PhD, Hills, Thomas Mbbs PhD, Huang, David T. M. D. M. P. H.; Horvat, Christopher M. M. D.; Hunt, Beverley J. M. D. PhD, Ichihara, Nao M. D. M. P. H. PhD, Lamontagne, Francois M. D.; Leavis, Helen L. M. D. PhD, Linstrum, Kelsey M. M. S.; Litton, Edward M. D. PhD, Marshall, John C. M. D.; McAuley, Daniel F. M. D.; McGlothlin, Anna PhD, McGuinness, Shay P. M. D.; Middeldorp, Saskia M. D. PhD, Montgomery, Stephanie K. MSc, Morpeth, Susan C. M. D. PhD, Murthy, Srinivas M. D.; Neal, Matthew D. M. D.; Nichol, Alistair D. M. D. PhD, Parke, Rachael L. PhD, Parker, Jane C. B. N.; Reyes, Luis F. M. D. PhD, Saito, Hiroki M. D. M. P. H.; Santos, Marlene S. M. D. Mshs, Saunders, Christina T. PhD, Serpa-Neto, Ary PhD MSc M. D.; Seymour, Christopher W. M. D. MSc, Shankar-Hari, Manu M. D. PhD, Singh, Vanessa, Tolppa, Timo Mbbs, Turgeon, Alexis F. M. D. MSc, Turner, Anne M. M. P. H.; van de Veerdonk, Frank L. M. D. PhD, Green, Cameron MSc, Lewis, Roger J. M. D. PhD, Angus, Derek C. M. D. M. P. H.; McArthur, Colin J. M. D.; Berry, Scott PhD, G Derde, Lennie P. M. D. PhD, Webb, Steve A. M. D. PhD, Gordon, Anthony C. Mbbs M. D..
JAMA ; 327(13):1247, 2022.
Article in English | ProQuest Central | ID: covidwho-1801957

ABSTRACT

Importance The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participants In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Interventions Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control;n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures The primary end point was organ support–free days (days alive and free of intensive care unit–based respiratory or cardiovascular organ support) within 21 days, ranging from −1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support–free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Results The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years;521 [33.6%] female). The median for organ support–free days was 7 (IQR, −1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23];95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62];adjusted absolute difference, 5% [95% CrI, −0.2% to 9.5%];97% posterior probability of efficacy). Among survivors, the median for organ support–free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28];adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%];99.4% probability of harm). Conclusions and Relevance Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support–free days within 21 days.

3.
JMIR Res Protoc ; 2022 Apr 14.
Article in English | MEDLINE | ID: covidwho-1789311

ABSTRACT

BACKGROUND: Lessening Organ Dysfunction with VITamin C (LOVIT) is a blinded multicentre randomized clinical trial that compared high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor. OBJECTIVE: To describe a pre-specified statistical analysis plan (SAP) for LOVIT, written prior to unblinding and locking of the trial database. METHODS: The SAP was designed by the LOVIT principal investigators and statisticians and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes and describes the planned primary, secondary, and subgroup analyses. RESULTS: The SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% confidence interval in a generalized linear mixed model with binomial distribution and log link and considering site as a random effect. We will perform a secondary analysis adjusting for pre-specified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status. CONCLUSIONS: We have developed a SAP for the LOVIT trial and will adhere to it in the analysis phase. CLINICALTRIAL: ClinicalTrials.gov identifier: NCT03680274 (21 September 2018).

