Screening for latent tuberculosis in migrants-status quo and future challenges.

OBJECTIVES: To review the evidence that migrants from tuberculosis (TB) high-incidence countries migrating to TB low-incidence countries significantly contribute to active TB cases in the counties of destination, primarily through reactivation of latent TB. METHODS: This is a narrative review. The different screening programs in the countries of destination are reviewed either based on screening and preventive treatment of latent TB pre or more commonly - post arrival. RESULTS: Screening can be performed using interferon-gamma release assays (IGRA) or tuberculin skin tests (TST). Preventive treatment of latent TB is using either monotherapy with isoniazid, or in combination with rifampicin or rifapentine. We discuss the ethical issues of preventive treatment in asymptomatic individuals and how these are addressed in different screening programs. CONCLUSION: Screening migrants from TB high endemic countries to TB low endemic countries is beneficial. There is a lack of standardization and agreement on screening protocols, follow up and treatment.

RNA therapeutics for diarrhea.

Diarrhea is caused by a variety of bacterial and viral agents, inflammatory conditions, medications, and hereditary conditions. Secretory diarrhea involves several ion and solute transporters, activation of the cyclic nucleotide and Ca2+ signaling pathways, as well as intestinal epithelial secretion. In many cases of secretory diarrhea, activation of Cl- channels, such as the cystic transmembrane conduction regulator and the Ca2+stimulated Cl- channel fibrosis, promote secretion while concurrently inhibiting Na+ transport expressing fluid absorption. Current diarrhea therapies include rehydration and electrolyte replacement via oral rehydration solutions, as well as medications that target peristalsis or fluid secretion. The rising understanding of RNA function and its importance in illness has encouraged the use of various RNAs to operate selectively on "untreatable" proteins, transcripts, and genes. Some RNA-based medications have received clinical approval, while others are currently in research or preclinical studies. Despite major obstacles in the development of RNA-based therapies, many approaches have been investigated to improve intracellular RNA trafficking and metabolic stability.

Deferoxamine in the management of COVID-19 adult patients admitted to ICU: a prospective observational cohort study.

COVID-19 infection is associated with high mortality, and despite extensive studying the scientific society is still working to find a definitive treatment. Some experts postulated a beneficial role of Deferoxamine. Aim: The aim of this study was to compare the outcomes of COVID-19 adult patients admitted to the ICU who received deferoxamine to those who received standard of care. Methods: Prospective observational cohort study, in the ICU of a tertiary referral hospital in Saudi Arabia to compare all-cause hospital mortality between COVID-19 patients who received deferoxamine and standard of care. Results: A total of 205 patients were enrolled, with an average age of 50.1±14.3, 150 patients received standard of care only, and 55 patients received deferoxamine additionally. Hospital mortality was lower in deferoxamine group (25.5 vs. 40.7%, 95% CI=1.3-29.2%; P=0.045). Clinical status score upon discharge was lower in deferoxamine group (3.6±4.3 vs. 6.2±4, 95% CI: 1.4-3.9; P<0.001), as was the difference between discharge score and admission score (indicating clinical improvement). More patients admitted with mechanical ventilation were successfully extubated in the deferoxamine group (61.5 vs. 14.3%, 95% CI: 15-73%; P=0.001), with a higher median ventilator-free days. There were no differences between groups in adverse events. Deferoxamine group was associated with hospital mortality [odds ratio=0.46 (95% CI: 0.22-0.95); P=0.04]. Conclusions: Deferoxamine may have mortality and clinical improvement benefits in COVID-19 adults admitted to ICU. Further powered and controlled studies are required.

Multinational prospective study of incidence and risk factors for central-line-associated bloodstream infections in 728 intensive care units of 41 Asian, African, Eastern European, Latin American, and Middle Eastern countries over 24 years.

