Meta-analysis of arbidol versus lopinavir/ritonavir in the treatment of coronavirus disease 2019.
Journal of medical virology. 2022;(4):1513-1522
OBJECTIVES To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method. METHODS The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19. RESULTS The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. CONCLUSIONS Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.
Efficacy and Safety of Dapagliflozin versus Liraglutide in Patients with Overweight or Obesity and Type 2 Diabetes Mellitus: A Randomised Controlled Clinical Trial in Tianjin, China.
Journal of diabetes research. 2022;:4126995
Objective: We aimed to clarify the efficacy of dapagliflozin versus liraglutide in patients with overweight or obesity and type 2 diabetes mellitus (T2DM) at the beginning of the coronavirus disease 2019 (COVID-19) pandemic. Methods: T2DM patients with overweight or obesity who visited the Metabolic Disease Management Center at Tianjin Fourth Central Hospital from October 2019 to January 2020 were recruited and randomised to receive dapagliflozin or liraglutide for 24 weeks. Changes in blood glucose and lipid levels, blood pressure, and body weight, as well as the occurrence of hypoglycaemia and other adverse events, were compared. Results: 309 patients completed the study (143 in liraglutide group and 166 in dapagliflozin group). After 24 weeks, HbA1c, fasting blood glucose (FPG), and 2 h postprandial blood glucose (2hPG) levels significantly decreased from 8.80% ± 1.41% to 7.02% ± 1.05%, 10.41 ± 3.13 to 7.59 ± 2.16 mmol/L, and 17.90 ± 4.39 to 10.12 ± 2.47 mmol/L, respectively, in the dapagliflozin group, and from 8.92% ± 1.49% to 6.78% ± 1.00%, 10.04 ± 2.99 to 7.20 ± 1.63 mmol/L, and 17.30 ± 4.39 to 10.13 ± 4.15 mmol/L, respectively, in the liraglutide group. Changes in HbA1c, FPG, and 2hPG levels between groups were not significantly different. Systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) level significantly decreased from 144.1 ± 19.1 to 139.7 ± 16.2 mmHg (p = 0.001) and from 3.21 ± 0.94 to 2.98 ± 0.89 mmol/L (p = 0.014), respectively, in the dapagliflozin group. After COVID-19 outbreak, the number of patients taking sleep-promoting drugs increased from 4.9% to 9.4% (p = 0.029). Conclusions: Liraglutide and dapagliflozin had strong hypoglycaemic effects in patients with overweight or obesity and T2DM at the beginning of the COVID-19 pandemic. Dapagliflozin may be beneficial in improving SBP and LDL-C levels; however, further research is warranted.
Prospective predictive performance comparison between clinical gestalt and validated COVID-19 mortality scores.
Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2022;(2):415-420
Most COVID-19 mortality scores were developed at the beginning of the pandemic and clinicians now have more experience and evidence-based interventions. Therefore, we hypothesized that the predictive performance of COVID-19 mortality scores is now lower than originally reported. We aimed to prospectively evaluate the current predictive accuracy of six COVID-19 scores and compared it with the accuracy of clinical gestalt predictions. 200 patients with COVID-19 were enrolled in a tertiary hospital in Mexico City between September and December 2020. The area under the curve (AUC) of the LOW-HARM, qSOFA, MSL-COVID-19, NUTRI-CoV, and NEWS2 scores and the AUC of clinical gestalt predictions of death (as a percentage) were determined. In total, 166 patients (106 men and 60 women aged 56±9 years) with confirmed COVID-19 were included in the analysis. The AUC of all scores was significantly lower than originally reported: LOW-HARM 0.76 (95% CI 0.69 to 0.84) vs 0.96 (95% CI 0.94 to 0.98), qSOFA 0.61 (95% CI 0.53 to 0.69) vs 0.74 (95% CI 0.65 to 0.81), MSL-COVID-19 0.64 (95% CI 0.55 to 0.73) vs 0.72 (95% CI 0.69 to 0.75), NUTRI-CoV 0.60 (95% CI 0.51 to 0.69) vs 0.79 (95% CI 0.76 to 0.82), NEWS2 0.65 (95% CI 0.56 to 0.75) vs 0.84 (95% CI 0.79 to 0.90), and neutrophil to lymphocyte ratio 0.65 (95% CI 0.57 to 0.73) vs 0.74 (95% CI 0.62 to 0.85). Clinical gestalt predictions were non-inferior to mortality scores, with an AUC of 0.68 (95% CI 0.59 to 0.77). Adjusting scores with locally derived likelihood ratios did not improve their performance; however, some scores outperformed clinical gestalt predictions when clinicians' confidence of prediction was <80%. Despite its subjective nature, clinical gestalt has relevant advantages in predicting COVID-19 clinical outcomes. The need and performance of most COVID-19 mortality scores need to be evaluated regularly.
