Delayed Fatal Pulmonary Hemorrhage Following COVID-19 Vaccination: Case Report, Batch Analysis, And Proposed Autopsy Checklist (preprint)

We present a case of a 47-year-old male who died unexpectedly from acute pulmonary hemorrhage 555 days after completing the BNT162b2 (Pfizer) COVID-19 vaccination primary series. Before death, he exhibited symptoms of a mild respiratory infection. Despite a healthy medical history and no medication use, the patient’s condition rapidly deteriorated and he experienced severe respiratory distress, followed by cardiopulmonary arrest with evidence of profuse pulmonary bleeding. Autopsy findings revealed massive lung congestion without embolism, normal heart size, moderate coronary atherosclerosis without myocardial infarction, and no evidence of other hemorrhagic events. The patient tested negative for COVID-19 and other respiratory pathogens at autopsy. Despite these findings, the medical examiner determined the cause of death was attributed to atherosclerotic and hypertensive cardiovascular disease, without considering the recent pulmonary hemorrhage and unremarkable medical history. Investigation into the vaccine batch indicated a higher-than-average number of serious adverse events, including fatalities. The patient's BNT162b2 batch was among the top 2.8% for reported deaths. Moreover, the autopsy failed to investigate potential contributions from the vaccine, such as the presence of the Spike protein or related antibodies. The evidence suggests that the pulmonary hemorrhage, exacerbated by a viral infection, was the immediate cause of death, with the COVID-19 vaccine potentially playing a role in the development of cardiopulmonary pathology and hemorrhage. We propose autopsy protocols for COVID-19 vaccine recipients to better investigate vaccine-related pathologies among those with one or more prior injections.

Intracardiac Thrombus in COVID-19 Inpatients: A Nationwide Study of Incidence, Predictors and Outcomes (preprint)

Background: COronaVIrus Disease 2019 (COVID-19) has been observed to be associated with a hypercoagulable state. Intracardiac thrombosis is a serious complication but has seldom been evaluated in COVID-19 patients. We assessed the incidence, associated factors, and outcomes of COVID-19 patients with intracardiac thrombosis. Methods: COVID-19 inpatients during 2020 were retrospectively identified from the national inpatient sample (NIS) database, and data retrieved regarding clinical characteristics, intracardiac thrombosis, and adverse outcomes. Multivariable logistic regression was performed to identify the clinical factors associated with intracardiac thrombosis and in-hospital mortality and morbidities. Results: A total of 1,683,785 COVID-19 inpatients were identified in 2020 from NIS, with a mean age of 63.8 {+/-} 1.6 years, and 32.2% females. Intracardiac thrombosis was present in 0.001% (1,830) patients. Overall, in-hospital outcomes include all-cause mortality 13.2% (222,695/1,683,785), cardiovascular mortality 3.5%, cardiac arrest 2.6%, acute coronary syndrome (ACS) 4.4%, heart failure 16.1%, stroke 1.3% and acute kidney injury (AKI) 28.3%. The main factors associated with intracardiac thrombosis were a history of congestive heart failure and coagulopathy. Intracardiac thrombosis was independently associated with a higher risk of in-hospital all-cause mortality (OR: 3.32, 95% CI: 2.42-4.54, p<0.001), cardiovascular mortality (OR: 2.95, 95% CI: 1.96-4.44, p<0.001), cardiac arrest (OR: 2.04, 95% CI: 1.22-3.43, p=0.006), ACS (OR: 1.62, 95% CI: 1.17-2.22, p=0.003), stroke (OR: 3.10, 95% CI: 2.11-4.56, p<0.001), and AKI (OR: 2.13 95% CI: 1.68-2.69, p<0.001), but not incident heart failure (p=0.27). Conclusion: Although intracardiac thrombosis is rare in COVID-19 inpatients, its presence was independently associated with higher risks of in-hospital mortality and most morbidities. Prompt investigations and treatments for intracardiac thrombosis are warranted when there is a high index of suspicion and a confirmed diagnosis respectively.

COVID-19-specific adult basic life support guideline strategies for chiropractors and other healthcare providers to maximize the safety and efficacy of resuscitation: a commentary.