OBJECTIVE: To identify central-line (CL)-associated bloodstream infection (CLABSI) incidence and risk factors in low- and middle-income countries (LMICs). DESIGN: From July 1, 1998, to February 12, 2022, we conducted a multinational multicenter prospective cohort study using online standardized surveillance system and unified forms. SETTING: The study included 728 ICUs of 286 hospitals in 147 cities in 41 African, Asian, Eastern European, Latin American, and Middle Eastern countries. PATIENTS: In total, 278,241 patients followed during 1,815,043 patient days acquired 3,537 CLABSIs. METHODS: For the CLABSI rate, we used CL days as the denominator and the number of CLABSIs as the numerator. Using multiple logistic regression, outcomes are shown as adjusted odds ratios (aORs). RESULTS: The pooled CLABSI rate was 4.82 CLABSIs per 1,000 CL days, which is significantly higher than that reported by the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC NHSN). We analyzed 11 variables, and the following variables were independently and significantly associated with CLABSI: length of stay (LOS), risk increasing 3% daily (aOR, 1.03; 95% CI, 1.03-1.04; P < .0001), number of CL days, risk increasing 4% per CL day (aOR, 1.04; 95% CI, 1.03-1.04; P < .0001), surgical hospitalization (aOR, 1.12; 95% CI, 1.03-1.21; P < .0001), tracheostomy use (aOR, 1.52; 95% CI, 1.23-1.88; P < .0001), hospitalization at a publicly owned facility (aOR, 3.04; 95% CI, 2.31-4.01; P <.0001) or at a teaching hospital (aOR, 2.91; 95% CI, 2.22-3.83; P < .0001), hospitalization in a middle-income country (aOR, 2.41; 95% CI, 2.09-2.77; P < .0001). The ICU type with highest risk was adult oncology (aOR, 4.35; 95% CI, 3.11-6.09; P < .0001), followed by pediatric oncology (aOR, 2.51;95% CI, 1.57-3.99; P < .0001), and pediatric (aOR, 2.34; 95% CI, 1.81-3.01; P < .0001). The CL type with the highest risk was internal-jugular (aOR, 3.01; 95% CI, 2.71-3.33; P < .0001), followed by femoral (aOR, 2.29; 95% CI, 1.96-2.68; P < .0001). Peripherally inserted central catheter (PICC) was the CL with the lowest CLABSI risk (aOR, 1.48; 95% CI, 1.02-2.18; P = .04). CONCLUSIONS: The following CLABSI risk factors are unlikely to change: country income level, facility ownership, hospitalization type, and ICU type. These findings suggest a focus on reducing LOS, CL days, and tracheostomy; using PICC instead of internal-jugular or femoral CL; and implementing evidence-based CLABSI prevention recommendations.

Assessment of Proinflammatory Cytokines Among Patients with Middle East Respiratory Syndrome Coronavirus Infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant morbidity and mortality. This study was performed to assess the proinflammatory cytokines profile among MERS-CoV patients. A total of 46 MERS-CoV-infected patients (27 symptomatic and 19 asymptomatic) were assessed and compared with 52 normal healthy controls for plasma levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-17, IL-7, IL-6, interferon (IFN)-α, and IL-15 using a customized luminex kit. Whereas asymptomatic MERS-CoV patients and controls were no different; the mean plasma levels among MERS-CoV symptomatic patients were significantly higher than the normal controls: IL-1ß (16.89 ± 1.23 vs. 12.80 ± 0.59 pg/mL; p < 0.001), TNF-α (14.04 ± 0.93 vs. 10.35 ± 0.29 pg/mL; p < 0.0001), IL-17 (14.3 ± 0.89 vs. 11.47 ± 0.61 pg/mL; p < 0.001), IL-7 (21.56 ± 1.00 vs. 16.31 ± 0.30 pg/mL; p < 0.0001), IL-6 (156.5 ± 37.90 vs. 18.60 ± 1.59 pg/mL; p < 0.0001), and IFN-α (68.73 ± 13.06 vs. 23.57 ± 1.05 pg/mL; p < 0.0001). The mean plasma levels of IL-7 (24.81 ± 1.63 vs. 19.79 ± 0.94 pg/mL; p < 0.01), IL-6 (312.7 ± 94.67 vs. 101.2 ± 25.67 pg/mL; p < 0.01), and IFN-α (89.00 ± 18.97 vs. 51.05 ± 8.68 pg/mL; p < 0.05) were significantly elevated among MERS-CoV symptomatic patients with fatal outcome compared with MERS-CoV symptomatic patients who survived. Only IL-7 was found to have a higher risk ratio of mortality (4.76, 95% confidence interval: 1.5-14.94; p < 0.01). No differences were observed in IL-15 levels among the groups. Significantly elevated proinflammatory cytokines among symptomatic MERS-CoV-infected patients may contribute to manifestations of cytokine storm frequently observed among critically ill MERS-CoV patients and IL-7 may serve as a marker for disease activity.

