Observational study on implications of the COVID-19-pandemic for cardiopulmonary resuscitation in out-of-hospital cardiac arrest: qualitative and quantitative insights from a model region in Germany.

BACKGROUND: The city of Freiburg has been among the most affected regions by the COVID-19 pandemic in Germany. In out of hospital cardiac arrest (OHCA) care, all parts of the rescue system were exposed to profound infrastructural changes. We aimed to provide a comprehensive overview of these changes in the resuscitation landscape in the Freiburg region. METHODS: Utstein-style quantitative data on OHCA with CPR initiated, occurring in the first pandemic wave between February 27th, 2020 and April 30th, 2020 were compared to the same time periods between 2016 and 2019. Additionally, qualitative changes in the entire rescue system were analyzed and described. RESULTS: Incidence of OHCA with attempted CPR did not significantly increase during the pandemic period (11.1/100.000 inhabitants/63 days vs 10.4/100.000 inhabitants/63 days, p = 1.000). In witnessed cases, bystander-CPR decreased significantly from 57.7% (30/52) to 25% (4/16) (p = 0.043). A severe pre-existing condition (PEC) was documented more often, 66.7% (16/24) vs 38.2% (39/102) there were longer emergency medical services (EMS) response times, more resuscitation attempts terminated on scene, 62.5% (15/24) vs. 34.3% (35/102) and less patients transported to hospital (p = 0.019). Public basic life support courses, an app-based first-responder alarm system, Kids Save Lives activities and a prehospital extracorporeal CPR (eCPR) service were paused during the peak of the pandemic. CONCLUSION: In our region, bystander CPR in witnessed OHCA cases as well as the number of patients transported to hospital significantly decreased during the first pandemic wave. Several important parts of the resuscitation landscape were paused. The COVID-19 pandemic impedes OHCA care, which leads to additional casualties. Countermeasures should be taken.

[Complaints and clinical findings six months after COVID-19: outpatient follow-up at the University Medical Center Freiburg]. / Persistierende Beschwerden 6 Monate nach COVID-19 ­ Erfahrungen aus der COVID-19-Nachsorgeambulanz des Universitätsklinikums Freiburg.

BACKGROUND: Increasing evidence suggests that some patients suffer from persistent symptoms for months after recovery from acute COVID-19. However, the clinical phenotype and its pathogenesis remain unclear. We here present data on complaints and results of a diagnostic workup of patients presenting to the post-COVID clinic at the University Medical Center Freiburg. METHODS: Retrospective data analysis of persistently symptomatic patients presenting to our clinic at least 6 months after onset of acute COVID-19. All patients were assessed by a doctor and routine laboratory analysis was carried out. Quality of life was assessed using SF-36 questionnaire. In case of specific persisting symptoms, further organ-specific diagnostic evaluation was performed, and patients were referred to respective departments/specialists. FINDINGS: 132 Patients (58 male, 74 female; mean age 53.8 years) presented to our clinic at least 6 months after COVID-19. 79 (60 %) had been treated as outpatients and 53 (40 %) as inpatients. Most common complaints were persistent fatigue (82 %) and dyspnea on exertion (61 %). Further common complaints were impairments of concentration (54 %), insomnia (43 %), and impairments of smell or taste (35 %). Quality of life was reduced in all sections of the SF-36 questionnaire, yielding a reduced working capacity. Significant pathological findings in laboratory, echocardiographic and radiological work-up were rare. Impairments in lung function tests were more common in previously hospitalized patients. CONCLUSION: Patients presenting 6 months after onset of acute COVID-19 suffer from a diverse spectrum of symptoms with impaired quality of life, also referred to as Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Further research is needed to determine the frequency of these post-COVID syndromes and their pathogenesis, natural course and treatment options. Evaluation and management should be multi-disciplinary.

Incidence and predictors of delirium on the intensive care unit after acute myocardial infarction, insight from a retrospective registry.

