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Introduction: There is currently great interest in establishing the relationship between the severity of SARSCOV-2 infection in hypertensive patients who use angiotensin II antagonists (AIIRAs). Objective: To study the relationship between the previous use of angiotensin II antagonists (ARB) in hypertensive patients and mortality from COVID-19. Materials and methods: A retrospective observational study was carried out in a tertiary care hospital in Lima, Peru, in hypertensive patients hospitalized in March 2021 for severe COVID-19. Results: A total of 101 patients entered the study, with a mean age of 70.1 + 12.0 and 48% male. ARB users and non-users were 45 (45.6%) and 56 (54.4%), respectively. The Charlson Comorbidity Index was higher in the ARB group (3.6 + 1.56 vs 3.04 + 1.24) (p<0.05). Total and male vs women mortality, among those using ARBs or not, were 57.8% vs 62% (p = 0.633) and 36.36% vs 63.64% (p <0.05), respectively. Mean lactate dehydrogenase concentration was lower in those taking ARBs compared to non-users, 394.18 + 152.3 vs 503.5 + 252.7 (p<0.05);No significant difference was observed in the leukocyte count and serum levels of C-Reactive Protein, Ferritin, D-dimer and fibrinogen. Conclusion: Among hospitalized COVID-19 patients with hypertension, prior use of ARBSs was not associated with mortality risk. © Revista del Cuerpo Medico Hospital Nacional Almanzor Aguinaga Asenjo.All rights reserved.
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Introduction: In the context of the global health emergency due to SARS-CoV-2 pandemic, ivermectin has been repurposed in some Latin American countries to treat COVID-19;in these countries its use as self-medication has been frequent (1). Ivermectin-induced liver injury, though extremely rare(2,3), had been previously described even before the COVID-19 pandemic Objective: To characterize clinical features of liver injury associated with ivermectin when used as self-medication for treating COVID-19. Method(s): Clinical records of those patients diagnosed with severe COVID-19 at the Emergency Room in Rebagliati Hospital in Lima, Peru, during March 2021, were carefully revised. To establish diagnosis of drug-induced liver injury (DILI) and causality assessment, the criteria of DILI-Expert Working Group and the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM), respectively, were used Results: Out of 327 patients identified, 38 took ivermectin as selfmedication (11%);of those 38, five were diagnosed with liver injury presumably related to that medication (13.2%). The mean age of those patients who developed the condition was 49.3 (12.3) [men, 4;woman, 1]. The mean (standard deviation) of Tomographic Severity Score (TSS), C-reactive protein, ferritin levels, Lymphocyte count and D-dimer were 52.2% (22.6), 13.8 (12.2) mg/dl, 1325.375 (239.7072) ng/ml, 2.0 (2.0) K/mul and 0.9 (0.7) lg/ml. The patients had no identified risk factors, but two;one patient had type I diabetes mellitus, and other, obesity. Mean daily ivermectin dose, duration, and total ivermectin dose were 32.9 (21.8) mg/day, 2.6 (0.6) days, and 89.6 (71.4) mg, respectively. As an average, liver injury occurred 11 (3.8) days after the start of treatment, none developed jaundice. Mean levels of alanine aminotransferase, alkaline phosphatase, gammaglutamyltransferase were increased 8 (4.4), 1.66 (0.9), 10.9 (5.0) times above the upper limit of normal. Two patients presented a hepatocellular pattern, 2 mixed and 1 cholestatic. All cases were mild and recovered. As for causality assessment, 4 cases were considered as ''possible'', and one, as ''highly probable''. Conclusion(s): Given its widespread use in some countries, ivermectininduced liver injury requires further pharmacovigilance studies when used for treating COVID-19.