Multinational prospective cohort study of rates and risk factors for ventilator-associated pneumonia over 24 years in 42 countries of Asia, Africa, Eastern Europe, Latin America, and the Middle East: Findings of the International Nosocomial Infection Control Consortium (INICC).

Objective: Rates of ventilator-associated pneumonia (VAP) in low- and middle-income countries (LMIC) are several times above those of high-income countries. The objective of this study was to identify risk factors (RFs) for VAP cases in ICUs of LMICs. Design: Prospective cohort study. Setting: This study was conducted across 743 ICUs of 282 hospitals in 144 cities in 42 Asian, African, European, Latin American, and Middle Eastern countries. Participants: The study included patients admitted to ICUs across 24 years. Results: In total, 289,643 patients were followed during 1,951,405 patient days and acquired 8,236 VAPs. We analyzed 10 independent variables. Multiple logistic regression identified the following independent VAP RFs: male sex (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.16-1.28; P < .0001); longer length of stay (LOS), which increased the risk 7% per day (aOR, 1.07; 95% CI, 1.07-1.08; P < .0001); mechanical ventilation (MV) utilization ratio (aOR, 1.27; 95% CI, 1.23-1.31; P < .0001); continuous positive airway pressure (CPAP), which was associated with the highest risk (aOR, 13.38; 95% CI, 11.57-15.48; P < .0001); tracheostomy connected to a MV, which was associated with the next-highest risk (aOR, 8.31; 95% CI, 7.21-9.58; P < .0001); endotracheal tube connected to a MV (aOR, 6.76; 95% CI, 6.34-7.21; P < .0001); surgical hospitalization (aOR, 1.23; 95% CI, 1.17-1.29; P < .0001); admission to a public hospital (aOR, 1.59; 95% CI, 1.35-1.86; P < .0001); middle-income country (aOR, 1.22; 95% CI, 15-1.29; P < .0001); admission to an adult-oncology ICU, which was associated with the highest risk (aOR, 4.05; 95% CI, 3.22-5.09; P < .0001), admission to a neurologic ICU, which was associated with the next-highest risk (aOR, 2.48; 95% CI, 1.78-3.45; P < .0001); and admission to a respiratory ICU (aOR, 2.35; 95% CI, 1.79-3.07; P < .0001). Admission to a coronary ICU showed the lowest risk (aOR, 0.63; 95% CI, 0.51-0.77; P < .0001). Conclusions: Some identified VAP RFs are unlikely to change: sex, hospitalization type, ICU type, facility ownership, and country income level. Based on our results, we recommend focusing on strategies to reduce LOS, to reduce the MV utilization ratio, to limit CPAP use and implementing a set of evidence-based VAP prevention recommendations.

Middle East Respiratory Syndrome Coronavirus Infection Elicits Long-lasting Specific Antibody, T and B Cell Immune Responses in Recovered Individuals.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic zoonotic betacoronavirus and a global public health concern. Better undersetting of the immune responses to MERS-CoV is needed to characterize the correlates of protection and durability of the immunity and to aid in developing preventative and therapeutic interventions. Although MERS-CoV-specific circulating antibodies could persist for several years post-recovery, their waning raises concerns about their durability and role in protection. Nonetheless, memory B and T cells could provide long-lasting protective immunity despite the serum antibodies levels. METHODS: Serological and flow cytometric analysis of MERS-CoV-specific immune responses were performed on samples collected from a cohort of recovered individuals who required intensive care unit (ICU) admission as well as hospital or home isolation several years after infection to characterize the longevity and quality of humoral and cellular immune responses. RESULTS: Our data showed that MERS-CoV infection could elicit robust long-lasting virus-specific binding and neutralizing antibodies as well as T- and B-cell responses up to 6.9 years postinfection regardless of disease severity or need for ICU admission. Apart from the persistent high antibody titers, this response was characterized by B-cell subsets with antibody-independent functions as demonstrated by their ability to produce tumor necrosis factor α (TNF-α), interleukin (IL)-6, and interferon γ (IFN-γ) cytokines in response to antigen stimulation. Furthermore, virus-specific activation of memory CD8+ and CD4+ T cell subsets from MERS-recovered patients resulted in secretion of high levels of TNF-α, IL-17, and IFN-γ. CONCLUSIONS: MERS-CoV infection could elicit robust long-lasting virus-specific humoral and cellular responses.