OBJECTIVES: This study aimed to identify the incidence and potential risk factors for delirium after myocardial infarction (MI). BACKGROUND: Delirium is a common complication on intensive care units. Data on incidence and especially on predictors of delirium in patients after acute MI are rare. METHODS: In this retrospective study, all patients hospitalized for MI treated with coronary angiography in an university hospital in 2018 were included and analyzed. Onset of delirium within the first 5 days after MI was attributed to the MI and was defined by a Nursing Delirium screening scale (NuDesc) ≥2. This score is taken as part of daily care in every patient on intensive care unit three times a day by especially trained nurses. RESULTS: A total of 624 patients with MI (age 68.5 ± 13.2 years, ST-elevation MI 41.6%, hospital mortality 3.2%) were included in the study. Delirium was detected in 10.9% of all patients. In the subgroup of patients with a stay on the intensive care unit (ICU) for more than 24 hr (n = 229), delirium was detected in 29.7%. Hospital and ICU stay were significantly longer in patients with delirium (p < .001). Delirium was an independent predictor of prolonged ICU-stay. Independent predictors of delirium were age, dementia, alcohol abuse, cardiac arrest, hypotension, and leucocytosis. Infarct size or presentation with ST-elevation were not associated with incidence of delirium. CONCLUSION: Development of delirium is frequent after acute MI and prolongs hospitalization. Incidence of delirium is associated with clinical instability, preexisting comorbidity, and age rather than MI type or size.

Influence of immunosuppression in patients with severe acute respiratory distress syndrome on veno-venous extracorporeal membrane oxygenation therapy.

Prognosis of patients suffering from acute respiratory distress syndrome (ARDS) is poor. This is especially true for immunosuppressed patients. It is controverisal whether these patients should receive veno-venous extracorporeal membrane oxygenation (VV ECMO) while evidence on this topic is sparse. We report retrospective data of a single-center registry of patients with severe ARDS requiring ECMO support between October 2010 and June 2019. Patients were analyzed by their status of immunosuppression. ECMO weaning success and hospital survival were analyzed before and after propensity score matching (PSM). Moreover, ventilator free days (VFD) were compared. A total of 288 patients were analyzed (age 55 years, 67% male), 88 (31%) presented with immunosuppression. Survival rates were lower in immunosuppressed patients (27% vs. 53%, P < .001 and 27% vs. 48% after PSM, P = .006). VFD (60 days) were lower for patients with immunosuppression (11.9 vs. 22.4, P < .001), and immunosuppression was an independent predictor for mortality in multivariate analysis. Hospital survival was 20%, 14%, 35%, and 46% for patients with oncological malignancies, solid organ transplantation, autoimmune diseases, and HIV, respectively. In this analysis immunosuppression was an independent predictor for mortality. However, there were major differences in the weaning and survival rates between the etiologies of immunosuppression which should be considered in decision making.

Outcome of acute respiratory distress syndrome requiring extracorporeal membrane oxygenation in Covid-19 or influenza: A single-center registry study.

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is used to sustain blood oxygenation and decarboxylation in severe acute respiratory distress syndrome (ARDS). It is under debate if V-V ECMO is as appropriate for coronavirus disease 2019 (Covid-19) ARDS as it is for influenza. In this retrospective study, we analyzed all patients with confirmed SARS-CoV-2 or influenza A/B infection, ARDS and V-V ECMO, treated at our medical intensive care unit (ICU) between October 2010 and June 2020. Baseline and procedural characteristics as well as survival 30 days after ECMO cannulation were analyzed. A total of 62 V-V ECMO patients were included (15 with Covid-19 and 47 with influenza). Both groups had similar baseline characteristics at cannulation. Thirty days after ECMO cannulation, 13.3% of all patients with Covid-19 were discharged alive from our ICU compared to 44.7% with influenza (P = .03). Patients with Covid-19 had fewer ECMO-free days (0 (0-9.7) days vs. 13.2 (0-22.1) days; P = .05). Cumulative incidences of 30-day-survival showed no significant differences (48.6% in Covid-19 patients, 63.7% in influenza patients; P = .23). ICU treatment duration was significantly longer in ARDS patients with V-V ECMO for Covid-19 compared to influenza. Thirty-day mortality was higher in Covid-19, but not significant.

Intracerebral Hemorrhage in COVID-19 Patients with Pulmonary Failure: A Propensity Score-Matched Registry Study.

