Effectiveness of famotidine on the risk of poor prognosis in patients with COVID-19: A nationwide cohort study in Korea.

Objective: Famotidine has been proposed as a promising candidate for the treatment of coronavirus disease 2019 (COVID-19). However, there is limited research on the association of famotidine with the poor prognosis of COVID-19. Methods: The Korean nationwide cohort included 6,556 patients who tested positive on RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The poor COVID-19-related outcomes were defined on the basis of having encountered the composite outcome of high oxygen therapy, intensive care unit admission, administration of mechanical ventilation, or death. In addition, we performed exposure-driven propensity score matching for no H2-blocker use versus current famotidine use, and other H2-blocker use versus current famotidine use. Results: 4,785 (73.0%) patients did not use a H2-blocker, 393 (6.0%) patients were currently used famotidine, and 1,292 (19.7%) patients currently used H2-blocker other than famotidine. In multivariable analysis after matching (no H2-blocker use versus current famotidine use), there was no significant association between current famotidine use and composite outcomes (adjusted odd ratios [aOR]: 1.30, 95% confidence interval [CI]: 0.55-3.06). On the other hand, another matched cohort (other H2-blocker use versus current famotidine use), demonstrated a positive association between current famotidine use and composite outcomes (aOR: 3.56, 95% CI: 1.03-12.28). Conclusions: Our study results did not support the potential of famotidine as a therapeutic agent for COVID-19. A rather unexpected result could be observed in the comparisons between current famotidine use and other H2-blocker use; it was observed that current famotidine use increased the risk of poor COVID-19 related outcomes. Further studies are needed to clearly prove the causal relationship with several H2-blockers, including famotidine.

Association between the fatty liver index and the risk of severe complications in COVID-19 patients: a nationwide retrospective cohort study.

BACKGROUND: Research on the association of non-alcoholic fatty liver disease (NAFLD) with prognosis in COVID-19 has been limited. We investigated the association between the fatty liver index (FLI), a non-invasive and simple marker of NAFLD, and the severe complications of COVID-19 patients in South Korea. METHODS: We included 3122 COVID-19-positive patients from the nationwide COVID-19 cohort dataset in South Korea between January and June 2020. The FLI was calculated using triglyceride, body mass index, glutamyl transpeptidase, and waist circumference, which were obtained from the national health screening program data. Severe complications related to COVID-19 were defined as the composite of mechanical ventilation, intensive care unit treatment, high-oxygen flow therapy, and death within 2 months after a COVID-19 infection. We performed a multivariate logistic regression analysis for the development of severe complications in COVID-19 patients. RESULTS: The mean ± standard deviation of FLI were 25.01 ± 22.64. Severe complications from COVID-19 occurred in 223 (7.14%) patients, including mechanical ventilation in 82 (2.63%) patients, ICU admission in 126 (4.04%), high-flow oxygen therapy in 75 (2.40%), and death in 94 (3.01%) patients, respectively. The multivariate analysis indicated that the highest tertile (T3) of FLI was positively associated with severe complications from COVID-19 (adjusted odds ratio (OR): 1.77, 95% confidence interval (CI) (1.11-2.82), P = 0.017) compared with the lowest tertile (T1). CONCLUSIONS: Our study demonstrated that FLI, which represents NAFLD, was positively associated with an increased risk of severe complications from COVID-19. FLI might be used as a prognostic marker for the severity of COVID-19.

A disproportionality analysis for the association of central nervous system demyelinating diseases with COVID-19 vaccination using the World Health Organization pharmacovigilance database.

