Interactions between Gender and Sepsis-Implications for the Future.

Sex and gender dimorphisms are found in a large variety of diseases, including sepsis and septic shock which are more prevalent in men than in women. Animal models show that the host response to pathogens differs in females and males. This difference is partially explained by sex polarization of the intracellular pathways responding to pathogen-cell receptor interactions. Sex hormones seem to be responsible for this polarization, although other factors, such as chromosomal effects, have yet to be investigated. In brief, females are less susceptible to sepsis and seem to recover more effectively than males. Clinical observations produce more nuanced findings, but men consistently have a higher incidence of sepsis, and some reports also claim higher mortality rates. However, variables other than hormonal differences complicate the interaction between sex and sepsis, including comorbidities as well as social and cultural differences between men and women. Conflicting data have also been reported regarding sepsis-attributable mortality rates among pregnant women, compared with non-pregnant females. We believe that unraveling sex differences in the host response to sepsis and its treatment could be the first step in personalized, phenotype-based management of patients with sepsis and septic shock.

Resource allocation.

PURPOSE OF REVIEW: The coronavirus disease 2019 pandemic and recent global recessions have brought to the forefront of the medical-political discussion the fact that medical resources are finite and have focused a spotlight on fair allocation and prioritization of healthcare resources describe why this review is timely and relevant. RECENT FINDINGS: This review presents past and present concepts related to the ethics of resource allocation. Included are discussions regarding the topics of who should determine resource allocation, what types of research require allocation, methods currently in use to determine what resources are appropriate and which should be prioritized.describe the main themes in the literature covered by the article. SUMMARY: Models for resource allocation must differentiate between different types of resources, some of which may require early preparation or distribution. Local availability of specific resources, supplies and infrastructure must be taken into consideration during preparation. When planning for long durations of limited resource availability, the limitations of human resilience must also be considered. Preparation also requires information regarding the needs of the specific population at hand (e.g. age distributions, disease prevalence) and societal preferences must be acknowledged within possible limits.

Outcome predictors and patient progress following delivery in pregnant and postpartum patients with severe COVID-19 pneumonitis in intensive care units in Israel (OB-COVICU): a nationwide cohort study.

BACKGROUND: A key unresolved controversy in severe COVID-19 pneumonitis in pregnancy is the optimum timing of delivery and whether delivery improves or worsens maternal outcomes. We aimed to assess clinical data on every intensive care unit (ICU) day for pregnant and postpartum women admitted to the ICU with COVID-19, with a particular focus on the days preceding and following delivery. METHODS: In this multicentre, nationwide, prospective and retrospective cohort study, we evaluated all pregnant women who were admitted to an ICU in Israel with severe COVID-19 pneumonitis from the 13th week of gestation to the 1st week postpartum. We excluded pregnant patients in which the ICU admission was unrelated to severe COVID-19 pneumonitis. We assessed maternal and neonatal outcomes and longitudinal clinical and laboratory ICU data. The primary overall outcome was maternal outcome (worst of the following: no invasive positive pressure ventilation [IPPV], use of IPPV, use of extracorporeal membrane oxygenation [ECMO], or death). The primary longitudinal outcome was Sequential Organ Failure Assessment (SOFA) score, and the secondary longitudinal outcome was the novel PORCH (positive end-expiratory pressure [PEEP], oxygenation, respiratory support, chest x-ray, haemodynamic support) score. Patients were classified into four groups: no-delivery (pregnant at admission and no delivery during the ICU stay), postpartum (ICU admission ≥1 day after delivery), delivery-critical (pregnant at admission and receiving or at high risk of requiring IPPV at the time of delivery), or delivery-non-critical (pregnant at admission and not critically ill at the time of delivery). FINDINGS: From Feb 1, 2020, to Jan 31, 2022, 84 patients were analysed: 34 patients in the no-delivery group, four in postpartum, 32 in delivery-critical, and 14 in delivery-non-critical. The delivery-critical and postpartum groups had worse outcomes than the other groups: 26 (81%) of 32 patients in the delivery-critical group and four (100%) of four patients in the postpartum group required IPPV; 12 (38%) and three (75%) patients required ECMO, and one (3%) and two (50%) patients died, respectively. The delivery-non-critical and no-delivery groups had far better outcomes than other groups: six (18%) of 34 patients and two (14%) of 14 patients required IPPV, respectively; no patients required ECMO or died. Oxygen saturation (SpO2), SpO2 to fraction of inspired oxygen (FiO2) ratio (S/F ratio), partial pressure of arterial oxygen to FiO2 ratio (P/F ratio), ROX index (S/F ratio divided by respiratory rate), and SOFA and PORCH scores were all highly predictive for adverse maternal outcome (p<0·0001). The delivery-critical group deteriorated on the day of delivery, continued to deteriorate throughout the ICU stay, and took longer to recover (ICU duration, Mantel-Cox p<0·0001), whereas the delivery-non-critical group improved rapidly following delivery. The day of delivery was a significant covariate for PORCH (p<0·0001) but not SOFA (p=0·09) scores. INTERPRETATION: In patients who underwent delivery during their ICU stay, maternal outcome deteriorated following delivery among those defined as critical compared with non-critical patients, who improved following delivery. Interventional delivery should be considered for maternal indications before patients deteriorate and require mechanical ventilation. FUNDING: None.

Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline.

This rapid practice guideline provides evidence-based recommendations for the use of awake proning in adult patients with acute hypoxemic respiratory failure due to COVID-19. The panel included 20 experts from 12 countries, including one patient representative, and used a strict conflict of interest policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the guidelines in intensive care, development, and evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation (GRADE) method we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. We conducted an electronic vote, requiring >80% agreement amongst the panel for a recommendation to be adopted. The panel made a strong recommendation for a trial of awake proning in adult patients with COVID-19 related hypoxemic acute respiratory failure who are not invasively ventilated. Awake proning appears to reduce the risk of tracheal intubation, although it may not reduce mortality. The panel judged that most patients would want a trial of awake proning, although this may not be feasible in some patients and some patients may not tolerate it. However, given the high risk of clinical deterioration amongst these patients, awake proning should be conducted in an area where patients can be monitored by staff experienced in rapidly detecting and managing clinical deterioration. This RPG panel recommends a trial of awake prone positioning in patients with acute hypoxemic respiratory failure due to COVID-19.

Distribution of Aeration and Pulmonary Blood Volume in Healthy, ARDS and COVID-19 Lungs: A Dual-Energy Computed Tomography Retrospective Cohort Study.

RATIONALE AND OBJECTIVES: 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). 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 has unique ranges of aeration and pulmonary blood volumes. MATERIALS AND METHODS: This retrospective, single-center study of DE-CTPAs included patients with COVID-19, NC-ARDS (Berlin criteria), and controls. Patients with macroscopic pulmonary embolisms 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 milds, 10 moderate-severe), six 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 normally aerated areas in NC-ARDS -37.4 (IQR-52.5-30.2-) and moderate-severe COVID-19 -33.5(IQR-44.2-28.5). The 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.

Decompressive Laparotomy for Veno-Venous Extracorporeal Membrane Oxygenation Failure due to Intra-Abdominal Hypertension in Critically Ill COVID-19 Patient.

The use of extracorporeal membrane oxygenation (ECMO) has increased over the course of the SARS-CoV-2 pandemic. Intra-abdominal hypertension resulting in abdominal compartment syndrome (ACS) during ECMO support is a rare but life-threatening complication, with previous case series describing mortality rates of 44%-100%. Bleeding complications, linked to both patient-related and device-related factors, also characterize prolonged ECMO support and have been reported in up to 60% of ECMO patients. We hereby describe a critically ill COVID-19 patient who underwent emergent bed-side decompressive laparotomy for acute ECMO failure related to the development of ACS. The discussion is focused on surgical considerations including the delicate balance between anticoagulation and thrombosis, as anticoagulation-free ECMO support may be required due to hemorrhagic complications.

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study.

PURPOSE: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. METHODS: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. RESULTS: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%-50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. CONCLUSIONS: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality.

Low versus high dose anticoagulation in patients with Coronavirus 2019 pneumonia at the time of admission to critical care units: A multicenter retrospective cohort study in the Beaumont healthcare system.

PURPOSE: Coagulopathy is common in patients with COVID-19. The ideal approach to anticoagulation remains under debate. There is a significant variability in existing protocols for anticoagulation, and these are mostly based on sporadic reports, small studies, and expert opinion. MATERIALS AND METHODS: This multicenter retrospective cohort study evaluated the association between anticoagulation dose and inpatient mortality among critically ill COVID-19 patients admitted to the intensive care units (ICUs) or step-down units (SDUs) of eight Beaumont Healthcare hospitals in Michigan, USA from March 10th to April 15th, 2020. RESULTS: Included were 578 patients with a median age of 64 years; among whom, 57.8% were males. Most patients (n = 447, 77.3%) received high dose and one in four (n = 131, 22.7%) received low dose anticoagulation. Overall mortality rate was 41.9% (n = 242). After adjusting for potential confounders (age, sex, race, BMI, ferritin level at hospital admission, intubation, comorbidities, mSOFA, and Padua score), administration of high anticoagulation doses at the time of ICU/SDU admission was associated with decreased inpatient mortality (OR 0.564, 95% CI 0.333-0.953, p = 0.032) compared to low dose. CONCLUSION: Treatment with high dose anticoagulation at the time of ICU/SDU admission was associated with decreased adjusted mortality among critically ill adult patients with COVID-19.