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Introduction: In the face of the global health emergency due to SARS-CoV-2, Ivermectin has been, among other drugs, repurposed in some Latin American countries to treat COVID-19 [1]. Studies are needed on the safety of Ivermectin for this new indication. VigiBase is the WHO pharmacovigilance database that registers all Individual Case Safety Reports (ICSRs) from more than 130 countries. Objective(s): To review in VigiBase the reports of serious hepatic disorders in adults associated with the use of Ivermectin for COVID- 19. Method(s): We extracted, in men or women aged >= 18 years between 1 January 2020 and 7 march 2021, all ICSRs registered as ''serious'' associated with the use of ivermectin, and established the prevalence of serious hepatic disorders when Ivermectin was indicated for COVID-19 Results: During the study period, there were 1,393 ICSRs in Vigi- Base associated with Ivermectin, of which 60 (4.3%) were registered as ''serious'';in 25 of those, Ivermectin had been used for COVID-19. Out of those 25, five reported serious cases of hepatic disorders (hepatitis, hepatocellular injury, cholestasis, increased alanine aminotransferase and aspartate aminotransferase, abnormal liver function test). Three patients were male and overall mean age was 59.2 +/- 9.7 years. Ivermectin was administered during a mean of 2.5 +/- 2.4 days, and the mean daily dose was 14.3 +/- 2.9 mg. Two patients simultaneously received other drugs (Remdesivir, Hydroxychloroquine, Azithromycin). Two patients had concurrent conditions (strongyloidiasis, diabetes mellitus). Only in 2 patients liver enzyme data were reported. In all patients the evolution was favorable after stopping the drug (de-challenge), and no patient was re-exposed (rechallenge). Causality analysis was reported in 3 cases, qualifying as possible or probable. Conclusion(s): The safety of the use of Ivermectin should be studied more exhaustively, especially as regards the probability of hepatic disorders when used for COVID-19.
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Introduction: One of the known adverse reactions among long-term proton pump inhibitor (PPI) users, especially the elderly, is that it increases the risk of community-acquired pneumonia [1]. The probable mechanism is that the increase in gastric pH produces a decrease in elimination or an increase in colonization of bacteria;PPIs promote the proliferation of bacteria in the mouth and oropharynx and would increase in this manner the risk of pneumonia [2]. In COVID-19, lungs are particularly at risk. Currently, there is a great interest in establishing the relationship between the severity and mortality of SARS-CoV-2 infection in patients using PPIs [3]. Objective(s): To explore the relationship between the previous use of PPIs and mortality due to COVID-19 Methods: A retrospective observational study was carried out in a tertiary care hospital in Lima, Peru. Patients hospitalized in March 2021 for severe SARS-CoV-2 infection, confirmed by molecular tests (reverse transcription polymerase chain reaction), were included. Severe COVID-19 disease was defined as peripheral oxygen saturation on admission less than 93% (without supplemental oxygen) or pulmonary involvement greater than 30% (on the total severity score or TSS) in the lung tomography Results: A total of 327 patients entered the study (mean age, 61.36 +/- 16.0 years;male, 59.95%). PPIs users and non-users were 10 (3.06%) and 317 (96.94%), respectively. The mean age, Charlson score and total severity score (TSS) between PPIs users and non-users were 68.8 +/- 17.11 vs. 61.12 +/- 15.93 (p = 0.134), 3.6 +/- 2.32 vs. 2.25 +/- 1.715 (p = 0.019) and 55 +/- 25.28 vs. 48.44 +/- 24.30 (P = 0.399), respectively. Mortality in those using and not using PPIs were 80.0% (8 out of 10) and 38.49% (122 out of 317), respectively (Crude odds ratio, 6.39;95% confidence interval 1.34-30.61;p = 0.008). No significant difference was observed in the leukocyte count, mean lactate dehydrogenase concentration, Ferritin, D-dimer and fibrinogen and serum levels of C-Reactive Protein, in those users of PPIs compared to nonusers. Conclusion(s): Among hospitalized patients for severe SARS-CoV-2 infection, prior use of PPIs was associated with a higher mortality risk. This association does not necessary imply causality. Further research would be required to clarify potential mechanisms. Keywords: COVID-19, SARS-COV-2, proton pump inhibitor, mortality (Source: DeCS-BIREME).