4.
Butler-Laporte, Guillaume, Povysil, Gundula, Kosmicki, Jack, Cirulli, Elizabeth, Drivas, Theodore, Furini, Simone, Saad, Chadi, Schmidt, Axel, Olszewski, Pawel, Korotko, Urszula, Quinodoz, Mathieu, Çelik, Elifnaz, Kundu, Kousik, Walter, Klaudia, Jung, Junghyung, Stockwell, Amy, Sloofman, Laura, Charney, Alexander, Jordan, Daniel, Beckmann, Noam, Przychodzen, Bartlomiej, Chang, Timothy, Pottinger, Tess, Shang, Ning, Brand, Fabian, Fava, Francesca, Mari, Francesca, Chwialkowska, Karolina, Niemira, Magdalena, Pula, Szymon, Baillie, Kenneth, Stuckey, Alex, Ganna, Andrea, Karczewski, Konrad, Veerapen, Kumar, Bourgey, Mathieu, Bourque, Guillaume, Eveleigh, Robert J. M.; Forgetta, Vincenzo, Morrison, David, Langlais, David, Lathrop, Mark, Mooser, Vincent, Nakanishi, Tomoko, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklos, Marincevic-Zuniga, Yanara, Nordlund, Jessica, Schiabor Barrett, Kelly, Lee, William, Bolze, Alexandre, White, Simon, Riffle, Stephen, Tanudjaja, Francisco, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Casadei, Nicolas, Motameny, Susanne, Alaamery, Manal, Massadeh, Salam, Aljawini, Nora, Almutairi, Mansour, Arabi, Yaseen, Alqahtan, Saleh, Al Harthi, Fawz, Almutairi, Amal, Alqubaishi, Fatima, Alotaibi, Sarah, Binowayn, Albandari, Alsolm, Ebtehal, Bardisy, Hadeel El, Fawzy, Mohammad, Geschwind, Daniel, Arteaga, Stephanie, Stephens, Alexis, Butte, Manish, Boutros, Paul, Yamaguchi, Takafumi, Tao, Shu, Eng, Stefan, Sanders, Timothy, Tung, Paul, Broudy, Michael, Pan, Yu, Gonzalez, Alfredo, Chavan, Nikhil, Johnson, Ruth, Pasaniuc, Bogdan, Yaspan, Brian, Smieszek, Sandra, Rivolta, Carlo, Bibert, Stephanie, Bochud, Pierre-Yves, Dabrowski, Maciej, Zawadzki, Pawel, Sypniewski, Mateusz, Kaja, Elżbieta, Chariyavilaskul, Pajaree, Nilaratanakul, Voraphoj, Hirankarn, Nattiya, Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Kawai, Yosuke, Hasegawa, Takanori, Naito, Tatsuhiko, Namkoong, Ho, Edahiro, Ryuya, Kimura, Akinori, Ogawa, Seishi, Kanai, Takanori, Fukunaga, Koichi, Okada, Yukinori, Imoto, Seiya, Miyano, Satoru, Mangul, Serghei, Abedalthagafi, Malak, Zeberg, Hugo, Grzymski, Joseph, Washington, Nicole, Ossowski, Stephan, Ludwig, Kerstin, Schulte, Eva, Riess, Olaf, Moniuszko, Marcin, Kwasniewski, Miroslaw, Mbarek, Hamdi, Ismail, Said, Verma, Anurag, Goldstein, David, Kiryluk, Krzysztof, Renieri, Alessandra, Ferreira, Manuel, Richards, Brent, Initiative, Covid- Host Genetics, De, C. O. I. Host Genetics Group, Study, Gen-Covid Multicenter, Gen, Omicc Consortium, Japan, Covid-Task Force, Regeneron Genetics, Center.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332108

ABSTRACT

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,048 severe disease cases and 571,009 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p=5.41×10 -7 ). These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.

5.
JPEN J Parenter Enteral Nutr ; 45(S2): 79-84, 2021 11.
Article in English | MEDLINE | ID: covidwho-1767367

ABSTRACT

Despite a mounting evidentiary base, controversies surrounding critical care nutrition support persist. Anchored by a case of a 60-year-old male with esophageal cancer who develops acute hypoxemic respiratory failure and septic shock, five panelists from the American Society of Parenteral and Enteral Nutrition (ASPEN) 2021 Pre-Conference discuss key clinical dilemmas in critical care nutrition, including hierarchy of evidence, bedside evaluation of malnutrition, optimal protein dose, use of fiber, and therapies targeting gut function and gut microbiota .


