A Retrospective Analysis of COVID-19 mRNA Vaccine Breakthrough Infections - Risk Factors and Vaccine Effectiveness (preprint)

Importance: Little is known about COVID vaccine breakthrough infections and their risk factors. Objective: To identify risk factors associated with COVID19 breakthrough infections among vaccinated individuals and to reassess the effectiveness of COVID19 vaccination against severe outcomes using realworld data. Design, Setting, and Participants: We conducted a series of observational retrospective analyses using the electronic health records (EHRs) of Columbia University Irving Medical Center/New York Presbyterian (CUIMC/NYP) up to September 21, 2021. New York adult residence with PCR test records were included in this analysis. Main Outcomes and Measures: Poisson regression was used to assess the association between breakthrough infection rate in vaccinated individuals and multiple risk factors, including vaccine brand, demographics, and underlying conditions while adjusting for calendar month, prior number of visits and observational days. Logistic regression was used to assess the association between vaccine administration and infection rate by comparing a vaccinated cohort to a historically matched cohort in the pre-vaccinated period. Infection incident rate was also compared between vaccinated individuals and longitudinally matched unvaccinated individuals. Cox regression was used to estimate the association of the vaccine and COVID19 associated severe outcomes by comparing breakthrough cohort and two matched unvaccinated infection cohorts. Results: Individuals vaccinated with Pfizer/BNT162b2 (IRR against Moderna/mRNA1273 [95% CI]: 1.66 [1.17 - 2.35]); were male (1.47 [1.11 - 1.94%]); and had compromised immune systems (1.48 [1.09 - 2.00]) were at the highest risk for breakthrough infections. Vaccinated individuals had a significant lower infection rate among all subgroups. An increased incidence rate was found in both vaccines over the time. Among individuals infected with COVID19, vaccination significantly reduced the risk of death (adj. HR: 0.20 [0.08 - 0.49]). Conclusion and Relevance: While we found both mRNA vaccines were effective, Moderna/mRNA1273 had a lower incidence rate of breakthrough infections. Both vaccines had increased incidence rates over the time. Immunocompromised individuals were among the highest risk groups experiencing breakthrough infections. Given the rapidly changing nature of the SARSCoV2, continued monitoring and a generalizable analysis pipeline are warranted to inform quick updates on vaccine effectiveness in real time.

Diabetic Ketoacidosis and Mortality in COVID-19 Infection (preprint)

Background: Hyperglycemic patients with or without a history of diabetes have increased morbidity and mortality from COVID-19. Published case reports describe patients with COVID-19 and simultaneous presentation of diabetic acidosis (DKA), however there is limited data on the prevalence, predictors and outcomes of DKA in patients hospitalized with COVID-19.Methods: Patients with COVID-19 were identified from the electronic medical record. DKA was defined by standardized criteria. Proportional hazard regression models were used to determine risk factors for, and mortality from DKA in COVID-19.Findings: Of 2366 patients admitted for COVID-19, 157 (6.6%) patients developed DKA. Ninety-four percent of patients with incident DKA had a history of type 2 diabetes, while 5.7% patients had no prior diagnosis of diabetes. Patients with compared to without DKA had increased hospital length of stay and in-patient mortality. Each unit of higher HbA1c predicted a 47% increased risk of incident DKA (HR 1.47, 95% CI 1.40-1.54). Risk factors for mortality included older age (HR 1.07 per 5 years, 95% CI 1.06 - 1.08) and need for pressors (HR 2.33, 95% CI 1.82-2.98). An interaction between use of glucocorticoids and older age and pressor use indicated a protective effect of glucocorticoid use with both increasing age and for patients on pressors.Interpretation: The combination of DKA and COVID-19 is associated with greater mortality, driven by older age and severity of COVID-19 disease. Improved outpatient treatment of diabetes may prevent the development of DKA in patients with COVID-19.Funding Statement: None.Declaration of Interests: JSS, MBB, DJM, JZ, PK, SM, MTY and UBP have no disclosures. TLN: AmgenEthics Approval Statement: This study protocol was approved by the Institutional Review Board of Columbia University Irving Medical Center and the requirement for informed consent was waived.

Melatonin is significantly associated with survival of intubated COVID-19 patients (preprint)

Background Respiratory distress requiring intubation is the most serious complication associated with coronavirus disease 2019 (COVID-19). Methods In this retrospective study, we used survival analysis to determine whether or not mortality following intubation was associated with hormone exposure in patients treated at New York Presbyterian/ Columbia University Irving Medical Center. Here, we report the overall hazards ratio for each hormone for exposure before and after intubation for intubated and mechanically ventilated patients. Results Among the 189,987 patients, we identified 948 intubation periods across 791 patients who were diagnosed with COVID-19 or infected with SARS-CoV2 and 3,497 intubation periods across 2,981 patients who were not. Melatonin exposure after intubation was statistically associated with a positive outcome in COVID-19 (demographics and comorbidities adjusted HR: 0.131, 95% CI: 7.76E-02 - 0.223, p-value = 8.19E-14) and non-COVID-19 (demographics and comorbidities adjusted HR: 0.278, 95% CI: 0.142 - 0.542, p-value = 1.72E-04) intubated patients. Additionally, melatonin exposure after intubation was statically associated with a positive outcome in COVID-19 patients (demographics and comorbidities adjusted HR: 0.127, 95% CI: 6.01E-02 - 0.269, p-value = 7.15E-08). Conclusions Melatonin exposure after intubation is significantly associated with a positive outcome in COVID-19 and non-COVID-19 patients. Additionally, melatonin exposure after intubation is significantly associated with a positive outcome in COVID-19 patients requiring mechanical ventilation. While our models account for many covariates, including clinical history and demographics, it is impossible to rule out confounding or collider biases within our population. Further study into the possible mechanism of this observation is warranted.