The association between immunosuppressants use and COVID-19 adverse outcomes: national COVID-19 cohort in South Korea.

BACKGROUND: There is uncertainty of the effect of immunosuppression, including corticosteroids, before COVID-19 infection on COVID-19 outcomes. The aim of this study was to investigate the relationship between prehospitalization immunosuppressants use (exposure) and COVID-19 patient outcomes. METHODS: We conducted a population-based retrospective cohort study using a nationwide healthcare claims database of South Korea as of May 15, 2020. Confirmed COVID-19 infection in hospitalized individuals aged 40 years or older were included for analysis. We defined exposure variable by using inpatient and outpatient prescription records of immunosuppressants from the database. Our primary endpoint was a composite endpoint of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Inverse probability of treatment weighting (IPTW)-adjusted logistic regression analyses were used, to estimate odds ratio (OR) and 95% confidence intervals (CI), comparing immunosuppressants users and non-users. RESULTS: We identified 4,349 patients, for which 1,356 were immunosuppressants users and 2,993 were non-users. Patients who used immunosuppressants were at increased odds of the primary endpoint of all-cause death, ICU admission and mechanical ventilation use (IPTW OR =1.32; 95% CI: 1.06-1.63), driven by higher odds of all-cause mortality (IPTW OR =1.63; 95% CI: 1.21-2.26). Patients who used corticosteroids (n=1,340) were at increased odds of the primary endpoint (IPTW OR =1.33; 95% CI: 1.07-1.64). CONCLUSIONS: Immunosuppressant use was associated with worse outcomes among COVID-19 patients. These findings support the latest guidelines from the CDC that people on immunosuppressants are at high risk of severe COVID-19 and that immunocompromised people may benefit from booster COVID-19 vaccinations.

The prognostic role of anticoagulants in COVID-19 patients: national COVID-19 cohort in South Korea.

BACKGROUND: There currently exists a paucity of data on whether pre-admission anticoagulants use may have benefits among COVID-19 patients by preventing COVID-19 associated thromboembolism. The aim of this study was to assess the association between pre-admission anticoagulants use and COVID-19 adverse outcomes. METHODS: We conducted a population-based cohort studying using the Health Insurance Review and Assessment Service (HIRA) claims data released by the South Korean government. Our study population consisted of South Koreans who were aged 40 years or older and hospitalized with COVID-19 between 1 January 2020 through 15 May 2020. We defined anticoagulants users as individuals with inpatient and outpatient prescription records in 120 days before cohort entry. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Individual components of the primary endpoint were secondary endpoints. We compared the risk of endpoints between the anticoagulants users and non-users by logistic regression models, with the standardized mortality ratio weighting (SMRW) adjustment. RESULTS: In our cohort of 4,349 patients, for the primary endpoint of mortality, mechanical ventilation and ICU admission, no difference was noted between anticoagulants users and non-users (SMRW OR 1.11, 95% CI: 0.60-2.05). No differences were noted, among individual components. No effect modification was observed by age, sex, history of atrial fibrillation and thromboembolism, and history of cardiovascular disease. When applying the inverse probability of treatment weighting (IPTW) and SMRW with doubly robust methods in sensitivity analysis, anticoagulants use was associated with increased odds of the primary endpoint. CONCLUSIONS: Pre-admission anticoagulants were not determined to have a protective role against severe COVID-19 outcomes.

The association between statin and COVID-19 adverse outcomes: national COVID-19 cohort in South Korea.

BACKGROUND: There currently exist limited and conflicting clinical data on the use of statins in coronavirus disease 2019 (COVID-19) patients. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins. METHODS: We performed a population-based retrospective cohort study using South Korea's nationwide healthcare claim database. We identified consecutive patients hospitalized with COVID-19 and aged 40 years or older. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry to capture patients who are chronic statin users and, therefore, receive statin prescriptions as infrequently as every 8 months. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, mechanical ventilation use and cardiovascular outcomes [myocardial infarction (MI), transient cerebral ischemic attacks (TIA) or stroke]. We compared the risk of outcomes between statin users and non-users using logistic regression models after inverse probability of treatment weighting (IPTW) adjustment. RESULTS: Of 234,427 subjects in the database, 4,349 patients were hospitalized with COVID-19 and aged 40+ years. In total, 1,115 patients were statin users (mean age =65.9 years; 60% female), and 3,234 were non-users (mean age =58.3 years; 64% female). Pre-hospitalization statin use was not significantly associated with increased risk of the primary endpoint [IPTW odds ratio (OR) 0.82; 95% confidence interval (CI): 0.60-1.11]. Subgroup analysis showed a protective role of antecedent statin use for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, P for interaction: 0.0087). CONCLUSIONS: Pre-hospitalization statin use is not detrimental and may be beneficial amongst hypertensive COVID-19 patients. Further investigation into statin is needed for more conclusive effects of statins for treatment of COVID-19.