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Introduction: In the context of the global health emergency due to SARS-CoV-2 pandemic, ivermectin has been repurposed in some Latin American countries to treat COVID-19;in these countries its use as self-medication has been frequent (1). Ivermectin-induced liver injury, though extremely rare(2,3), had been previously described even before the COVID-19 pandemic Objective: To characterize clinical features of liver injury associated with ivermectin when used as self-medication for treating COVID-19. Methods: Clinical records of those patients diagnosed with severe COVID-19 at the Emergency Room in Rebagliati Hospital in Lima, Peru, during March 2021, were carefully revised. To establish diagnosis of drug-induced liver injury (DILI) and causality assessment, the criteria of DILI-Expert Working Group and the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM), respectively, were used Results: Out of 327 patients identified, 38 took ivermectin as selfmedication (11%);of those 38, five were diagnosed with liver injury presumably related to that medication (13.2%). The mean age of those patients who developed the condition was 49.3 (12.3) [men, 4;woman, 1]. The mean (standard deviation) of Tomographic Severity Score (TSS), C-reactive protein, ferritin levels, Lymphocyte count and D-dimer were 52.2% (22.6), 13.8 (12.2) mg/dl, 1325.375 (239.7072) ng/ml, 2.0 (2.0) K/pl and 0.9 (0.7) pg/ml. The patients had no identified risk factors, but two;one patient had type I diabetes mellitus, and other, obesity. Mean daily ivermectin dose, duration, and total ivermectin dose were 32.9 (21.8) mg/day, 2.6 (0.6) days, and 89.6 (71.4) mg, respectively. As an average, liver injury occurred 11 (3.8) days after the start of treatment, none developed jaundice. Mean levels of alanine aminotransferase, alkaline phosphatase, gammaglutamyltransferase were increased 8 (4.4), 1.66 (0.9), 10.9 (5.0) times above the upper limit of normal. Two patients presented a hepatocellular pattern, 2 mixed and 1 cholestatic. All cases were mild and recovered. As for causality assessment, 4 cases were considered as possible, and one, as highly probable. Conclusion: Given its widespread use in some countries, ivermectininduced liver injury requires further pharmacovigilance studies when used for treating COVID-19.
ABSTRACT
Introduction: In the face of the global health emergency due to SARS-CoV-2, Ivermectin has been, among other drugs, repurposed in some Latin American countries to treat COVID-19 [1]. Studies are needed on the safety of Ivermectin for this new indication. VigiBase is the WHO pharmacovigilance database that registers all Individual Case Safety Reports (ICSRs) from more than 130 countries. Objective: To review in VigiBase the reports of serious hepatic disorders in adults associated with the use of Ivermectin for COVID19. Methods: We extracted, in men or women aged > 18 years between 1 January 2020 and 7 march 2021, all ICSRs registered as serious associated with the use of ivermectin, and established the prevalence of serious hepatic disorders when Ivermectin was indicated for COVID-19 Results: During the study period, there were 1,393 ICSRs in VigiBase associated with Ivermectin, of which 60 (4.3%) were registered as serious;in 25 of those, Ivermectin had been used for COVID-19. Out of those 25, five reported serious cases of hepatic disorders (hepatitis, hepatocellular injury, cholestasis, increased alanine aminotransferase and aspartate aminotransferase, abnormal liver function test). Three patients were male and overall mean age was 59.2 ± 9.7 years. Ivermectin was administered during a mean of 2.5 ± 2.4 days, and the mean daily dose was 14.3 ± 2.9 mg. Two patients simultaneously received other drugs (Remdesivir, Hydroxychloroquine, Azithromycin). Two patients had concurrent conditions (strongyloidiasis, diabetes mellitus). Only in 2 patients liver enzyme data were reported. In all patients the evolution was favorable after stopping the drug (de-challenge), and no patient was re-exposed (rechallenge). Causality analysis was reported in 3 cases, qualifying as possible or probable. Conclusion: The safety of the use of Ivermectin should be studied more exhaustively, especially as regards the probability of hepatic disorders when used for COVID-19
