Unusual presentation of benzodiazepine withdrawal with Takotsubo syndrome: a case report.

Background: Thousands of people suffer from anxiety, depression, and insomnia every day, with benzodiazepines being one of the strategies used to treat these conditions. Withdrawal from its long-term use can lead to potentially life-threatening complications, including Takotsubo syndrome. The authors highlight an atypical case of Takotsubo syndrome secondary to benzodiazepine withdrawal, a rare life-threatening complication of acute substance withdrawal. Case summary: A 58-year-old female presented to the emergency department with altered mental status and acute pulmonary oedema after discontinuing her prescribed benzodiazepines 3 days prior to presentation. Electrocardiogram (ECG) demonstrated anterior ST-segment elevation, with Q-wave and T-wave inversion with prolonged QT interval. Troponin I concentration and B-type natriuretic peptide were elevated to 5407 ng/L (normal ≤ 16 ng/L) and to 1627.0 pg/L (normal ≤ 100 pg/mL), respectively. Echocardiogram showed ballooning of the left ventricle (LV) apex with dyskinesia of the mid and apical segments, with LV function of 15%. Coronary angiography was normal, but left ventriculography showed severe LV systolic dysfunction with akinesis of the mid and apical LV segments and hyperdynamic basal segments. A presumptive diagnosis of benzodiazepine withdrawal-induced Takotsubo syndrome was made, and patients' symptoms, ECG findings, and LV dysfunction resolved after benzodiazepine administration. Six months post discharge, the patient remained asymptomatic with a normal biventricular function, and a beta-blocker was successfully introduced as part of a lifelong plan. Discussion: A diagnosis of benzodiazepine withdrawal-induced Takotsubo syndrome is an underrecognized and challenging diagnosis, due to its atypical clinical presentation. High degree of clinical suspicion for this syndrome is crucial, since favourable prognosis depends on prompt diagnosis and treatment.

ECMO for drug-refractory electrical storm without a reversible trigger: a retrospective multicentric observational study.

AIMS: Drug-refractory electrical storm (ES) is a life-threatening medical emergency. We describe the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in drug-refractory ES without a reversible trigger, for which specific guideline recommendations are still lacking. METHODS AND RESULTS: Retrospective observational study in four Iberian centres on the indications, treatment, complications, and outcome of drug-refractory ES not associated with acute coronary syndromes, decompensated heart failure, drug toxicity, electrolyte disturbances, endocrine emergencies, concomitant acute illness with fever, or poor compliance with anti-arrhythmic drugs, requiring VA-ECMO for circulatory support. Thirty-four (6%) out of 552 patients with VA-ECMO for cardiogenic shock were included [71% men; 57 (44-62) years], 65% underwent cardiopulmonary resuscitation before VA-ECMO implantation, and 26% during cannulation. Left ventricular unloading during VA-ECMO was used in 8 (24%) patients: 3 (9%) with intraaortic balloon pump, 3 (9%) with LV vent, and 2 (6%) with Impella. Thirty (88%) had structural heart disease and 8 (24%) had an implantable cardioverter-defibrillator. The drug-refractory ES was mostly due to monomorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) (59%), isolated monomorphic VT (26%), polymorphic VT (9%), or VF (6%). Thirty-one (91%) required deep sedation, 44% overdrive pacing, 36% catheter ablation, and 26% acute autonomic modulation. The main complications were nosocomial infection (47%), bleeding (24%), and limb ischaemia (21%). Eighteen (53%) were weaned from VA-ECMO, and 29% had heart transplantation. Twenty-seven (79%) survived to hospital discharge (48 (33-82) days). Non-survivors were older [62 (58-67) vs. 54 (43-58); P < 0.01] and had a higher first rhythm disorder-to-ECMO interval [0 (0-2) vs. 2 (1-11) days; P = 0.02]. Seven (20%) had rehospitalization during follow-up [29 (12-48) months], with ES recurrence in 6%. CONCLUSIONS: VA-ECMO bridged drug-refractory ES without a reversible trigger with a high success rate. This required prolonged hospital stays and coordination between the ECMO centre, the electrophysiology laboratory, and the heart transplant programme.

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections.

PURPOSE: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). METHODS: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. RESULTS: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. CONCLUSION: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.

Cardiac Adverse Events and Remdesivir in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial.

