Características clínicas y evolución de los síntomas en pacientes con covid-19 / Clinical characteristics and evolution of symptoms in patients with COVID-19

RESUMEN Introducción: muchos casos de covid-19 son asintomáticos al ingresar. El desarrollo de síntomas pudiera tener relación con la terapéutica empleada. Objetivo: caracterizar clínicamente los pacientes infectados con SARS-CoV-2 y la evolución de los síntomas en relación con el ingreso, en el Hospital Militar Docente Dr. Mario Muñoz Monroy, de Matanzas. Materiales y métodos: estudio retrospectivo de las historias clínicas de pacientes ingresados confirmados con SARS-CoV-2 hasta el 26 de junio de 2020. Se estudiaron 145 pacientes, divididos en dos grupos: sintomáticos y asintomáticos al ingresar. Se recabaron datos demográficos, antecedentes patológicos personales, síntomas y evolución, parámetros humorales, tratamiento, estadía hospitalaria y complicaciones. Se utilizaron las pruebas de Chi cuadrado y de U de Mann-Whitney, según el tipo de variable. Resultados: la mayoría de los pacientes ingresó sintomático. Solo hasta 19 años predominaron los asintomáticos. Los hipertensos, diabéticos y con insuficiencia renal tuvieron mayor proporción de sintomáticos al momento del ingreso. Un pequeño grupo (n= 38) nunca desarrollo síntomas. En los sintomáticos predominaron tos, malestar general, fiebre, dolor faríngeo, congestión nasal, anosmia y falta de aire. Posterior al ingreso prevalecieron diarreas, dispepsia y vómitos. Los sintomáticos tuvieron mayores valores de enzimas hepáticas, más infección respiratoria baja y distress respiratorio, así como estadía hospitalaria extensa, ingreso en cuidados intensivos y fallecidos. Conclusiones: más de la mitad de los pacientes ingresaron con predominio de síntomas generales y respiratorios. Después del ingreso predominó la sintomatología digestiva, posiblemente relacionada con la terapéutica empleada. Los pacientes sintomáticos al ingresar, tuvieron peores parámetros humorales, más complicaciones y estadía hospitalaria más prolongada (AU).

ABSTRACT Introduction: many cases of covid-19 are asymptomatic when admitted to the hospital. The development of symptoms may be related to the therapies used. Objective: to characterize clinically the patients infected with SARS-CoV-2 and the evolution of symptoms in relation to admission, in the Military Hospital Dr. Mario Muñoz Monroy, of Matanzas. Materials and methods: retrospective study of clinical records of SARS-CoV-2-confirmed patients admitted up to June 26, 2020. 145 patients were studied, divided into two groups: symptomatic and asymptomatic ones at admission. Demographic data, personal pathological history, symptoms and evolution, humoral parameters, treatment, hospital stay and complications were collected. The Chi square and Mann-Whire U tests were used, depending on the type of variable. Results: most patients were symptomatic at admission. Asymptomatic ones predominated only up to 19 years. Hypertensive, diabetic and renal impaired patients had a higher proportion of symptoms at admission. A small group (n = 38) never developed symptoms. Cough, general discomfort, fever, pharyngeal pain, nasal congestion, anosmia and shortness of breath were the predominated symptoms. Diarrhea, dyspepsia and vomiting prevailed after admission. The symptomatic patients showed higher liver enzyme values, more low respiratory infection and respiratory distress, and also had more extended hospital stay, admission to intensive care and deceases. Conclusions: more than half of the patients were admitted with predominance of general and respiratory symptoms. After admission, digestive symptoms predominated, possibly related to the therapies used. Symptomatic patients on admission had worse humoral parameters, more complications and longer hospital stay (AU).

A Review of the Health Protective Effects of Phenolic Acids against a Range of Severe Pathologic Conditions (Including Coronavirus-Based Infections).

Phenolic acids comprise a class of phytochemical compounds that can be extracted from various plant sources and are well known for their antioxidant and anti-inflammatory properties. A few of the most common naturally occurring phenolic acids (i.e., caffeic, carnosic, ferulic, gallic, p-coumaric, rosmarinic, vanillic) have been identified as ingredients of edible botanicals (thyme, oregano, rosemary, sage, mint, etc.). Over the last decade, clinical research has focused on a number of in vitro (in human cells) and in vivo (animal) studies aimed at exploring the health protective effects of phenolic acids against the most severe human diseases. In this review paper, the authors first report on the main structural features of phenolic acids, their most important natural sources and their extraction techniques. Subsequently, the main target of this analysis is to provide an overview of the most recent clinical studies on phenolic acids that investigate their health effects against a range of severe pathologic conditions (e.g., cancer, cardiovascular diseases, hepatotoxicity, neurotoxicity, and viral infections-including coronaviruses-based ones).