Preparing for mass casualty events despite COVID-19.

Preparedness for mass casualty events is essential at local, national, and global levels. Much more needs to be done by all stakeholders to avoid unnecessary morbidity and mortality despite the challenges that COVID-19 continues to present. In this editorial, we highlight the challenges and solutions for mass casualty incident preparations.

Infection control in the intensive care unit: expert consensus statements for SARS-CoV-2 using a Delphi method.

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.

Cardiopulmonary resuscitation in special circumstances.

Cardiopulmonary resuscitation prioritises treatment for cardiac arrests from a primary cardiac cause, which make up the majority of treated cardiac arrests. Early chest compressions and, when indicated, a defibrillation shock from a bystander give the best chance of survival with a good neurological status. Cardiac arrest can also be caused by special circumstances, such as asphyxia, trauma, pulmonary embolism, accidental hypothermia, anaphylaxis, or COVID-19, and during pregnancy or perioperatively. Cardiac arrests in these circumstances represent an increasing proportion of all treated cardiac arrests, often have a preventable cause, and require additional interventions to correct a reversible cause during resuscitation. The evidence for treating these conditions is mostly of low or very low certainty and further studies are needed. Irrespective of the cause, treatments for cardiac arrest are time sensitive and most effective when given early-every minute counts.

Experimental and Compassionate Drug Use During the First Wave of the COVID-19 Pandemic: A Retrospective Single-Center Study.

INTRODUCTION: Concomitant experimental/compassionate drug administration has been all-pervasive in the treatment of COVID-19 patients. The objective of this study was to study the relationship between patient severity, the number of experimental/compassionate medications received (main outcome measure), and patient outcomes [survival to hospital discharge and length of hospital stay (LOS)]. METHODS: Retrospective analysis of data collected in real time during the first pandemic wave in a tertiary care hospital. Data included patient demographics, comorbidities, admission vital signs, laboratory values, most extreme respiratory intervention during hospitalization, and data regarding treatment with compassionate/experimental drugs during their stay. RESULTS: Overall, 292 PCR-confirmed patients with symptoms of COVID-19 were studied (March/April, 2020). Increasing respiratory support correlated with both LOS and mortality. Patients were more likely to receive more than 1 experimental/compassionate drugs as respiratory support escalated, ranging from 3% (n = 4/136) among patients on room air to 77.3% (n = 17/22) of mechanically ventilated/ECMO patients (P < 0.001, linear by linear association). The mean number of experimental/compassionate drugs received also increased with escalating respiratory support (P < 0.001, one-way ANOVA). After adjustment for severity of patient condition, administration of more experimental/compassionate drugs was unrelated to survival (P = 0.24), but was related to increased LOS (P < 0.001). CONCLUSION: Patients that were hospitalized in worse condition were more likely to receive more experimental/compassionate drugs. Treatment was unrelated to survival but may have been related to LOS. This finding raises questions regarding the results of studies on medication effects that adjusted for multiple drug administration.

Don't forget arterial thrombosis in patients with COVID-19: A case series

Introduction The acute disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS COV-2) is accompanied by a hypercoagulable state. Multiple publications have described the venous thromboembolic events associated with coronavirus disease 2019 (COVID-19) but arterial thromboembolic events have yet to be described. Cases description We describe five COVID-19 patients that developed severe morbidity as a result of occlusive arterial thromboembolic events occurring despite treatment with low molecular weight heparin. All cases presented with an acute confusional state and were accompanied by rapid elevations of lactate and D-dimers and leukocytes. The end organs involved were the kidneys, spleen, liver, lungs, central nervous system, intestines and limbs. Only one of the five patients survived. Conclusion COVID-19 is associated with not only venous but also arterial thromboembolic events. Further research is required to clarify the incidence, causes and possible modes of prevention of this potentially lethal disease complication.

Personalized mechanical ventilation in acute respiratory distress syndrome.

A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume (VT) is a standard of care, further individualization of VT may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust VT and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.

Mortality after in-hospital cardiac arrest in patients with COVID-19: A systematic review and meta-analysis.