Cost-effectiveness analysis of statins for the treatment of hospitalized COVID-19 patients.

BACKGROUND: A recent systematic review and meta-analysis reporting on thirteen published cohorts investigating 110,078 patients demonstrated that patients who were administered statins after their COVID-19 diagnosis and hospitalization were had a lower risk of mortality. While these findings are encouraging, given competing COVID-19 treatment approaches, it is unclear if statin use should be prioritized and if its use is a cost-effective treatment options for hospitalized COVID-19 patients. In this study, we report on a cost-effectiveness analysis of statin-containing treatment regimens for hospitalized COVID-19 patients. METHODS: A Markov model was used to compare statin use and no statin use among hospitalized COVID-19 patients from a United States healthcare perspective. The cycle length was one week, with a time horizon of 4 weeks. A Monte Carlo microsimulation with 20,000 samples were used. All analyses were conducted using TreeAge Pro Healthcare Version 2021 R1.1. RESULTS: The mean cost for patients receiving statins in addition to usual care was $31,623 (SD $20,331), whereas the mean cost for patients not receiving statins was $33,218 (SD $25,440). The mean effectiveness for the two cohorts were 1.73 (SD 0.96) and 1.71 (SD 1.00), respectively. CONCLUSIONS: This analysis demonstrated that treatment of hospitalized COVID-19 patients with statins was both cheaper and more effective than treatment without statins; statin-containing therapy dominates over non-statin therapy. Statin medications for the treatment of COVID-19 should be further investigated in randomized controlled trials, especially considering its cost-effective nature. Optimistically and pending the results of future randomized trials, statins should be considered for use broadly for the treatment of hospitalized COVID-19 patients.

Colchicine use in patients with COVID-19: A systematic review and meta-analysis.

INTRODUCTION: Colchicine may inhibit inflammasome signaling and reduce proinflammatory cytokines, a purported mechanism of COVID-19 pneumonia. The aim of this systematic review and meta-analysis is to report on the state of the current literature on the use of colchicine in COVID-19 and to investigate the reported clinical outcomes in COVID-19 patients by colchicine usage. METHODS: The literature was searched from January 2019 through January 28, 2021. References were screened to identify studies that reported the effect of colchicine usage on COVID-19 outcomes including mortality, intensive care unit (ICU) admissions, or mechanical ventilation. Studies were meta-analyzed for mortality by the subgroup of trial design (RCT vs observational) and ICU status. Studies reporting an risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were analyzed separately. RESULTS: Eight studies, reporting on 16,248 patients, were included in this review. The Recovery trial reported equivalent mortality between colchicine and non-colchicine users. Across the other studies, patients who received colchicine had a lower risk of mortality-HR of 0.25 (95% CI: 0.09, 0.66) and OR of 0.22 (95% CI: 0.09, 0.57). There was no statistical difference in risk of ICU admissions between patients with COVID-19 who received colchicine and those who did not-OR of 0.26 (95% CI: 0.06, 1.09). CONCLUSION: Colchicine may reduce the risk of mortality in individuals with COVID-19. Further prospective investigation may further determine the efficacy of colchicine as treatment in COVID-19 patients in various care settings of the disease, including post-hospitalization and long-term care.

Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study.

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells. METHODS: We conducted a cohort study using South Korea's nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding. RESULTS: Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13-2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96-2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49-4.14). CONCLUSIONS: While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.

Effect of famotidine on hospitalized patients with COVID-19: A systematic review and meta-analysis.

INTRODUCTION: Famotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with Coronavirus disease 2019 (COVID-19). The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19. METHODS: Five databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated. RESULTS: Four studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death-HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%. CONCLUSION: Based on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further randomized controlled trials (RCTs) may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.

The protective association between statins use and adverse outcomes among COVID-19 patients: A systematic review and meta-analysis.

