Antigen rapid tests, nasopharyngeal PCR and saliva PCR to detect SARS-CoV-2: A prospective comparative clinical trial.

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).

[Covid-19 crisis: testing and vaccination in the light of diminishing returns]. / Crise du Covid-19 : le testing et la vaccination à l'aune des rendements décroissants.

At the time of the assessment of the sanitary measures taken to fight the crisis, we have analysed the testing and vaccination following the grid well known in health economics: the law of diminishing returns. In the first phase, the returns are positive and increasing, the increase in benefits being faster than the increase in costs. In the second phase, returns are still positive but decreasing, with costs increasing faster than benefits. In the third and last phase, the returns become negative, with benefits decreasing despite an increase in costs. Both testing and vaccination, which were very beneficial at the beginning of the crisis, progressively followed a trajectory of diminishing returns with the extension of the measures to wider populations (asymptomatic or young persons), or for example with the emergence of the Omicron variant.

À l'heure du bilan des mesures sanitaires prises pour juguler la crise, nous avons soumis le testing et la vaccination à la grille d'analyse connue en économie de la santé : la loi des rendements décroissants. Dans une première phase, les rendements sont positifs et croissants, l'augmentation des bénéfices étant plus rapide que celle des coûts. Dans une deuxième phase, les rendements sont toujours positifs mais décroissants, l'augmentation des coûts étant plus rapide que celle des bénéfices. Dans une troisième et dernière phase, les rendements deviennent négatifs, les bénéfices diminuant malgré une augmentation des coûts. Tant le testing que la vaccination, très bénéfiques au début de la crise, ont progressivement suivi une trajectoire de rendements décroissants avec l'extension des mesures à des populations plus larges (asymptomatiques ou jeunes), ou par exemple avec l'apparition du variant Omicron.

Expert guidance for COVID-19 vaccine deployment in Switzerland: a Delphi process.

BACKGROUND AND AIM: Vaccines providing protection against COVID-19 are a core tool for ending the pandemic. Though international organisations created guidance in 2020 for vaccine deployment, this had to be adapted for each country's situation and values. We aimed to assist public health decision makers by identifying areas of consensus among Swiss experts for the deployment of one or more novel COVID-19 vaccines. METHODS: An electronic, modified Delphi process between September and November 2020. We recruited a convenience sample of experts working in Switzerland from a variety of specialities, who completed two anonymous questionnaires. They voted on clarification questions and guidance statements from 0 (complete disagreement) to 10 (complete agreement). Responses for guidance statements with a median ≥8 and a lower inter-quartile range bound ≥7 were considered as reaching consensus. RESULTS: Sixty-five experts accepted (66% response rate), with 47 completing the first questionnaire (72%), and 48 the second (74%). Statements reaching consensus included: in the first phase we should vaccinate front-line healthcare professionals and people ≥65 years with risk factors; widespread vaccination of children and adolescents should not be an early priority; and vaccines should be provided free of charge in the setting of national or cantonal vaccination campaigns. Statements not reaching consensus included: early vaccination of people living with someone with risk factors who are not themselves at risk; vaccination of people with previous confirmed or suspected COVID-19; and whether vaccination should be mandatory for individuals with certain activities, such as front-line healthcare professionals. CONCLUSIONS: Experts reached consensus on several statements that were available for decision-makers when making key decisions for COVID-19 vaccine deployment in Switzerland. Statements without consensus highlighted areas requiring expert and public dialogue. The modified Delphi process allowed us to rapidly synthesise views from a broad panel of experts on sensitive topics, and could be considered for a broad range of issues during public health crises.

[Pharmacovigilance - mRNA COVID-19 vaccines : current state of knowledge on their adverse effects]. / Pharmacovigilance - Vaccins à ARNm contre le Covid-19 : le point sur les effets indésirables.

The COVID-19 pandemic has stimulated the rapid development and large-scale use of technologically innovative vaccines, such as the mRNA vaccines Spikevax (Moderna) and Comirnaty (Pfizer-BioNTech). This unprecedented deployment has challenged pharmacovigilance, requiring combined skills in safety monitoring, prompt data analysis and continuous dissemination of knowledge. Main recognised adverse events of these vaccines are moderate and transient, linked to their significant reactogenicity. Active post-marketing surveillance has identified rare adverse events such as myopericarditis and a variety of skin reactions. A number of potential rare adverse events are being evaluated and could be retained at the individual level, but do not question the overall safety of these vaccines.

La pandémie de Covid-19 a conduit au développement rapide de vaccins à la technologie innovante, utilisés à large échelle, dont les vaccins à ARNm Spikevax (Moderna) et Comirnaty (Pfizer-BioNTech). Ce déploiement sans précédent défie la pharmacovigilance, nécessitant d'allier un suivi attentif de la sécurité, une analyse rapide des données et une diffusion continue des connaissances. Les principaux effets indésirables reconnus pour ces vaccins sont modérés et transitoires, liés à leur importante réactogénicité. Une pharmacovigilance active a permis d'identifier des effets indésirables rares, tels que des myopéricardites et diverses réactions cutanées. Un certain nombre d'effets indésirables rares potentiels sont en cours d'évaluation et pourraient être retenus à l'échelle individuelle, mais ne remettent pas en cause la sécurité vaccinale globale.

Which strategy for using medical and community masks? A prospective analysis of their environmental impact.

