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COVID-19 has a broad spectrum of clinical manifestations associated with the host immune response heterogeneity. Despite the advances in COVID-19 research, it is still crucial to seek a panel of molecular markers that enable accurate stratification of COVID-19 patients. Here, we performed a study that combined analysis of blood transcriptome, demographic data, clinical aspects and laboratory findings from 66 participants classified into different degrees of COVID-19 severity and healthy subjects. We identified a perturbation in blood-leukocyte transcriptional profile associated with COVID-19 aggravation, which was mainly related to processes that disfavoured lymphocyte activation and favoured neutrophil activation. This transcriptional profile stratified patients according to COVID-19 severity. Hence, it enabled identification of a turning point in transcriptional dynamics that distinguished disease outcomes and non-hospitalized from hospitalized moderate patients. Central genes of this unique neutrophil signature were S100A9, ANXA3, CEACAM6, VNN1, OLFM4, IL1R2, TCN1 and CD177. Our study indicates the molecular changes that are linked with the differing clinical aspects presented by humans when suffering from COVID-19, which involve neutrophil activation.
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COVID-19 , Humanos , COVID-19/genética , Neutrófilos , Transcriptoma , BiomarcadoresRESUMEN
Aim: The aim of this randomised, double-blind, placebo-controlled pilot clinical trial is to evaluate the capacity of a mouthwash to reduce SARS-CoV-2 viral load in the saliva of patients with COVID-19. Methods: Twenty-three symptomatic SARS-CoV-2-positive outpatients were selected andrandomised into two groups and registered at NTC 04563689. Both groups rinsed and gargled for one minute with either distilled water (Placebo) or with 0.05% Cetylpyridinium chloride (CPC) plus 0.12% Chlorhexidine (CHX) mouthwash (PERIOAID Intensive Careï). Saliva samples were collected before the use of placebo or mouthwash and after 15 minutes and 1 and 2 hours of either of the above treatment. A saliva sample was also taken five days after regular use of placebo or mouthwash twice daily. The virus was detected by qRT-PCR. Results: A great heterogeneity in the viral load values was observed at baseline in both groups for nasopharyngeal and saliva samples. Most of the patients who used the mouthwash (8/12) had a significant decrease in baseline viral load after 15 min (greater than 99% reduction). This inhibitory effect was maintained for up to two hours in 10 of the 12 patients. At five days, SARS-CoV-2 RNA was detectedin only 1 patient from the mouthwash group and in 5 from the placebo group. Conclusions: This study points out that a CPC mouthwash can reduce the viral load in saliva of COVID-positive patients. This finding may be important in transmission control of SARS-CoV-2. Nevertheless, the clinical relevance of CPC mouthwash-reduction on SARS-CoV-2 shedding in saliva requires further study.
Objetivo: El objetivo de este ensayo clínico piloto aleatorizado, doble ciego y controlado con placebo es evaluar la capacidad de un enjuague bucal para reducir la carga viral del SARS-CoV-2 en la saliva de pacientes con COVID-19. Materiales y métodos:Veintitrés pacientes ambulatorios positivos para SARS-CoV-2 sintomáticos fueron seleccionados y aleatorizados en dos grupos y registrados en el NTC 04563689. Ambos grupos se enjuagaron y hicieron gárgaras durante un minuto con agua destilada (placebo) o con cloruro decetilpiridinio al 0 ,05 % (CPC). ) más enjuague bucal con Clorhexidina (CHX) al 0,12% (PERIOAID Intensive Care). Se recolectaron muestras de saliva antes del uso de placebo o enjuague bucal y después de 15 minutos y 1 y 2 horas de cualquiera de los tratamientos anteriores. También se tomó una muestra de saliva cinco días después del uso regular de placebo o enjuague bucal dos veces al día. El virus fue detectado por qRT-PCR. Resultados:Se demostró una gran heterogeneidad en los valores de carga viral al inicio del estudio en grupos ambos para muestras de nasofaringe y saliva. La mayoría de los pacientes que usaron el enjuague bucal (8/12) tuvieron una disminución significativa en la carga viral inicial después de 15 minutos (reducción superior al 99 %). Este efecto inhibidor se mantuvo hasta dos horas en 10 de los 12 pacientes. A los cinco días, se detectó ARN del SARS-CoV-2 en solo 1 paciente del grupo de enjuague bucal y en 5 del grupo de placebo. Conclusiones:Este señala que un enjuague bucal CPC puedereducir la carga viral en saliva de pacientes COVID positivos. Este hallazgo puede ser importante en el control de la transmisión del SARS-CoV-2. Sin embargo, la relevancia clínica de la reducción del enjuague bucal con CPC en la excreción de SARS-CoV-2 en la saliva requiere más estudios.