Um olhar para o recém-nascido no contexto da Covid-19: revisão integrativa / An overview of newborn care in the Covid-19 context: an integrative review / Una mirada al recién nacido en el contexto de la Covid-19: revisión integrativa

OBJETIVO: Investigar manifestações clínicas, fatores de risco, tratamento e prevenção em recém-nascidos acometidos pela COVID-19 relatados na literatura científica. MÉTODO: Revisão integrativa realizada no mês de maio de 2020, nas bases de dados LILACS, MEDLINE e Biblioteca Virtual em Saúde, por meio de combinações entre os termos controlados newborn, COVID-19, SARS-CoV-2. RESULTADOS: Sete estudos compuseram a amostra final, sendo cinco publicações provenientes da China, onde foram relatados os primeiros casos de infecção neonatal. DISCUSSÃO: A prática baseada em evidências é fundamental para o cuidado ao recém-nascido diante do atual contexto pandêmico. Assim, atualizações sobre abordagens terapêuticas são necessárias. CONCLUSÃO: Medidas de prevenção são importantes, visto que existem lacunas relacionadas ao tratamento da COVID-19 em recém-nascidos. As manifestações clínicas podem variar desde sintomas respiratórios até gastrointestinais e cutâneos. Embora os casos relatados pareçam ser adquiridos no período pós-natal, faz-se necessário mais estudos e evidências para elucidar o risco de transmissão vertical.

OBJECTIVE: To investigate clinical manifestations, risk factors, treatment, and prevention of newborns affected by COVID-19 reported in the scientific literature. METHOD: This was an integrative review carried out in May 2020 in the LILACS, MEDLINE, and Virtual Health Library databases, via the combination of the controlled terms newborn, COVID-19, SARS-CoV-2. RESULTS: Seven studies composed the final sample, five of which were from China, where the first cases of neonatal infection were reported. DISCUSSION: Evidence-based practice is essential for neonatal care in light of the current pandemic context, which requires constant updates about therapeutic approaches. CONCLUSION: Prevention measures are important, because there are gaps related to COVID-19 treatment in newborns. Clinical manifestations can vary from respiratory symptoms to gastrointestinal and cutaneous symptoms. Although the cases reported seem to have been acquired in the postnatal period, more studies and evidence are needed to clarify the risk of vertical transmission.

OBJETIVO: Investigar las manifestaciones clínicas, factores de riesgo, tratamiento y prevención de recién nacidos infectados por COVID-19 informados en la literatura científica. MÉTODO: Revisión integrativa realizada en mayo de 2020 en bases de datos LILACS, MEDLINE y Biblioteca Virtual en Salud, utilizándose combinaciones entre los términos controlados newborn, COVID-19, SARS-CoV-2. RESULTADOS: Muestra final integrada por siete estudios, cinco de ellos publicaciones de China, donde se reportaron los primeros casos de infección neonatal. DISCUSIÓN: La práctica basada en evidencias es fundamental para el cuidado del recién nacido ante el contexto pandémico actual. Las actualizaciones sobre abordajes terapéuticos resultan necesarias. CONCLUSIÓN: Las medidas preventivas son importantes, considerando existencia de brechas para tratamiento de la COVID-19 en recién nacidos. Las manifestaciones clínicas varían desde síntomas respiratorios hasta gastrointestinales y cutáneos. Aunque los casos reportados remiten a infección en período posnatal, son necesarios más estudios y evidencias para determinar el riesgo de transmisión vertical.

Development and validation of indirect ELISA for antibody detection against different protein antigens of porcine epidemic diarrhea virus in the colostrum and milk of sows.

The objectives of this study are to develop and optimize indirect ELISA based on three coating antigens of porcine epidemic diarrhea virus (PEDV), recombinant spike (S12), nucleocapsid (N), and whole viral (WV) proteins, for the detection of IgG and IgA antibodies in colostrum and milk and to evaluate the diagnostic sensitivity (DSe) and diagnostic specificity (DSp) of the assay as a diagnostic method. Colostrum (n = 347) and milk (n = 272) samples from sows were employed in this assay. Indirect ELISA based on three coating antigens was assessed by receiver operating characteristic (ROC) curve analysis with a virus neutralization (VN) test as a reference method, and the cutoff value for calculating DSe and DSp was determined. S12-ELISA showed higher DSe and DSp of IgG and IgA detection compared to N- and WV-ELISA in both colostrum and milk samples. Moreover, S12-ELISA showed perfect agreement and a high correlation with the VN test, which was better than the N- and WV-ELISA for both IgG and IgA detection in colostrum and milk. In contrast, N-ELISA showed lower DSe and DSp compared to S12- and WV-ELISA, along with a correlation with VN and substantial agreement with the VN test. Nevertheless, our developed ELISAs have accuracy for repeatability in both inter- and intra-assay variation. Overall, this research demonstrates that S12-ELISA is more suitable than WV- and N-ELISA to detect IgG and IgA antibodies against PEDV from both colostrum and milk samples.

Relationship between leukocyte, neutrophil, lymphocyte, platelet counts, and neutrophil to lymphocyte ratio and polymerase chain reaction positivity.

