Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19

ImportanceType 2 diabetes (T2DM) and obesity are significant risk factors for mortality in Covid19. Metformin has sex specific immunomodulatory effects which may elucidate treatment mechanisms in COVID-19. Objective: We sought to identify whether metformin reduced mortality from Covid19 and if sex specific interactions exist. DesignRetrospective review of de-identified claims from UnitedHealth Groups Clinical Discovery Database. Unadjusted and multivariate models were conducted to assess risk of mortality based on metformin and tumor necrosis factor alpha (TNF) inhibitors as home medications in individuals with T2DM and obesity, controlling for comorbidities, medications, demographics, and state. Heterogeneity of effect was assessed by sex. SettingThe database includes all 50 states in the United States. Participants: Persons with at least 6 months of continuous coverage from UnitedHealth Group in 2019 who were hospitalized with Covid-19. Persons in the metformin group had > 90 days of metformin claims in the 12 months before hospitalization. Results6,256 persons were included; 52.8% female; mean age 75 years. Metformin was associated with decreased mortality in women by logistic regression, OR 0.792 (0.640, 0.979); mixed effects OR 0.780 (0.631, 0.965); Cox proportional-hazards: HR 0.785 (0.650, 0.951); and propensity matching, OR of 0.759 (0.601, 0.960). There was no significant reduction in mortality among men. TNF inhibitors were associated with decreased mortality, by propensity matching in a limited model, OR 0.19 (0.0378, 0.983). ConclusionsMetformin was significantly associated with reduced mortality in women with obesity or T2DM in observational analyses of claims data from individuals hospitalized with Covid-19. This sex-specific finding is consistent with metformins reduction of TNF in females over males, and suggests that metformin conveys protection in Covid-19 through TNF effects. Prospective studies are needed to understand mechanism and causality. Key PointsO_ST_ABSQuestionC_ST_ABSMetformin has many anti-inflammatory effects, including sex-specific effects on TNF. Is metformin protective from the Sars-CoV-2 virus, and does the effect differ by sex? FindingsMetformin was associated with reduced mortality in women who were hospitalized with Covid-19, but not in men who were hospitalized with Covid-19. MeaningThe sex-dependent survival by metformin use points towards TNF reduction as a key mechanism for protection from Covid-19.

Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease-19

BackgroundWhether angiotensin-converting enzyme (ACE) Inhibitors and angiotensin receptor blockers (ARBs) mitigate or exacerbate SARS-CoV-2 infection remains uncertain. In a national study, we evaluated the association of ACE inhibitors and ARB with coronavirus disease-19 (COVID-19) hospitalization and mortality among individuals with hypertension. MethodsAmong Medicare Advantage and commercially insured individuals, we identified 2,263 people with hypertension, receiving [≥]1 antihypertensive agents, and who had a positive outpatient SARS-CoV-2 test (outpatient cohort). In a propensity score-matched analysis, we determined the association of ACE inhibitors and ARBs with the risk of hospitalization for COVID-19. In a second study of 7,933 individuals with hypertension who were hospitalized with COVID-19 (inpatient cohort), we tested the association of these medications with in-hospital mortality. We stratified all our assessments by insurance groups. ResultsAmong individuals in the outpatient and inpatient cohorts, 31.9% and 29.8%, respectively, used ACE inhibitors and 32.3% and 28.1% used ARBs. In the outpatient study, over a median 30.0 (19.0 - 40.0) days after testing positive, 12.7% were hospitalized for COVID-19. In propensity score-matched analyses, neither ACE inhibitors (HR, 0.77 [0.53, 1.13], P = 0.18), nor ARBs (HR, 0.88 [0.61, 1.26], P = 0.48), were significantly associated with risk of hospitalization. In analyses stratified by insurance group, ACE inhibitors, but not ARBs, were associated with a significant lower risk of hospitalization in the Medicare group (HR, 0.61 [0.41, 0.93], P = 0.02), but not the commercially insured group (HR: 2.14 [0.82, 5.60], P = 0.12; P-interaction 0.09). In the inpatient study, 14.2% died, 59.5% survived to discharge, and 26.3% had an ongoing hospitalization. In propensity score-matched analyses, neither use of ACE inhibitor (0.97 [0.81, 1.16]; P = 0.74) nor ARB (1.15 [0.95, 1.38]; P = 0.15) was associated with risk of in-hospital mortality, in total or in the stratified analyses. ConclusionsThe use of ACE inhibitors and ARBs was not associated with the risk of hospitalization or mortality among those infected with SARS-CoV-2. However, there was a nearly 40% lower risk of hospitalization with the use of ACE inhibitors in the Medicare population. This finding merits a clinical trial to evaluate the potential role of ACE inhibitors in reducing the risk of hospitalization among older individuals, who are at an elevated risk of adverse outcomes with the infection.