BACKGROUND: Hypercoagulability in Coronavirus Disease 2019 (COVID-19) causes deep vein thrombosis and pulmonary embolism necessitating systemic anticoagulation. Case reports of intracerebral hemorrhages in ventilated COVID-19 patients warrant precaution. It is unclear, however, if COVID-19 patients with acute respiratory distress syndrome (ARDS) with or without veno-venous extracorporeal membrane oxygenation therapy (VV-ECMO) have more intracerebral hemorrhages (ICH) compared to other ARDS patients. METHODS: We conducted a retrospective observational single-center study enrolling all patients with ARDS from 01/2018 to 05/2020. PCR-positive SARS-CoV-2 patients with ARDS were allocated to the COVID-19 group. Propensity score matching was performed for age, VV-ECMO, and bleeding risk. RESULTS: A total of 163 patients with moderate or severe ARDS were identified, 47 (28.8%) in the COVID-19 group, and 116 (71.2%) in the non-COVID-19 group. In 63/163 cases (38.7%), VV-ECMO therapy was required. The ICU survival was 52.8%. COVID-19 patients were older, more often male, and exhibited a lower SOFA score, but the groups showed similar rates of VV-ECMO therapy. Treatments with antiplatelet agents (p = 0.043) and therapeutic anticoagulation (p = 0.028) were significantly more frequent in the COVID-19 patients. ICH was detected in 22 patients (13.5%) with no statistical difference between the groups (11.2 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.21). Propensity score matching confirmed similar rates of ICH in both groups (12.8 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.57), thus leveling out possible confounders. CONCLUSIONS: Intracerebral hemorrhage was detected in every tenth patient with ARDS. Despite statistically higher rates of antiplatelet therapy and therapeutic anticoagulation in COVID-19 patients, we found a similar rate of ICH in patients with ARDS due to COVID-19 compared to other causes of ARDS.

Prone positioning in severe ARDS requiring extracorporeal membrane oxygenation.

BACKGROUND: Prone positioning (PP) has shown to improve survival in patients with severe acute respiratory distress syndrome (ARDS). To this point, it is unclear if PP is also beneficial for ARDS patients treated with veno-venous extracorporeal membrane oxygenation (VV ECMO) support. METHODS: We report retrospective data of a single-centre registry of patients with severe ARDS requiring VV ECMO support between October 2010 and May 2018. Patients were allocated to the PP group if PP was performed during VV ECMO treatment or the supine positioning group. VV ECMO weaning success and hospital survival were analysed before and after propensity score matching. RESULTS: A total of 158 patients could be analysed, and 38 patients (24.1%) received PP. There were no significant differences in VV ECMO weaning rate (47.4% vs. 46.7%, p = 0.94) and hospital survival (36.8% vs. 36.7%, p = 0.98) between the prone and supine groups, respectively. The analysis of 38 propensity score matched pairs also showed no difference in hospital survival (36.8% vs. 36.8%, p = 1.0) or VV ECMO weaning rate (47.4% vs. 44.7%, p = 0.82). Hospital survival was superior in the subgroup of patients treated with early PP (cutoff < 17 h via Youden's Index) as compared to late or no PP (81.8% vs. 33.3%, p = 0.02). CONCLUSION: In this propensity score matched cohort of severe ARDS patients requiring VV ECMO support, prone positioning at any time was not associated with improved weaning or survival. However, early initiation of prone positioning was linked to a significant reduction of hospital mortality.

Comparison of different anticoagulation strategies for renal replacement therapy in critically ill patients with COVID-19: a cohort study.