BACKGROUND: Exposure to viral or bacterial pathogens increases the number of neutrophils with a relative decrease in lymphocytes, leading to elevated neutrophil to lymphocyte ratio (NLR). This study aimed to investigate whether differences in NLR among real-time polymerase chain reaction (PCR)-positive and -negative patients presenting with a prediagnosis of COVID-19 pneumonia could be useful in the differential diagnosis. METHODS: The study included 174 patients admitted because of suspected COVID-19 infection between March and April 2020. Patients were divided into two groups: PCR-negative and PCR-positive. Hemogram, NLR, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, ferritin, D-dimer, C-reactive protein, procalcitonin, troponin, and coagulation parameters were analyzed. RESULTS: On comparison of laboratory parameters between both groups at presentation, PCR-positive patients were significantly more likely to have leukopenia (p < 0.001), thrombocytopenia (p = 0.006), neutropenia (p < 0.001), lymphopenia (p = 0.001), and increased NLR (p = 0.003). Furthermore, PCR-positive patients showed significant elevations of ferritin (p = 0.012) and procalcitonin (p = 0.038) and significant lower potassium levels (p = 0.05). CONCLUSION: COVID-19 pneumonia has become a major global health problem. Early diagnosis and treatment of these patients are crucial, as COVID-19 pneumonia shows a rapid progression in most cases. Thus, leukopenia, thrombocytopenia, elevated NLR, and elevated ferritin may be useful as supplementary diagnostic tests in these patients, which may allow early initiation of treatment and may contribute to preventing progression in patients with abnormal results.

Antiviral activity of bioactive phytocompounds against coronavirus: An update.

Viral infections are one of the main cause of diseases worldwide due to the rising trends of migration, urbanization and global mobility of humans. The outbreak of corona virus diseases caused by SARS-CoV (year 2003), MERS-CoV (year 2012) and SARS-CoV-2 (year 2019) raised global health concerns. The side effects associated with the conventional drugs and increase in cases of anti-microbial resistance have led the researchers to switch to natural sources, especially plants, as they have immense potential to be used as antiviral agents. The aim of the article is to summarize the evidences of the bioactive phytocompounds from different plants as an effective alternative for the treatment of infections caused by coronaviruses. However, the use of most plant compounds succumbs to limitations due to lack of experimental evidences and safety studies. Therefore, further research and studies are required to validate their therapeutic uses for wide application of plant-based medicine, including anti-virals.

Características clínico-epidemiológicas de los pacientes ingresados en el Hospital "Amalia Simoni" durante la pandemia Covid-19 / Clinical-epidemiologic characteristics of the patients admitted in the Hospital "Amalia Simoni" during the Covid-19 pandemics

RESUMEN Introducción: desde los finales del año pasado en Wuhan, se informó de una neumonía de etiología desconocida, que llevó a la Organización Mundial de la Salud a declarar la infección por SARS-CoV-2, como una emergencia sanitaria denominándola como enfermedad por coronavirus 2019 (COVID-19). En Cuba se confeccionó un programa de enfrentamiento, en el cual la atención hospitalaria, siguió un riguroso protocolo de atención a pacientes positivos de la COVID-19, en áreas de cuidados mínimos, intensivos o progresivos. Objetivo: caracterizar clínica/epidemiológica pacientes positivos de la COVID-19, ingresados en el Hospital "Amalia Simoni". Materiales y métodos: se realizó un estudio descriptivo, transversal de 1 066 ingresos en el Hospital "Amalia Simoni", de marzo-mayo del 2020. Se revisaron historias clínicas y se obtuvo: edad, sexo, procedencia, sintomatología, comorbilidades y evolución epidemiológica. Datos que se evaluaron mediante estadísticas descriptivas. Resultados: se halló un predominio de edad media, sin diferencias de sexo, predominaron los casos de la ciudad de Camagüey y de los municipios con mayor urbanización. Prevalecieron la tos y la fiebre, además de la mitad de los casos sin comorbilidades, con solo un pequeño porcentaje de casos confirmados. Conclusiones: con un enfoque basado en la medicina preventiva en los casos estudiados, predominó la edad media, de procedencia de áreas urbanizadas con mayor población y aglomeraciones sociales. Se destacó que el ingreso precoz, basada en la pesquisa de la Atención Primaria logró disminuir los casos confirmados a un pequeño porcentaje, al igual que los graves y un solo fallecido (AU).

