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Nasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)-and thus transmissibility. In October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration. Out of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2-38.4%) by RDT, 39.8% (36.6-43.0%) by saliva PCR, 40.1% (36.9-43.3%) by NP PCR, and 41.5% (38.3-44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3-33.3), 31.4% (28.4-34.5), 31.5% (28.5-34.6), and 31.6% (28.6-34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6-90.6%) for all positive patients, 94.5% (91.5-96.7%) for those with VL≥105 and 96.5% (93.6-98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4-96.9%), 86.1% (78.6-91.7%) and 84.1% (76.9-89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5-99.3%), 97.8% (92.1-99.7%) and 95.3% (89.4-98.5%) respectively. No patient with VL<104 was detected by RDT. Specificity of RDT was 100% (99.3-100%) compared to any PCR. RDT sensitivity was similar <4 days (87.8%, 83.5-91.3%) and ≥4 days (85.7%, 75.9-92.6%) after symptoms onset (p = 0.6). Sensitivity of saliva and NP PCR were 95.7% (93.1-97.5%) and 96.5% (94.1-98.1%), respectively, compared to the other PCR. RDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing. ClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).

Background New vaccines with broader protection against SARS-CoV-2 are needed to reduce the risk of immune escape and provide broad and long-lasting cellular immunity. The objectives of the naNO-COVID trial were to evaluate the safety and immunogenicity of a CD8 + T cell, gold nanoparticle-based, peptide COVID-19 vaccine. Methods A randomized, double-blind, vehicle-controlled, phase 1 trial in healthy adults to receive PepGNP-Covid19 or Vehicle-GNP, followed over 180 days, using a dose-escalation strategy. Results Twenty participants received PepGNP-Covid19 (low dose [LD] or high dose [HD], n  = 10 each) and six Vehicle-GNP (LD or HD, n  = 3 each). Vaccinations were safe. No serious adverse events were reported. Most of the adverse events were mild, two adverse events of special interest related to the product (fever and fatigue). Reactogenicity was similar overall between vaccine, comparator, and doses. Virus-specific humoral responses in LD PepGNP-Covid19 and Vehicle-GNP groups coincided with SARS-CoV-2 infections. PepGNP-Covid19 vaccination induced the modulation of Covid19-specific CD137 + CD69 + CD8 + , and an increase at day 35 particularly in central and effector memory T cells in LD group, and in late effector memory cells in HD group. Conclusions The favourable safety profile and cellular responses observed support further development of PepGNP-Covid19. Trial registration ClinicalTrials.gov, NCT05113862, approved 09.11.2021.

Background Safety of live vaccines in patients treated with immunosuppressive therapies is not well known, resulting in contradictory vaccination recommendations. We describe here the first case of vaccine-associated measles in a patient on natalizumab treatment. Case presentation A young female patient with relapsing-remitting multiple sclerosis on natalizumab treatment received the live attenuated measles, mumps, and rubella vaccine in preparation for a change in her treatment in favour of fingolimod, with established immunosuppressive qualities. Seven days after receiving the vaccine, our patient experienced diffuse muscle pain, fatigue, and thereafter developed a fever and then an erythematous maculopapular rash, compatible with vaccine associated measles. This was later confirmed by a positive measles RT-PCR throat swab. The patient’s symptoms resolved without any sequelae. Conclusion In this case report we review the immunosuppressive qualities of natalizumab and the evidence in favour and against live vaccines in patients on this treatment. Our findings reveal the insufficient understanding of the immunosuppressive effects of new immunomodulators, and thus of the safety of live vaccines in patients on such medications. While this case triggers precaution, there is insufficient evidence to conclude that natalizumab treatment could favor the onset of vaccine-associated measles.

