Presence of rare potential pathogenic variants in subjects under 60 years old with very severe or fatal COVID-19

Background/Objectives: Genetic variants affecting host defense against pathogens may help explain COVID-19 fatal outcomes. Our aim was to identify rare genetic variants related to COVID-19 severity in a selected group of patients under 60 years who required intubation or resulting in death. Method(s): Forty-four very severe COVID-19 patients were selected from the Spanish STOP-Coronavirus cohort, which comprises more than 3,500 COVID-19 patients. Genotype was performed by whole exome sequencing and variants were selected by using a gene panel of 867 candidate genes (immune response, primary immunodeficiencies or coagulation, among other). Variants were filtered, priorized and their potential pathogenicity was assessed following ACGM criteria. Result(s): We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic (26%). Mostly, the candidate variants were located in genes related to immune response (38%), congenital disorders of glycosylation (14%) or damaged DNA binding genes (9%). A network analysis, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks enriched in carbohydrate metabolism and in DNA metabolism and repair processes. Conclusion(s): The variants identified affect different, but interrelated, functional pathways such as immune response and glycosylation. Further studies are needed for confirming the ultimate role of the new candidate genes described in the present study on COVID-19 severity.

Rapid protocols to support COVID-19 clinical diagnosis based on hematological parameters

Purpose: In December 2019, the Covid-19 pandemic began in the world. To reduce mortality, in addiction to mass vaccination, it is necessary to massify and accelerate clinical diagnosis, as well as creating new ways of monitoring patients that can help in the construction of specific treatments for the disease. Objective: In this work, we propose rapid protocols for clinical diagnosis of COVID-19 through the automatic analysis of hematological parameters using evolutionary computing and machine learning. These hematological parameters are obtained from blood tests common in clinical practice. Method: We investigated the best classifier architectures. Then, we applied the particle swarm optimization algorithm (PSO) to select the most relevant attributes: serum glucose, troponin, partial thromboplastin time, ferritin, D-dimer, lactic dehydrogenase, and indirect bilirubin. Then, we assessed again the best classifier architectures, but now using the reduced set of features. Finally, we used decision trees to build four rapid protocols for Covid-19 clinical diagnosis by assessing the impact of each selected feature. The proposed system was used to support clinical diagnosis and assessment of disease severity in patients admitted to intensive and semi-intensive care units as a case study in the city of Paudalho, Brazil. Results: We developed a web system for Covid-19 diagnosis support. Using a 100-tree random forest, we obtained results for accuracy, sensitivity, and specificity superior to 99%. After feature selection, results were similar. The four empirical clinical protocols returned accuracies, sensitivities and specificities superior to 98%. Conclusion: By using a reduced set of hematological parameters common in clinical practice, it was possible to achieve results of accuracy, sensitivity, and specificity comparable to those obtained with RT-PCR. It was also possible to automatically generate clinical decision protocols, allowing relatively accurate clinical diagnosis even without the aid of the web decision support system. © 2023, The Author(s), under exclusive licence to The Brazilian Society of Biomedical Engineering.

Machine Learning Approaches for Temporal and Spatio-Temporal Covid-19 Forecasting: A Brief Review and a Contribution