BACKGROUND: We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with Coronavirus Disease 2019 (COVID-19) receiving remdesivir plus standard of care (SoC) compared to SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. METHODS: This post-hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19 (NCT04315948). Any first AE occurring between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves and Kaplan-Meier estimates were calculated for event rates. RESULTS: Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (HR 1.0, 95% CI 0.7-1.5, p = 0.98), even when evaluating serious and non-serious cardiac AEs separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between remdesivir and control groups in the occurrence of different cardiac AE subclasses, including arrhythmic events (HR 1.1, 95% CI: 0.7-1.7, p = 0.68). CONCLUSIONS: Remdesivir treatment was not associated with an increased risk of cardiac AEs, whether serious or not, and regardless of AE severity, compared to control, in patients hospitalized with moderate or severe COVID-19. This is consistent with the results of other randomized controlled trials and meta-analyses.

Critically ill patients with high predicted mortality: Incidence and outcome / Pacientes en cuidados intensivos con alta mortalidad prevista: Incidencia y evolución

Objective As calculated by the severity scores, an unknown number of patients are admitted to the Intensive Care Unit (ICU) with a very high risk of death. Clinical studies have poorly addressed this population, and their prognosis is largely unknown. Design Post hoc analysis of a multicenter, cohort, longitudinal, observational, retrospective study (CIMbA). Setting Sixteen Portuguese multipurpose ICUs. Patients Patients with a Simplified Acute Physiology Score II (SAPS II) predicted hospital mortality above 80% on admission to the ICU (high-risk group); A comparison with the remaining patients was obtained. Interventions None. Main Variables of Interest Hospital, 30 days, 1 year mortality. Results We identified 4546 patients (59.9% male), 12.2% of the whole population. Their SAPS II predicted hospital mortality was 89.0±5.8%, whilst the observed mortality was lower, 61.0%. This group had higher mortality, both during the first 30 days (aHR 3.52 [95% CI 3.34–3.71]) and from day 31 to day 365 after ICU admission (aHR 1.14 [95%CI 1.04–1.26]), respectively. However, their hospital standardized mortality ratio was similar to the other patients (0.69 vs. 0.69, P=.92). At one year of follow-up, 30% of patients in the high-risk group were alive. Conclusions Roughly 12% of patients admitted to the ICU for more than 24h had a SAPS II score predicted mortality above 80%. Their hospital standardized mortality was similar to the less severe population and 30% were alive after one year of follow-up. (AU)

Objetivo Según las escalas de gravedad, un número indeterminado de pacientes ingresan en la Unidad de Cuidados Intensivos (UCI) con riesgo de muerte muy elevado. Este grupo ha sido poco abordado en los estudios clínicos y se desconoce en gran medida su pronóstico. Diseño Análisis post-hoc de estudio multicéntrico, de cohortes, longitudinal, observacional y retrospectivo (CIMbA). Âmbito Dieciséis UCI polivalentes portuguesas. Pacientes Pacientes con mortalidad hospitalaria prevista en el Simplified Acute Physiology Score II (SAPS II) superior al 80% nel ingreso en la UCI (grupo de alto riesgo); se compararon con los restantes. Intervenciones Ninguna. Variables de interés principals Mortalidad hospitalaria, a 30 días y 1 año. Resultados Se identificaron 4546 pacientes (59.9% hombres), 12.2% da población. La mortalidad hospitalaria estimada por lo SAPS II fue de 89.0±5.8%, aunque la observada fue inferior, 61.0%. Este grupo presentó mayor mortalidad, tanto durante los primeros 30 días (aHR 3.52 [IC 95%: 3.34–3.71]) y desde el día 31 hasta el día 365 después del ingreso en UCI (aHR 1.14 [IC 95%: 1.04–1.26]). Sin embargo, su índice de mortalidad hospitalaria estandarizada fue similar a los otros pacientes (0.69 vs. 0.69; P=.92). Al primer año de seguimiento, 30% de los pacientes de alto riesgo estaban vivos. ConclusionesAproximadamente 12% de los pacientes ingresados en la UCI durante más de 24 horas tenían una mortalidad prevista por SAPS II superior al 80%. Su mortalidad hospitalaria estandarizada fue similar a la de la población menos grave y el 30% estaban vivos después de un año de seguimiento. (AU)

Cardiac Tamponade Complicating Extracorporeal Membrane Oxygenation: An Extracorporeal Life Support Organization Registry Analysis.