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Objective: To analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients' immunological response. Methods: Serum samples were obtained from 231 COVID-19 positive patients from Macaé, in Rio de Janeiro state, in Brazil, from June 2020 until January 2021. The production of IgA, IgM, IgG, and IgE against S glycoprotein was analyzed using the S-UFRJ assay, taking into account the age, gender, and viral load. Results: Analysis of antibody production over 7 months revealed that IgA positivity gradually decreased after the first month. Additionally, the highest percentage of IgM positivity occurred in the first month (97% of patients), and declined after this period, while IgG positivity remained homogeneous for all 7 months. The same analysis for IgE revealed that almost all samples were negative. The comparison of antibody production between genders showed no significant difference. Regarding the age factor and antibody production, patients aged ≥60 years produced almost twice more IgA than younger ones (17-39 years old). Finally, a relationship between viral load and antibody production was observed only for older patients. Conclusions: Our work provides an overview of long-term production of antibodies against SARS-CoV-2, suggesting prolonged production of IgA and IgM antibodies for 3 months and continued IgG production for over 7 months. In addition, it identified a correlation between viral load and IgM titers in the older group and, finally, different IgA production between the age groups.
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COVID-19 , SARS-CoV-2 , Humanos , Femenino , Masculino , Adolescente , Adulto Joven , Adulto , Anticuerpos Antivirales , Inmunoglobulina G , Brasil/epidemiología , Inmunoglobulina M , Inmunoglobulina A , Inmunoglobulina ERESUMEN
Introduction: Subjects with asymptomatic infections are not generally admitted to health care facilities, however, they may benefit from antiviral therapy. Objective: To evaluate the contribution to treatment with combined therapy based on recombinant human interferon alpha 2b + Lopinavir/Ritonavir + Chloroquine versus Lopinavir/Ritonavir + Chloroquine in asymptomatic and symptomatic patients. Material and Methods: An observational study was carried out in patients with a positive diagnosis of COVID-19 from April 1st to July 30th, 2020. From a total of 308 patients treated with interferon + Lopinavir/Ritonavir + Chloroquine, we selected a statistically representative sample of 40 patients using a simple randomization process. As a control group, 27 patients who only received treatment with Lopinavir/Ritonavir + Chloroquine were selected. These patients underwent determinations of anti-SARS-CoV-2 antibodies, determinations of inflammatory markers, and follow-up by RT-PCR to evaluate the time length of negativization. Results: The group treated with interferon had a significantly shorter time to negativization. Patients treated with interferon showed a significant decrease in inflammatory markers at the time of hospital discharge and they had an increase in antibody titers at two and four months after hospital discharge, compared to the group of patients who did not receive interferon. Conclusions: The treatment with exogenous interferon in patients with COVID-19 had a significant contribution to the regulation of the immune response of the patients(AU)
Introducción: Los sujetos con infección asintomática generalmente no son admitidos en centros de asistencia médica, sin embargo, pueden beneficiarse de la terapia antiviral. Objetivo: evaluar la contribución al tratamiento de la terapia combinada basada en interferón alfa 2b recombinante humano + Lopinavir/Ritonavir + Cloroquina contra Lopinavir/Ritonavir + Cloroquina en pacientes asintomáticos y sintomáticos. Material y Métodos: Se realizó un estudio observacional en pacientes con diagnóstico positivo de COVID-19, durante los días del 1 de abril al 30 de julio de 2020. De un total de 308 pacientes tratados con interferón + Lopinavir/Ritonavir + Cloroquina, se seleccionaron mediante un proceso de aleatorización simple, una muestra estadísticamente representativa de 40 pacientes. Como grupo control se seleccionaron 27 pacientes que solo recibieron tratamiento con Lopinavir/Ritonavir + Cloroquina. Estos pacientes se sometieron a determinaciones de anticuerpos anti-SARS-CoV-2, determinaciones de marcadores inflamatorios y seguimiento por RT-PCR para evaluar el tiempo de negativización. Resultados: El grupo tratado con interferón tuvo un tiempo significativamente más corto de negativización. Los pacientes tratados con interferón mostraron una disminución significativa de los marcadores inflamatorios en el momento del alta hospitalaria y tuvieron un incremento de los títulos de anticuerpos a los dos y cuatro meses posteriores al alta hospitalaria, en comparación con el grupo de pacientes que no recibió interferón. Conclusiones: El tratamiento con interferón exógeno en pacientes con COVID-19 tuvo una contribución significativa en la regulación de la respuesta inmune de los pacientes(AU)