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients have a high risk of acute kidney injury (AKI) that requires renal replacement therapy (RRT). A state of hypercoagulability reduces circuit life spans. To maintain circuit patency and therapeutic efficiency, an optimized anticoagulation strategy is needed. This study investigates whether alternative anticoagulation strategies for RRT during COVID-19 are superior to administration of unfractionated heparin (UFH). METHODS: Retrospective cohort study on 71 critically ill COVID-19 patients (≥18 years), admitted to intensive care units at a tertiary health care facility in the southwestern part of Germany between February 26 and May 21, 2020. We collected data on the disease course, AKI, RRT, and thromboembolic events. Four different anticoagulatory regimens were administered. Anticoagulation during continuous veno-venous hemodialysis (CVVHD) was performed with UFH or citrate. Anticoagulation during sustained low-efficiency daily dialysis (SLEDD) was performed with UFH, argatroban, or low molecular weight heparin (LMWH). Primary outcome is the effect of the anticoagulation regimen on mean treatment times of RRT. RESULTS: In patients receiving CVVHD, mean treatment time in the UFH group was 21.3 h (SEM: ±5.6 h), in the citrate group 45.6 h (SEM: ±2.7 h). Citrate anticoagulation significantly prolonged treatment times by 24.4 h (P = .001). In patients receiving SLEDD, mean treatment time with UFH was 8.1 h (SEM: ±1.3 h), with argatroban 8.0 h (SEM: ±0.9 h), and with LMWH 11.8 h (SEM: ±0.5 h). LMWH significantly prolonged treatment times by 3.7 h (P = .008) and 3.8 h (P = .002), respectively. CONCLUSIONS: UFH fails to prevent early clotting events in the dialysis circuit during COVID-19. For patients, who do not require effective systemic anticoagulation, regional citrate dialysis is the most effective strategy. For patients, who require effective systemic anticoagulation, the usage of LMWH results in the longest circuit life spans. The proposed anticoagulatory strategies are safe, can easily be monitored, and allow an individualized treatment.

Epinephrine, inodilator, or no inotrope in venoarterial extracorporeal membrane oxygenation implantation: a single-center experience.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can be a rescue therapy for patients in cardiogenic shock or in refractory cardiac arrest. After cannulation, vasoplegia and cardiac depression are frequent. In literature, there are conflicting data on inotropic therapy in these patients. METHODS: Analysis of a retrospective registry of all patients treated with VA-ECMO in a university hospital center between October 2010 and December 2018 for cardiogenic shock or extracorporeal cardiopulmonary resuscitation (eCPR) with a focus on individual early inotropic therapy. RESULTS: A total of 231 patients (age 58.6 ± 14.3, 29.9% female, 58% eCPR, in-house survival 43.7%) were analyzed. Of these, 41.6% received no inotrope therapy within the first 24 h (survival 47.9%), 29.0% received an inodilator (survival 52.2%), and 29.0% received epinephrine (survival 25.0%). Survival of patients with epinephrine was significantly worse compared to other patient groups when evaluating 30-day survival (p = 0.034/p = 0.005) and cumulative incidence of in-hospital death (p = 0.001). In a multivariate logistic regression analysis, treatment with epinephrine was associated with mortality in the whole cohort (OR 0.38, p = 0.011) as well as after propensity score matching (OR 0.24, p = 0.037). We found no significant differences between patients with inodilator treatment and those without. CONCLUSION: Early epinephrine therapy within the first 24 h after cannulation for VA-ECMO was associated with poor survival compared to patients with or without any inodilator therapy. Until randomized data are available, epinephrine should be avoided in patients on VA-ECMO.

Influence of low-flow time on survival after extracorporeal cardiopulmonary resuscitation (eCPR).

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support under extracorporeal cardiopulmonary resuscitation (eCPR) is the last option and may be offered to selected patients. Several factors predict outcome in these patients, including initial heart rhythm, comorbidities, and bystander cardiopulmonary resuscitation (CPR). We evaluated outcomes of all VA-ECMO patients treated within the last 5 years at our center in respect to low-flow duration during CPR. METHODS: We report retrospective registry data on all patients with eCPR treated at a university hospital between October 2010 and May 2016. RESULTS: A total of 133 patients (mean age 58.7 ± 2.6 years, Simplified Acute Physiology Score II score at admission 48.1 ± 3.4) were included in the analysis. The indication for eCPR was either in-hospital or out-of-hospital cardiac arrest without return of spontaneous circulation (n = 74 and 59, respectively). There was a significant difference in survival rates between groups (eCPR in-hospital cardiac arrest [IHCA] 18.9%, eCPR out-of-hospital cardiac arrest [OHCA] 8.5%; p < 0.042). Mean low-flow duration (i.e., duration of mechanical CPR until VA-ECMO support) was 59.6 ± 5.0 minutes in all patients and significantly shorter in IHCA patients than in OHCA patients (49.6 ± 5.9 vs. 72.2 ± 7.4 minutes, p = 0.001). Low-flow time strongly correlated with survival (p < 0.001) and was an independent predictor of mortality. CONCLUSIONS: Time to full support is an important and alterable predictor of patient survival in eCPR, suggesting that VA-ECMO therapy should be established as fast as possible in the selected patients destined for eCPR.

