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1.
PLoS One ; 16(3): e0248128, 2021.
Article in English | MEDLINE | ID: covidwho-1575679

ABSTRACT

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Pandemics/prevention & control , Data Management/methods , Drug Therapy, Combination/methods , Female , Hospitalization , Humans , Male , SARS-CoV-2/drug effects
2.
PLoS One ; 16(7): e0255228, 2021.
Article in English | MEDLINE | ID: covidwho-1334774

ABSTRACT

OBJECTIVES: The development of a prognostic mortality risk model for hospitalized COVID-19 patients may facilitate patient treatment planning, comparisons of therapeutic strategies, and public health preparations. METHODS: We retrospectively reviewed the electronic health records of patients hospitalized within a 13-hospital New Jersey USA network between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2, with follow-up through May 29, 2020. With death or hospital discharge by day 40 as the primary endpoint, we used univariate followed by stepwise multivariate proportional hazard models to develop a risk score on one-half the data set, validated on the remainder, and converted the risk score into a patient-level predictive probability of 40-day mortality based on the combined dataset. RESULTS: The study population consisted of 3123 hospitalized COVID-19 patients; median age 63 years; 60% were men; 42% had >3 coexisting conditions. 713 (23%) patients died within 40 days of hospitalization for COVID-19. From 22 potential candidate factors 6 were found to be independent predictors of mortality and were included in the risk score model: age, respiratory rate ≥25/minute upon hospital presentation, oxygenation <94% on hospital presentation, and pre-hospital comorbidities of hypertension, coronary artery disease, or chronic renal disease. The risk score was highly prognostic of mortality in a training set and confirmatory set yielding in the combined dataset a hazard ratio of 1.80 (95% CI, 1.72, 1.87) for one unit increases. Using observed mortality within 20 equally sized bins of risk scores, a predictive model for an individual's 40-day risk of mortality was generated as -14.258 + 13.460*RS + 1.585*(RS-2.524)^2-0.403*(RS-2.524)^3. An online calculator of this 40-day COVID-19 mortality risk score is available at www.HackensackMeridianHealth.org/CovidRS. CONCLUSIONS: A risk score using six variables is able to prognosticate mortality within 40-days of hospitalization for COVID-19. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT04347993.


Subject(s)
COVID-19/mortality , Hospital Mortality , Hospitalization , Models, Biological , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Time Factors
3.
BMC Infect Dis ; 21(1): 72, 2021 Jan 14.
Article in English | MEDLINE | ID: covidwho-1067195

ABSTRACT

BACKGROUND: Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting. METHODS: We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching. RESULTS: Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available. CONCLUSIONS: In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.


Subject(s)
COVID-19/drug therapy , Hydroxychloroquine/administration & dosage , Adult , Aged , COVID-19/virology , Female , Hospitalization , Humans , Logistic Models , Male , Middle Aged , New Jersey , Outpatients/statistics & numerical data , Retrospective Studies , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Severity of Illness Index
4.
PLoS One ; 15(8): e0237693, 2020.
Article in English | MEDLINE | ID: covidwho-713539

ABSTRACT

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antimalarials/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/pharmacology , Azithromycin/therapeutic use , COVID-19 , Child , Child, Preschool , Coronavirus Infections/mortality , Coronavirus Infections/virology , Drug Therapy, Combination , Female , Follow-Up Studies , Hospitalization , Humans , Infant , Infant, Newborn , Intensive Care Units , Interleukin-6/antagonists & inhibitors , Kaplan-Meier Estimate , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , Young Adult
5.
Lancet Rheumatol ; 2(10): e603-e612, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-713006

ABSTRACT

Background: Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19. Methods: We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA). We included patients (aged ≥18 years) with laboratory-confirmed COVID-19 who needed support in the ICU. We obtained data from a prospective observational database and compared outcomes in patients who received tocilizumab with those who did not. We applied a multivariable Cox model with propensity score matching to reduce confounding effects. The primary endpoint was hospital-related mortality. The prospective observational database is registered on ClinicalTrials.gov, NCT04347993. Findings: Between March 1 and April 22, 2020, 764 patients with COVID-19 required support in the ICU, of whom 210 (27%) received tocilizumab. Factors associated with receiving tocilizumab were patients' age, gender, renal function, and treatment location. 630 patients were included in the propensity score-matched population, of whom 210 received tocilizumab and 420 did not receive tocilizumab. 358 (57%) of 630 patients died, 102 (49%) who received tocilizumab and 256 (61%) who did not receive tocilizumab. Overall median survival from time of admission was not reached (95% CI 23 days-not reached) among patients receiving tocilizumab and was 19 days (16-26) for those who did not receive tocilizumab (hazard ratio [HR] 0·71, 95% CI 0·56-0·89; p=0·0027). In the primary multivariable Cox regression analysis with propensity matching, an association was noted between receiving tocilizumab and decreased hospital-related mortality (HR 0·64, 95% CI 0·47-0·87; p=0·0040). Similar associations with tocilizumab were noted among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher. Interpretation: In this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited. Funding: None.

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