Background Sub-optimal healthcare quality in low-resource settings is attributed in part to poor adherence to clinical guidelines. Clinical decision support systems (CDSS) help to integrate guideline-based algorithms into logical workflows and improve adherence to evidence-based recommendations, and hence quality of care. However, the process of translating paper-based guidelines into electronic algorithmic formats is often complex, inefficient, expensive, and error-prone due to reliance on advanced software development skills and clinical knowledge. Methods In response to these challenges, we developed open-source software called the Medical Algorithm Suite (medAL- suite ), consisting of four components, with a primary goal of increasing efficiency, accuracy, and transparency of CDSS creation by giving experienced clinicians, rather than software developers, greater control over the process. At the heart of the software suite is the medAL- creator that allows clinicians to design algorithms using a code-free drag-and-drop interface. Algorithms are subsequently automatically deployed in medAL-reader to service level clinicians in health facilities. CDSS implementers use medAL- data and medAL- hub to manage configuration, versioning, and deployment. Results Since its development, the medAL- suite has been used to digitalize complex primary care guidelines and deployed in large-scale clinical studies in Tanzania, Rwanda, Kenya, Senegal, and India, leading to notable outcomes such as the reduction of inappropriate antibiotic prescriptions and improvement in care quality. Over 300,000 pediatric outpatient consultations have been completed in Rwanda and Tanzania to date using the digital algorithm. Discussion The medAL- suite focused on democratized development, process-centric design, point-of-care utility, touch-screen interface, low cost, and low power consumption to contribute to sustainable digital systems in low-resource settings. Important future developments and adaptations as the software evolves should emphasize interoperability and scalability, primarily via integrating CDSS functionality into electronic medical records for a streamlined user experience that supports improved service quality at the point-of-care. Clinical trial number Not applicable.

The COVID-19 pandemic highlighted health inequities for vulnerable populations and the need for more equitable care and access to vaccination. This article described the implementation of a COVID-19 vaccination program for undocumented migrants in a regional academic center of general medicine and public health (Unisanté). The vaccination program’s specific components included: triple coordination between the health authorities, the regional center and community partners, a walk-in and free service, no health insurance required, qualified nursing and administrative staff with previous experience with vulnerable populations, translated information materials and interpreters, a guarantee of confidentiality and a widespread communication campaign within the communities. In total, 2’351 undocumented migrants from 97 nationalities received at least one dose of mRNA COVID-19 vaccine (Spikevax) and 2242 were considered fully vaccinated. Although it was hard to assess its global effectiveness, the program vaccinated a significant number of undocumented adult migrants in the Canton of Vaud. The difficulties linked to the pandemic context, the heavy workload for healthcare staff and the limited resources were overcome by strong collaborations between the different actors involved throughout the program. Targeted public health policies, such as vaccination programs for undocumented migrants, are essential to guarantee equitable care, especially in pandemic times.

Background Nasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)—and thus transmissibility. Methods In October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration. Results Out of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2–38.4%) by RDT, 39.8% (36.6–43.0%) by saliva PCR, 40.1% (36.9–43.3%) by NP PCR, and 41.5% (38.3–44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3–33.3), 31.4% (28.4–34.5), 31.5% (28.5–34.6), and 31.6% (28.6–34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6–90.6%) for all positive patients, 94.5% (91.5–96.7%) for those with VL≥105 and 96.5% (93.6–98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4–96.9%), 86.1% (78.6–91.7%) and 84.1% (76.9–89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5–99.3%), 97.8% (92.1–99.7%) and 95.3% (89.4–98.5%) respectively. No patient with VL<104 was detected by RDT. Specificity of RDT was 100% (99.3–100%) compared to any PCR. RDT sensitivity was similar <4 days (87.8%, 83.5–91.3%) and ≥4 days (85.7%, 75.9–92.6%) after symptoms onset (p = 0.6). Sensitivity of saliva and NP PCR were 95.7% (93.1–97.5%) and 96.5% (94.1–98.1%), respectively, compared to the other PCR. Conclusions RDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing. Trial registration ClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).