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Introduction: One of the known adverse reactions among long-term proton pump inhibitor (PPI) users, especially the elderly, is that it increases the risk of community-acquired pneumonia [1]. The probable mechanism is that the increase in gastric pH produces a decrease in elimination or an increase in colonization of bacteria;PPIs promote the proliferation of bacteria in the mouth and oropharynx and would increase in this manner the risk of pneumonia [2]. In COVID-19, lungs are particularly at risk. Currently, there is a great interest in establishing the relationship between the severity and mortality of SARS-CoV-2 infection in patients using PPIs [3]. Objective: To explore the relationship between the previous use of PPIs and mortality due to COVID-19 Methods: A retrospective observational study was carried out in a tertiary care hospital in Lima, Peru. Patients hospitalized in March 2021 for severe SARS-CoV-2 infection, confirmed by molecular tests (reverse transcription polymerase chain reaction), were included. Severe COVID-19 disease was defined as peripheral oxygen saturation on admission less than 93% (without supplemental oxygen) or pulmonary involvement greater than 30% (on the total severity score or TSS) in the lung tomography Results: A total of 327 patients entered the study (mean age, 61.36 ± 16.0 years;male, 59.95%). PPIs users and non-users were 10 (3.06%) and 317 (96.94%), respectively. The mean age, Charlson score and total severity score (TSS) between PPIs users and non-users were 68.8 ± 17.11 vs. 61.12 ± 15.93 (p = 0.134), 3.6 ± 2.32 vs. 2.25 ± 1.715 (p = 0.019) and 55 ± 25.28 vs. 48.44 ± 24.30 (P = 0.399), respectively. Mortality in those using and not using PPIs were 80.0% (8 out of 10) and 38.49% (122 out of 317), respectively (Crude odds ratio, 6.39;95% confidence interval 1.34-30.61;p = 0.008). No significant difference was observed in the leukocyte count, mean lactate dehydrogenase concentration, Ferritin, D-dimer and fibrinogen and serum levels of C-Reactive Protein, in those users of PPIs compared to nonusers. Conclusion: Among hospitalized patients for severe SARS-CoV-2 infection, prior use of PPIs was associated with a higher mortality risk. This association does not necessary imply causality. Further research would be required to clarify potential mechanisms.
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This study aimed to determine the relationship between ABO blood groups and mortality in patients hospitalized for severe SARS-CoV-2 infection. An observational and retrospective research was conducted in a tertiary care hospital in Lima, Peru. A total of 203 patients with a mean age of 62.58 ± 16.45 years were included in the research, out of whom 71.92 % were males. The frequency of O, A and B blood groups were 75.37 %, 17.24 % and 7.39 %, respectively. An association with mortality from severe COVID-19 infection was found with non-A blood groups (O group or B group), with a PR (prevalence ratio) of 2.25 and 95% CI (confidence interval) of 1.07 – 4.71. When adjusting the main variables, the association with PR remained in 2.78 and 95% CI in 1.06 – 7.24. In conclusion, patients hospitalized for severe SARS-CoV-2 infection with O and B blood groups seem to be associated with higher mortality rates than those with A blood group.
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We are very close to completing two years since the start of the COVID-19 pandemic. Even though vaccines have been developed and applied to more than 4 billion people in the world, SARS-CoV-2 continues to be a challenge for humanity. Therefore, it is important to study modifiable risk factors that may increase the severity of COVID-19, and one of the most discussed has been vitamin D. Currently, there is some evidence of association between low serum 25-hydroxyvitamin D [25(OH)D3] and increased mortality and severity due to SARS-CoV-2 infection. Before the pandemic, experimental evidence in animal and human studies had reported that an acute inflammatory process can cause a secondary decrease in 25(OH)D3. COVID-19 can be associated with a severe inflammatory process with an elevation of inflammatory markers;in this light, the reported association between low 25(OH)D3 and COVID-19 severity and/or mortality may be an epiphenomenon of the inflammatory process induced by SARS-CoV-2 and be an example of reverse causality. Copyright © 2022 Via Medica.
