Factors influencing the performance of rapid SARS-CoV-2 antigen tests under field condition.

BACKGROUND: Globally, real-time reverse transcription-polymerase chain reaction (rRT-PCR) is the reference detection technique for SARS-CoV-2, which is expensive, time consuming, and requires trained laboratory personnel. Thus, a cost-effective, rapid antigen test is urgently needed. This study evaluated the performance of the rapid antigen tests (RATs) for SARS-CoV-2 compared with rRT-PCR, considering different influencing factors. METHODS: We enrolled a total of 214 symptomatic individuals with known COVID-19 status using rRT-PCR. We collected and tested paired nasopharyngeal (NP) and nasal swab (NS) specimens (collected from same individual) using rRT-PCR and RATs (InTec and SD Biosensor). We assessed the performance of RATs considering specimen types, viral load, the onset of symptoms, and presenting symptoms. RESULTS: We included 214 paired specimens (112 NP and 100 NS SARS-CoV-2 rRT-PCR positive) to the analysis. For NP specimens, the average sensitivity, specificity, and accuracy of the RATs were 87.5%, 98.6%, and 92.8%, respectively, when compared with rRT-PCR. While for NS, the overall kit performance was slightly lower than that of NP (sensitivity 79.0%, specificity 96.1%, and accuracy 88.3%). We observed a progressive decline in the performance of RATs with increased Ct values (decreased viral load). Moreover, the RAT sensitivity using NP specimens decreased over the time of the onset of symptoms. CONCLUSION: The RATs showed strong performance under field conditions and fulfilled the minimum performance limit for rapid antigen detection kits recommended by World Health Organization. The best performance of the RATs can be achieved within the first week of the onset of symptoms with high viral load.

Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: an open-label randomized clinical trial.

Povidone-iodine (PVP-I) is a time-tested antiseptic agent with excellent virucidal (99.99%) properties. Repurposing it against coronavirus disease-19 (COVID-19) is a relatively newer concept and has been sparsely tested in vivo. The most common route of entry of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the nasopharynx. Averting colonization of the virus could be one of the best options to reduce the incidence of infection. PVP-I gargle and mouthwash were found to be effective in vitro rapid inactivation against SARS-CoV-2 on a smaller scale (Hassandarvish et al. in BDJ 1-4, 2020, Pelletier et al. in ENTJ 1-5, 2020). However, efficacy in humans is lacking. To assess the virucidal effect of PVP-I against SARS-CoV-2 located in the nasopharynx was the objective of this parallel armed randomized clinical trial. We screened all RT-PCR-confirmed COVID-19 cases aged 18 years and above with symptoms. Written informed consent was obtained before randomization. Nasopharyngeal clearance of SARS-CoV-2 was tested after single time application of PVP-I nasal irrigation (NI) at diluted concentrations of .4%, .5% and .6% and PVP-I nasal spray (NS) at diluted concentrations of .5% and .6%. All groups were compared to the corresponding controls (distilled water). The primary outcome was viral clearance in a repeat RT-PCR (qualitative), and the secondary outcome was the number of adverse events. Final data analysis was performed using the statistical software SPSS (Version 20). A total of 189 confirmed COVID-19 cases were randomized into seven groups: 27 patients in each group. Of all, 159 (84.1%) were male, and 30 (15.9%) were female. We observed a statistically significant proportion of nasopharyngeal clearance with all strengths of PVP-I NI and PVP-I NS compared to the corresponding controls. Additionally, 0.5% NI was significantly better than 0.5% NS for viral clearance (p = 0.018) and had the highest nasopharyngeal clearance among all strengths (n = 25, 92.6%). 0.6% NS is better than CNS and 0.5%NS in viral clearance. The only adverse event was nasal irritation recorded in two patients each in the 0.4% and 0.6% PVP-I NI groups (Tables 1 and 2). PVP-I NI and NS are proved as effective virucidal agent against SARS-CoV-2 in human body. Our recommendation is to use PVP-I in naopharynx (as well as oropharynx) to prevent COVID-19.

Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: A structured summary of a study protocol for an open-label randomized clinical trial.