A comparison of health care worker-collected foam and polyester nasal swabs in convalescent COVID-19 patients

BackgroundThe exponential growth of COVID-19 cases and testing has created supply shortages at various points in the testing workflow. As of April 15, 2020 FDA recommendations only allowed for the use of nasopharyngeal, flocked mid turbinate, or foam nasal swabs, all of which are in very low supply. Polyester swabs are more readily available and mass producible. We compare the performance of polyester and foam swabs stored in different transport media. MethodsBoth polyester and foam nasal swabs were collected from convalescent COVID-19 patients at a single visit. Using the foam nasal swabs as the comparator, sensitivity of the polyester swabs in each media were calculated, three by three tables were constructed to measure concordance, and cycle threshold (Ct) values were compared. Findings126 visits had polyester and foam swabs stored in viral transport media (VTM), 51 had polyester and foam swabs stored in saline, and 63 had a foam swab in VTM and a polyester swab stored in a dry tube. Using nasal foam swabs as a comparator, polyester nasal swabs had a sensitivity of 86{middle dot}5% when both samples were stored in VTM, 86{middle dot}7% when both samples were stored in saline, and 72{middle dot}4% when the polyester swab was stored dry and the foam swab was stored in VTM. Polyester and foam Ct values from the same visit were correlated, but polyester swabs showed decreased performance for cases with a viral load near the detection threshold and higher Ct values on average. InterpretationPolyester nasal swabs showed a reduction in performance from foam nasal swabs, but may still provide a viable sample collection method given the current supply shortages and public health emergency. FundingLaboratory testing was conducted with financial support from Thermo Fisher Scientific.

Patient-collected tongue, nasal, and mid-turbinate swabs for SARS-CoV-2 yield equivalent sensitivity to health care worker collected nasopharyngeal swabs

BackgroundCurrent testing for SARS-CoV-2 requires health care workers to collect a nasopharyngeal (NP) sample from a patient. NP sampling requires the use of personal protective equipment that are in limited supply, is uncomfortable for the patient, and reduces clinical efficiency. This study explored the equivalency of patient-collected tongue, anterior nares (nasal), and mid-turbinate (MT) samples to health care worker-collected NP samples for detecting SARS-CoV-2. MethodsPatients presenting to five urgent care facilities with symptoms indicative of an upper respiratory infection provided self-collected samples from three anatomic sites along with a health care worker-collected NP sample. Using NP as the comparator, sensitivities and one-sided 95% confidence intervals for the tongue, nasal, and MT samples for detection of SARS-CoV-2 were calculated. ResultsThe sensitivity for detecting SARS-CoV-2 in patient-collected tongue, nasal, and mid-turbinate samples was 89.8% (95% CI: 80.2 -100.0), 94.0 (95% CI: 84.6-100.0) and 96.2 (95% CI: 87.7-100.0), respectively. Among samples yielding positive results, cycle threshold (Ct) values (a measure of viral load) had correlation coefficients of 0.48, 0.78, and 0.86 between the NP samples and the tongue, nasal, and MT samples, respectively. ConclusionsPatient-collected nasal and MT samples demonstrated high sensitivity for SARS-CoV-2 detection using health care worker-collected NP samples as the comparator. Among patients testing positive with NP samples, nasal and MT Ct values demonstrated high correlations with those Ct values of the NP samples. Patient-collected nasal or MT sampling may improve efficiency for COVID-19 testing while reducing the risk of exposure of the health workforce.