ABSTRACT Introduction: from the end of the last year in Wuhan, China, it was informed an unknown etiology pneumonia leading the World Health Organization to declare the infection with SARS-CoV-2 a sanitary emergency naming it coronavirus disease 2019 (Covid-19). A confrontation program was elaborated in Cuba, in which hospital care followed a rigorous protocol to take care to Covid-19-positive patients in areas of minimal, intensive and progressive care. Objective: to clinically/epidemiologically characterize Covid-19-positive patients admitted in the Hospital "Amalia Simoni". Materials and methods: a cross-sectional, descriptive study was carried out in 1 066 patients admitted in the Hospital "Amalia Simoni" in the period March-May 2020. Clinical records were reviewed and data gathered were age, sex, origin, symptomatology, co-morbidities and epidemiological evolution, data obtained through descriptive statistics. Results: it was found the predominance of medium age, without sex differences; the cases of patients from the city of Camaguey and from the municipalities with biggest urbanization predominated. Cough and fever prevailed; half of cases did not have comorbidities, and only a little percent of cases was confirmed. Conclusions: with an approach based in preventive medicine, medium age, and provenance from urban areas with bigger population and social concentrations predominated in the studied cases. It was showed that precocious admission, based on the Primary Health Care screening, succeeded in diminish confirmed cases to a little percent, as diminished the seriously ill ones; only one patient died (AU).

The management of "fragile" and suspected COVID-19 surgical patients during pandemic: an Italian single-center experience.

BACKGROUND: During Coronavirus disease (COVID-19) pandemic entire countries rapidly ran out of intensive care beds, occupied by critically ill infected patients. Elective surgery was initially halted and acute non-deferrable surgical care drastically limited. The presence of COVID-19 patients into intensive care units (ICU) is currently decreasing but their congestion have restricted our therapeutic strategies during the last months. METHODS: In the COVID-19 era eighteen patients (8 men, 10 women) with a mean age of 80 years, needing undelayable abdominal surgery underwent awake open surgery at our Department. Prior to surgery, all patients underwent COVID-19 investigation. In all cases locoregional anesthesia (LA) was performed. Intraoperative and postoperative pain has been monitored and regularly assessed. A distinct pathway has been set up to keep patients of uncertain COVID-19 diagnosis separated from all other patients. RESULTS: Mean operative time was 104 minutes. In only one case conversion to general anesthesia was necessary. Postoperative pain was always well controlled. None of them required postoperative intensive care support. Only one perioperative complication occurred. Early readmissions after surgery were never observed. CONCLUSIONS: On the basis of our experience awake laparotomy under LA resulted feasible, safe, painless and, in specific cases, the only viable option. For patients presenting fragile cardiovascular and respiratory, reserves and in whom general anesthesia (GA) would presumably increase morbidity and mortality we encourage LA as an alternative to GA. In the COVID-19 era, it has become part of our ICU-preserving strategy allowing us to carry out undeferrable surgeries.

CovEMERALD: Assessing the feasibility and preliminary effectiveness of remotely delivered Eye Movement Desensitisation and Reprocessing following Covid-19 related critical illness: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Primary Objective: To determine the feasibility of delivering a protocolised, remote, online, Eye Movement Desensitisation and Reprocessing (EMDR) intervention, within 12-weeks of hospital discharge, for adult survivors of Covid-19 related critical illness. Secondary objectives: To investigate whether remotely delivered EMDR can improve psychological outcome following Covid-19 related critical illness, specifically Post-Traumatic Stress Disorder (PTSD), anxiety and depression. TRIAL DESIGN: This is a single centre, randomised controlled cohort feasibility trial. PARTICIPANTS: Participants will be recruited following discharge from the Intensive Care Unit at University Hospital Southampton, United Kingdom. Eligible patients will have received mechanical ventilation for a minimum of 24 hours, tested Covid-19 positive by polymerase chain reaction, will be over the age of 18 years and have the capacity to provide informed consent. Patients will be excluded if they have pre-existing cognitive impairment, pre-existing psychotic diagnosis or are not expected to survive post-hospital discharge. INTERVENTION AND COMPARATOR: Group one: patients in the control arm will receive their standard package of prescribed care, following discharge home from hospital. If they experience any adverse physical or psychological health-conditions, they will access care through the usual available channels. Group two: patients randomly allocated to the intervention arm will receive their standard package of prescribed care, following discharge home from hospital. In addition, they will be referred to the Intensive Psychological Therapies Service in Poole, United Kingdom. They will receive an online appointment within 12-weeks of discharge home from hospital. They will receive a maximum of eight, weekly sessions of EMDR, delivered by a trained psychological therapist, following the Recent Traumatic Episode Protocol (R-TEP). Appendices 1 and 2 of the attached trial protocol contain a detailed description of the R-TEP intervention, written in accordance with the Template for Intervention Description and Replication (TIDieR) checklist and guide. MAIN OUTCOMES: The primary outcome from this trial will be feasibility. Feasibility will be determined by recruitment rates, expressed as a percentage of eligible patients approached, completion of the EMDR intervention, completion of final assessment at 6-months, incidence of attributable adverse events and protocol adherence by the psychological therapists. Secondary, exploratory outcomes will be assessed by comparison between the control and intervention groups at 6-months post-hospital discharge. Psychometric evaluation will consist of the PTSD Checklist-Civilian Version and Hospital Anxiety and Depression Scale. In addition, we will assess health-related quality of life using the EQ5D-5L, physical activity using wrist worn activity monitors and nutritional state using the Council of Nutrition Appetite Questionnaire. RANDOMISATION: Consenting participants will be randomly allocated to intervention or usual care using an internet-based system (ALEATM). Participants will be randomly assigned, on a 1:1 ratio, to receive either standard care (control) or the standard care plus online EMDR R-TEP (Intervention) BLINDING (MASKING): Due to the nature of the intervention, participants cannot be blinded to group allocation. 6-month patient reported outcome measures will be completed using an online, electronic case report form. Group allocation will be masked during data analysis. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This is a feasibility study, the results of which will be used to power a definitive study if appropriate. We anticipate a 25% mortality /loss to follow-up. A total of 26 patients will be recruited to this study, 13 patients in each arm. TRIAL STATUS: CovEMERALD opened to recruitment on 23rd September 2020 with an anticipated recruitment period of 6-months. We are using protocol version number 1.2 (1st June 2020) TRIAL REGISTRATION: CovEMERALD was registered on clinicaltrials.gov NCT04455360 on 2nd July 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Clinical characteristics of re-positive COVID-19 patients in Huangshi, China: A retrospective cohort study.