Parasitic lung diseases.

Parasitic lung diseases are caused by a number of parasites as a result of transient passage in the lung or as a result of an immunologic reaction. The clinical presentation may be in the form of focal or cystic lesions, pleural effusion or diffuse pulmonary infiltrates. With increasing globalisation, it is important to consider parasitic infections in the differential diagnosis of lung diseases. This is particularly important since early identification and prompt therapy result in full cure of these conditions. In this review, we summarise the most common parasitic lung diseases.

Differential expression of carcinoembryonic antigen-related cell adhesion molecule-5 (CEACAM5) and dipeptidyl peptidase-4 (DPP4) with detection of Middle East respiratory syndrome-coronavirus in peripheral blood.

BACKGROUND: Middle East respiratory syndrome-coronavirus (MERS-CoV) utilizes CD26 (dipeptidyl peptidase-4) and CD66e or CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5) receptors for cell infection. Peripheral blood mononuclear cells (PBMCs) play a critical role in mounting adaptive immune response against the virus. This study was performed to assess the expression of CD26 and CD66e on PBMCs and their susceptibility to MERS-CoV infection. METHODS: Surface expression of CD26 and CD66e receptors on PBMCs from MERS-CoV patients (n = 20) and healthy controls (n = 20) was assessed by flow cytometry and the soluble forms were determined by enzyme-linked immunosorbent assay (ELISA). MERS-CoV UpE and Orf1a genes in PBMCs were detected by using Altona diagnostics reverse transcription polymerase chain reaction (RT-PCR) kit. RESULTS: Mean fluorescent intensity (MFI) of CD66e was significantly higher on CD4 + lymphocytes (462.4 ± 64.35 vs 325.1 ± 19.69; p < 0.05) and CD8 + lymphocytes (533.8 ± 55.32 vs 392.4 ± 37.73; p < 0.04) from patients with MERS-CoV infection compared to the normal controls. No difference in MFI for CD66e was observed on monocytes (381.8 ± 40.34 vs 266.8 ± 20.6; p = 0.3) between the patients and controls. Soluble form of CD66e among MERS-CoV patients was also higher than the normal controls (mean= 338.7 ± 58.75 vs 160.7 ± 29.49 ng/mL; p < 0.01). Surface expression of CD26 on PBMCs and its soluble form were no different between the groups. MERS-CoV was detected by RT-PCR in 16/20 (80%) patients from whole blood, among them 8 patients were tested in PBMCs, 4/8 (50%) patients were positive. CONCLUSION: Increased expression levels of CD66e (CEACAM5) may contribute to increased susceptibility of PBMCs to MERS-CoV infection and disease progression.

Common intestinal parasitic infections among patients living in Riyadh, Saudi Arabia: Prevalence and demographic associations (A cross-sectional retrospective study).