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InTrodUcTIon: There is experimental and clinical evidence that the serum concentration of 25-hydroxyvita-min D [25(OH)D)] may decrease in acute systemic inflammatory responses;in this context, low values may not necessarily indicate a pre-existing deficiency. This may also apply to low 25(OH)D levels found in the context of the systemic inflammatory response caused by SARS-CoV-2 infection. To conduct a systematic review of the relationship between serum 25(OH)D and the concentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor a (TNF-a) in acutely hospitalized patients with SARS-CoV-2 infection. MATerIAL And MeTHods: We searched PubMed, EMBASE, Google Scholar and the Cochrane Database of Systematic Reviews for studies published between January 2020 and February 2021. In each study, the authors compared levels of inflammatory markers between patients reported as having low levels of 25(OH) D and those above the study cut-off. resULTs: 18 studies were included (n = 3482, mean age 63.5 ± 9.3 years, 56.9% men). The cut-off for the definition of low 25(OH)D varied across studies. In all studies, mean values for inflammatory markers were higher in the low 25(OH)D groups. These differences were statistically significant (p < 0.05) in 6/15 studies with CRP, 4/8 with IL-6 and 0/1 with TNF-a. concLUsIons: Markers of acute systemic inflammatory response were elevated in patients with SARSCoV-2 infection and low concentrations of 25(OH)D. Therefore, the vitamin D status in those patients should be interpreted with caution, and studies should be designed to assess whether hypovitaminosis D could be an epiphenomenon. Copyright © 2021 Via Medica.
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Background/Introduction: Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID);it is considered as relatively safe and is widely used in the world. However, at the beginning of the COVID-19 pandemic, ibuprofen was associated with an increase in severity or mortality of the infection [1-4]. Objective/Aim: To conduct a meta-analysis of the association between ibuprofen use and SARS-CoV-2 infection severity or mortality. Methods: We searched PubMed, EMBASE, Google Scholar and the Cochrane Database of Systematic Reviews for observational studies published between January 2020 and May 2021. Studies were included if they contained data on ibuprofen use and SARS-CoV-2 infection severity or mortality. Information upon study design, location, year of publication, number of participants, sex, age at baseline, outcome and exposure definitions was gathered. The quality of studies included was assessed with the Newcastle-Ottawa Scale (NOS). The analysis was performed based on a random-effects model;the summary effect and its confidence interval were calculated. Results: Eight observational studies comprising a total of 1785.730 participants were identified for inclusion (cohort, 5;case-control, 2;cross-sectional, 1). Mean age was 54.4 (SD 12.6) years-old and 50.2% were men. The mean NOS score of included studies was 7.7 (range 7-9). The studies were from Austria, Denmark (2), Israel, Saudi Arabia, UK (2) and USA. Patients exposed to ibuprofen while infected with SARS-CoV-2 had not higher severity or mortality;summary odds ratios were 0.81 (95% CI 0.58-1.12, p = 0.14) and 0.95 (95% CI 0.79-1.14, p = 0.42), respectively. Conclusion: At present, the available evidence does not support the hypothesis of an increased SARS-CoV-2 risk associated with ibuprofen. However, more evidence needs to accumulate before this controversy can be resolved.