A cluster of patients with coronavirus disease 2019 (COVID-19) underwent repeated positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA tests after they were discharged from the hospital. We referred to them as re-positive (RP) patients in this study. We aimed to describe the clinical characteristics of these patients in a retrospective cohort study. After being treated for COVID-19, the patients underwent 14 days of quarantine following their discharge from the Huangshi Hospital of Traditional Chinese Medicine and the Huangshi Hospital of Youse. Two additional sequential SARS-CoV-2 RNA tests were performed at the end of quarantine. The median age of the 368 patients was 51 years, and 184 (50%) patients were female. A total of 23 RP patients were observed at follow-up. Using multivariate Cox regression analysis, risk factors associated with RP included a higher ratio of lymphocyte/white blood cell on admission (adjusted HR 7.038; 95% CI, 1.911-25.932; P = 0.0034), lower peak temperature during hospitalization (adjusted HR, 0.203; 95% CI, 0.093-0.443; P<0.0001), and the presence of comorbidities, particularly hypertension or chronic diseases in the respiratory system (adjusted HR, 3.883; 95% CI, 1.468-10.273; P = 0.0063). Antivirus treatment with arbidol was associated with a lower likelihood of re-positive outcomes (adjusted HR, 0.178; 95% CI, 0.045-0.709; P = 0.0144).

COVID-19 pandemic and biological therapy in rheumatologic disorders: how to deal with?

The outbreak of coronavirus disease 2019 (COVID-19) has involved more than 159 countries and more than 5 million people worldwide. A 40-year-old man with a history of rheumatoid arthritis treated with prednisolone, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologic agents was admitted with chief complaints of fever, chills, malaise, myalgia, and dyspnea. Chest computed tomography showed bilateral subsegmental atelectasis and diffuse ground-glass opacities in both lungs inducing the suspicion of COVID-19 infection. The oro-nasopharynx swab sample for COVID-19 polymerase chain reaction was positive. In addition to supportive care, lopinavir/ritonavir 400/100 mg twice daily and oseltamivir (75 mg) twice daily were started in combination with a starting dose of hydroxychloroquine (400 mg). The methotrexate dose was decreased, and the dose of prednisolone was increased to 30 mg for 10 days. Azathioprine and adalimumab were continued at previous doses. The use of biologic agents and DMARDs in rheumatic patients is a serious challenge in the COVID-19 pandemic. In conclusion, during the COVID-19 pandemic, due to the key roles of cytokines in the promotion of the disease, the rheumatic patients may benefit from continuing their previous treatment, which may have protective effects.

Vitamin deficiency as risk factor for SARS-CoV-2 infection: correlation with susceptibility and prognosis.

OBJECTIVE: In 2019, an infection provoked by SARS-CoV-2 virus arose in Wuhan, China. Currently, there is still no definite and efficacious therapy for SARS-CoV-2 infection. Moreover, our understanding of the physiopathology of the infection, and risk elements for severity and mortality, is incomplete. PATIENTS AND METHODS: One largely neglected element that could affect prognosis of SARS-CoV-2 infection is the vitamin status of population. The purpose of this review is to evaluate whether a vitamin insufficiency could provoke an augmented risk of SARS-CoV-2 infection or the appearance of major complications. In particular, we evaluated the presence of studies related to the state and effects of vitamin D, C, B, and A in subjects with SARS-CoV-2 disease. RESULTS: Although, actually, the interest in a possible use for vitamin supplementation in SARS-CoV-2 patients is essentially based on indirect data, we tried to examine the evidence about a favorable effect of vitamin supplementation in the therapy of the infection and its complications. CONCLUSIONS: Supplements with vitamin A, B, C, D, and E could represent an inexpensive and sufficiently safe approach, and a useful therapeutic complement. However, solid clinical research data are expected to support such claim.

