Reverse Transcription-polymerase Chain Reaction Negativity Research Articles

The Efficacy and Safety of Imusil® Tablets in the Treatment of Adult Patients With Mild COVID-19: A Prospective, Randomized, Multicenter, Open-Label Study.

Introduction Coronavirus disease 2019 (COVID-19) is a serious concern of the new era. Along with antiviral synthetic medications, there is a need to discover efficacious herbal antiviral medicines with minimum side effects in patients against COVID-19. This study aimed to assess the efficacy and safety of Imusil® among patients with mild COVID-19. Methods A prospective, randomized, multicenter, open-label, interventional study was conducted in patients with mild COVID-19 infection. Patients received either Imusil one tablet four times a day (seven days) along with the standard of care (SoC) or only SoC. The study endpoints were reverse transcription-polymerase chain reaction (RT-PCR) negativity, changes in cycle threshold (CT), clinical improvement, changein blood inflammatory indexes, and safety assessment. Results A total of 100 patients were enrolled, and 98 received at least one dose of treatment. The median age of patients was 36.0 years, and 58 were males. By day 4, 85.4% of patients in the Imusil+SoC group tested negative for RT-PCR compared to 64% of patients exhibiting the same outcome in the SoC group(P=0.0156). After eight days, clinical improvement was observed in all patients from the Imusil+SoC group, while in the SoC group, clinical improvement was observed in 94.0% of patients (P=0.4947). During follow-up visits, the average C-reactive protein (CRP) levels decreased from baseline in both treatment groups. The decrease in the levels of CRP (-7.3 mg/dL versus-5.5 mg/dL), D-dimer (-231.0 ng/mL versus-151.6 ng/mL), and interleukin 6 (IL-6) (-2.3 pg/mL versus-2.0 pg/mL) at eight days was comparatively higher in the Imusil+SoC group versus the SoC group. There were no serious treatment-emergent adverse events in the drug arm. Conclusion Imusil provides effective antiviral activity and safety in mild COVID-19 patients. Imusil ensures faster RT-PCR negativity and clinical improvement and ensures effective reduction of inflammatory markers such as CRP, D-dimer and interleukin 6.

Efficacy and Safety of Molnupiravir in Mild COVID-19 Patients in India.

Background At the peak of the coronavirus disease 2019 (COVID-19) pandemic, the need for an orally administered agent to prevent the progression ofacute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became increasingly evident, which was the impetus behind our investigations with molnupiravir. Molnupiravir has been shown to be effective in preventing hospitalizations and/or clinical complications in patients with mild-to-moderate COVID-19. In this study, we evaluate the efficacy and safety of molnupiravir in Indian patients with mild SARS-CoV-2 infection and at least one risk factor for disease progression (CTRI/2021/05/033739). Methodology This was a phase III, multicenter, randomized, open-label, controlled study conducted in Indian adults aged 18-60 years with mild SARS-CoV-2, reverse transcription polymerase chain reaction (RT-PCR)-positive within 48 hours of enrollment in the study, and within five days of first symptom onset. Enrolled patients were randomized to treatment arms in a 1:1 ratio to receive molnupiravir or placebo in addition to the standard of care (SoC) for SARS-CoV-2 infection. The SoC was in compliance with Government of India guidelines that were in force at the time. The primary endpoint was the rate of hospitalization up to day 14. Safety endpoints included incidence of adverse events (AEs). Results Eligible patients were randomized in a 1:1 ratio to receive molnupiravir in addition to SoC treatment (n = 608) or SoC alone (n = 610). In the molnupiravir group, nine (1.48%) patients required hospitalization versus 26 (4.26%) patients in the control group (risk difference = -2.78%; 95% CI = -4.65, -0.90; p = 0.0053). Overall, 45 (3.70%) patients reported 47 AEs during the study, most of which were mild and resolved completely. The molnupiravir group reported 30 AEs compared to 17 AEs in the control group. Headache and nausea were the two most commonly reported AEs. Conclusions The molnupiravir arm showed a lower rate of hospitalization and a shorter time for the improvement of clinical symptoms coupled with early RT-PCR negativity. Molnupiravir was well tolerated, and AEs were mild and rare. The addition of molnupiravir to standard therapy has the potential to prevent the progression of mild COVID-19 disease to the severe form.

Dynamics of Reverse Transcription-Polymerase Chain Reaction and Serologic Test Results in Children with SARS-CoV-2 Infection

ObjectivesTo determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion.Study designThe Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (<14 and ≥14 days after diagnosis) phase.ResultsIn total, 324 patients were included in the study. The median time to RT-PCR negativity was 17 days (IQR, 8-29 days), and 35% of patients remained positive more than 4 weeks after the first RT-PCR test. The probability of RT-PCR negativity did not differ across groups defined by sex, disease severity, immunosuppressive drugs, or clinical phenotype. Globally, 24% of children failed to seroconvert after infection. Seroconversion was associated with hospitalization, persistence of RT-PCR positivity, and days of fever.ConclusionsTime to RT-PCR negativity was long, regardless of the severity of symptoms or other patient features. This finding should be considered when interpreting RT-PCR results in a child with symptoms, especially those with mild symptoms. Seroprevalence and postimmunization studies should consider that 11 in 4 infected children fail to seroconvert.