OBJECTIVE: General: To assess the virucidal efficacy of povidone iodine (PVP-I) on COVID-19 virus located in the nasopharynx Specific: i. To evaluate the efficacy of povidone iodine (PVP-I) to removeCOVID-19 virus located in the nasopharynx ii. To assess the adverse events of PVP-I TRIAL DESIGN: This is a single-center, open-label randomized clinical trial with a 7-arm parallel-group design. PARTICIPANTS: The study will be conducted at Dhaka Medical College Hospital, Dhaka, Bangladesh. INCLUSION CRITERIA: All RT-PCR-confirmed COVID-19 cases aged between 15-90 years with symptoms for the past 4 days will be screened. Those who give informed consent, are willing to participate, and accept being randomized to any assigned group will also be considered for final inclusion. EXCLUSION CRITERIA: Patients with known sensitivity to PVP-I aqueous antiseptic solution or any of its listed excipients or previously diagnosed thyroid disease or who had a history of chronic renal failure: stage ≥3 by estimated glomerular filtration rate (eGFR) Modification of Diet in Renal Disease (MDRD) or had acute renal failure (KDIGO ≥stage 2: creatinine ≥2 times from the baseline) or patients who required invasive or noninvasive ventilation or planned within the next 6 hours were considered for exclusion. Moreover, lactating or pregnant women will also be restricted to include here. INTERVENTION AND COMPARATOR: This RCT consist of seven arms: Arm-1 (intervention group): will receive povidone iodine (PVP-I) nasal irrigation (NI) at a concentration of 0.4% Arm-2 (intervention group): will receive PVP-I nasal irrigation at a concentration of 0.5% Arm-3 (intervention group): will receive PVP-I nasal irrigation at a concentration of 0.6%. Arm-4 (intervention group): will receive PVP-I nasal spray (NS) at a concentration of 0.5%. Arm-5 (intervention group): will receive PVP-I nasal spray at a concentration of 0.6%. Arm-6 (placebo comparator group): will receive distilled water through NI Arm-7 (Placebo comparator group): will receive distilled water through NS The intervention arms will be compared to the placebo comparator arms. Other supportive and routine care will be the same in both groups. MAIN OUTCOMES: The primary outcome is the proportion of cases that remain COVID-19 positive following the intervention. It will be assessed from 1 minutes to 15 minutes after the intervention. Any occurrence of adverse effects following the intervention will be documented as a secondary outcome. RANDOMIZATION: The assignment to the study (intervention) or control (comparator) 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 consenting procedures. BLINDING (MASKING): This is an open-label clinical trial, and no blinding or masking will be performed. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 189 confirmed cases of COVID-19 will be randomized into seven groups. In each arm, a total of 27 participants will be recruited. TRIAL STATUS: The current trial protocol is Version 1.5 from September 10, 2020. Recruitment began September 30, 2020 and is anticipated to be completed, including data analysis by February 28, 2021. TRIAL REGISTRATION: The trial protocol has been registered in the ClinicalTrials.gov on September 16, 2020. NCT Identifier number: NCT04549376 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in 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.

Emergence of Mobile Colistin Resistance (mcr-8) in a Highly Successful Klebsiella pneumoniae Sequence Type 15 Clone from Clinical Infections in Bangladesh.

The emergence of mobilized colistin resistance genes (mcr) has become a serious concern in clinical practice, compromising treatment options for life-threatening infections. In this study, colistin-resistant Klebsiella pneumoniae harboring mcr-8.1 was recovered from infected patients in the largest public hospital of Bangladesh, with a prevalence of 0.3% (3/1,097). We found mcr-8.1 in an identical highly stable multidrug-resistant IncFIB(pQil) plasmid of ∼113 kb, which belonged to an epidemiologically successful K. pneumoniae clone, ST15. The resistance mechanism was proven to be horizontally transferable, which incurred a fitness cost to the host. The core genome phylogeny suggested the clonal spread of mcr-8.1 in a Bangladeshi hospital. Core genome single-nucleotide polymorphisms among the mcr-8.1-positive K. pneumoniae isolates ranged from 23 to 110. It has been hypothesized that mcr-8.1 was inserted into IncFIB(pQil) with preexisting resistance loci, blaTEM-1b and blaCTX-M-15, by IS903B Coincidentally, all resistance determinants in the plasmid [mcr-8.1, ampC, sul2, 1d-APH(6), APH(3'')-Ib, blaTEM-1b, blaCTX-M-15] were bracketed by IS903B, demonstrating the possibility of intra- and interspecies and intra- and intergenus transposition of entire resistance loci. This is the first report of an mcr-like mechanism from human infections in Bangladesh. However, given the acquisition of mcr-8.1 by a sable conjugative plasmid in a successful high-risk clone of K. pneumoniae ST15, there is a serious risk of dissemination of mcr-8.1 in Bangladesh from 2017 onwards.IMPORTANCE There is a marked paucity in our understanding of the epidemiology of colistin-resistant bacterial pathogens in South Asia. A report by Davies and Walsh (Lancet Infect Dis 18:256-257, https://doi.org/10.1016/S1473-3099(18)30072-0, 2018) suggests the export of colistin from China to India, Vietnam, and South Korea in 2016 was approximately 1,000 tons and mainly used as a poultry feed additive. A few reports forecast that the prevalence of mcr in humans and livestock will increase in South Asia. Given the high prevalence of blaCTX-M-15 and blaNDM in India, Bangladesh, and Pakistan, colistin has become the invariable option for the management of serious infections, leading to the emergence of mcr-like mechanisms in South Asia. Systematic scrutiny of the prevalence and transmission of mcr variants in South Asia is vital to understanding the drivers of mcr genes and to initiate interventions to overcome colistin resistance.