In December 2019 an outbreak of a new disease happened, in Wuhan city, China, in which the symptoms were very similar to pneumonia. The disease was attributed to SARS-CoV-2 as the infectious agent and it was called the new coronavirus or Covid-19. In March 2020, the World Health Organization declared a worldwide pandemic of the new coronavirus. We have already counted more than 110 million cases and almost 2.5 million deaths worldwide. In order to assist in decision-making to contain the disease, several scientists around the world have engaged in various efforts, and they have proposed a lot of systems and solutions for tracking, monitoring, and predicting confirmed cases and deaths from Covid-19. Mathematical models help to analyze and understand the evolution of the disease, but understanding the disease was not enough, it was necessary to understand the problem in a quantitative way to lead the decision-making during the pandemic. Several initiatives have made use of Artificial Intelligence, and models were designed using machine learning algorithms with features for temporal and spatio-temporal investigation and prediction of cases of Covid-19. Among the algorithms used are Support Vector Machine (SVM), Random Forest, Multilayer Perceptron (MLP), Graph Neural Networks (GNNs), Ecological Niche Models (ENMs), Long-Short Term Memory Networks (LSTM), linear regression, and others. And these had good results, and to analyze them, the Root Mean Squared Error (RMSE), Log Root Mean Squared Error (RMSLE), correlation coefficient, and others were used as metrics. Covid-19 presents a huge problem to public health worldwide, so it is of utmost importance to investigate it, and with these two approaches it is possible to track not only how the disease evolves but also to know which areas are at risk. And these solutions can help in supporting decision-making by health managers to make the best decisions for the disease that is in the outbreak. This chapter aims to present a literature review and a brief contribution to the use of machine learning methods for temporal and spatio-temporal prediction of Covid-19, using Brazil and its federative units as a case study. From canonical methods to deep networks and hybrid committee-based, approaches will be investigated. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

The role of anxiety, fear and resilience in preventive behaviors against COVID-19: a cross-sectional study with nursing students

Objectives: This study aims to explore the relationships between resilience, fear of COVID-19, anxiety and use of preventive behaviors related to COVID-19 among nursing students. Methods: A cross-sectional study was conducted with 220 first-year nursing students during 2020. Results: A significant relationship emerged between resilience (p <.05), fear of COVID-19 (p =.01), anxiety (p <.01) and use of preventive behaviors. Overall, the independent predictors were fear of COVID-19 (p =.003) and male sex (p =.016). Conclusions: It is essential to develop resilience among students further to increase their preventive behaviors against COVID-19.

Antibiotic Prescription in COVID Intensive Care Unit (ICU): Empiric Treatment vs. FilmArray Pneumonia (FAP) Panel Guided Treatment

Background. The empiric prescription of antibiotics in COVID 19 ICU patients is frequent due to the severity of disease and presentation of patients with septic shock. In this study we compared two approaches of antimicrobial prescription: empiric use vs. FilmArray pneumonia (FAP) panel guided treatment. We evaluated costs of intervention, clinical outcomes as development of hospital acquired infections (HAI), length of stay and mortality. Methods. Retrospective study. Patients with severe COVID-19 infection hospitalized in ICU of two institutions in Pereira were included. The prescription of antibiotic without FAP panel was defined as empiric. The prescription according to FAP panel results was defined as guided. Data analysis was performed in Epiinfo version 7.5.2.0. The study protocol was approved by the ethics committee of Universidad Tecnologica de Pereira. Results. 252 patients were included, 180 received empiric therapy and 72 were FAP panel guided. The median age was 65 years (IQR 53-73), the PaO2/FiO2 ratio mean was 108 (IQR 64-130). In the group of empiric treatment, 21 (11.67%) patients presented confirmed bacterial infection. Patients on guided antimicrobial therapy presented less HAI (RR 0,54 (IC 95% 0.30-0.95) p 0.02). The median length of stay in ICU was 16 days for both groups. Klebsiella pneumoniae was the most frequent bacteria identified during the first episode of infection followed of Pseudomonas aeruginosa. Mortality on guided group was 54% Vs. 42% on empiric group (p< 0,3). Meropenem was the main antibiotic prescribed (DDD empiric 3.17 Vs. 1.8DDDguided) followed of cefepime (DDD empiric 0.9 Vs. DDD guided 0.12). The median cost of antimicrobial treatment in the empiric group was US$530 (US$30-US$1579) per patient compared to the median cost of guided prescription that was US$292 (US$16-US $8767). When including the cost of FAP panel, the median cost per patient treatment course was US$429 (US$153-US$8904) p< 0.7. Conclusion. Implementation of a guided antimicrobial therapy using FAP panel could be useful and cost effective in COVID-19 ICU patients to reduce antimicrobial consumption and adverse outcomes related to the inappropriate use of antibiotics without significant impact on mortality or length of stay.