OBJECTIVES: Cardiac tamponade is a potentially life-threatening complication during extracorporeal membrane oxygenation (ECMO). In this study, the authors assessed the incidence, patient characteristics, and risk factors for mortality of cardiac tamponade during ECMO. DESIGN: The authors queried the Extracorporeal Life Support Organization (ELSO) Registry from 1997 to 2021 for all adults with cardiac tamponade as a reported complication during ECMO. PARTICIPANTS: Cardiac tamponade was reported in 2,176 (64% men; 53.8 ± 0.33 years) of 84,430 adults (2.6%). MEASUREMENTS AND MAIN RESULTS: Venoarterial ECMO was the main configuration (78%), followed by venovenous ECMO (VV ECMO) (18%), for cardiac (67%), pulmonary (21%) support, and extracorporeal cardiopulmonary resuscitation (ECPR) (12%). Percutaneous cannulation was performed in 51%, with the femoral vein and femoral artery as the most common sites for drainage and return cannulae, with dual-lumen cannulae in 39% of VV ECMO. Hospital survival was lower (35% v 49%; p < 0.01) when compared with that of all adults from the ELSO Registry. In multivariate analysis, age, aortic dissection and/or rupture, COVID-19, ECPR, pre-ECMO renal-replacement therapy, and prone position are associated with hospital mortality, whereas ECMO for pulmonary support is associated with hospital survival. Similarly, renal, cardiovascular, metabolic, neurologic, and pulmonary complications occurred more frequently in nonsurvivors. CONCLUSIONS: Cardiac tamponade is a rare complication during ECMO that, despite being potentially reversible, is associated with high hospital mortality. Venoarterial ECMO is the most common configuration. ECMO for pulmonary support was associated with higher survival, and ECPR was associated with higher mortality. In these patients, other ECMO-related complications were frequently reported and associated with hospital mortality.

Genomic and epidemiological insight of an outbreak of carbapenemase-producing Enterobacterales in a Portuguese hospital with the emergence of the new KPC-124.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) is an increasing problem in healthcare settings. This study aimed to identify the source of a CPE outbreak that occurred in 2022, in a tertiary hospital in the North of Portugal, to identify exposed patients, and to assess the risk of becoming CPE-positive following hospital admission. METHODS: A multi-disciplinary investigation was conducted including descriptive, analytical, and molecular epidemiology, environmental screening, and assessment of infection control measures. Clinical and environmental isolates were analyzed using whole-genome sequencing and phylogenetic analysis. Additionally, a prospective observational cohort study was conducted to further investigate the risk factors associated with the emergence of new cases in cohorts of CPE-negative admitted patients. RESULTS: We observed the presence of multispecies KPC-, IMP-, and/or NDM-producing isolates. Genetically indistinguishable clinical and environmental isolates were found on the same room/ward. The ST45 KPC-3-producing Klebsiella pneumoniae clone was the responsible for the outbreak. During patients' treatment, we detected the emergence of resistance to ceftazidime-avibactam, associated with mutations in the blaKPC-3 gene (blaKPC-46, blaKPC-66 and blaKPC-124, the last variant never previously reported), suggesting a vertical evolutionary trajectory. Patients aged ≥ 75 years, hygiene/feeding-care dependent, and/or subjected to secretion aspiration were risk factors for CPE colonization after hospital admission. Additionally, cases with previous admission to the emergency department suggest that CPE dissemination may occur not only during hospitalization but also in the emergency department. CONCLUSION: Overall, the study highlights that selection pressure with antibiotics, like ceftazidime-avibactam, is a contributing factor to the emergence of new ß-lactamase variants and antibiotic resistance. It also shows that the hospital environment can be a significant source of CPE transmission, and that routine use of infection control measures and real-time molecular epidemiology investigations are essential to ensure the long-term termination of CPE outbreaks and prevent future resurgences.

Pneumococcal Septic Shock Syndrome: A Deadly Condition Despite Vaccination.

Invasive pneumococcal disease is a serious infection with an elevated case-fatality rate that can be even higher among patients with asplenia. Its impact has been blunted by the widespread use of vaccines; even recently, in 2021, two new pneumococcal conjugate vaccines emerged. The authors present a case of a 58-year-old male, splenectomised with the immunisation schedule complete, who died of invasive pneumococcal disease with a fulminant course. It is highlighted that fever in a patient with impaired splenic function is an emergency, and despite the success of immunisation in reducing pneumococcal carriage and invasive disease, serotypes continue to change. Also, the local epidemiology may help guide situations where the immunisation recommendations are dubious regarding the implementation of the new vaccines.

Ultrasonography to Access Diaphragm Dysfunction and Predict the Success of Mechanical Ventilation Weaning in Critical Care: A Narrative Review.