A Mortality Prediction Score for Patients With Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO): The PREDICT VV-ECMO Score.

Mortality prediction for patients with the severe acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO) is challenging. Clinical variables at baseline and on day 3 after initiation of ECMO support of all patients treated from October 2010 through April 2020 were analyzed. Multivariate logistic regression analysis was used to identify score variables. Internal and external (Monza, Italy) validation was used to evaluate the predictive value of the model. Overall, 272 patients could be included for data analysis and creation of the PREDICT VV-ECMO score. The score comprises five parameters (age, lung fibrosis, immunosuppression, cumulative fluid balance, and ECMO sweep gas flow on day 3). Higher score values are associated with a higher probability of hospital death. The score showed favorable results in derivation and external validation cohorts (area under the receiver operating curve, AUC derivation cohort 0.76 [95% confidence interval, CI, 0.71-0.82] and AUC validation cohort 0.74 [95% CI, 0.67-0.82]). Four risk classes were defined: I ≤ 30, II 31-60, III 61-90, and IV ≥ 91 with a predicted mortality of 28.2%, 56.2%, 84.8%, and 96.1%, respectively. The PREDICT VV-ECMO score suggests favorable performance in predicting hospital mortality under ongoing ECMO support providing a sound basis for further evaluation in larger cohorts.

[Hypothermic temperature control after successful resuscitation of out-of-hospital cardiac arrest in adults : Statement from the resuscitation and postresuscitation treatment working groups of the German Society of Medical Intensive Care and Emergency Medicine (DGIIN) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), the German Society for Interdisciplinary Emergency and Acute Medicine (DGINA) and the Austrian Association of Emergency Medicine (AAEM)]. / Hypotherme Temperaturkontrolle nach erfolgreicher Wiederbelebung eines außerklinischen Herz-Kreislauf-Stillstands beim Erwachsenen : Statement der Arbeitsgruppen Reanimation und Post-Reanimationsbehandlung in der Deutschen Gesellschaft für Internistische Intensiv- und Notfallmedizin (DGIIN) und Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI), der Deutschen Gesellschaft Interdisziplinäre Notfall- und Akutmedizin (DGINA) und der Österreichischen Gesellschaft für Notfallmedizin (AAEM).

In Germany per year approximately 60,000 and in Austria 5,000 adult patients suffer from out-of-hospital cardiac arrest. Only 10-15% of these patients survive without neurological damage. For decades hypothermic temperature control has been a central component of post-resuscitation treatment, but is controversial due to recently published studies.

Survival prediction using the Freiburg index of post-TIPS survival (FIPS) in critically ill patients with acute- on chronic liver failure: A retrospective observational study.

Background and aim: Liver cirrhosis in patients treated in the intensive care unit (ICU) is associated with high mortality. Well established scores are useful to allow for assessment of prognosis and support ICU treatment guidance. However, currently used scoring systems often do not reflect the complexity of critically ill patients. Therefore, we tested the newly developed Freiburg index-of post-TIPS survival (FIPS) score in order to assess its potential role for prognostication of cirrhotic patients in the ICU. Methods: A total of 310 patients with liver cirrhosis treated in the ICU between 2010 and 2021 were enrolled in this retrospective observational study. Prognostic factors for mortality and 28-day mortality were assessed. Moreover, using c indices the prognostic discrimination of different prognostic scores was analyzed. Results: The FIPS score allowed to discriminate patients with high ICU mortality and within 28-days after ICU treatment (ICU mortality: 42.2 vs. 59.9%, p = 0.008 and 28-day mortality: 43.3 vs. 74.1%, p < 0.001). However, the FIPS score in its current composition showed no superior prognostic discrimination compared to other established scores. Multivariable analyses identified the FIPS score (HR 1.25 [1.04-1.49], p = 0.015) and lactate at admission (HR 1.07 [1.04-1.09], p < 0.001) as significant predictors of ICU mortality. Lactate at admission substantially improved patient risk stratification within each FIPS risk groups. Conclusion: Similar to other commonly used scores, the FIPS score in its current composition does not allow a sufficiently reliable prognostication of critically ill patients treated in the ICU. However, adding lactate as additional factor to the FIPS score may improve its prognostic ability.