Background: This study aimed to determine the prevalence and associated factors of intestinal parasitic infections (IPIs) among patients referred from different primary healthcare centers (PHC) in Riyadh, Kingdom of Saudi Arabia. Material & methods: A cross-sectional retrospective study conducted at Riyadh Regional Laboratory (RRL). All stool samples that are requested for intestinal parasite detection by physicians from PHCs across the Riyadh Region during year 2020 are referred to the RRL. The data recorded included age, sex, nationality, PHC location, and the stool analysis result with the type of parasite detected. Results: The data of 1148 patients were collected and statistically analyzed. IPIs were present in 296 (25.8%) patients, among whom 40 were infected with more than one parasite. The rate of infection with intestinal protozoa (95.4%) was higher than that with intestinal helminths (4.6%). Sixty (17.4%) infections were caused by pathogenic intestinal parasites, including pathogenic protozoa and helminths. The most common pathogenic protozoa were Entamoeba histolytica/dispar, which represented 9.3% of all IPIs and 72.7% of infections caused by pathogenic protozoa. Saudi nationals were the predominant population infected with pathogenic protozoa (44.0%). Ascaris lumbricoides was the most common helminth infection (56.3%) among patients. Nonpathogenic IPIs were detected at a higher rate (82.6%) than pathogenic IPIs (17.4%), with the predominant protozoa being Blastocystis hominis (61.0%). A higher rate of IPIs was observed in expatriates than in Saudi nationals (229 [33.6%] vs. 67 [14.3%], respectively) (P = 0.0000). Conclusions: Among the 12 different nationalities in our study cohort, the prevalence was the lowest in Saudi nationals (14.3%). The prevalence of B. hominis was high in all areas and nationalities, affecting all age groups among the patients referred for stool analysis. The implementation of preventive measures and awareness programs regarding sanitation and personal hygiene are needed.

Characteristics of healthcare workers with COVID-19: A retrospective descriptive study in a quaternary care center in Riyadh, Saudi Arabia.

BACKGROUND: The aim of this study was to describe the epidemiological and clinical presentation of Healthcare Workers (HCWs) affected by COVID-19. METHODS: A cross-sectional retrospective study was conducted at King Saud Medical City (KSMC), Saudi Arabia (KSA). All KSMC employees who acquired COVID-19 between March 22nd to July 15th, 2020 have been included. Their data has been anonymously analyzed. FINDINGS: During the study period, among the 12000 HCWs working at KSMC, 9.75% tested positive for COVID-19. The source of HCWs infections was mainly community acquired (85%) which included incidences of transmission in hospital dormitories. Transmission among coworkers was the main source of hospital acquired incidences. Direct patient care was reported in 99.8% of study subjects among the high-risk areas, compared to 3.4% in low-risk areas (p-value <0.001), 12-h shifts were more common in the medium and high-risk areas, and at least one symptom was reported by 93.1% of HCWs in high-risk areas compared to 81.6% in low-risk areas (p-value <0.001). CONCLUSION: In KSA, for HCWs, reducing lapses in compliance with masking in non-patient care areas should be considered. In KSA the role that hospital dormitories play in the community transmission of COVID-19 among HCWs need further studies.

Comparison of severity of immunized versus non-immunized COVID-19 patients admitted to ICU: A prospective observational study.

BACKGROUND: Vaccines against COVID-19 show high efficacy, yet, infection is still being detected among immunized patients, although with blunted severity. The purpose of this study was to assess the severity of COVID-19 infection among immunized versus non-immunized COVID-19 patients admitted to ICU. METHOD: A prospective observational cohort study, including all COVID-19 patients admitted to intensive care unit between January 1st, 2021 and June 30th, 2021 were eligible for inclusion. A comparison of severity upon hospitalization of immunized versus non-immunized patients on a 7-level ordinal scale was conducted, using ordinal logistic regression. RESULTS: 592 patients were enrolled, 524 (88.5%) non-immunized, 63 (10.6%) partially immunized, and 5 (0.9%) fully immunized, partially and fully immunized patients were grouped together. Majority of immunized patients (86.7%) were symptomatic before 21 days of immunization. Non-immunized group had fewer patients in the lower severity categories, while more patients in the higher severity categories compared to immunized group. At least one dose of immunization was associated with reduction of odds of moving up severity scale (OR = 0.2 [95% CI: 0.15-0.4]; p < 0.001) in a well fitted ordinal logistic regression model. At least one dose of immunization was associated with lower adjusted odds of 30 day all-cause mortality (OR = 0.45 [95% CI: 0.23-0.89]; p = 0.02). Non-immunized group had higher mortality rate (43.9% versus 29.4% [95% CI: 1.5 to 25.8]; p = 0.02). CONCLUSION: Most COVID-19 patients admitted to ICU were non-immunized, most of the partially immunized patients got infected before immunity could develop, and fully immunized patients were likely non-responders. At least one dose of immunization significantly decreases severity of the disease across all ordinal severity categories, and is significantly associated with lower 30 day all-cause mortality. Accordingly, immunization status may have to be considered when deciding on disposition of COVID-19 patients at the point of triage.