BACKGROUND: Limited information is available on associations between COVID-19 vaccines and central nervous system (CNS) demyelinating diseases. OBJECTIVES: We investigated potential safety signals for CNS demyelinating diseases related to COVID-19 vaccines using the World Health Organization pharmacovigilance database. METHODS: Disproportionality analyses of CNS demyelinating disease following COVID-19 vaccination were performed by calculating the information component (IC) or the reporting odds ratio (ROR) compared with those for the entire database and for all other viral vaccines. RESULTS: We identified 715 cases of optic neuritis, 515 of myelitis, 220 of acute disseminated encephalomyelitis (ADEM), and 2840 total CNS demyelinating events adverse drug reactions from July 2020 through February 2022. For mRNA-based and ChAdOx1 nCoV-19 vaccines, there were no potential safety signals of disproportionality for optic neuritis (IC₀₂₅ = -0.93, ROR₀₂₅ = 0.38; IC₀₂₅ = -1.76, ROR₀₂₅ = 0.26), myelitis (IC₀₂₅ = -0.69, ROR₀₂₅ = 0.50; IC₀₂₅ = -0.63, ROR₀₂₅ = 0.53), ADEM (IC₀₂₅ = -1.05, ROR₀₂₅ = 0.33; IC₀₂₅ = -1.76, ROR₀₂₅ = 0.20), or overall CNS demyelinating disease events (IC₀₂₅ = -0.66, ROR₀₂₅ = 0.52; IC₀₂₅ = -1.31, ROR₀₂₅ = 0.34) compared with other viral vaccines. CONCLUSION: As with other viral vaccines, our disproportionality analyses indicate that the risk of COVID-19 vaccine-associated CNS demyelinating disease was low.

Associations of neuralgic amyotrophy with COVID-19 vaccination: Disproportionality analysis using the World Health Organization pharmacovigilance database.

INTRODUCTION/AIMS: There are limited studies on the association of COVID-19 vaccination with neuralgic amyotrophy (NA). Therefore, we evaluated the association between COVID-19 vaccination and the occurrence of NA. METHODS: We explored unexpected safety signals for NA related to COVID-19 vaccination through disproportionality analysis using VigiBase, the World Health Organization's pharmacovigilance database. RESULTS: On October 15, 2021, 335 cases of NA were identified in the database. The median time to onset of NA after vaccination was around 2 weeks. A significant signal of disproportionality of NA was observed for the ChAdOx1 nCoV-19 vaccine (AstraZeneca) (information component [IC]025  = 0.33, reporting odds ratio [ROR]025  = 1.30) and two mRNA-based COVID-19 vaccines (BNT162b2 [Pfizer and BioNTech] and mRNA-1273 [Moderna]) (IC025  = 1.74, ROR025  = 3.82) compared with the entire database. However, when compared with influenza vaccines, we did not detect any signal of disproportionality of NA for both the ChAdOx1 nCoV-19 vaccine (IC025  = -2.71, ROR025  = 0.05) and mRNA-based COVID-19 vaccines (IC025  = -1.38, ROR025  = 0.13). DISCUSSION: A weak association was observed between NA and COVID-19 vaccines. However, the risk did not surpass that of influenza vaccines.

Associations of Guillain-Barré syndrome with coronavirus disease 2019 vaccination: Disproportionality analysis using the World Health Organization pharmacovigilance database.

Vaccinations against the severe acute respiratory syndrome coronavirus 2 which causes COVID-19 have been administered worldwide. We aimed to investigate associations of COVID-19 vaccination with the occurrence of Guillain-Barré syndrome (GBS). We explored potential safety signals regarding the development of GBS using disproportionality analyses to compare COVID-19 vaccination with all adverse drug reaction (ADR) reports and influenza vaccines reported to VigiBase. As of October 15, 2021, a total of 2163 cases (0.13%) of GBS and its variants (including 46 cases of Miller-Fisher syndrome and 13 cases of Bickerstaff's encephalitis) were identified in entire ADR database after vaccination with the ChAdOx1 nCoV-19 (AstraZeneca, Cambridge, UK) or the two messenger RNA-based COVID-19 (BNT162b2; Pfizer and BioNTech) or mRNA-1273; Moderna) vaccines. The median time to onset of GBS after vaccination was around 2 weeks. The ChAdOx1 nCoV-19 and two messenger RNA-based COVID-19 vaccines demonstrated a higher risk for GBS against entire database (information component [IC]025  = 1.73 reporting odds ratio [ROR]025  = 3.51; IC025  = 1.07, ROR025  = 2.22, respectively). When compared with influenza vaccines, neither the ChAdOx1 nCoV-19 nor mRNA-based vaccines were found to be associated with greater risks of GBS (IC025  = -1.84, ROR025  = 0.11; IC025  = -1.86, ROR025  = 0.06, respectively). Although potential safety signals associated with GBS COVID-19 vaccines have been identified, the risk of GBS from COVID-19 vaccines were low and did not surpass those of influenza vaccines; however, because of the heterogeneity of the sources of information in the WHO pharmacovigilance database, further epidemiological studies are warranted to confirm these observations.

Association of Cerebral Venous Thrombosis with mRNA COVID-19 Vaccines: A Disproportionality Analysis of the World Health Organization Pharmacovigilance Database.