Effectiveness of SinergiAPS, an intervention based on Patient Feedback to Improve Patient Safety in Primary Care: a randomized clinical trial in Spain

Aims: To evaluate the effectiveness of SinergiAPS (a patient-centred audit and feedback intervention) in improving patient safety in primary healthcare (PHC) centres. Method(s): We conducted a cluster randomized controlled clinical trial in 59 PHC centres in Spain. We audited all the participant centres, assessing their level of patient safety based on the administration of the Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) questionnaire to 75 patients/centre. Then, PHC centres were randomly allocated to receive the SinergiAPS intervention or usual care. Only the intervention centres were fed back with the audit results. They received: (1) a bespoke feedback report with quantitative (scale and item level scores) and qualitative (free text) results;(2) a set of educational materials (based on available evidence-based strategies for addressing patient safety problems);and (3) a structured template to record and monitor their safety improvement plans. The intervention was remotely delivered using a bespoke web tool. The primary outcome was patient safety culture among professionals (MOSPSC questionnaire). Secondary outcomes were patient-reported patient safety (mean scores of five PREOS-PC questionnaire scales), and rate of avoidable hospital admissions. After 12 months follow-up, we conducted 14 semi-structured qualitative interviews with PHC professionals to explore their perceptions of the intervention and to identify implementation barriers. Result(s): We successfully recruited 1053 professionals out of 1971 (53%) invited professionals (81% women;mean (SD) age 49 (10) years). The post-intervention followup rate was 75% (793/1053). No significant differences were observed at 12 months between groups in patient safety culture score (intervention: 3.60 [95%CI 3.55-3.64] vs. control: 3.64 [95%CI 3.60-3.68]), or in any of the secondary outcomes. The qualitative interviews revealed that the response to the COVID-19 pandemic (which in Spain started 6 weeks after starting to deliver feedback reports) severely limited the ability of PHC centres to use the intervention resources as planned. Despite its low ''reach'', the intervention presented high acceptability and perceived utility. Conclusion(s): In the context of a health emergency, SinergiAPS did not improve patient safety in Spanish PHC centres. Future studies are needed to evaluate its effectiveness in contexts more consistent with usual practice.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients Una consideración terapéutica diferencial para el uso de corticoesteroides en COVID-19 según los diferentes fenotipos clínicos establecidos en pacientes críticos

Objective To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design A secondary analysis derived from multicenter, observational study. Setting Critical Care Units. Patients Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions Corticosteroids vs. no corticosteroids. Main variables of interest Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0;95% CI: 0.98–1.15). Corticosteroids were administered in 298/537 (55.5%) patients of “A” phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55–1.33]). A total of 338/623 (54.2%) patients in “B” phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49–1.05]). Finally, 535/857 (62.4%) patients in “C” phenotype received corticosteroids. In this phenotype HR (0.75 [0.58–0.98]) and sHR (0.79 [0.63–0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Adapting evaluation method of skills acquisition in basic cardiopulmonary resuscitation among year 5 and year 6 primary school pupils during the COVID-19 lockdown: a pilot study.

OBJECTIVE: This longitudinal descriptive study aimed to evaluate cognitive skills acquisition in basic Cardiopulmonary Resuscitation (bCPR) among a group of Year 5 and Year 6 primary school pupils. The study made use of online tools due to the impossibility of conventional methods during the COVID-19 lockdown. MATERIALS AND METHODS: Pupils received formal training in bCPR. Training was imparted uniformly by a teacher at the school (qualified in Basic Life Support -BLS- and Advanced Life Support -ALS- training by the CPR National Plan). The skills acquired (those proposed as essential for bCPR training by the European Resuscitation Council) were evaluated fifteen weeks later. Skills acquisition was evaluated by means of an online questionnaire developed specifically for the study. RESULTS: In all the cognitive skills included in bCPR training, the acquisition level achieved was over 65%. Acquisition of knowledge of the anatomical areas at which cardiac massage must be applied and the means of emergency systems activation was high, while 25.5% of pupils knew the order in which maneuvers should be performed. Pupils' self-confidence and self-perception of their capacity to act when faced with a real CPR situation increased significantly. CONCLUSIONS: Primary school pupils learned all the cognitive skills involved in bCPR, showing high levels of skills acquisition and positive self-perception of their capacity to apply them.

