Adapting international clinical trials during COVID-19 and beyond.

BACKGROUND: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration. THE NEW WORKING MODEL: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for good clinical practice, the development of a library of study-specific training videos, and interactive virtual training sessions, including practical laboratory-focused training sessions. We also report changes from in-person monitoring to remote monitoring as well as the development of a more localized network of clinical trial monitors to support hybrid models with in-person and remote monitoring depending on identified risks at each site. We established a virtual network across different trial and study sites with the objective to further build capacity for good clinical practice-compliant antimalarial trials and foster cross-country and cross-study site collaboration. CONCLUSION: The forced adaptation of these new strategies has come with advantages that we did not envisage initially. This includes improved, more frequent engagement through the established network with opportunities for increased south-to-south support and a substantially reduced carbon footprint and budget savings. Our new approach is challenging for study sites with limited prior experience but this can be overcome with hybrid models. Capacity building for laboratory-based work remains difficult using a virtual environment. The changes to our working model are likely to last, even after the end of the pandemic, providing a more sustainable and equitable approach to our research.

Direct Nasal Swab for Rapid Test and Saliva as an Alternative Biological Sample for RT-PCR in COVID-19 Diagnosis.

Accurate and early diagnoses are prerequisites for prompt treatment. For coronavirus disease 2019 (COVID-19), it is even more crucial. Currently, choice of methods include rapid diagnostic tests and reverse transcription polymerase chain reaction (RT-PCR) using samples mostly of respiratory origin and sometimes saliva. We evaluated two rapid diagnostic tests with three specimen types using viral transport medium (VTM) containing naso-oropharyngeal (NOP) swabs, direct nasal and direct nasopharyngeal (NP) samples from 428 prospective patients. We also performed RT-PCR for 428 NOP VTM and 316 saliva samples to compare results. The sensitivity of the SD Biosensor Standard Q COVID-19 antigen (Ag) test kit drastically raised from an average of 65.55% (NOP VTM) to 85.25% (direct nasal samples), while RT-PCR was the gold standard. For the CareStart kit, the sensitivity was almost similar for direct NP swabs; the average was 84.57%. The specificities were ≥95% for both SD Biosensor Standard Q and CareStart COVID-19 Ag tests in all platforms. The kits were also able to detect patients with different variants as well. Alternatively, RT-PCR results from saliva and NOP VTM samples showed high sensitivities of 96.45% and 95.48% with respect to each other as standard. The overall results demonstrated high performance of the rapid tests, indicating the suitability for regular surveillance at clinical facilities when using direct nasal or direct NP samples rather than NOP VTM. Additionally, the analysis also signifies not showed that RT-PCR of saliva can be used as an choice of method to RT-PCR of NOP VTM, providing an easier, non-invasive sample collection method. IMPORTANCE There are several methods for the diagnosis of coronavirus disease 2019 (COVID-19), and the choice of methods depends mostly on the resources and level of sensitivity required by the user and health care providers. Still, reverse transcription polymerase chain reaction (RT-PCR) has been chosen as the best method using direct naso-oropharyngeal swabs. There are also other methods of fast detection, such as rapid diagnostic tests (RDTs), which offer result within 15 to 20 min and have become quite popular for self-testing and in the clinical setting. The major drawback of the currently used RT-PCR method is compliance, as it may cause irritation, and patients often refuse to test in such a way. RDTs, although inexpensive, suffer from low sensitivity due to technical issues. In this article, we propose saliva as a noninvasive source for RT-PCR samples and evaluate various specimen types at different times after infection for the best possible output from COVID-19 rapid tests.

Health hazards related to using masks and/or personal protective equipment among physicians working in public hospitals in Dhaka: A cross-sectional study.

BACKGROUND: Wearing masks or personal protective equipment (PPE) has become an integral part of the occupational life of physicians due to the coronavirus disease 2019 (COVID-19) pandemic. Most physicians have been developing various health hazards related to the use of different protective gears. This study aimed to determine the burden and spectrum of various health hazards associated with using masks or PPE and their associated risk factors. METHODS: This cross-sectional survey was conducted in Dhaka Medical College from March 01-May 30, 2021, among physicians from different public hospitals in Dhaka, Bangladesh. We analyzed the responses of 506 physicians who completed case record forms through Google forms or hard copies. FINDINGS: The mean (SD) age of the respondents was 35.4 [7.7], and 69.4% were men. Approximately 40% were using full PPE, and 55% were using N-95 masks. A total of 489 (96.6%) patients experienced at least one health hazard. The reported severe health hazards were syncope, severe dyspnea, severe chest pain, and anaphylaxis. Headache, dizziness, mood irritation, chest pain, excessive sweating, panic attack, and permanent facial disfigurement were the minor health hazards reported. Extended periods of work in the COVID-19-unit, reuse of masks, diabetes, obesity, and mental stress were risk factors for dyspnea. The risk factors for headaches were female sex, diabetes, and previous primary headaches. Furthermore, female sex and reusing masks for an extended period (> 6 h) were risk factors for facial disfigurement. The risk factors for excessive sweating were female sex and additional evening office practice for an extended period. CONCLUSIONS: Healthcare workers experienced several occupational hazards after using masks and PPE. Therefore, an appropriate policy is required to reduce such risks.

Clinical Evaluation of a New Antigen-Based COVID-19 Rapid Diagnostic Test from Symptomatic Patients.

Accurate diagnosis at the right moment is the prerequisite for treatment of any disease. Failure to correctly diagnose a disease can result in highly detrimental effects, unmistakably a crucial factor during the COVID-19 pandemic. RT-PCR is the gold standard for COVID-19 detection while there are other test procedures available, such as LAMP, X-Ray, and ELISA. However, these tests are expensive, require sophisticated equipment and a highly trained workforce, and multiple hours or even days are often required to obtain the test results. A rapid and cheap detection system can thus render a solution to the screening system on a larger scale and be added as an aid to the current detection processes. Recently, some rapid antigen-based COVID-19 tests devices have been developed and commercialized. In this study, we evaluated the clinical performance of a new rapid detection device (OnSite® COVID-19 Ag Rapid Test by CTK Biotech Inc., Poway, CA, USA) on COVID-19 symptomatic patients (n = 380). The overall sensitivity and specificity were 91.0% (95% CI: 84.8-95.3%) and 99.2% (95% CI: 97.1-99.9), against gold standard RT-PCR. The kit was capable of detecting patients even after 06 days of onset of symptoms and the sensitivity can be maximized to 98% in samples with an average RT-PCR Ct ≤ 26.48, demonstrating a high potential of the kit for clinical diagnosis of symptomatic patients in healthcare facilities.

A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness.

Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.