Cerebral venous thrombosis (CVT), a rare thrombotic event that can cause serious neurologic deficits, has been reported after some ChAdOx1 nCoV-19 vaccinations against coronavirus disease 2019 (COVID-19). However, there are few reports of associations between COVID-19 mRNA vaccination and CVT. We retrospectively analyzed CVT occurrence, time of onset after vaccination, outcomes (recovered/not recovered), and death after COVID-19 vaccination from adverse drug reactions (ADR) reports in VigiBase. A disproportionality analysis was performed regarding COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) and the ChAdOx1 nCoV-19 vaccine. We identified 756 (0.07%) CVT cases (620 (0.05%) after BNT162b2 and 136 (0.01%) after mRNA-1273) of 1,154,023 mRNA vaccine-related ADRs. Significant positive safety signals were noted for COVID-19 mRNA vaccines (95% lower end of information component = 1.56; reporting odds ratio with 95% confidence interval (CI) = 3.27). The median days to CVT onset differed significantly between the BNT162b2 and ChAdOx1 nCoV-19 vaccines (12 (interquartile range, 3-22) and 11 (interquartile range, 7-16), respectively; p = 0.02). Fewer CVT patients died after receiving mRNA vaccines than after receiving the ChAdOx1 nCoV-19 vaccine (odds ratio, 0.32; 95% CI, 0.22-0.45; p < 0.001). We noted a potential safety signal for CVT occurrence after COVID-19 mRNA vaccination. Therefore, awareness about the risk of CVT, even after COVID-19 mRNA vaccination, is necessary.

A Disproportionality Analysis for Association of Systemic Capillary Leak Syndrome with COVID-19 Vaccination Using the World Health Organization Pharmacovigilance Database.

Systemic capillary leak syndrome (SCLS) is a rare and potentially life-threatening disorder characterized by reversible plasma extravasation and vascular collapse. This study aimed to investigate the association between different types of COVID-19 vaccine and SCLS in a real-world setting. We used individual case safety reports of SCLS after COVID-19 vaccination from the WHO pharmacovigilance database, VigiBase. A disproportionality analysis of ChAdOx1 nCoV-19 and mRNA-based vaccines was performed. The information component (IC) and reporting odds ratio (ROR) were calculated from the entire database and viral vaccines data subset. A positive 95% lower end of the IC (IC025) value (>0) using Bayesian neural network analysis and lower end of the ROR 95% confidence interval (ROR025) ≥1 were defined as the ADR signal detection threshold. A total of 101 (0.004%) events of SCLS were identified. A significant potential signal of disproportionality of SCLS was noted in ChAdOx1 nCoV-19 when applied as the denominator for entire database (IC025 = 0.24, ROR025 = 1.23) and all viral vaccines (IC025 = 0.41, ROR025 = 1.59). No significant potential signal was noted for two mRNA-based vaccines as denominators for the entire database (IC025 = -0.49, ROR025 = 0.71) and all viral vaccines (IC025 = -0.32, ROR025 = 0.77). Contrary to ChAdOx1 nCoV-1, no safety signal for developing SCLS was identified for mRNA-based vaccines.

Association of triglyceride-glucose index with prognosis of COVID-19: A population-based study.

BACKGROUND: Triglyceride-glucose (TyG) index is a simple and reliable surrogate marker for insulin resistance. Epidemiology studies have shown that insulin resistance is a risk factor for various infectious diseases. We evaluated the prognostic value of TyG index measured before the COVID-19 infection in COVID-19 infected patients. METHODS: From a nationwide COVID-19 cohort dataset in Korea, we included COVID-19 patients diagnosed between Jan and Jun 2020. Based on the nationwide health screening data between 2015 and 2018, TyG index was calculated as ln [triglyceride (mg/dL) × fasting glucose level (mg/dL)/2]. Primary outcome is development of severe complications of COVID-19 defined as composite of mechanical ventilation, intensive care unit care, high-flow oxygen therapy, and mortality within two months after the diagnosis of COVID-19. RESULTS: This study included 3887 patients with COVID-19 confirmed by reverse transcription polymerase chain reaction. Mean ± standard deviation of TyG index was 8.54 ± 0.61. Severe complications of COVID-19 were noted in 289 (7.44%) patients. In the multivariate logistic regression, TyG index was positively associated with severe complications of COVID-19 (adjusted odds ratio: 1.42, 95% confidence interval [1.12-1.79]). CONCLUSIONS: In COVID-19 infected patients, high TyG index was associated with increased risk for severe complications. TyG index might be useful predictor for the severity of COVID-19 infection.