INTRODUCTION: Weaning failure is common in mechanically ventilated patients, and whether ultrasound (US) can predict weaning outcome remains controversial. This review aims to evaluate the diaphragmatic function measured by US as a predictor of weaning outcome. METHODS: PubMed was searched to identify original articles about the use of diaphragmatic US in ICU patients. A total of 61 citations were retrieved initially; available data of 26 studies were included in this review. RESULTS: To assess diaphragmatic dysfunction in adults, six studies evaluated excursion, five evaluated thickening fraction, and both in nine. Despite heterogeneity in the diagnostic accuracy of diaphragm US among the studies, the sonographic indices showed good diagnostic performance for predicting weaning outcome. CONCLUSIONS: Diaphragmatic US can be a useful and accurate tool to detect diaphragmatic dysfunction in critically ill patients and predict weaning outcome.

Critically ill patients with high predicted mortality: Incidence and outcome.

OBJECTIVE: As calculated by the severity scores, an unknown number of patients are admitted to the Intensive Care Unit (ICU) with a very high risk of death. Clinical studies have poorly addressed this population, and their prognosis is largely unknown. DESIGN: Post hoc analysis of a multicenter, cohort, longitudinal, observational, retrospective study (CIMbA). SETTING: Sixteen Portuguese multipurpose ICUs. PATIENTS: Patients with a Simplified Acute Physiology Score II (SAPS II) predicted hospital mortality above 80% on admission to the ICU (high-risk group); A comparison with the remaining patients was obtained. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Hospital, 30 days, 1 year mortality. RESULTS: We identified 4546 patients (59.9% male), 12.2% of the whole population. Their SAPS II predicted hospital mortality was 89.0±5.8%, whilst the observed mortality was lower, 61.0%. This group had higher mortality, both during the first 30 days (aHR 3.52 [95% CI 3.34-3.71]) and from day 31 to day 365 after ICU admission (aHR 1.14 [95%CI 1.04-1.26]), respectively. However, their hospital standardized mortality ratio was similar to the other patients (0.69 vs. 0.69, P=.92). At one year of follow-up, 30% of patients in the high-risk group were alive. CONCLUSIONS: Roughly 12% of patients admitted to the ICU for more than 24h had a SAPS II score predicted mortality above 80%. Their hospital standardized mortality was similar to the less severe population and 30% were alive after one year of follow-up.

Occurrence and predictors of delirium in critically ill older patients: a prospective cohort study.

Objectives: This study aims to analyze the occurrence of delirium in critically ill older patients and to identify predictors of delirium. Methods: This prospective study included critically ill older patients admitted into level II units of Intensive Care Medicine Department of a University Hospital. Patients with Glasgow Coma Scale score ≤11, traumatic brain injury, terminal disease, history of psychosis, blindness/deafness, or inability to understanding/speaking Portuguese were excluded. The Confusion Assessment Method-Short Form (CAM-4) was used to assess the presence of delirium. Results: The final sample (n = 105) had a median age of 80 years, most being female (56.2%), widowed (49.5%), and with complete primary education (53%). Through CAM-4, 36.2% of the patients had delirium. The delirium group was more likely to have previous cognitive decline (48.6% vs 19.6%, P = .04) and severe dependency in instrumental activities of daily living (34.3% vs 14.8%, P = .032), comparing with patients without delirium. The final multiple logistic regression model explained that patients with previous cognitive decline presented a higher risk for delirium (odds ratio: 4.663, 95% confidence Interval: 1.055-20.599, P = .042). Conclusions: These findings corroborate previous studies, showing that cognitive decline is an independent predictor for delirium in older patients. This study is an important contribution for the knowledge regarding the predictors of delirium. The recognition of these factors will help to identify patients who are at high risk for this syndrome and implement early screening and prevention strategies. However, further studies with larger samples, recruited from other clinical settings as well as analyzing other potential factors for delirium, will be needed.

Neurocritical care management supported by multimodal brain monitoring after acute brain injury.