The utilization of hydroxychloroquine to reduce the main signs and symptoms of COVID-19 patients, a cross-sectional study.

Hydroxychloroquine (HCQ) and chloroquine were found to have positive results in some non-randomized clinical trials with more benefit in decreasing the viral load of COVID-19. HCQ is a lysosomotropic and lipophilic drug that can penetrate cell membranes, and accumulates in the acidic lysosomes. The high concentration of alkaline HCQ increases the pH in lysosomes from the normal levels of 4.7-4.8 to 6 which leads to inhibition of lysosomes functions and thus, prevents the entry of coronavirus into cells. OBJECTIVES: The main aim of this study is to find out the appropriateness of using HCQ in asymptomatic/mildly symptomatic COVID-19 positive patients in an attempt to reduce the development of signs and symptoms of COVID-19 and severe disease. METHODOLOGY: Randomized selection, open-label trial to evaluate the efficacy of HCQ for patients presenting with asymptomatic COVID-19 upon diagnosis. Cases that met the inclusion criteria were divided into two arms [102 subjects to take HCQ (a loading dose of 400 mg twice daily given orally, followed by a maintenance dose of 200 mg twice daily for 4 days), and 100 subjects were used as a control group]. A follow-up for all the participants on daily basis for 14 days for any signs and symptoms (fever, cough, and shortness of breath). The main variables are action profile (represented by Area under the curve (AUC) for fever, cough, and shortness of breath statistically analyzed to differentiate between the two groups. RESULTS: Data in this study showed that HCQ was effective in reducing body temperature from the first day to the fifth day; this positive effect was significant with (p < 0.001) compared with subjects who didn't receive HCQ. While there was no significant effect on cough or Shortness of breath. CONCLUSION: The recommendation of this study is to utilize HCQ to all subjects with asymptomatic COVID-19 infection providing that these subjects are within the inclusion criteria of this study. There was no adverse drug reaction observed for HCQ on daily follow-up.

Adenovirus and RNA-based COVID-19 vaccines' perceptions and acceptance among healthcare workers in Saudi Arabia: a national survey.

OBJECTIVES: The aim of this study was to compare the perception, confidence, hesitancy and acceptance rate of various COVID-19 vaccine types among healthcare workers (HCWs) in Saudi Arabia, a nation with Middle East respiratory syndrome coronavirus experience. DESIGN: National cross-sectional, pilot-validated questionnaire. SETTING: Online, self-administered questionnaire among HCWs. PARTICIPANTS: A total of 2007 HCWs working in the Kingdom of Saudi Arabia participated; 1512 (75.3%) participants completed the survey and were included in the analysis. INTERVENTION: Data were collected through an online survey sent to HCWs during 1-15 November 2020. The main outcome measure was HCW acceptance of COVID-19 candidate vaccines. The associated factors of vaccination acceptance were identified through a logistic regression analysis and via measurement of the level of anxiety, using the Generalised Anxiety Disorder 7 scale. RESULTS: Among the 1512 HCWs who were included, 62.4% were women, 70.3% were between 21 and 40 years of age, and the majority (62.2%) were from tertiary hospitals. In addition, 59.5% reported knowing about at least one vaccine; 24.4% of the participants were sure about their willingness to receive the ChAdOx1 nCoV-19 vaccine, and 20.9% were willing to receive the RNA BNT162b2 vaccine. However, 18.3% reported that they would refuse to receive the Ad5-vectored vaccine, and 17.9% would refuse the Gam-COVID-Vac vaccine. Factors that influenced the differential readiness of HCWs included their perceptions of the vaccine's efficiency in preventing the infection (33%), their personal preferences (29%) and the vaccine's manufacturing country (28.6%). CONCLUSIONS: Awareness by HCWs of the several COVID-19 candidate vaccines could improve their perceptions and acceptance of vaccination. Reliable sources on vaccine efficiency could improve vaccine uptake, so healthcare authorities should use reliable information to decrease vaccine hesitancy among frontline healthcare providers.

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update.

BACKGROUND: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. METHODS: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. RESULTS: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. CONCLUSION: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.