Covid-19 vaccination-associated pitfalls on treatment response evaluation with CT Scans ovarian cancer patients

Introduction/Background*Some studies have highlighted the imaging finding of vaccine-associated lymphadenopathies post-Covid19 vaccines. That may have a direct impact on the diagnostic accuracy of oncologic patients. Therefore, imaging experts suggest postponing imaging explorations to 6 weeks away from vaccination. Nevertheless to postpone imaging can interfere in assessment of disease extent or clinical response of these patients. We aimed to emphasize the relevance of these findings in ovarian cancer (OC) patients.MethodologyWe report three cases of asymptomatic OC patients that presented enlarged lymphadenopathies in CT scans and who have received at least one dose of mRNA Covid-19 vaccine at 6, 8 and 28days prior to the CT examination, respectively.Result(s)*Two of them were considered as having benign vaccine-associated lymphadenopathies as they presented right supraclavicular and intrapulmonary lymphadenopathies with no other clinical findings, nevertheless a new CT scan was performed 3 months later to reassure diagnostic. The third patient, one year after being diagnosed by EOC, was diagnosed by Lymphoma. After finishing treatment, a PET/CT SCAN to response evaluation was performed, 6 days after of COVID-19 vaccination. All tumoral nodes except one hypermetabolic lymph located at the lateral side of left Iliac Artery disappeared. This lymph node was considered as either no responsive or relapsed from OC, and less likely vaccine-associated. After being resected a high grade carcinoma was found.Conclusion*The incidence of lymphadenopathies in vaccinated patients raises a challenge in the interpretation of imaging of OC patients. Present cases emphasize the need for an accurate clinical evaluation encompassing the type and timing of Covid-19 vaccination. This would also allow avoiding imaging misinterpretations and unnecessary further assessment. Evidence-based guidelines are needed as postponing imaging controls to 6 weeks away from vaccination may be problematic in assessment of clinical response in treated OC patients or newly diagnosed patients.The authors declare no conflicts of interest. None received grant support for this study neither for related clinical or research activity

[Systematic review of the prognostic utility of D-dimer, disseminated intravascular coagulation, and anticoagulant therapy in COVID-19 critically ill patients]. / Revisión sistemática sobre la utilidad pronóstica del dímero-D, coagulación intravascular diseminada y tratamiento anticoagulante en pacientes graves con COVID-19.

During the new pandemic caused by SARS-CoV-2, there is short knowledge regarding the management of different disease areas, such as coagulopathy and interpretation of D-dimer levels, its association with disseminated intravascular coagulation (DIC) and controversy about the benefit of anticoagulation. Thus, a systematic review has been performed to define the role of D-dimer in the disease, the prevalence of DIC and the usefulness of anticoagulant treatment in these patients. A literature search was performed to analyze the studies of COVID-19 patients. Four recommendations were drawn based on expert opinion and scientific knowledge, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The present review suggests the presence of higher levels of D-dimer in those with worse prognosis, there may be an overdiagnosis of DIC in the course of the disease and there is no evidence on the benefit of starting anticoagulant treatment based only on isolated laboratory data.