BACKGROUND: The emergence of an unprecedented novel severe acute respiratory syndrome coronavirus-2 (SARS-C0V-2), which causes the coronavirus disease 2019 (COVID-19) pandemic, has created new scenarios in basic life support (BLS) management. According to current evidence, SARS-CoV-2 can be transmitted airborne in aerosol particles during resuscitation. Research evidence found an alarming global increase in out-of-hospital cardiac arrests during the COVID-19 pandemic. Healthcare providers are legally obliged to respond to cardiac arrest as soon as possible. Chiropractors will likely encounter potential exercise-related and non-exercise-related cardiac emergencies at some point in their professional lives. They have a duty of care to respond to emergencies such as cardiac arrest. Chiropractors are increasingly involved in providing care, including emergency care, for athletes and spectators at sporting events. Also, exercise-related cardiac arrest in adult patients may occur during exercise testing or rehabilitation with exercise prescriptions in chiropractic and other healthcare settings. Little is known about the COVID-19 BLS guidelines for chiropractors. Knowledge of the current COVID-19-specific adult BLS guidelines is essential to developing an emergency response plan for the on-field and sideline management of exercise-related cardiac arrest and non-athletic, non-exercise-related cardiac arrest. MAIN TEXT: Seven peer-reviewed articles on the COVID-19-specific BLS guidelines, including two updates, were reviewed for this commentary. Responding to the COVID-19 pandemic, the national and international resuscitation organizations recommended interim COVID-19-specific BLS guidelines with precaution, resuscitation, and education strategies. BLS safety is paramount. A precautionary approach with the bare minimum of appropriate personal protective equipment for resuscitation is recommended. There was disagreement among the COVID-19 BLS guidelines on the level of personal protective equipment. All healthcare professionals should also undergo self-directed BLS e-learning and virtual skill e-training. The summarized COVID-19-specific adult BLS guideline strategies and protocols are tabled, respectively. CONCLUSIONS: This commentary provides a practical overview and highlights current evidence-based intervention strategies of the COVID-19-specific adult BLS guidelines that may help chiropractors and other healthcare providers reduce BLS-related exposures to SARS-CoV-2 and the risks of SARS-CoV-2 transmission and maximize the efficacy of resuscitation. This study is relevant to and impacts future COVID-19-related research in areas such as infection prevention and control.

[Impact of the COVID-19 pandemic on basic resuscitation and success rate after sudden cardiac arrest]. / A COVID­19-pandémia hatása a hirtelen szívmegállást követo alapszintu újraélesztésre és annak sikerességére.

Since the onset of the coronavirus disease, infection-related mortality has been tracked worldwide and the number of deaths caused by the virus is counted daily. The coronavirus pandemic has not only transformed our daily life, but reorganized the whole healthcare system. In response to the increased demand for hospital admissions, leaders in different countries have implemented a number of emergency actions. The restructuring has had both direct and indirect negative effects on the epidemiology of sudden cardiac death, the willingness of lay rescuer to give cardiopulmonary resuscitation and the use of automated external defibrillators, but these negative effects vary widely across continents and countries. In order to protect lay people and health workers as well as to prevent the spread of the pandemic, the previous recommendations of the European Resuscitation Council on basic and advanced life support have undergone a few modifications. Orv Hetil. 2023; 164(13): 483-487.

Retrospective diagnostic co-factors among Covid-19 cases sourced from Medicare, 1999-2021: an all-cause mortality review (preprint)

Introduction: SARS-CoV-2 infections co-occurred with other diverse pre-existing clinical conditions in mortality cases. We use encounter level health data to evaluate the impact of non-Covid-19 diagnostic events on all-cause mortality observed among Covid-19 positive cases billing Medicare. We further investigate prior diagnostic codes which occur in pre-pandemic study years among cases presenting to Medicare clinically with Covid-19 and cases with Covid-19 who experience all-cause mortality to inform patient population management. Methods: We aggregated encounter level records sourced from all Medicare beneficiaries from 1999-2021. Odds ratios were constructed using diagnostic history, age decile, study year and survival status. We used Generalized Linear Model (GLM) to predict the Decedent Observation Odds Ratio (DOOR) from study year, case observation odds ratio, age decile, non-covid conditions within counts of distinct covid-ever cases and their decedents. Odds ratios are relative to covid-never cases, or cases who didnot present with Covid-19 clinically. Results: High explanatory DOOR measures are observed for diagnostic codes commonly associated with inpatient Covid-19 mortality. High DOOR measures are also observed for individuals living with specific kinds of cancers, experiencing cardiac arrest or acute tubular necrosis. Conclusion: Covid-ever mortality is influenced by primary infection itself and exacerbations of pre-existing conditions. Consequences of primary infection are observable in GLM, as well as meaningful prior clinical risk factors such as cancer, diabetes, cardiac and respiratory disease. Long-covid conditions require surviving Covid-19 clinical presentation and are predictable from GLM models.