Subject(s)
Critical Illness , Malnutrition , Critical Care , Critical Illness/therapy , Enteral Nutrition , Humans , Male , Malnutrition/complications , Malnutrition/diagnosis , Malnutrition/therapy , Middle Aged , Nutritional Support , Parenteral Nutrition
6.
JAMA ; 327(13): 1247-1259, 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1750260

ABSTRACT

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Interventions: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Results: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). Conclusions and Relevance: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Subject(s)
COVID-19 , Venous Thromboembolism , Adult , Anticoagulants/therapeutic use , Aspirin/adverse effects , Bayes Theorem , Critical Illness/therapy , Female , Hemorrhage/chemically induced , Humans , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Respiration, Artificial , Venous Thromboembolism/drug therapy
7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322201

ABSTRACT

Background: Due to its supposed clinical efficacy, relative safety, and low cost, ascorbic acid represents an appealing option for clinicians to utilize in the context of a global health pandemic of COVID-19 patients. Objectives: The aim of this study was to evaluate the efficacy and safety of using ascorbic acid as adjunctive therapy in critically ill patients with COVID-19. Methods: : This was a multi-center, non-interventional, retrospective cohort study. All critically ill adult patients admitted to ICU with a confirmed COVID-19 between March 1st to December 31 st , 2020 were included in the final analysis. The study was conducted at two large governmental tertiary hospitals in Saudi Arabia. The purpose was to investigate the association between clinical outcomes with ascorbic acid use as an adjunctive therapy in COVID-19 after propensity score matching using baseline severity scores, systemic use of corticosteroids and study centers. Results: : A 739 patients were included in this study;296 patients were included after propensity score matching. There was no association between the administration of ascorbic acid and in-hospital mortality nor 30-day ICU mortality (OR (95%CI): 0.77 (0.476, 1.234), p-value=0.2738 and OR (95%CI): 0.73 (0.438 ,1.204), p-value=0.215 respectively). Using ascorbic acid was associated with lower incidence of thrombosis compared with the non-ascorbic acid group (6.1% vs. 13% respectively);OR (95%CI): 0.42 (0.184, 0.937), p-value=0.0342). Conclusion: Ascorbic acid use as an adjunctive therapy in COVID19 critically ill patients was not associated with mortality benefits;but associated with lower incidence of thrombosis. Further studies are required to confirm these findings.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-319567

ABSTRACT

Background: Extracorporeal membrane oxygenation (ECMO) use for severe Coronavirus disease 2019 (COVID-19) patients has evolved during the course of the pandemic. Early uncertainty regarding the role of ECMO during the current pandemic was based on the suboptimal initial experiences. However, more recent data suggests favorable outcomes in COVID-19 patients receiving ECMO support. We aimed to explore the epidemiology and outcomes of ECMO for COVID-19 related cardiopulmonary failure and evaluate outcomes of new centers versus established ones.Methods: This is a retrospective, multicenter international, observational study conducted in (19) ECMO centers in five countries from March 1, 2020, to September 30, 2020. We included 307 patients with COVID-19 who received ECMO for refractory hypoxemia and severe respiratory acidosis with or without circulatory failure. Data collection included Patients characteristics, demographic data, ECMO-related specific data, pre-ECMO patient condition, 24 hours post-ECMO initiation data, and outcome. The primary outcome is survival to home discharge. Secondary outcomes include mortality during ECMO, survival to decannulation, and outcomes stratified by center type in which patients were treated.Findings: Three hundred and seven COVID-19 patients received ECMO support during the study period. The median age was 45 years (37-52 IQR), and 81% were men. 178 (58%) patients survived ECMO, of whom 138 (45%) patients were discharged home, and 40 patients (13%) died post-ECMO decannulation while 128 patients (41.7%) died during ECMO. Patient outcomes in the new centers developed in response to the pandemic were similar to those of established centers.Interpretation: During pandemics, ECMO may provide favorable outcomes in highly select patients as resources allow. Outcomes in ECMO centers established during the pandemic were comparable to existing centers.Funding Statement: None.Declaration of Interests: Kiran Shekar acknowledges research support from the Metro North Hospital and Health Service and the Prince Charles Hospital Foundation. Dr. Brodie receives research support from ALung Technologies. He has been on the medical advisory boards for Baxter, Abiomed, Xenios, and Hemovent and is the President-Elect of the Extracorporeal Life Support Organization (ELSO). Dr. Combes reported receiving grants and personal fees from Maquet, Xenios, and Baxter and serving as the recent past president of the EuroELSO organization. Other authors have no conflict of interest.Ethics Approval Statement: After the SWAAC ELSO steering committee's authorization, IRB approval was obtained from the coordinating center King Saud Medical City in Riyadh - Saudi Arabia. The country representatives obtained IRB approval for each participating center as well.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-305264