A multi-center, randomized controlled trial by the Integrative Management in Japan for Epidemic Disease (IMJEDI study-RCT) on the use of Kampo medicine, kakkonto with shosaikotokakikyosekko, in mild-to-moderate COVID-19 patients for symptomatic relief and prevention of severe stage: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We aimed to test our hypothesis that additional administration of traditional Japanese (Kampo) medicine, kakkonto (kakkon-to: KT) and shosaikotokakikyosekko (sho-saiko-to-ka-kikyo-sekko: SSKKS), is more effective in relieving symptoms and preventing the onset of severe infection in mild-to-moderate COVID-19 patients compared to those treated only with conventional treatment. TRIAL DESIGN: The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator-sponsored, two-arm study. PARTICIPANTS: Patients and inpatients will be recruited from 8 Japanese academic and non-academic hospitals. The inclusion and exclusion criteria are as follows: Inclusion criteria: 1. Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2. Clinical stages of mild-to-moderate COVID-19 3. Symptomatic 4. ≥ 20 years of age 5. Male or female 6. Ability to communicate in Japanese 7. Outpatients and inpatients 8. Provided informed consent Exclusion criteria: 1. Difficulty in providing informed consent due to dementia, psychosis, or psychiatric symptoms 2. Allergic to Kampo or Western medicines used in this study 3. Pregnant and lactating 4. Unable to follow up 5. Participating in another clinical trial or interventional study 6. Hypokalemic or taking oral furosemide or steroids 7. Determined unsuitable for this study by the physician INTERVENTION AND COMPARATOR: Patients in the control group will receive conventional treatment with antipyretics, painkillers, or antitussives for symptoms that occurred after they contracted the SARS-CoV-2 infection. Patients in the Kampo group will receive 2.5 g of KT (TJ-1@TSUMURA and Co.) and 2.5 g of SSKKS (TJ-109@TSUMURA and Co.) 3 times a day, orally, for 14 days in addition to the conventional treatment as mentioned above. MAIN OUTCOMES: The number of days till at least one of the symptoms (fever, cough, sputum, malaise, shortness of breath) improves in the first 14 days of treatment. To assess the cough, sputum, malaise, and shortness of breath, a numeric rating scale will be used to define improvement in terms of a 2-point decrease in the number of days from the start of treatment for at least 2 days. Fever will be defined as an improvement when the temperature is less than 37 °C. RANDOMIZATION: Patients are randomized (1:1 ratio) to each group using the minimization method, with balancing of the arms with severity of disease stage and patient age (< 65, 65 to < 75, or ≥ 75 years). Computer-generated random numbers will be used for the minimization method. BLINDING (MASKING): Open-label with no blinding NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The main research hypothesis of this study is that the combination of Kampo medicine and conventional treatment will significantly improve the patients' symptoms (fever, fatigue, cough, sputum, and shortness of breath) during the first 14 days of treatment as compared with conventional treatment alone. Concerning the analysis of the primary endpoint, the duration of time before improvement of at least one of the common cold-like symptoms (fever, malaise, cough, sputum, and shortness of breath) will be estimated using the Kaplan-Meier method, and the survival curves will be compared between groups using the log-rank test. Assuming this method of analysis and based on previous studies reporting the efficacy of Kampo medicine for COVID-19 and H1N1 influenza patients, the median survival time in the Kampo medicine group is estimated as 3 days; this time will be 1.5 times longer in the control group. Assuming a one-sided significance level of 5%, a power of 70%, and an allocation ratio of 1:1, the required sample size is calculated as 126 cases. To compensate for a loss in follow-up, we plan to include 150 cases in both groups (Kampo group = 75, control group = 75). TRIAL STATUS: Protocol version 1.2 as of August 20, 2020 Recruitment start (expected): October 1, 2020 Recruitment finish (expected): October 31, 2023 TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) jRCTs021200020 . Registered on August 25, 2020 FULL PROTOCOL: The full protocol is attached as an additional file and is accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

COVID-19: the novel coronavirus disease and its manifestations and management in ophthalmology.

Coronavirus disease 2019 (COVID-19), a newly identified acute respiratory disease caused by a strain of novel coronavirus (SARS-CoV-2), has become a worldwide pandemic. From December 2019 to present, millions of cases have been reported, bringing unprecedented pressure on both health and epidemic prevention services in every country. As frontline healthcare workers, ophthalmologists face an increased threat of viral infection, not only because of close contact with patients during examinations or operations, but also due to evidence showing that ocular fluids such as tears or conjunctival secretions may carry the virus. The risk that healthcare workers face is emphasized by the loss of our colleagues who have sacrificed themselves in combating the virus. As a result, it is necessary to have a comprehensive understanding of the threats that we face. In the first part of this review, we start by explaining the structure of SARS-CoV-2 and examining its transmission and means of infection. Next, we summarize the latest scientific advancements of epidemiology, clinical presentations, and current treatments of COVID-19. In the second half of the review, we emphasize the ocular transmission, symptomatic manifestations, and the essential knowledge in an ophthalmology clinic setting. As the pandemic of COVID-19 continues to pose a threat to global health, we hope that this review makes a contribution to combating COVID-19.