Treatment of adult, child and newborn cardiac arrest victims with COVID-19. Recommendations from the Interamerican Society of Cardiology / Sociedad Interamericana de Cardiología (SIAC), Mexican National Cardiologists Association / Asociación Nacional de Cardiólogos de México (ANCAM) and Mexican Society of Cardiology / Sociedad Mexicana de Cardiología (SMC).

La pandemia de COVID-19 ha infligido grandes estragos a la población y en especial al personal de salud. Los esfuerzos de reanimación exigen modificaciones potenciales de las guías internacionales existentes de reanimación cardiopulmonar (RCP) debido al elevado índice de contagiosidad del virus SARS-CoV-2. Se considera que hasta 15% de los casos de COVID-19 tiene una enfermedad grave y 5% padece un trastorno crítico con una mortalidad promedio del 3%, la cual varía según sean el país y las características de los pacientes. La edad y las comorbilidades como la hipertensión arterial, enfermedad cardiovascular, obesidad y diabetes incrementan la mortalidad hasta 24%. También se ha informado un aumento reciente del número de casos de paro cardíaco extrahospitalario (PCEH). Aunque el paro cardíaco (PC) puede ser efecto de factores diversos en estos pacientes, en la mayoría de los casos se ha demostrado que el origen es respiratorio, con muy pocos casos de causa cardíaca. Se debe considerar la indicación de iniciar o continuar las maniobras de RCP por dos razones fundamentales: la posibilidad de sobrevida de las víctimas, que hasta la fecha se ha registrado muy baja, y el riesgo de contagiar al personal de salud, que es muy alto.The COVID-19 pandemic is having a large impact on the general population, but it has taken a specially high toll on healthcare personnel. Resuscitation efforts require potential modifications of the present Cardiopulmonary Resuscitation (CPR) international guidelines because of the transmissibility rate of the new SARS-CoV 2 virus. It has been seen that up to 15% of COVID-19 patients have a severe disease, 5% have a critical form of infection and the mean death rate is 3%, although there are significant differences according to the country that reports it and patients' baseline conditions that include age, presence of arterial hypertension, cardiovascular disease, diabetes or obesity. In these high risk subjects, mortality might go up to 24%. There are also reports of a recent increase in out-of-hospital cardiopulmonary arrest (OHCA) victims. Cardiac arrest (CA) in these subjects might be related to many causes, but apparently, that phenomenon is related to respiratory diseases rather than cardiac issues. In this context, the decision to start or continue CPR maneuvers has to be carefully assessed, because of the low survival rate reported so far and the high contagion risk among healthcare personnel.

Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial.

AIMS: In a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE study was conducted to test this pharmacogenetic hypothesis. METHODS AND RESULTS: dal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1-3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group [hazard ratio 0.88; 95% confidence interval (CI) 0.75-1.03; P = 0.12]. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65-0.96) for myocardial infarction, 0.92 (95% CI 0.64-1.33) for stroke, 1.21 (95% CI 0.91-1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60-9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70-0.98). CONCLUSION: Dalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype. CLINICAL TRIAL REGISTRATION: Trial registration dal-GenE ClinicalTrials.gov Identifier: NCT02525939.

Management of Intraoperative Cardiac Arrest.

Perioperative arrests are both uncommon and heterogeneous and have not been described or studied to the same extent as cardiac arrest in the community. These crises are usually witnessed, frequently anticipated, and involve a rescuer physician with knowledge of the patient's comorbidities and coexisting anesthetic or surgically related pathophysiology ultimately leading to better outcomes. This article reviews the most probable causes of intraoperative arrest and their management.

In-hospital cardiac arrest.

PURPOSE OF REVIEW: To describe our knowledge about in-hospital cardiac arrest (IHCA) including recent developments. RECENT FINDINGS: Improving trends in IHCA outcomes appear to have stalled or reversed since the COVID-19 pandemic. There are disparities in care based on patient sex, ethnicity and socioeconomic status that need to be tackled. The increased use of emergency treatment plans that include do-not attempt cardiopulmonary resuscitation recommendations will help to decrease the number of resuscitation attempts. System approaches and strong local leadership through resuscitation champions can improve patient outcomes. SUMMARY: In-hospital cardiac arrest is a global health problem with a 25% survival in high-income settings. There remain significant opportunities to both decrease the incidence of, and outcomes from IHCA.