AIM: To estimate the mortality rate, the rate of return of spontaneous circulation (ROSC) and survival with favorable neurological outcome in patients with COVID-19 after in-hospital cardiac arrest (IHCA) and attempted cardiopulmonary resuscitation (CPR). METHODS: PubMed, EMBASE, Web of Science, bioRxiv and medRxiv were surveyed up to 8th February 2021 for studies reporting data on mortality of patients with COVID-19 after IHCA. The primary outcome sought was mortality (in-hospital or at 30 days) after IHCA with attempted CPR. Additional outcomes were the overall rate of IHCA, the rate of non-shockable presenting rhythms, the rate of ROSC and the rate of survival with favorable neurological status. RESULTS: Ten articles were included in the systematic review and meta-analysis, for a total of 1179 COVID-19 patients after IHCA with attempted CPR. The estimated overall mortality rate (in-hospital or at 30 days) was 89.9% (95% Predicted Interval [P.I.] 83.1%-94.2%; 1060/1179 patients; I2 = 82%). The estimated rate of non-shockable presenting rhythms was 89% (95% P.I. 82.8%-93.1%; 1022/1205 patients; I2 = 85%), and the estimated rate of ROSC was 32.9% (95% P.I. 26%-40.6%; 365/1205 patients; I2 = 82%). The estimated overall rate of survival with favorable neurological status at 30 days was 6.3% (95% P.I. 4%-9.7%; 50/851 patients; I2 = 48%). Sensitivity analysis showed that COVID-19 patients had higher risk of death after IHCA than non COVID-19 patients (OR 2.34; 95% C.I. 1.37-3.99; number of studies = 3; 1215 patients). CONCLUSIONS: Although one of three COVID-19 patients undergoing IHCA may achieve ROSC, almost 90% may not survive at 30 days or to hospital discharge.

Mechanical ventilation parameters in critically ill COVID-19 patients: a scoping review.

BACKGROUND: The mortality of critically ill patients with COVID-19 is high, particularly among those receiving mechanical ventilation (MV). Despite the high number of patients treated worldwide, data on respiratory mechanics are currently scarce and the optimal setting of MV remains to be defined. This scoping review aims to provide an overview of available data about respiratory mechanics, gas exchange and MV settings in patients admitted to intensive care units (ICUs) for COVID-19-associated acute respiratory failure, and to identify knowledge gaps. MAIN TEXT: PubMed, EMBASE, and MEDLINE databases were searched from inception to October 30, 2020 for studies providing at least one ventilatory parameter collected within 24 h from the ICU admission. The quality of the studies was independently assessed using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. A total of 26 studies were included for a total of 14,075 patients. At ICU admission, positive end expiratory pressure (PEEP) values ranged from 9 to 16.5 cm of water (cmH2O), suggesting that high levels of PEEP were commonly used for setting MV for these patients. Patients with COVID-19 are severely hypoxemic at ICU admission and show a median ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ranging from 102 to 198 mmHg. Static respiratory system compliance (Crs) values at ICU admission were highly heterogenous, ranging between 24 and 49 ml/cmH2O. Prone positioning and neuromuscular blocking agents were widely used, ranging from 17 to 81 and 22 to 88%, respectively; both rates were higher than previously reported in patients with "classical" acute respiratory distress syndrome (ARDS). CONCLUSIONS: Available data show that, in mechanically ventilated patients with COVID-19, respiratory mechanics and MV settings within 24 h from ICU admission are heterogeneous but similar to those reported for "classical" ARDS. However, to date, complete data regarding mechanical properties of respiratory system, optimal setting of MV and the role of rescue treatments for refractory hypoxemia are still lacking in the medical literature.

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. METHODS: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). RESULTS: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. CONCLUSION: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. TRIAL REGISTRATION: The study was registered with Clinical trials.gov Identifier: NCT04534569.

QTc prolongation among hydroxychloroquine sulphate-treated COVID-19 patients: An observational study.

BACKGROUND: The liberal administration of hydroxychloroquine-sulphate (HCQ) to COVID-19 patients has raised concern regarding the risk of QTc prolongation and cardiac arrhythmias, particularly when prescribed with azithromycin. We evaluated the incidence of QTc prolongation among moderately and severely ill COVID-19 patients treated with HCQ and of the existence of concomitant alternative causes. METHODS: All COVID-19 patients treated with HCQ (between Mar 1 and Apr 14, 2020) in a tertiary medical centre were included. Clinical characteristics and relevant risk factors were collected from the electronic medical records. Individual patient QTc intervals were determined before and after treatment with HCQ. The primary outcome measure sought was a composite end point comprised of either an increase ≥60 milliseconds (ms) in the QTc interval compared with pre-treatment QTc, and/or a maximal QTc interval >500 ms RESULTS: Ninety patients were included. Median age was 65 years (IQR 55-75) and 57 (63%) were male. Thirty-nine patients (43%) were severely or critically ill. Hypertension and obesity were common (n = 23 each, 26%). QTc prolongation evolved in 14 patients (16%). Age >65 years, congestive heart failure, severity of disease, C-reactive protein level, hypokalaemia and furosemide treatment, were all associated with QTc prolongation. Adjusted analysis showed that QTc prolongation was five times more likely with hypokalaemia [OR 5, (95% CI, 1.3-20)], and three times more likely with furosemide treatment [OR 3 (95% CI, 1.01-13.7)]. CONCLUSION: In patients treated with HCQ, QTc prolongation was associated with the presence of traditional risk factors such as hypokalaemia and furosemide treatment.