INTRODUCTION: Statins may reduce a cytokine storm, which has been hypothesized as a possible mechanism of severe COVID-19 pneumonia. The aim of this study was to conduct a systematic review and meta-analysis to report on adverse outcomes among COVID-19 patients by statin usage. METHODS: Literatures were searched from January 2019 to December 2020 to identify studies that reported the association between statin usage and adverse outcomes, including mortality, ICU admissions, and mechanical ventilation. Studies were meta-analyzed for mortality by the subgroups of ICU status and statin usage before and after COVID-19 hospitalization. Studies reporting an odds ratio (OR) and hazard ratio (HR) were analyzed separately. RESULTS: Thirteen cohorts, reporting on 110,078 patients, were included in this meta-analysis. Individuals who used statins before their COVID-19 hospitalization showed a similar risk of mortality, compared to those who did not use statins (HR 0.80, 95% CI: 0.50, 1.28; OR 0.62, 95% CI: 0.38, 1.03). Patients who were administered statins after their COVID-19 diagnosis were at a lower risk of mortality (HR 0.53, 95% CI: 0.46, 0.61; OR 0.57, 95% CI: 0.43, 0.75). The use of statins did not reduce the mortality of COVID-19 patients admitted to the ICU (OR 0.65; 95% CI: 0.26, 1.64). Among non-ICU patients, statin users were at a lower risk of mortality relative to non-statin users (HR 0.53, 95% CI: 0.46, 0.62; OR 0.64, 95% CI: 0.46, 0.88). CONCLUSION: Patients administered statins after COVID-19 diagnosis or non-ICU admitted patients were at lower risk of mortality relative to non-statin users.

Socioeconomic disparities in Korea by health insurance type during the COVID-19 pandemic: a nationwide study.

OBJECTIVES: This study explored socioeconomic disparities in Korea using health insurance type as a proxy during the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a retrospective cohort study using Korea's nationwide healthcare database, which contained all individuals who received a diagnostic test for COVID-19 (n=232,390) as of May 15, 2020. We classified our cohort by health insurance type into beneficiaries of the National Health Insurance (NHI) or Medicaid programs. Our study outcomes were infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19-related outcomes, a composite of all-cause death, intensive care unit admission, and mechanical ventilation use. We estimated age-, sex-, and Charlson comorbidity index score-adjusted odds ratios (aORs) with 95% confidence intervals (CIs) using a multivariable logistic regression analysis. RESULTS: Of the 218,070 NHI and 14,320 Medicaid beneficiaries who received COVID-19 tests, 7,777 and 738 tested positive, respectively. The Medicaid beneficiaries were older (mean age, 57.5 vs. 47.8 years), more likely to be males (47.2 vs. 40.2%), and had a higher comorbidity burden (mean CCI, 2.0 vs. 1.7) than NHI beneficiaries. Compared to NHI beneficiaries, Medicaid beneficiaries had a 22% increased risk of SARS-CoV-2 infection (aOR, 1.22; 95% CI, 1.09 to 1.38), but had no significantly elevated risk of COVID-19-related outcomes (aOR 1.10, 95% CI 0.77 to 1.57); the individual events of the composite outcome yielded similar findings. CONCLUSIONS: As socioeconomic factors, with health insurance as a proxy, could serve as determinants during the current pandemic, pre-emptive support is needed for high-risk groups to slow its spread.

Clinical outcomes of COVID-19 following the use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among patients with hypertension in Korea: a nationwide study.

OBJECTIVES: Recent evidence has shown no harm associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). We sought to further clarify the possible association between ACEI/ARB use and the risk of poor clinical outcomes of COVID-19. METHODS: From the completely enumerated COVID-19 cohort in Korea, we identified 1,290 patients with hypertension, of whom 682 had and 603 did not have records of ACEI/ARB use during the 30-day period before their COVID-19 diagnosis. Our primary endpoint comprised clinical outcomes, including all-cause mortality, use of mechanical ventilation, intensive care unit admission, and sepsis. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and a Poisson regression model to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for comparing outcomes between ACEI/ARB users and non-users. RESULTS: Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW-adjusted RR, 0.60; 95% CI, 0.42 to 0.85; p=0.005). For individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW-adjusted RR, 0.62; 95% CI, 0.35 to 1.09; p=0.097) or respiratory events (IPTW-adjusted RR, 0.99; 95% CI, 0.84 to 1.17; p=0.904). Subgroup analysis showed a trend toward a protective role of ACEIs and ARBs against overall outcomes in men (IPTW-adjusted RR, 0.84; 95% CI, 0.69 to 1.03; pinteraction=0.008) and patients with pre-existing respiratory disease (IPTW-adjusted RR, 0.74; 95% CI, 0.60 to 0.92; pinteraction=0.002). CONCLUSIONS: We present clinical evidence to support continuing ACE/ARB use in COVID-19 patients with hypertension based on the completely enumerated Korean cohort.