Systematic review of the prognostic utility of D-dimer, disseminated intravascular coagulation and anticoagulant therapy in COVID-19 critically ill patients

Resumen Durante la nueva pandemia causada por SARS-CoV-2, existe poca evidencia en relación a varios aspectos de la enfermedad, como es el caso de la coagulopatía e interpretación de los niveles de dímero D, su asociación con coagulación intravascular diseminada (CID) y controversia en cuanto al beneficio de la anticoagulación. Por ello, se ha realizado una revisión sistemática para definir el rol del dímero D en la enfermedad, la prevalencia y valor pronóstico de la CID y la utilidad del tratamiento anticoagulante en dichos pacientes. Se realizó una búsqueda bibliográfica y análisis de la literatura sobre pacientes con COVID-19. Se elaboraron cuatro recomendaciones basadas en la opinión de expertos y en el conocimiento científico, según el sistema Grading of Recommendations Assesment, Development and Evaluation (GRADE). La presente revisión en pacientes con COVID-19 sugiere la presencia de mayores niveles de dímero D en aquellos con peor pronóstico, que puede haber un sobrediagnóstico de CID en el curso de la enfermedad y que no existe evidencia sobre el beneficio de iniciar tratamiento anticoagulante basándose únicamente en datos aislados de laboratorio. During the new pandemic caused by SARS-CoV-2, there is short knowledge regarding the management of different disease areas, such as coagulopathy and interpretation of D-dimer levels, its association with disseminated intravascular coagulation (DIC) and controversy about the benefit of anticoagulation. Thus, a systematic review has been performed to define the role of D-dimer in the disease, the prevalence of DIC and the usefulness of anticoagulant treatment in these patients. A literature search was performed to analyze the studies of COVID-19 patients. Four recommendations were drawn based on expert opinion and scientific knowledge, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The present review suggests the presence of higher levels of D-dimer in those with worse prognosis, there may be an overdiagnosis of DIC in the course of the disease and there is no evidence on the benefit of starting anticoagulant treatment based only on isolated laboratory data.

Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic

Objective To describe the clinical and respiratory characteristics of a cohort of 43 patients with COVID-19 after an evolutive period of 28 days. Design A prospective, single-center observational study was carried out. Setting Intensive care. Patients Patients admitted due to COVID-19 and respiratory failure. Interventions None. Variables Automatic recording was made of demographic variables, severity parameters, laboratory data, assisted ventilation (HFO: high-flow oxygen therapy and IMV: invasive mechanical ventilation), oxygenation (PaO2, PaO2/FiO2) and complications. The patients were divided into three groups: survivors (G1), deceased (G2) and patients remaining under admission (G3). The chi-squared test or Fisher exact test (categorical variables) was used, along with the Mann-Whitney U-test or Wilcoxon test for analyzing the differences between medians. Statistical significance was considered for p < 0.05. Results A total of 43 patients were included (G1 = 28 [65.1%], G2 = 10 [23.3%] and G3 = 5[11.6%]), with a mean age of 65 years (range 52-72), 62% males, APACHE II 18 (15-24), SOFA 6 (4-7). Arterial hypertension (30.2%) and obesity (25.6%) were the most frequent comorbidities. High-flow oxygen therapy was used in 62.7% of the patients, with failure in 85%. In turn, 95% of the patients required IMV and 85% received ventilation in prone decubitus. In the general population, initial PaO2/FiO2 improved after 7 days (165 [125-210] vs.194 [153-285];p = 0.02), in the same way as in G1 (164 [125-197] vs. 207 [160-294];p = 0.07), but not in G2 (163 [95-197] vs. 135 [85-177]). No bacterial coinfection was observed. The incidence of IMV-associated pneumonia was high (13 episodes/1000 days of IMV). Conclusions Patients with COVID-19 require early IMV, a high frequency of ventilation in prone decubitus, and have a high incidence of failed HFO. The lack of improvement of PaO2/FiO2 at 7 days could be a prognostic marker. Resumen Objetivo Describir las características clínicas y respiratorias de una cohorte de 43 pacientes con COVID-19 tras 28 días de evolución. Diseño Prospectivo observacional en un solo centro Ámbito Medicina intensiva Pacientes Pacientes ingresados por COVID-19 e insuficiencia respiratoria Intervenciones Ninguna. Variables Se obtuvieron de forma automática variables demográficas, de gravedad, de laboratorio, de asistencia ventilatoria recibida (OAF: oxigenoterapia alto flujo y VMI: ventilación mecánica invasiva), de oxigenación (PaO2, PaO2/FiO2) y de complicaciones. Los pacientes se dividieron en 3 grupos: supervivientes(G1), fallecidos(G2) y aquellos que continuaban ingresados(G3). Se utilizó “chi” cuadrado o Fisher (variables categóricas) y “U” Mann-Whitney o Wilcoxon para analizar la diferencia entre medianas. Se consideró significativo un valor de p < 0.05. Resultados Se incluyeron 43 pacientes (G1 = 28[65,1%],G2 = 10[23,3%] y G3 = 5[11,6%]), edad 65(52-72) años, 62% hombres, APACHE II 18(15-24), SOFA 6(4-7), Hipertensión arterial(30,2%) y obesidad(25,6%) fueron las comorbilidades más frecuentes. La OAF fue usada en el 62,7% de pacientes, 85% fracasó. El 95% de los pacientes necesitó VMI y el 85% ventilación en prono. En la población general, la PaO2/FiO2 inicial mejoró a los 7 días (165[125-210] vs. 194[153-285], p = 0.02), al igual que en G1(164[125-197] vs. 207[160-294], p = 0.07) pero no en G2 (163[95-197] vs. 135[85-177]). No se observó co-infección bacteriana. El desarrollo de neumonía asociada a la VMI fue elevado (13 episodios/1000 días de VMI). Conclusiones Los pacientes con Covid-19 requieren VMI precoz, elevada frecuencia de ventilación en prono y presentan alta prevalencia de fracaso a OAF. La falta de mejoría de la PaO2/FiO2 a los 7 días podría ser un marcador de pronóstico.