[Clinical benefit of Tocilizumab and other immunomodulating agents for treatment of COVID-19]. / Klinischer Nutzen von Tocilizumab und anderen immunmodulatorischen Substanzen bei COVID-19.

The pathophysiological course of COVID-19 can be distinguished in a phase of viral replication and an inflammatory phase. Hyperinflammatory processes promote the development of severe COVID-19. Therefore, immunomodulating agents came into focus. Dexamethasone has already become standard of care for treatment of severe COVID-19. Two large randomized trials and a meta-analysis of collectively nine randomized trials showed a reduced mortality in patients with severe COVID-19 if Tocilizumab - an IL-6-rezeptor antagonist - was added to standard of care. Treatment with Baricitinib - a JAK 1/2 inhibitor - may also be beneficial for patients without or on low oxygen supplementation. National and international guidelines recommend Tocilizumab for treatment of severe COVID-19. Treatment with JAK inhibitors is an option for hospitalized patients with moderate COVID-19. It should be emphasized that comedication of JAK inhibitors and Tocilizumab is not recommended. Further high quality research is required for the widespread use of immunomodulating agents in COVID-19.

Coronary angiography following out-of-hospital cardiac arrest (OHCA): a review of outcomes and clinical considerations.

INTRODUCTION: In patients suffering a sudden out-of-hospital cardiac arrest (OHCA), the prevalence of a coronary artery lesion as the underlying cause is relatively high, but many other causes have been described. For this reason, identifying patients who would benefit from an emergency coronary angiography is important. AREAS COVERED: In the present manuscript, we reviewed the literature covering some relevant studies regarding the role of coronary angiography in patients with OHCA, including our local algorithm for the management of patients with OHCA. We particularly focused on the selection of patients who would benefit from an emergency coronary angiography, the time period until the performance of the angiography, the role of extracorporeal cardiopulmonary resuscitation (ECPR), the identification of a coronary artery lesion as the underlying cause of cardiac arrest and clinical outcomes. EXPERT OPINION: In summary, a local standard algorithm for the management of patients with OHCA appears favorable. An emergency coronary angiography should be advised in patients with a presumed cardiac cause and without obvious non-cardiac cause. A shockable initial rhythm, ST elevation in the post-resuscitation ECG, a previously known coronary artery disease, and ECPR are important predictors of cardiac cause of OHCA.

Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is an independent risk factor for mortality, which affects about 5% of hospitalized coronavirus disease-2019 (COVID-19) patients and up to 25-29% of severely ill COVID-19 patients. Lopinavir/ritonavir and hydroxychloroquine show in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have been used for the treatment of COVID-19. Both, lopinavir and hydroxychloroquine are metabolized by cytochrome P450 (CYP) 3A4. The impact of a triple therapy with lopinavir/ritonavir and hydroxychloroquine (triple therapy) on kidney function in COVID-19 is currently not known. METHODS: We retrospectively analyzed both non-ICU and ICU patients with COVID-19 receiving triple therapy for the incidence of AKI. Patients receiving standard therapy served as a control group. All patients were hospitalized at the University Hospital of Freiburg, Germany, between March and April 2020. A matched-pair analysis for the National Early Warning Score (NEWS) 2 was performed to control for the severity of illness among non-intensive care unit (ICU) patients. RESULTS: In non-ICU patients, the incidence of AKI was markedly increased following triple therapy (78.6% vs. 21.4% in controls, p = 0.002), while a high incidence of AKI was observed in both groups of ICU patients (triple therapy: 80.0%, control group: 90.5%). ICU patients treated with triple therapy showed a trend towards more oliguric or anuric kidney injury. We also observed a linear correlation between the duration of the triple therapy and the maximum serum creatinine level (p = 0.004, R2 = 0.276, R = 0.597). CONCLUSION: Triple therapy is associated with an increase in the incidence of AKI in non-ICU COVID-19 patients. The underlying mechanisms may comprise a CYP3A4 enzyme interaction, and may be relevant for any future therapy combining hydroxychloroquine with antiviral agents.