ABSTRACT
PurposeThere 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. MethodsWe 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 outcome 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, comparing immunosuppressants users and non-users. ResultsWe identified 4,349 patients, for which 1,356 were immunosuppressants users and 2,903 were non-users. Patients who used immunosuppressants were at increased odds of the primary outcome of all-cause death, ICU admission and mechanical ventilation use (IPTW OR 1.32; 95% CI: 1.06 - 1.63). Patients who used corticosteroids were at increased odds of the primary outcome (IPTW OR 1.33; 95% CI: 1.07 - 1.64). ConclusionWe support the latest guidelines from the CDC, that people on immunosuppressants are at high risk of severe COVID-19 and immunocompromised people may need booster COVID-19 vaccinations. FundingYGCs work was partially supported by 2020R1G1A1A01006229 awarded by the National Research Foundation of Korea.
ABSTRACT
BackgroundThere currently exists limited and conflicting clinical data on the use of statins amongst COVID-19 patients. Given the both paucity and lack of consensus among data on statins efficacy and safety amongst COVID-19 patients, the current guideline is to continue statin in COVID-19 patients, who have previously been treated with statins. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins, in terms of COVID-19 outcomes. MethodsWe conducted population-based retrospective study using South Koreas nationwide healthcare database as of May 15 2020. We identified 4,349 patients hospitalized with COVID-19 and aged 40 years or older. The cohort entry was defined as the date of hospitalization. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry, and non-users were those without such records during this period. Our primary outcome was a composite endpoint 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 conducted inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis to estimate odds ratio (OR) and corresponding 95% confidence intervals (CI), to compare outcomes between statin users and non-users. Findings1,115 patients were statin users (mean age = 65.9 years; 60% female), and 3,234 were non-users (mean age = 58.3 years; 64% female). Statin use was not associated with increased risk of the primary outcome (IPTW OR 0.82; 95% CI: 0.60-1.11). Subgroup analysis showed a protective role of statins, for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, p for interaction: 0.0087). InterpretationGiven that statins are not detrimental and that it may be beneficial amongst hypertensive patients and relatively cheap, we would encourage further investigation into statin for the prevention and treatment of COVID-19. FundingYGCs work was partially supported by 2020R1G1A1A01006229 awarded by the National Research Foundation of Korea. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThere is limited and conflicting data reporting on statin use among COVID-19 patients, and its association with COVID-19 outcomes Added value of this studyWe report no difference in COVID-19 outcomes between patients who used and did not use statins prior to COVID-19 diagnosis, except in hypertensive patients in which statins was shown to have a protective effect. Implications of all the available evidenceAs statins are not detrimental and relatively cheap, we encourage further investigation into statin for the prevention and treatment of COVID-19.
ABSTRACT
IntroductionA recent systematic review and meta-analysis by our group reported on thirteen published cohorts investigating 110,078 patients. Patients administered statins after their COVID-19 diagnosis and hospitalization were found to have a lower risk of mortality. Given this reported superiority, a logical next question would be whether statins are cost-effective treatment options for hospitalized COVID-19 patients. In this paper, we report on a cost-effectiveness analysis of statin-containing treatment regimens for hospitalized COVID-19 patients, from a United States healthcare perspective. MethodsA Markov model was used, to compare statin use and no statin use among hospitalized COVID-19 patients. 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. ResultsTreatment 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. ConclusionStatin for treatment of COVID-19 should be further investigated in RCTs, especially considering its cost-effective nature. Optimistically and pending the results of future RCTs, statins may also be used broadly for treatment of hospitalized COVID-19 patients.
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IntroductionFamotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with 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. MethodsFive 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. ResultsFour 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%. ConclusionBased 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 RCTs may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.
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IntroductionStatins 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. MethodsLiteratures 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. ResultsThirteen 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). ConclusionPatients administered statins after COVID-19 diagnosis or non-ICU admitted patients were at lower risk of mortality relative to non-statin users.
ABSTRACT
IntroductionColchicine 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. MethodsThe 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. ResultsEight 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). ConclusionColchicine 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.
ABSTRACT
An outbreak of a novel human coronavirus infection emerged in Wuhan, China in December 2019. Two months later, the World Health Organization (WHO) announced SARS-CoV-2 as the name for the new virus and COVID-19 for the associated illness. On March 12, 2020, the WHO officially declared COVID-19 as a pandemic. The scientific community has raced to find effective therapeutic agents against the virus. Gautret et al 2020 is among one of the first purportedly positive trials of hydroxychloroquine for the treatment of COVID-19. However, it is imperative that a thorough analysis and understanding of trial data be undertaken prior to making claims about safety and efficacy. Our group assessed the statistical robustness of the trial using the Fragility Index (FI). The FI provides a numerical quantification of a clinical trials conclusions. The index is based on iterative statistical calculations to determine the minimum number of events within a trial that would theoretically need to change from positive to negative in order for the trials endpoint to convert from significant to non-significant; the higher the index, the more statistically robust the study results. For the Gautret et al trial, one endpoint had an FI of 1, two had indices of 2, and another had an index of 4. The primary endpoint of viral clearance on day 6 had an FI of 4. This indicates that if 4 events were to change from positive to negative, the conclusion of the trial would become mathematically non-significant. This index is comparable to many other published trials of established agents; the median FI across the reported literature appears to be 2. In conclusion, the trial results reported by Gautret et al are statistically robust, assuming that data quality is not compromised; however, the study was an open-label trial with non-homogenous groups, with analysis conducted per-protocol. Additionally, SARS-CoV-2 Reverse Transcriptase-PCR (RT-PCR) testing was not conducted in a systematic way amongst the two groups. Further analyses of this trial and future trials of antiviral agents with potential activity against SARS-CoV-2 should be performed with complementary epidemiologic and statistical techniques to determine whether the trials results are clinically important and/or should be explored in depth. Given the statistically robust results reported by Gautret et al, despite the studys inherent methodological and analytical flaws, hydroxychloroquine should be studied as a potential agent against COVID-19 in larger clinical trials.