OBJECTIVE: To evaluate the association between different intensive care units and levels of brain monitoring with outcomes in acute brain injury. METHODS: Patients with traumatic brain injury and subarachnoid hemorrhage admitted to intensive care units were included. Neurocritical care unit management was compared to general intensive care unit management. Patients managed with multimodal brain monitoring and optimal cerebral perfusion pressure were compared with general management patients. A good outcome was defined as a Glasgow outcome scale score of 4 or 5. RESULTS: Among 389 patients, 237 were admitted to the neurocritical care unit, and 152 were admitted to the general intensive care unit. Neurocritical care unit management patients had a lower risk of poor outcome (OR = 0.228). A subgroup of 69 patients with multimodal brain monitoring (G1) was compared with the remaining patients (G2). In the G1 and G2 groups, 59% versus 23% of patients, respectively, had a good outcome at intensive care unit discharge; 64% versus 31% had a good outcome at 28 days; 76% versus 50% had a good outcome at 3 months (p < 0.001); and 77% versus 58% had a good outcome at 6 months (p = 0.005). When outcomes were adjusted by SAPS II severity score, using good outcome as the dependent variable, the results were as follows: for G1 compared to G2, the OR was 4.607 at intensive care unit discharge (p < 0.001), 4.22 at 28 days (p = 0.001), 3.250 at 3 months (p = 0.001) and 2.529 at 6 months (p = 0.006). Patients with optimal cerebral perfusion pressure management (n = 127) had a better outcome at all points of evaluation. Mortality for those patients was significantly lower at 28 days (p = 0.001), 3 months (p < 0.001) and 6 months (p = 0.001). CONCLUSION: Multimodal brain monitoring with autoregulation and neurocritical care unit management were associated with better outcomes and should be considered after severe acute brain injury.

Standardized approach for extubation during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome: a prospective observational study.

BACKGROUND: Extubation during extracorporeal oxygenation (ECMO) in severe acute respiratory distress syndrome (ARDS) has not been well studied. Despite the potential benefits of this strategy, weaning from ECMO before liberation from invasive mechanical ventilation remains the most frequent approach. Our aim was to evaluate the safety and feasibility of a standardized approach for extubation during ECMO in patients with severe ARDS. RESULTS: We conducted a prospective observational study to assess the safety and feasibility of a standardized approach for extubation during ECMO in severe ARDS among 254 adult patients across 4 intensive care units (ICU) from 2 tertiary ECMO centers over 6 years. This consisted of a daily assessment of clinical and gas exchange criteria based on an Extracorporeal Life Support Organization guideline, with extubation during ECMO after validation by a dedicated intensive care medicine specialist. Fifty-four (21%) patients were extubated during ECMO, 167 (66%) did not reach the clinical criteria, and in 33 (13%) patients, gas exchange precluded extubation during ECMO. At ECMO initiation, there were fewer extrapulmonary organ dysfunctions (lower SOFA score [OR, 0.88; 95% CI, 0.79-0.98; P = .02] with similar PaO2/FiO2) when compared with patients not extubated during ECMO. Extubation during ECMO associated with shorter duration of invasive mechanical ventilation (7 (4-18) vs. 32 (18-54) days; P < .01) and of ECMO (12 (7-25) vs. 19 (10-41) days; P = .01). This was accompanied by a lower incidence of hemorrhagic shock (2 vs. 11%; P = .05), but more cannula-associated deep vein thrombosis (49 vs. 31%; P = .02) and failed extubation (20 vs. 6%; P < .01). There were no increased major adverse events. Extubation during ECMO is associated with a lower risk of all-cause death, independently of measured confounding (adjusted logistic regression OR 0.23; 95% confidence interval 0.08-0.69, P = .008). CONCLUSIONS: A standardized approach was safe and feasible allowing extubation during ECMO in 21% of patients with severe ARDS, selecting patients who will have a shorter duration of invasive mechanical ventilation, ECMO course, and ICU stay, as well as fewer infectious complications, and high hospital survival.

Association between SARS-CoV-2 viral kinetics and clinical score evolution in hospitalized patients.

The role of antiviral treatment in coronavirus disease 2019 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS-2) using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23) randomly assigned to either standard of care (SoC) or SoC + remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS-2 score lower than 3 (in patients with NEWS-2 <7 at hospitalization) or 5 (in patients with NEWS-2 ≥7 at hospitalization), distinguishing between patients with low or high viral load at hospitalization. The model can fit well the different observed patients trajectories, showing that clinical evolution is associated with viral dynamics, albeit with large interindividual variability. Remdesivir antiviral activity was 22% and 78% in patients with low or high viral loads, respectively, which is not sufficient to generate a meaningful effect on NEWS-2. However, simulations predicted that antiviral activity greater than 99% could reduce by 2 days the time to clinical improvement in patients with high viral load, irrespective of the NEWS-2 score at hospitalization, whereas no meaningful effect was predicted in patients with low viral loads. Our results demonstrate that time to clinical improvement is associated with time to viral clearance and that highly effective antiviral drugs could hasten clinical improvement in hospitalized patients with high viral loads.