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HumanosRESUMEN
Coronavirus disease 2019 (COVID-19) is highly transmittable through contact with respiratory droplets. The virus is also shed in fecal matter. Some patients may present with effects in more than one system; however, there are no defined biomarkers that can accurately predict the course or progression of the disease. The present study aimed to estimate the severity of the disease, to correlate the severity of the disease with biochemical predictors, to identify valuable biomarkers indicative of gastrointestinal disease, and to determine the cutoff values. A cross-sectional study was conducted on COVID-19 patients admitted to the Kafrelsheikh University Hospital (isolation unit) between July 10, 2020, and October 30, 2020. The diagnosis of COVID- 19 was confirmed via reverse transcription-polymerase chain reaction (RT-PCR), which was employed for the detection of the viral RNA. We conclude that lymphopenia, elevated C-reactive protein (CRP) level, and liver enzymes were among the most important laboratory findings in COVID-19 patients. Statistically significant differences in platelet count, neutrophil count, D-dimer level, and fecal calprotectin levels were observed among patients presenting with chest symptoms only and patients with both chest and gastrointestinal symptoms (p=0.004;<0.001; 0.010; 0.003; and<0.001, respectively). C-reactive protein, D-dimer, and fecal calprotectin levels positively correlated with disease severity. The cutoff value for fecal calprotectin that can predict gastrointestinal involvement in COVID-19 was 165.0, with a sensitivity of 88.1% and a specificity of 76.5%. (AU)
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Biomarcadores/análisis , Complejo de Antígeno L1 de Leucocito , COVID-19 , Análisis Químico de la SangreRESUMEN
BACKGROUND/AIM: COVID-19 may lead to progressive respiratory failure as a consequence of alveolar damage, resulting in death. The aim of this study was to evaluate cytogenetic damage in oral cells of COVID-19 patients by micronucleus assay. PATIENTS AND METHODS: A total of 11 COVID-19 patients aged 40.7±9.3 years (5 men and 6 women) were included in this study. For the control group, a total of 15 participants not infected with SARS-CoV-2 virus were included. The mean age was 41.6±6.2 years (5 men and 10 women). RESULTS: The results showed statistically significant differences (p<0.05) in micronucleated buccal mucosa cells of COVID-19 patients. In addittion, a statistically significant increase in karyolysis and karrhyorexis (p<0.05) was observed in COVID-19 patients compared to control. CONCLUSION: SARS-CoV-2 virus can induce mutagenesis and cytotoxicity in oral cells.
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COVID-19 , Mucosa Bucal , Adulto , Monitoreo Biológico , Análisis Citogenético , Daño del ADN , Femenino , Humanos , Masculino , Pruebas de Micronúcleos , Persona de Mediana Edad , SARS-CoV-2RESUMEN
The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) are new global problems. The understanding of the host immune response in COVID-19 and its implications in the development of therapeutic agents are new challenges. Here, we evaluated the development of immunoglobulin G (IgG) and neutralizing (Nt) antibodies in symptomatic hospitalized COVID-19 patients. We followed up 117 COVID-19 confirmed patients from a reference health center for COVID-19 during the epidemic in Santiago de Chile. One and two sequential blood samples from 117 to 68 cases were, respectively, obtained to evaluate the immune response. Immunofluorescence and neutralization assays in Vero E6 cells with a Chilean SARS-CoV-2 strain were performed. Out of the 68 patients, 44% were women and 56% men, and the most frequent comorbidities were hypertension (47.7%) and diabetes (27.4%). The most frequent symptoms or signs related to COVID-19 were dyspnea, cough, fever, myalgia, and headache. In all the study population, 76.1% and 60.7% of patients were positive for IgG and Nt antibodies in the first blood sample. All patients except one were positive for IgG and Nt antibodies in the second sample. IgG and Nt antibodies positivity increased significantly according to the disease evolution periods. Higher Nt antibody titers were observed in the first sample in patients under 60 years of age. Obese and diabetic patients had no increase in Nt antibodies, unlike normal weight and diabetes-free patients. Both hypertensive and normotensive patients showed a significant increase in Nt antibodies. These results show an early and robust immune response against SARS-CoV-2 infection during severe COVID-19.