ABSTRACT

Background: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). Methods: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. Results: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. Conclusion: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

10.
Sci Rep ; 11(1): 22548, 2021 11 19.
Article in English | MEDLINE | ID: covidwho-1628380

ABSTRACT

The objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 1-3) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy.


Subject(s)
Antibodies, Viral/immunology , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Critical Illness/mortality , Middle East Respiratory Syndrome Coronavirus/immunology , Adult , Aged , Antibodies, Viral/blood , Antibody Formation , Cohort Studies , Coronavirus Infections/therapy , Coronavirus Infections/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Intensive Care Units , Kinetics , Male , Middle Aged , Organ Dysfunction Scores , Renal Replacement Therapy , Survival Analysis
11.
Trials ; 23(1): 105, 2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1666670

ABSTRACT

BACKGROUND: Noninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation has multiple advantages over other oxygen support modalities but data about effectiveness are limited. METHODS: In this multicenter randomized trial of helmet noninvasive ventilation for COVID-19 patients, 320 adult ICU patients (aged ≥14 years or as per local standards) with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (ratio of arterial oxygen partial pressure to fraction of inspired oxygen < 200 despite supplemental oxygen with a partial/non-rebreathing mask at a flow rate of 10 L/min or higher) will be randomized to helmet noninvasive ventilation with usual care or usual care alone, which may include mask noninvasive ventilation, high-flow nasal oxygen, or standard oxygen therapy. The primary outcome is death from any cause within 28 days after randomization. The trial has 80% power to detect a 15% absolute risk reduction in 28-day mortality from 40 to 25%. The primary outcome will be compared between the helmet and usual care group in the intention-to-treat using the chi-square test. Results will be reported as relative risk  and 95% confidence interval. The first patient was enrolled on February 8, 2021. As of August 1, 2021, 252 patients have been enrolled from 7 centers in Saudi Arabia and Kuwait. DISCUSSION: We developed a detailed statistical analysis plan to guide the analysis of the Helmet-COVID trial, which is expected to conclude enrollment in November 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT04477668 . Registered on July 20, 2020.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Adult , Head Protective Devices , Humans , Noninvasive Ventilation/adverse effects , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapy , SARS-CoV-2
12.
Am J Infect Control ; 2022 Jan 23.
Article in English | MEDLINE | ID: covidwho-1629725