A Disproportionality Analysis for Association of Systemic Capillary Leak Syndrome with COVID-19 Vaccination Using the World Health Organization Pharmacovigilance Database

Systemic capillary leak syndrome (SCLS) is a rare and potentially life-threatening disorder characterized by reversible plasma extravasation and vascular collapse. This study aimed to investigate the association between different types of COVID-19 vaccine and SCLS in a real-world setting. We used individual case safety reports of SCLS after COVID-19 vaccination from the WHO pharmacovigilance database, VigiBase. A disproportionality analysis of ChAdOx1 nCoV-19 and mRNA-based vaccines was performed. The information component (IC) and reporting odds ratio (ROR) were calculated from the entire database and viral vaccines data subset. A positive 95% lower end of the IC (IC025) value (>0) using Bayesian neural network analysis and lower end of the ROR 95% confidence interval (ROR025) ≥1 were defined as the ADR signal detection threshold. A total of 101 (0.004%) events of SCLS were identified. A significant potential signal of disproportionality of SCLS was noted in ChAdOx1 nCoV-19 when applied as the denominator for entire database (IC025 = 0.24, ROR025 = 1.23) and all viral vaccines (IC025 = 0.41, ROR025 = 1.59). No significant potential signal was noted for two mRNA-based vaccines as denominators for the entire database (IC025 = −0.49, ROR025 = 0.71) and all viral vaccines (IC025 = −0.32, ROR025 = 0.77). Contrary to ChAdOx1 nCoV-1, no safety signal for developing SCLS was identified for mRNA-based vaccines.

Risk of COVID-19 Infection and of Severe Complications Among People With Epilepsy: A Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: The goal of this work was to evaluate whether patients with epilepsy were more susceptible to coronavirus disease 2019 (COVID-19) infection and at greater risk of severe complications when infected with COVID-19 compared with patients without epilepsy. METHODS: We included participants who underwent at least 1 severe acute respiratory syndrome coronavirus 2 real-time reverse-transcription PCR test between January 1 and June 4, 2020, from the Korean nationwide COVID-19 dataset. Epilepsy was defined according to the presence of diagnostic code in health claims data before the COVID-19 diagnosis. To investigate the association between epilepsy and the susceptibility for or severe complications of COVID-19, a 1:6 ratio propensity score matching (PSM) and logistic regression analysis were performed. Severe complications with COVID-19 infection were defined as a composite of the incidence of mechanical ventilation, intensive care unit admission, and death within 2 months after COVID-19 diagnosis. RESULTS: Among 212,678 study participants who underwent a COVID-19 test, 3,919 (1.8%) had a history of epilepsy. After PSM, there was no significant difference in COVID-19 PCR positivity according to epilepsy history (odds ratio [OR] 0.86, 95% CI 0.67-1.11). Of the 7,713 individuals with confirmed COVID-19 infection, 72 (0.9%) had a history of epilepsy. Among the patients with COVID-19, severe complications occurred in 444 (5.8%) individuals. After PSM, the presence of epilepsy was associated with the occurrence of severe complications after COVID-19 infection (OR 2.05, 95% CI 1.04-4.04). Mortality after COVID-19 infection did not differ according to the presence of epilepsy history (OR 1.55, 95% CI 0.65-3.70). DISCUSSION: The presence of epilepsy was not associated with increased susceptibility to COVID-19 infection or mortality related to the infection. However, there was an increased risk of severe complications with COVID-19 in patients with epilepsy; therefore, careful management and monitoring may be necessary.

Association of Alzheimer's Disease with COVID-19 Susceptibility and Severe Complications: A Nationwide Cohort Study.