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Background: Hypertension and type 2 diabetes increase the risk of severe SARS-CoV-2 infection. On the other hand, homozygous ACE deletion polymorphism (DD) has been associated with these two diseases and risk of acute respiratory distress syndrome. The aim of the study was to conduct a meta-analysis of the association between ACE gene I/D polymorphism (DD, II and DI) and severity of SARS-CoV-2 infection in hospitalized patients. Material and methods: We searched PubMed, EMBASE and Google Scholar for studies published between January 2020 and April 2021. We included case-control studies evaluating the association between ACE I/D and severity of SARS-CoV-2 infection in hospitalized patients, were there was sufficient genotype or allele frequency data to calculate IRR (incidence rate ratio) and 95% confidence intervals (CIs). Results: Five studies were included (mean age 58.5 years and 61% men), combining to a total of 786 patients. Four studies were conducted in Caucasians. Overall, patients who had homozygous co-dominance genotype DD were at 47% higher risk of severe COVID-19 compared with II or ID (IRR: 1.47;95% CI: 1.15–1.89;p = 0.002). Conclusions: The ACE DD genotype may confer a greater risk of severe COVID-19 in hospitalized patients. Further studies including more diverse ethnic groups are necessary to fully establish this association. Copyright © 2021 Via Medica
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Background. It has been postulated that metformin could have anti-SARS-CoV-2 action. This raises the hypothesis that people who take metformin may have lower SARS-CoV-2 severity and/or mortality. Objectives. To conduct a meta-analysis of the association between the use of Metformin and risk of severity and mortality in SARS-CoV-2 infection. Methods. we searched PubMed, EMbASE, google scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv and Research Square) for studies published between December 2019 and January 2021. Data was extracted on study location, year of publication, design, number of participants, sex, age at baseline, body mass index, and exposure and outcome definition. Effect statistics were pooled using random effects models with 95% confidence intervals (CI). The quality of included studies was assessed with the newcastle-Ottawa Scale (nOS). Results. Thirty-two observational studies were included, combining to a total sample of 44306 participants. The mean nOS score of included studies was 7.9. Results suggested that metformin use was associated with a reduced risk of SARS-CoV-2 mortality (OR = 0.56, 95% CI: 0.46–0.68, P < 0.001;22 studies) but not with disease severity (OR = 0.85, 95% CI: 0.71–1.02, P = 0.077;15 studies). In the subgroup analysis, metformin reduces the risk of mortality (OR = 0.69, 95% CI: 0.55–0.88;P = 0.002) and severity (OR = 0.83, 95% CI: 0.70–0.97, P = 0.023) in patients aged 70 and above. Conclusions. The use of metformin was associated to lower risk of mortality from SARS-CoV-2 infection. This association does not imply causation and further research is required to clarify potential mechanisms. © 2021 Via Medica. All rights reserved.
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Background: The mechanism of entry of SARS-CoV-2 into the human host cell is through the ACE2 receptor. During the pandemic, a hypothesis has been proposed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) could be risk factors for the development of severe SARS-CoV-2 infection. The objective of the study was to conduct a meta-analysis of the association between ACEI or ARB use and SARS-CoV-2 infection severity or mortality. Material and methods: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for observational studies published between December 2019 and August 4, 2020 Studies were included if they contained data on ACEI or ARB use and SARS-CoV-2 infection severity or mortality. Effect statistics were pooled using random-effects models. The quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Data on study design, study location, year of publication, number of participants, sex, age at baseline, outcome definition, exposure definition, effect estimates and 95% CIs were extracted. Results: Twenty-six studies (21 cohort studies and 5 case-control studies) were identified for inclusion, combining to a total sample of 361467 participants. Mean age was 61.48 (SD 8.26) years and 51.63% were men. The mean NOS score of included studies was 7.85 (range: 7-9). Results suggested that ACEI or ARB use did not increase the risk of severe disease or mortality from SARS-CoV-2 infection (OR = 0.88, 95% CI: 0.75-1.02, p > 0.05). Conclusions: At present, the evidence available does not support the hypothesis of increased SARS-CoV-2 risk with ACEI or ARB drugs. Copyright © 2020 Via Medica, ISSN 2449-6170