ABSTRACT

BACKGROUND: The higher risk of COVID-19 in health care workers (HCWs) is well-known. However, the risk within HCWs is not fully understood. The objective was to compare the COVID-19 risk in intensive care unit (ICU) vs non-ICU locations. METHODS: A prospective surveillance study was conducted among HCWs at a large tertiary care facility in Riyadh between March 1st to November 30th, 2020. HCWs included both clinical (provide direct patient care) and nonclinical positions (do not provide direct patient care). RESULTS: A total 1,594 HCWs with COVID-19 were included; 103 (6.5%) working in ICU and 1,491 (93.5%) working in non-ICU locations. Compared with non-ICU locations, ICU had more nurses (54.4% vs 22.1%, P < .001) and less support staff (2.9% vs 53.1%, P < .001). COVID-19 infection was similar in ICU and non-ICU locations (9.0% vs 9.8%, P = .374). However, it was significantly higher in ICU nurses (12.3% vs 6.5%, P < .001). Support staff had higher risk than other HCWs, irrespective of ICU working status (15.1% vs 7.2%, P < 0.001). The crude relative risk of COVID-19 in ICU vs non-ICU locations was 0.92, 95% confidence interval ( was 0.76-1.11 (P = .374). However, relative risk adjusted for professional category was significantly increased to 1.23, 95% confidence interval 1.01-1.50 (P = .036). CONCLUSIONS: ICU had a significantly higher risk of COVID-19 infection only after adjusting for the distribution and risk of different professional categories. The latter is probably determined by both exposure level and protection practices. The finding underscores the importance of strict implementation of preventive measures among all HCWs, including those performing nonclinical services.

13.
Critical care clinics ; 2022.
Article in English | EuropePMC | ID: covidwho-1615015

ABSTRACT

High-flow nasal oxygen (HFNO) and non-invasive ventilation (NIV) via face-mask or helmet have been increasingly used in the management of acute hypoxemic respiratory failure (AHRF) due to COVID-19 with the premise of reducing the need for invasive mechanical ventilation and possibly mortality. However, their use carries the risk of delaying intubation and nosocomial infection transmission. To this date, most studies on the effectiveness of these modalities are observational and suggest that HFNO and NIV have a role in the management of AHRF due to COVID-19. A randomized controlled trial among patients with COVID-19 showed that helmet NIV versus HFNO led to a lower intubation rate but no difference in survival or the duration of respiratory support. The RECOVERY respiratory support trial demonstrated that CPAP, but not HFNO reduced a composite outcome of tracheal intubation or mortality within 30-days compared with conventional oxygen therapy. Additional trials are ongoing and are evaluating different aspects of noninvasive respiratory support in patients with AHRF due to COVID-19.

14.
Clin Immunol ; 234: 108911, 2022 01.
Article in English | MEDLINE | ID: covidwho-1588089

ABSTRACT

BACKGROUND: Natural killer (NK) cells play an essential role against viruses. NK cells express killer cell immunoglobulin-like receptors (KIRs) which regulate their activity and function. The polymorphisms in KIR haplotypes confer differential viral susceptibility and disease severity caused by infections. We investigated the association between KIR genes and COVID-19 disease severity. METHODS: 424 COVID-19 positive patients were divided according to their disease severity into mild, moderate and severe. KIR genes were genotyped using next generation sequencing (NGS). Association between KIR genes and COVID-19 disease severity was conducted and significant correlations were reported. RESULTS: In the COVID-19 patients, KIR Bx genotype was more common than AA genotype. The Bx genotype was found more frequently in patients with mild disease, while in severe disease the AA genotype was more common than the Bx genotype. The KIR2DS4 gene carried the highest risk for severe COVID-19 infection (OR 8.48, pc= 0.0084) followed by KIR3DL1 (OR 7.61, pc= 0.0192). CONCLUSIONS: Our findings suggest that KIR2DS4 and KIR3DL1 genes carry risk for severe COVID-19 disease.