BACKGROUND: Identification of patients at high susceptibility and high risk of developing serious complications related to coronavirus disease 2019 (COVID-19) infection is clinically important in the face of the COVID-19 pandemic. OBJECTIVE: To investigate whether patients with Alzheimer's disease (AD) are more susceptible to COVID-19 infection and whether they have a higher risk of developing serious complications. METHODS: We retrospectively reviewed the Korean nationwide population-based COVID-19 dataset for participants who underwent real-time reverse transcription polymerase chain reaction assays for COVID-19 between January 1 and June 4, 2020. A 1 : 3 ratio propensity score matching and binary logistic regression analysis were performed to investigate the association between AD and the susceptibility or severe complications (i.e., mechanical ventilation, intensive care unit admission, or death) of COVID-19. RESULTS: Among 195,643 study participants, 5,725 participants had AD and 7,334 participants were diagnosed with COVID-19. The prevalence of participants testing positive for COVID-19 did not differ according to the presence of AD (p = 0.234). Meanwhile, AD was associated with an increased risk of severe COVID-19 complications (OR 2.25 [95% CI 1.54-3.28]). Secondary outcome analyses showed that AD patients had an increased risk for mortality (OR 3.09 [95% CI 2.00-4.78]) but were less likely to receive mechanical ventilation (OR 0.42 [95% CI 0.20-0.87]). CONCLUSION: AD was not associated with increased susceptibility to COVID-19 infection, but was associated with severe COVID-19 complications, especially with mortality. Early diagnosis and active intervention are necessary for patients with AD suspected COVID-19 infection.

Associations of heart failure with susceptibility and severe complications of COVID-19: A nationwide cohort study.

Infection is associated with occurrence and worsening of heart failure (HF). However, studies on the association of susceptibility and severe complications of coronavirus disease 2019 (COVID-19) with HF history are limited. From the Korean nationwide COVID-19 data set, 212,678 participants with at least one severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction (RT-PCR) test were included between January 1 and June 4, 2020. To investigate the association of HF with susceptibility and severe complications of COVID-19, 1:4 ratio propensity score matching (PSM) and logistic regression analysis were performed. The primary outcome was a composite outcome of mechanical ventilation, intensive care unit (ICU) admission, and death. After PSM, COVID-19 PCR positivity did not show a significant difference according to HF history in multivariable analysis (odds ratio [OR]: 0.91, 95% confidence interval (CI) (0.79-1.04), p = 0.146). Of 7630 individuals with confirmed COVID-19 infection, 310 (4.1%) had HF history. The overall primary outcome occurred in 426 (5.6%) individuals, including 159 (2.1%) cases of mechanical ventilation, 254 (3.3%) cases of ICU admission, and 215 (2.8%) cases of death. In multivariate logistic analysis, presence of HF history was associated independently with primary outcome (OR: 1.99, 95% CI: 1.42-2.79, p < 0.001), particularly mortality (OR: 2.02, 95% CI: 1.36-3.00, p < 0.001). Our study demonstrated that HF history is associated poor prognosis, particularly mortality, in COVID-19. Patients with HF can have severe complication if infected with COVID-19; therefore, careful management are necessary.

Association of atrial fibrillation with infectivity and severe complications of COVID-19: A nationwide cohort study.

Infection is associated with the occurrence, recurrence, and progression of atrial fibrillation (AF), and is also closely related to poor prognosis. However, studies of the relationship between infectivity and severe complications of coronavirus infectious disease-19  (COVID-19) with a history of AF are limited. To estimate infectivity and severity of complications in COVID-19 patients with a history of AF, this study was done. From the Korean nationwide COVID-19 dataset, 212 678 participants with at least one severe acute respiratory syndrome coronavirus 2 (COVID-19) test were included between January 1 and June 4, 2020. AF was defined according to at least two outpatient hospital visits or one admission with an ICD-10 code of "I48" before the COVID-19 test. To investigate the association of AF with infectivity and severe complications of COVID-19, 1:4 ratio propensity score matching (PSM) was performed. Severe complications of COVID-19 were defined as a composite outcome of mechanical ventilation, intensive care unit admission, and death within 2 months after COVID-19 diagnosis. Among 212 678 participants who underwent the COVID-19 test, there were 7713 COVID-19 positive patients. After PSM, COVID-19 PCR positivity did not show a significant difference according to the presence of AF (odds ratio [OR]: 0.79, 95% confidence interval [CI]: [0.60-1.04]). Of 7713 COVID-19 patients, 62 (0.8%) had a history of AF and severe complications occurred in 444 (5.7%) patients. After PSM, AF was associated with the development of severe complications (OR: 2.04, 95% CI: [1.10-3.79]) and mortality (OR: 2.09, 95% CI: [1.01-4.31]) of COVID-19. We found that AF was associated with an increased risk of severe complications in COVID-19 infected patients.