International consumer protection in times of COVID-19

The COVID-19 crisis has generated great concern among consumers, requiring the intervention of States in order to protect their interests and rights. This analysis has focused attention on issues related to the determination of the applicable law to consumer contracts in those international cases affected by the Coronavirus, as well as the interrelation that exists between those state consumer protection measures and the Rome I Regulation. © 2020 Ibero-American Law Institute. All rights reserved.

Remdesivir-COVID-19: drug interactions in dentistry.

OBJECTIVE: Remdesivir is a nucleotide analogue prodrug that inhibits viral RNA polymerases. It has been recognized recently as a promising antiviral drug against a wide array of RNA viruses (including SARS/MERS-CoV5). We aimed at determining which drugs used in dentistry interact with Remdesivir in order to avoid adverse reactions that may worsen the condition of patients with COVID-19. MATERIALS AND METHODS: A literature review was conducted to identify potential drug interactions between remdesivir (used in the treatment of COVID-19) and drugs prescribed in dentistry. The search was made in the databases PubMed and MEDLINE and official websites using key terms remdesivir, drug interactions and dentistry for articles published up to 31st July 2020. RESULTS: According to the articles reviewed, a total of 279 drugs interact with Remdesivir. Two major interactions have been reported, 277 moderate drug interactions, and one with alcohol/food. The drug interactions involving drugs prescribed in dentistry are all moderate drug interactions and are (according to drug group): (1) antibiotics: azithromycin, clavulanate, doxycycline, erythromycin, levofloxacin; (2) antifungals: clotrimazole, fluconazole, itraconazole, ketoconazole; (3) non-steroidal anti-inflammatories (NAIDS): celecoxib diclofenac, etodolac, flurbiprofen, ibuprofen, ketoprofen, ketorolac, mefenamic acid, naproxen, piroxicam. CONCLUSIONS: It is clinically necessary for oral health professionals to be aware of possible drug interactions that may occur between remdesivir and drugs commonly prescribed in dentistry in order to prevent adverse reactions that may even endanger the life of a patient with COVID-19.