INTRODUCTION: The use of personal protective equipment, especially medical masks, increased dramatically during the COVID-19 crisis. Medical masks are made of synthetic materials, mainly polypropylene, and a majority of them are produced in China and imported to the European market. The urgency of the need has so far prevailed over environmental considerations. OBJECTIVE: Assess the environmental impact of different strategies for the use of face mask. METHOD: A prospective analysis was conducted to assess the environmental impact of different strategies for the use of medical and community masks. Eight scenarios, differentiating the typologies of masks and the modes of reuse are compared using three environmental impact indicators: the Global Warming Potential (GWP100), the ecological scarcity (UBP method, from German 'Umweltbelastungpunkte') and the plastic leakage (PL). This study attempts to provide clear recommendations that consider both the environmental impact and the protective effectiveness of face masks used in the community. RESULTS: The environmental impact of single-use masks is the most unfavourable, with a GWP of 0.4-1.3 kg CO2 eq., depending on the transport scenario, and a PL of 1.8 g, for a 1 month protection against COVID-19. The use of home-made cotton masks and prolonged use of medical masks through wait-and-reuse are the scenarios with the lowest impact. CONCLUSION: The use of medical masks with a wait and reuse strategy seems to be the most appropriate when considering both environmental impact and effectiveness. Our results also highlight the need to develop procedures and the legal/operational framework to extend the use of protective equipment during a pandemic.

Aetiology of fever in returning travellers and migrants: a systematic review and meta-analysis.

BACKGROUND: Numerous publications focus on fever in returning travellers, but there is no known systematic review considering all diseases, or all tropical diseases causing fever. Such a review is necessary in order to develop appropriate practice guidelines. OBJECTIVES: Primary objectives of this review were (i) to determine the aetiology of fever in travellers/migrants returning from (sub) tropical countries as well as the proportion of patients with specific diagnoses, and (ii) to assess the predictors for specific tropical diseases. METHOD: Embase, MEDLINE and Cochrane Library were searched with terms combining fever and travel/migrants. All studies focusing on causes of fever in returning travellers and/or clinical and laboratory predictors of tropical diseases were included. Meta-analyses were performed on frequencies of etiological diagnoses. RESULTS: 10 064 studies were identified; 541 underwent full-text review; 30 met criteria for data extraction. Tropical infections accounted for 33% of fever diagnoses, with malaria causing 22%, dengue 5% and enteric fever 2%. Non-tropical infections accounted for 36% of febrile cases, with acute gastroenteritis causing 14% and respiratory tract infections 13%. Positive likelihood ratios demonstrated that splenomegaly, thrombocytopenia and hyperbilirubinemia were respectively 5-14, 3-11 and 5-7 times more likely in malaria than non-malaria patients. High variability of results between studies reflects heterogeneity in study design, regions visited, participants' characteristics, setting, laboratory investigations performed and diseases included. CONCLUSION: Malaria accounted for one-fifth of febrile cases, highlighting the importance of rapid malaria testing in febrile returning travellers, followed by other rapid tests for common tropical diseases. High variability between studies highlights the need to harmonize study designs and to promote multi-centre studies investigating predictors of diseases, including of lower incidence, which may help to develop evidence-based guidelines. The use of clinical decision support algorithms by health workers which incorporate clinical predictors, could help standardize studies as well as improve quality of recommendations.

Performance of RT-PCR on Saliva Specimens Compared With Nasopharyngeal Swabs for the Detection of SARS-CoV-2 in Children: A Prospective Comparative Clinical Trial.

BACKGROUND: Saliva reverse transcriptase-Polymerase chain reaction (RT-PCR) is an attractive alternative for the detection of severe acute respiratory syndrome coronavirus 2 in adults with less known in children. METHODS: Children with coronavirus disease 2019 symptoms were prospectively enrolled in a 1-month comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR. Detection rates and sensitivities of saliva and NP RT-PCR were compared as well as discordant NP and saliva RT-PCR findings including viral loads (VLs). RESULTS: Of 405 patients enrolled, 397 patients had 2 tests performed. Mean age was 12.7 years (range, 1.2-17.9). Sensitivity of saliva was 85.2% (95% confidence interval: 78.2%-92.1%) when using NP as the standard; sensitivity of NP was 94.5% (89.8%-99.2%) when saliva was considered as the standard. For a NP RT-PCR VL threshold of ≥103 and ≥104 copies/mL, sensitivity of saliva increases to 88.7% and 95.2%, respectively. Sensitivity of saliva and NP swabs was, respectively, 89.5% and 95.3% in patient with symptoms less than 4 days (P = 0.249) and 70.0% and 95.0% in those with symptoms ≥4-7 days (P = 0.096). The 15 patients who had an isolated positive NP RT-PCR were younger (P = 0.034), had lower NP VL (median 5.6 × 103 vs. 3.9 × 107, P < 0.001), and could not drool saliva at the end of the sampling (P = 0.002). VLs were lower with saliva than with NP RT-PCR (median 8.7 cp/mL × 104; interquartile range 1.2 × 104-5.2 × 105; vs. median 4.0 × 107 cp/mL; interquartile range, 8.6 × 105-1 × 108; P < 0.001). CONCLUSIONS: While RT-PCR testing on saliva performed more poorly in younger children and likely after longer duration of symptoms, saliva remains an attractive alternative to NP swabs in children.

Performance du frottis nasopharyngé-PCR pour le diagnostic du Covid-19 - Recommandations pratiques sur la base des premières données scientifiques

The Covid-19 pandemic imposes new diagnostic strategies in order to optimize the medical care of our patients. The current biblio-graphy, although of low quality, shows a sensitivity of 56 to 83 % for the Covid-19 PCR. Even though one negative test can exclude a Covid-19 in the majority of cases, the NPV (Negative Predictive Value) decreases with increasing prevalence (pre-test probability). This finding suggests the need for strict auto-isolation of patients until the resolution of their symptoms. For patients that present with typical symptoms, who have a presumed Covid-19 prevalence of -40-50 %, a negative test should be interpreted with caution and a repeat test may be needed.