Subject(s)
COVID-19/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic/genetics , Receptors, KIR/genetics , Adult , COVID-19/metabolism , Female , Gene Frequency/genetics , Genotype , Humans , Killer Cells, Natural/metabolism , Male , Middle Aged , SARS-CoV-2/pathogenicity
15.
Crit Care ; 25(1): 424, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1577182

ABSTRACT

The preferential use of the oral/enteral route in critically ill patients over gut rest is uniformly recommended and applied. This article provides practical guidance on enteral nutrition in compliance with recent American and European guidelines. Low-dose enteral nutrition can be safely started within 48 h after admission, even during treatment with small or moderate doses of vasopressor agents. A percutaneous access should be used when enteral nutrition is anticipated for ≥ 4 weeks. Energy delivery should not be calculated to match energy expenditure before day 4-7, and the use of energy-dense formulas can be restricted to cases of inability to tolerate full-volume isocaloric enteral nutrition or to patients who require fluid restriction. Low-dose protein (max 0.8 g/kg/day) can be provided during the early phase of critical illness, while a protein target of > 1.2 g/kg/day could be considered during the rehabilitation phase. The occurrence of refeeding syndrome should be assessed by daily measurement of plasma phosphate, and a phosphate drop of 30% should be managed by reduction of enteral feeding rate and high-dose thiamine. Vomiting and increased gastric residual volume may indicate gastric intolerance, while sudden abdominal pain, distension, gastrointestinal paralysis, or rising abdominal pressure may indicate lower gastrointestinal intolerance.


Subject(s)
Enteral Nutrition , Intensive Care Units , Critical Illness , Food, Formulated , Humans , Residual Volume
16.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294117

ABSTRACT

Background It is unclear whether screening for sepsis using an electronic alert in hospitalized ward patients improves outcomes. The objective of the SCREEN (Stepped-wedge Cluster Randomized Controlled Trial of Electronic Early Notification of Sepsis in Hospitalized Ward Patients) trial is to evaluate whether an electronic screening for sepsis compared to no screening among hospitalized ward patients reduces all-cause 90-day in-hospital mortality. Methods and design This study is designed as a stepped-wedge cluster randomized controlled trial in which the unit of randomization or cluster is the hospital ward. An electronic alert for sepsis was developed in the electronic medical record (EMR), with the feature of being active (visible to treating team) or masked (inactive in EMR frontend for the treating team but active in the backend of the EMR). Forty-five clusters in 5 hospitals are randomized into 9 sequences of 5 clusters each to receive the intervention (active alert) over 10 periods, 2-months each, the first being the baseline period. Data are extracted from EMR and are compared between the intervention (active alert) and control group (masked alert). The primary outcome of all-cause hospital mortality by day 90 will be compared using a generalized linear mixed model with a binary distribution and a log-link function to estimate the relative risk as a measure of effect. We will include two levels of random effects to account for nested clustering within wards and periods and two levels of fixed effects;hospitals and COVID-19 ward status. Results will be expressed as relative risk with a 95% confidence interval (CI). Conclusion The SCREEN trial provides an opportunity for a novel trial design and analysis of routinely collected and entered data to evaluate the effectiveness of an intervention (alert) for a common medical problem (sepsis in ward patients). In this statistical analysis plan, we outline details of the planned analyses in advance of trial completion. Prior specification of the statistical methods and outcomes analysis will facilitate unbiased analyses of these important clinical data. Trial registration ClinicalTrials.gov NCT04078594 . Registered on September 6, 2019, https://clinicaltrials.gov/ct2/show/NCT04078594