Nationwide Analysis of Cardiac Arrest Outcomes During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic had a significant impact on the chain of survival following cardiac arrest. However, large population-based reports of COVID-19 in patients hospitalized after cardiac arrest are limited. The National Inpatient Sample database was queried for cardiac arrest admissions during 2020 in the United States. Propensity score matching was used to match patients with and without concurrent COVID-19 according to age, race, sex, and comorbidities. Multivariate logistic regression analysis was used to identify predictors of mortality. A weighted total of 267,845 hospitalizations for cardiac arrest were identified, among which 44,105 patients (16.5%) had a concomitant diagnosis of COVID-19. After propensity matching, cardiac arrest patients with concomitant COVID-19 had higher rate of acute kidney injury requiring dialysis (64.9% vs 54.8%) mechanical ventilation >24 hours (53.6% vs 44.6%) and sepsis (59.4% vs 40.4%) compared to cardiac arrest patients without COVID-19. In contrast, cardiac arrest patients with COVID-19 had lower rates of cardiogenic shock (3.2% vs 5.4%, P < 0.001), ventricular tachycardia (9.6% vs 11.7%, P < 0.001), and ventricular fibrillation (6.7% vs 10.8%, P < 0.001), and a lower utilization of cardiac procedures. In-hospital mortality was higher in patients with COVID-19 (86.9% vs 65.5%, P < 0.001) and, on multivariate analysis, a diagnosis of COVID-19 was an independent predictor of mortality. Among patients hospitalized following a cardiac arrest during 2020, concomitant COVID-19 infection was associated with significantly worse outcomes characterized by an increased risk of sepsis, pulmonary and renal dysfunction, and death.

Impact of Coronavirus Disease 2019 Pandemic on Cardiac Arrest and Emergency Care.

The incidence of both out-of-hospital and in-hospital cardiac arrest increased during the coronavirus disease 2019 (COVID-19) pandemic. Patient survival and neurologic outcome after both out-of-hospital and in-hospital cardiac arrest were reduced. Direct effects of the COVID-19 illness combined with indirect effects of the pandemic on patient's behavior and health care systems contributed to these changes. Understanding the potential factors offers the opportunity to improve future response and save lives.

Performance of digital early warning score (NEWS2) in a cardiac specialist setting: retrospective cohort study.

INTRODUCTION: Patients with cardiovascular diseases (CVD) are at significant risk of developing critical events. Early warning scores (EWS) are recommended for early recognition of deteriorating patients, yet their performance has been poorly studied in cardiac care settings. Standardisation and integrated National Early Warning Score 2 (NEWS2) in electronic health records (EHRs) are recommended yet have not been evaluated in specialist settings. OBJECTIVE: To investigate the performance of digital NEWS2 in predicting critical events: death, intensive care unit (ICU) admission, cardiac arrest and medical emergencies. METHODS: Retrospective cohort analysis. STUDY COHORT: Individuals admitted with CVD diagnoses in 2020; including patients with COVID-19 due to conducting the study during the COVID-19 pandemic. MEASURES: We tested the ability of NEWS2 in predicting the three critical outcomes from admission and within 24 hours before the event. NEWS2 was supplemented with age and cardiac rhythm and investigated. We used logistic regression analysis with the area under the receiver operating characteristic curve (AUC) to measure discrimination. RESULTS: In 6143 patients admitted under cardiac specialties, NEWS2 showed moderate to low predictive accuracy of traditionally examined outcomes: death, ICU admission, cardiac arrest and medical emergency (AUC: 0.63, 0.56, 0.70 and 0.63, respectively). Supplemented NEWS2 with age showed no improvement while age and cardiac rhythm improved discrimination (AUC: 0.75, 0.84, 0.95 and 0.94, respectively). Improved performance was found of NEWS2 with age for COVID-19 cases (AUC: 0.96, 0.70, 0.87 and 0.88, respectively). CONCLUSION: The performance of NEWS2 in patients with CVD is suboptimal, and fair for patients with CVD with COVID-19 to predict deterioration. Adjustment with variables that strongly correlate with critical cardiovascular outcomes, that is, cardiac rhythm, can improve the model. There is a need to define critical endpoints, engagement with clinical experts in development and further validation and implementation studies of EHR-integrated EWS in cardiac specialist settings.