A comparative analysis for anti-viral drugs: Their efficiency against SARS-CoV-2.
International immunopharmacology. 2021;:107232
Coronavirus, known as the coronavirus pandemic, is continuing its spread across the world, with over 42 million confirmed cases in 189 countries and more than 1.15 million deaths. Although, scientists focus on the finding novel drugs and vaccine for SARS-CoV-2, there is no certain treatment for it. Antiviral drugs such as; oseltamivir, favipiravir, umifenovir, lopinavir, remdesivir, hydroxychloroquine, chloroquine, azithromycin, ascorbic acid, corticosteroids, are mostly used for patients. They prevent cytokine storm that is the main reason of deaths related to SARS-CoV-2. In addition, anti-inflammatory agents have critical roles to inhibit the lung injury and multisystem organ dysfunction. The combination with anti-viral drugs with other drugs displays high synergistic effects. In the present study, the drugs used for Covid-19 are analyzed and compare the efficiency for the Covid-19 patients from the different continents including USA, South Korea, Italy, Spain, Germany, Russia, Brazil, Turkey, and China. Nowadays, all countries tried to find vaccine and new drug candidates for SARS-CoV-2, but anti-viral drugs may be the best candidates for the treatment of Covid-19 before finding novel anti-Covid drug.
The US Strategic National Stockpile Ventilators in Coronavirus Disease 2019: A Comparison of Functionality and Analysis Regarding the Emergency Purchase of 200,000 Devices.
BACKGROUND Early in the coronavirus disease 2019 (COVID-19) pandemic, there was serious concern that the United States would encounter a shortfall of mechanical ventilators. In response, the US government, using the Defense Production Act, ordered the development of 200,000 ventilators from 11 different manufacturers. These ventilators have different capabilities, and whether all are able to support COVID-19 patients is not evident. RESEARCH QUESTION Evaluate ventilator requirements for affected COVID-19 patients, assess the clinical performance of current US Strategic National Stockpile (SNS) ventilators employed during the pandemic, and finally, compare ordered ventilators' functionality based on COVID-19 patient needs. STUDY DESIGN AND METHODS Current published literature, publicly available documents, and lay press articles were reviewed by a diverse team of disaster experts. Data were assembled into tabular format, which formed the basis for analysis and future recommendations. RESULTS COVID-19 patients often develop severe hypoxemic acute respiratory failure and adult respiratory defense syndrome (ARDS), requiring high levels of ventilator support. Current SNS ventilators were unable to fully support all COVID-19 patients, and only approximately half of newly ordered ventilators have the capacity to support the most severely affected patients; ventilators with less capacity for providing high-level support are still of significant value in caring for many patients. INTERPRETATION Current SNS ventilators and those on order are capable of supporting most but not all COVID-19 patients. Technologic, logistic, and educational challenges encountered from current SNS ventilators are summarized, with potential next-generation SNS ventilator updates offered.
Comparison between Nutric Score and modified nutric score to assess ICU mortality in critically ill patients with COVID-19.
Clinical nutrition ESPEN. 2021;:479-482
BACKGROUND AND AIMS NUTrition Risk in the Critically ill (NUTRIC score) and modified Nutric score (mNUTRIC score) have been validated as screening tool for quantifying risk of adverse outcome in patients admitted in intensive care department. They differ for the measurement of IL-6 levels. In patients with COVID-19 disease the inflammatory response plays a crucial role leading to cytochine storm responsible of multiple organ damage. In this population, levels of IL-6 have been measured as indicator of inflammatory status. Aim of the study is to compare prognostic performance of both scores in predicting ICU mortality between patients with COVID-19 disease. METHODS A single centre, retrospective, cohort study on patients admitted in ICU with confirmed diagnosis of COVID-19 was performed. Prognostic performance of NUTRIC score and mNUTRIC score were assessed and compared for discriminative abilities for ICU-mortality. RESULTS 43 patients were enrolled, age 64 (55; 70), BMI 28 ± 4. Mean NUTRIC score was 2.5 ± 1, mNUTRIC was 2.6 ± 1.1. Mortality was 39.5%, all patients had low nutritional risk according to both scores (≤5 and ≤ 4 for NUTRIC and mNUTRIC score respectively). The discriminative ability of Nutric Score for ICU mortality was 0.675 (95% CI: 0.524-0.825), while that of mNutric score was 0.655 (0.513-0.861), p = 0.667. CONCLUSIONS Prognostic performance of Nutric score and mNutric score is comparable, but the discriminative ability is low even in patients with high inflammatory status as in COVID-19 affected population. These scores may not be appropriate in patients with COVID-19 for the determination of nutritional risk.
Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.
JAMA pediatrics. 2021;(8):817-826
Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.
Comparing the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID-19 patients.
Journal of medical virology. 2021;(12):6557-6565
The purpose of this study was to compare the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID-19 patients based on clinical and laboratory parameters. We prospectively evaluated the clinical and laboratory outcomes of 62 moderate to severe COVID-19 patients during a 10-day treatment plan. Patients were randomly assigned to either KH (receiving Lopinavir/Ritonavir [Kaletra] plus Hydroxychloroquine) or ADH (receiving Atazanavir/Ritonavir, Dolutegravir, and Hydroxychloroquine) groups. During this period, clinical and laboratory parameters and outcomes such as intensive care unit (ICU) admission or mortality rate were recorded. Compared to the KH group, after the treatment period, patients in the ADH group had higher activated partial thromboplastin time (aPTT) (12, [95% confidence interval [CI]: 6.97, 17.06), p = <0.01), international normalized ratio (INR) (0.17, [95% CI: 0.07, 0.27), p = <0.01) and lower C-reactive protein (CRP) (-14.29, (95% CI: -26.87, -1.71), p = 0.03) and potassium (-0.53, (95% CI: -1.03, -0.03), p = 0.04) values. Moreover, a higher number of patients in the KH group needed invasive ventilation (6 (20%) vs. 1 (3.1%), p = 0.05) and antibiotic administration (27 (90%) vs. 21(65.6), p = 0.02) during hospitalization while patients in the ADH group needed more corticosteroid administration (9 (28.1%) vs. 2 (6.7%), p = 0.03). There was no difference in mortality rate, ICU admission rate, and hospitalization period between the study groups. Our results suggest that the Atazanavir/Dolutegravir treatment regimen may result in a less severe disease course compared to the Lopinavir/Ritonavir treatment regimen and can be considered as an alternative treatment option beside standard care. However, to confirm our results, larger-scale studies are recommended.
Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.
The New England journal of medicine. 2021;(6):497-511
BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).
Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study.
CONTEXT Calcifediol has been proposed as a potential treatment for COVID-19 patients. OBJECTIVE To compare the administration or not of oral calcifediol on mortality risk of patients hospitalized because of COVID-19. DESIGN Retrospective, multicenter, open, non-randomized cohort study. SETTINGS Hospitalized care. PATIENTS Patients with laboratory-confirmed COVID-19 between 5 February and 5 May 2020 in five hospitals in the South of Spain. INTERVENTION Patients received calcifediol (25-hydroxyvitamin D3) treatment (0.266 mg/capsule, 2 capsules on entry and then one capsule on day 3, 7, 14, 21, and 28) or not. MAIN OUTCOME MEASURE In-hospital mortality during the first 30 days after admission. RESULTS A total of 537 patients were hospitalized with COVID-19 (317 males (59%), median age, 70 years), and 79 (14.7%) received calcifediol treatment. Overall, in-hospital mortality during the first 30 days was 17.5%. The OR of death for patients receiving calcifediol (mortality rate of 5%) was 0.22 (95% CI, 0.08 to 0.61) compared to patients not receiving such treatment (mortality rate of 20%; p < 0.01). Patients who received calcifediol after admission were more likely than those not receiving treatment to have comorbidity and a lower rate of CURB-65 score for pneumonia severity ≥ 3 (one point for each of confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, systolic blood pressure < 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg, and age ≥ 65 years), acute respiratory distress syndrome (moderate or severe), c-reactive protein, chronic kidney disease, and blood urea nitrogen. In a multivariable logistic regression model, adjusting for confounders, there were significant differences in mortality for patients receiving calcifediol compared with patients not receiving it (OR = 0.16 (95% CI 0.03 to 0.80). CONCLUSION Among patients hospitalized with COVID-19, treatment with calcifediol, compared with those not receiving calcifediol, was significantly associated with lower in-hospital mortality during the first 30 days. The observational design and sample size may limit the interpretation of these findings.