17.
Trials ; 22(1): 828, 2021 Nov 22.
Article in English | MEDLINE | ID: covidwho-1528691

ABSTRACT

BACKGROUND: It is unclear whether screening for sepsis using an electronic alert in hospitalized ward patients improves outcomes. The objective of the Stepped-wedge Cluster Randomized Trial of Electronic Early Notification of Sepsis in Hospitalized Ward Patients (SCREEN) trial is to evaluate whether an electronic screening for sepsis compared to no screening among hospitalized ward patients reduces all-cause 90-day in-hospital mortality. METHODS AND DESIGN: This study is designed as a stepped-wedge cluster randomized trial in which the unit of randomization or cluster is the hospital ward. An electronic alert for sepsis was developed in the electronic medical record (EMR), with the feature of being active (visible to treating team) or masked (inactive in EMR frontend for the treating team but active in the backend of the EMR). Forty-five clusters in 5 hospitals are randomized into 9 sequences of 5 clusters each to receive the intervention (active alert) over 10 periods, 2 months each, the first being the baseline period. Data are extracted from EMR and are compared between the intervention (active alert) and control group (masked alert). During the study period, some of the hospital wards were allocated to manage patients with COVID-19. The primary outcome of all-cause hospital mortality by day 90 will be compared using a generalized linear mixed model with a binary distribution and a log-link function to estimate the relative risk as a measure of effect. We will include two levels of random effects to account for nested clustering within wards and periods and two levels of fixed effects: hospitals and COVID-19 ward status in addition to the intervention. Results will be expressed as relative risk with a 95% confidence interval. CONCLUSION: The SCREEN trial provides an opportunity for a novel trial design and analysis of routinely collected and entered data to evaluate the effectiveness of an intervention (alert) for a common medical problem (sepsis in ward patients). In this statistical analysis plan, we outline details of the planned analyses in advance of trial completion. Prior specification of the statistical methods and outcome analysis will facilitate unbiased analyses of these important clinical data. TRIAL REGISTRATION: ClinicalTrials.gov NCT04078594 . Registered on September 6, 2019.


Subject(s)
COVID-19 , Sepsis , Electronics , Hospitals , Humans , SARS-CoV-2 , Sepsis/diagnosis , Sepsis/therapy
18.
JAMA ; 326(17): 1690-1702, 2021 Nov 02.
Article in English | MEDLINE | ID: covidwho-1525402

ABSTRACT

IMPORTANCE: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. OBJECTIVE: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONS: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURES: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11 secondary outcomes. Serious adverse events were reported in 3.0% (32/1075) of participants in the convalescent plasma group and in 1.3% (12/905) of participants in the no convalescent plasma group. CONCLUSIONS AND RELEVANCE: Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.


Subject(s)
COVID-19/therapy , ABO Blood-Group System , Adult , Aged , Critical Illness/therapy , Female , Hospital Mortality , Humans , Immunization, Passive , Length of Stay , Logistic Models , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Treatment Failure , Vasoconstrictor Agents/therapeutic use
19.
J Infect Public Health ; 15(1): 142-151, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1525853

ABSTRACT

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.


Subject(s)
COVID-19 , Critical Care , Humans , Intensive Care Units , SARS-CoV-2 , Saudi Arabia
20.
Lancet Infect Dis ; 22(3): e74-e87, 2022 03.
Article in English | MEDLINE | ID: covidwho-1510480

ABSTRACT

During the current COVID-19 pandemic, health-care workers and uninfected patients in intensive care units (ICUs) are at risk of being infected with SARS-CoV-2 as a result of transmission from infected patients and health-care workers. In the absence of high-quality evidence on the transmission of SARS-CoV-2, clinical practice of infection control and prevention in ICUs varies widely. Using a Delphi process, international experts in intensive care, infectious diseases, and infection control developed consensus statements on infection control for SARS-CoV-2 in an ICU. Consensus was achieved for 31 (94%) of 33 statements, from which 25 clinical practice statements were issued. These statements include guidance on ICU design and engineering, health-care worker safety, visiting policy, personal protective equipment, patients and procedures, disinfection, and sterilisation. Consensus was not reached on optimal return to work criteria for health-care workers who were infected with SARS-CoV-2 or the acceptable disinfection strategy for heat-sensitive instruments used for airway management of patients with SARS-CoV-2 infection. Well designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.


Subject(s)
COVID-19 , Consensus , Infection Control/standards , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Intensive Care Units/standards , SARS-CoV-2/isolation & purification , COVID-19 Vaccines/administration & dosage , Delphi Technique , Health Personnel/standards , Humans , Personal Protective Equipment/standards
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