Acute care pathway assessed through performance indicators during the COVID-19 pandemic in OECD countries (2020-2021): a scoping review (preprint)

Background: The COVID-19 pandemic severely impacted health systems, leading to care disruptions for non-COVID patients. Performance indicators to continuously monitor acute care, timely reported and internationally accepted, lacked during the COVID-19 pandemic in OECD countries. Methods: Scoping review. Search in Embase and MEDLINE databases. Acute care performance indicators were collected and collated following the care pathway; indicators related to acute general surgery were analyzed separately. Results: A total of 152 studies were included. 2354 indicators regarding general acute care and 301 indicators related to acute general surgery were collected and collated. Indicators focusing on pre-hospital services reported a decreasing trend in the volume of patients: from 225 indicators, 110 (49%) reported a decrease. An increasing trend in pre-hospital treatment times was reported by most of the indicators (n=41;70%) and a decreasing trend in survival rates of out-of-hospital cardiac arrest (n=61;75%). Concerning care provided in the emergency department, most of the indicators (n=752;71%) showed a decreasing trend in admissions, across all levels of urgency (n=26, 51% of highly urgent/level 1 indicators; n=20, 56% of level 2; n=31, 67% of level 3 and 4; and n=43, 78% of non-urgent/level 5 indicators). Indicators assessing the volume of diagnostic and treatment procedures signaled reductions: 65% (n=85) of the indicators and 51% (n=54) of the indicators, respectively. Concerning the mortality rate after admission, most of the indicators (n=23;53%) reported an increasing trend. The subset of indicators assessing acute general surgery showed a decreasing trend in the volume of patients reported by most of the indicators (n=50,49%), stability in clinical severity at admission (n=36,53%), and stability in the volume of surgeries (n=14,47%). Most of the indicators (n=28,65%) reported no change in treatment approach and stable mortality rate (n=11,69%). Conclusions: This review summarizes the performance indicators available in the literature to assess the quality of acute care in OECD countries and their trends during the first year and a half of the COVID-19 pandemic (2020-July2021). These results highlight the relevance of assessing the acute care pathway more regularly and systematically across different clinical entities, to monitor care disruptions and improve the resilience of emergency services to crises.

Binding of SARS-CoV-2 non-structured protein 1 to 40S ribosome inhibits mRNA translation (preprint)

Experiments have shown that non-structural protein 1 (NSP1) of SARS-CoV-2 is a factor that restricts cellular gene expression and prevents mRNA translation in the ribosome 40S subunit. However, the molecular mechanism of this phenomenon remains unclear. To clarify this issue, all-atom steered molecular dynamics and coarse-grained alchemical simulations were used to compare the binding affinity of mRNA to 40S ribosome in the absence and presence of NSP1. We found that NSP1 binding to the 40S ribosome dramatically increases the binding affinity of mRNA, which, in agreement with experiment, suggests that NSP1 can stall mRNA translation. The mRNA translation has been found to be driven by electrostatic mRNA-40S ribosome interactions. Water molecules have been demonstrated to play an important role in stabilizing the mRNA-40S ribosome complex. The NSP1 residues that are critical in triggering a translation arrest have been identified.

Prospective QTc interval monitoring avoids cardiac toxicity of hydroxychloroquine and azithromycin in critically ill SARS-CoV-2 patients: a cohort study (preprint)

Purpose During the first wave of the SARS-Cov2 pandemic, the use of hydroxychloroquine and azithromycin raised safety concerns in terms of arrhythmias related to QT segment prolongation. The aim of this observational, prospective, single-center study was to describe cardiovascular events in critically ill patients who were mechanically ventilated for SARS-Cov2 pneumonia. Methods Patients included were prospectively monitored for QTc segment prolongation when treated with the association of hydroxychloroquine alone or in combination with azithromycin for Covid-19 pneumonia and treatment had to be stopped before QTc ≤ 500ms. Results 23 patients were prospectively included. Treatment had to be interrupted in 43.5% of patients and more often in the combination group. None of the patients displayed torsade de pointes or sudden cardiac arrest. Forty percent of patients in the combination group experienced atrial fibrillation. Cardiac Troponin I was elevated in 70% of all patients without electric signs of ischemia. Conclusion The association of hydroxychloroquine and azithromycin for treatment of Covid-19 pneumonia mandates the need for prospective evaluation of QTc especially in the presence of biological myocardial injury. The Institutional Review Board waived the need for consent to use prospectively collected clinical data and the study was appointed the serial number 2020-214.

Neurology of Systemic Disease: Selected Topics with a Focus on Women.

Sex differences exist within the neurologic complications of systemic disease. To promote new avenues for prevention and develop novel therapeutics, we highlight the role of sex in differential outcomes to infectious disease and cardiac arrest and educate the reader in paraneoplastic presentations that may herald underlying malignancies in women.

Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State.

Importance: Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events. Objective: To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19. Design, Setting, and Participants: Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020. Exposures: Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither. Main Outcomes and Measures: Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation). Results: Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings. Conclusions and Relevance: Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.