A model based on CT radiomic features for predicting RT-PCR becoming negative in coronavirus disease 2019 (COVID-19) patients

BackgroundCoronavirus disease 2019 (COVID-19) has emerged as a global pandemic. According to the diagnosis and treatment guidelines of China, negative reverse transcription-polymerase chain reaction (RT-PCR) is the key criterion for discharging COVID-19 patients. However, repeated RT-PCR tests lead to medical waste and prolonged hospital stays for COVID-19 patients during the recovery period. Our purpose is to assess a model based on chest computed tomography (CT) radiomic features and clinical characteristics to predict RT-PCR negativity during clinical treatment.MethodsFrom February 10 to March 10, 2020, 203 mild COVID-19 patients in Fangcang Shelter Hospital were retrospectively included (training: n = 141; testing: n = 62), and clinical characteristics were collected. Lung abnormalities on chest CT images were segmented with a deep learning algorithm. CT quantitative features and radiomic features were automatically extracted. Clinical characteristics and CT quantitative features were compared between RT-PCR-negative and RT-PCR-positive groups. Univariate logistic regression and Spearman correlation analyses identified the strongest features associated with RT-PCR negativity, and a multivariate logistic regression model was established. The diagnostic performance was evaluated for both cohorts.ResultsThe RT-PCR-negative group had a longer time interval from symptom onset to CT exams than the RT-PCR-positive group (median 23 vs. 16 days, p < 0.001). There was no significant difference in the other clinical characteristics or CT quantitative features. In addition to the time interval from symptom onset to CT exams, nine CT radiomic features were selected for the model. ROC curve analysis revealed AUCs of 0.811 and 0.812 for differentiating the RT-PCR-negative group, with sensitivity/specificity of 0.765/0.625 and 0.784/0.600 in the training and testing datasets, respectively.ConclusionThe model combining CT radiomic features and clinical data helped predict RT-PCR negativity during clinical treatment, indicating the proper time for RT-PCR retesting.

Evidence about the Chest CT diagnostic performance in the pandemic of SARS-CoV-2 infection: A smooth takeoff and hard landing.

According to all guidelines, the unique criterion for the diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the viral nucleic acid test by reverse transcription polymerase chain reaction (RT-PCR). That should always guide the isolation decision and the management conduction [1]. SARS-CoV-2 related pneumonia may manifest after 2 to 4 days following the coronavirus infection. Typical computed tomography (CT) feature of coronavirus (COVID-19) lung disease is the bilateral , peripheric or diffuse and patchy ground-glass opacities(GGO) with consolidations. Several other signs such as crazy paving pattern , interstitial thickening, reversed-halo or microvascular embolisms are less likely described and may evoke COVID-19 pneumonia in an appropriate context. The chest CT could be initially normal. The GGO have tendency of quick evolution till the seventh day and stabilize later till the 20th day of the COVID-19 infection. Lung lesions in severe cases involve more lung segments with larger sized GGO. the interlobular septal thickening and consolidations are constant. The pleural effusion and pneumothorax were rarely described [2]. The lack of sensitivity, insufficient stability, and relatively long processing time of RT-PCR gave a considerable place for the chest CT in the daily practice of COVID-19 patients. Several reports found exciting the confrontation between the CT and the RT-PCR results. The sensitivity of CT features in highly pandemic areas could reach 97%. The earlier CT chest signs and the improvement of pulmonary lesions before RT-PCR negativity made some authors recommend the CT chest as diagnostic screening tool [3-5]. However, we still believe that the recommendation of the CT as a new diagnostic tool could not be based only on likelihood ratios and temporary concordance with the reference gold standard test. The respect of the basic epidemiologic principles is always mandatory to enhance the conclusion’s value. These recommendations were not born from blinded comparison with the refence test such in controlled randomized trials. To avoid time-lead bias many studies did not consider other potential bias especially the confusion and the selection. Moreover, the CT result did not influence the decision of proceeding to the reference test in all the previous reports. In this pandemic era, a chest CT examination will include not only additional cost for personal protective equipment (PPE) and sterilization but also more risk for the radiology department staff [6]. The chest CT could be used to select patients candidate for RT-PCR. Its value in the management and the follow up of pulmonary lesions cannot be overstated. It could play a role in clinical decision making when the gold standard test is not available in highly pandemic areas. Most of the radiology societies all over the world were not recommending the CT as diagnostic test especially in large scale screening. The few metaanalysis available have discordant conclusions about the topic. Upcoming evidence-based reports should contribute more to that [7,8].

Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID).

Since its outbreak in December 2019, a series of clinical trials on coronavirus disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) Handbook: Version 1.0, a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine (TCM), evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (www.chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019 novel coronavirus (2019-nCoV) reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.

Dynamics of Ebola RNA Persistence in Semen: A Report From the Postebogui Cohort in Guinea.

This study modeled the presence of Ebola virus RNA in the semen of male Ebola survivors participating in the Postebogui study in Guinea. The median time of reverse-transcription polymerase chain reaction negativity was 46.4 days after symptom onset (95% confidence interval, 11-82.6). The results emphasize the importance of the World Health Organization recommendations for survivors' management.