Assessment of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: In this study, we investigate the effect of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in patients with COVID-19. TRIAL DESIGN: The current study is a single-center, randomized, double-blind, placebo-controlled clinical trial with parallel groups. PARTICIPANTS: The inclusion criteria include male and female patients≥18 years of age, with a confirmed diagnosis of SARS-CoV-2 infection via polymerase chain reaction (PCR) and/or antibody test and with written informed consent to participate in this trial. The exclusion criteria include regular use of any other supplement, severe and critical COVID-19 pneumonia, pregnancy and breastfeeding. This study is being conducted at Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. INTERVENTION AND COMPARATOR: Patients are randomly assigned to four groups. The first group (A) will take one capsule containing 5 mg of boron compounds twice a day for two weeks. The second group (B) will take one capsule containing 200 mg oleoylethanolamide twice a day for two weeks. The third group (C) will take one capsule containing 5 mg boron compounds with 200 mg oleoylethanolamide twice a day for two weeks, and the fourth group (D) does not receive any additional treatment other than routine treatments. Boron-containing compounds and oleoylethanolamide capsules will be synthesized at Nutrition Research Center of Tabriz University of Medical Sciences. MAIN OUTCOMES: The primary end point of this study is to investigate the recovery rate of clinical symptoms, including fever, dry cough, and fatigue, as well as preclinical features, including complete blood count (CBC), the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) profiles within two weeks of randomization. RANDOMISATION: Patients are randomized into four equal groups in a parallel design (allocation ratio 1:1). A randomized block procedure is used to divide subjects into one of four treatment blocks (A, B, C, and D) by a computer-generated allocation schedule. BLINDING (MASKING): The participants and investigators (enrolling, assessing, and analyzing) are blinded to the intervention assignments until the end of the study and data analysis. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The calculated total sample size is 40 patients, with 10 patients in each group. TRIAL STATUS: The protocol is Version 1.0, May 17, 2020. Recruitment began May 19, 2020, and is anticipated to be completed by October 19, 2020. TRIAL REGISTRATION: This clinical trial has been registered by the title of "Assessment of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in Patients with COVID-19: A double-blind randomized placebo-controlled clinical trial" in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20090609002017N35 ", https://www.irct.ir/trial/48058 . The registration date is 17 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The efficacy of Siddha Medicine, Kabasura Kudineer (KSK) compared to Vitamin C & Zinc (CZ) supplementation in the management of asymptomatic COVID-19 cases: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine. TRIAL DESIGN: A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial. PARTICIPANTS: Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded. INTERVENTION AND COMPARATOR: Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days. MAIN OUTCOMES: The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes. RANDOMISATION: The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures. BLINDING (MASKING): This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm. TRIAL STATUS: Protocol version 2.0 dated 16th May 2020. Recruitment is completed. The trial started recruitment on the 25th May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection TRIAL REGISTRATION: The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Atorvastatin and Aspirin as Adjuvant Therapy in Patients with SARS-CoV-2 Infection: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the impact of adding statin (atorvastatin) and/or aspirin on clinical deterioration in patients infected with SARS-CoV-2 who require hospitalisation. The safety of these drugs in COVID-19 patients will also be evaluated. TRIAL DESIGN: This is a single-centre, prospective, four-arm parallel design, open-label, randomized control trial. PARTICIPANTS: The study will be conducted at National Cancer Institute (NCI), Jhajjar, Haryana, which is a part of All India Institute of Medical Sciences (AIIMS), New Delhi, and has been converted into a dedicated COVID-19 management centre since the outbreak of the pandemic. All RT-PCR confirmed cases of SARS-CoV-2 infection with age ≥ 40 years and < 75 years requiring hospital admission (patients with WHO clinical improvement ordinal score 3 to 5) will be included in the trial. Written informed consent will be taken for all recruited patients. Patients with a critical illness (WHO clinical improvement ordinal score > 5), documented significant liver disease/dysfunction (aspartate transaminase [AST] / alanine aminotransferase [ALT] > 240), myopathy and rhabdomyolysis (creatine phosphokinase [CPK] > 5x normal), allergy or intolerance to statins or aspirin, prior statin or aspirin use within 30 days, history of active gastrointestinal bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, or inability to take oral or nasogastric medications will be excluded. Patients refusing to give written consent and taking drugs that are known to have a significant drug interaction with statin or aspirin [including cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitor, telaprevir, fibric acid derivatives (gemfibrozil), niacin, azole antifungals (itraconazole, ketoconazole), clarithromycin and colchicine] will also be excluded from the trial. INTERVENTION AND COMPARATOR: In this study, the benefit and safety of atorvastatin (statin) and/or aspirin as adjuvant therapy will be compared with the control group receiving usual care for management of COVID-19. Atorvastatin will be prescribed as 40 mg oral tablets once daily for ten days or until discharge, whichever is earlier. The dose of aspirin will be 75 mg once daily for ten days or until discharge, whichever is earlier. All other therapies will be administered according to the institute's COVID-19 treatment protocol and the treating physician's clinical judgment. MAIN OUTCOMES: All study participants will be prospectively followed up for ten days or until hospital discharge, whichever is longer for outcomes. The primary outcome will be clinical deterioration characterized by progression to WHO clinical improvement ordinal score ≥ 6 (i.e., endotracheal intubation, non-invasive mechanical ventilation, pressor agents, renal replacement therapy, ECMO requirement, and mortality). The secondary outcomes will be change in serum inflammatory markers (C-reactive protein and Interleukin-6), Troponin I, and creatine phosphokinase (CPK) from time zero to 5th day of study enrolment or 7th day after symptom onset, whichever is later. Other clinical outcomes that will be assessed include progression to Acute Respiratory Distress Syndrome (ARDS), shock, ICU admission, length of ICU admission, length of hospital admission, and in-hospital mortality. Adverse drug effects like myalgia, myopathy, rhabdomyolysis, hepatotoxicity, and bleeding will also be examined in the trial to assess the safety of the interventions. RANDOMISATION: The study will use a four-arm parallel-group design. A computer-generated permuted block randomization with mixed block size will be used to randomize the participants in a 1:1:1:1 ratio to group A (atorvastatin with conventional therapy), group B (aspirin with conventional therapy), group C (aspirin + atorvastatin with conventional therapy), and group D (control; only conventional therapy). BLINDING (MASKING): The study will be an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): As there is no existing study that has evaluated the role of aspirin and atorvastatin in COVID-19 patients, formal sample size calculation has not been done. Patients satisfying the inclusion and exclusion criteria will be recruited during six months of study period. Once the first 200 patients are included in each arm (i.e., total 800 patients), the final sample size calculation will be done on the basis of the interim analysis of the collected data. TRIAL STATUS: The institutional ethical committee has approved the study protocol (Protocol version 3.0 [June 2020]). Participant recruitment starting date: 28th July 2020 Participant recruitment ending date: 27th January 2021 Trial duration: 6 months TRIAL REGISTRATION: The trial has been prospectively registered in Clinical Trial Registry - India (ICMR- NIMS): Reference no. CTRI/2020/07/026791 (registered on 25 July 2020)]. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

COVID-19 pandemic and STEMI: pathway activation and outcomes from the pan-London heart attack group.

OBJECTIVES: To understand the impact of COVID-19 on delivery and outcomes of primary percutaneous coronary intervention (PPCI). Furthermore, to compare clinical presentation and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) with active COVID-19 against those without COVID-19. METHODS: We systematically analysed 348 STEMI cases presenting to the PPCI programme in London during the peak of the pandemic (1 March to 30 April 2020) and compared with 440 cases from the same period in 2019. Outcomes of interest included ambulance response times, timeliness of revascularisation, angiographic and procedural characteristics, and in-hospital clinical outcomes RESULTS: There was a 21% reduction in STEMI admissions and longer ambulance response times (87 (62-118) min in 2020 vs 75 (57-95) min in 2019, p<0.001), but that this was not associated with a delays in achieving revascularisation once in hospital (48 (34-65) min in 2020 vs 48 (35-70) min in 2019, p=0.35) or increased mortality (10.9% (38) in 2020 vs 8.6% (38) in 2019, p=0.28). 46 patients with active COVID-19 were more thrombotic and more likely to have intensive care unit admissions (32.6% (15) vs 9.3% (28), OR 5.74 (95%CI 2.24 to 9.89), p<0.001). They also had increased length of stay (4 (3-9) days vs 3 (2-4) days, p<0.001) and a higher mortality (21.7% (10) vs 9.3% (28), OR 2.72 (95% CI 1.25 to 5.82), p=0.012) compared with patients having PPCI without COVID-19. CONCLUSION: These findings suggest that PPCI pathways can be maintained during unprecedented healthcare emergencies but confirms the high mortality of STEMI in the context of concomitant COVID-19 infection characterised by a heightened state of thrombogenicity.

The first cohort of the COVID-19 patients in Vietnam and the national response to the pandemic.

The COVID-19 pandemic is a novel infectious disease pandemic with the agent SARS-CoV-2 virus which is currently affecting and causing damage globally. The outbreak has been crossing over 200 countries in the world. In the situation of the outbreak of COVID-19, Vietnam has first sixteen typical cases confirmed positive updated to Feb 28th, 2020. After completely applying the medical prevention and active control, Vietnam has the ability to take control of the outbreak of COVID-19 as a recent of WHO assessment. Vietnam has been reported as an effective country for prevention and control the outbreak of COVID-19. We retroactive reviewed our experience with 16 positive cases isolation. This article aims to present the first cohort of COVID-19 patients updated to Feb 28th, 2020 in Vietnam and sharing the national response to the pandemic.