BackgroundNasopharyngeal antigen Rapid Diagnostic Tests (RDTs) and saliva RT-PCR have shown variable performance to detect SARS-CoV-2.MethodsIn October 2020, we conducted a prospective trial involving patients presenting at testing centers with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR.ResultsOut of 949 patients enrolled, 928 patients had all three tests. 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 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, sensitivities were 96.6% (90.5-99.3%), 97.8% (92.1-99.7%) and 95.3% (89.4-98.5%) respectively. Specificity of RDT was 100% (99.3-100%) compared to any PCR. RDT sensitivity was similar <4 days (87.8%) and ≥4 days (85.7%) after symptoms onset (p=0.6). Sensitivities 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.ConclusionsThe high performance of RDTs allows rapid identification of COVID cases with immediate isolation of the vast majority of contagious individuals. RDT could be a game changer in primary care practices, and even more so in resource-constrained settings. PCR on saliva can replace NP PCR.ClinicalTrial.gov Identifier: NCT04613310

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 ≥10 3 and ≥10 4 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 × 10 3 vs. 3.9 × 10 7 , 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 × 10 4 ; interquartile range 1.2 × 10 4 -5.2 × 10 5 ; vs. median 4.0 × 10 7 cp/mL; interquartile range, 8.6 × 10 5 -1 × 10 8 ; 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.

BackgroundSaliva RT-PCR is an attractive alternative for the detection of SARS-CoV-2 in adults with much less known in children.MethodsChildren and adolescents with symptoms suggestive of COVID-19 were prospectively enrolled in a comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR between November and December 2020. Detection rates and sensitivities of saliva and NP RT-PCR were compared. Participants with discordant NP and saliva RT-PCR results including viral load (VL) were also analyzed.ResultOut of 405 patients enrolled, 397 patients had two tests performed. Mean age was 12.7 years (range 1.2-17.9). Detection rates were 22.9% (95%CI 18.8-27.1%) by saliva RT-PCR, 25.4% (21.2-29.7%) by NP RT-PCR, and 26.7% (22.4-31.1%) by any test. The sensitivity of saliva was 85.2% (78.2-92.1%) when using NP as the gold standard; in contrast, when saliva was considered the gold standard, the sensitivity of NP was 94.5% (89.8-99.2%).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 to 7 days (p=0.096). The 15 patients who had an isolated positive NP RT-PCR were significantly younger (p=0.034), had a lower NP VL (median 5.6×103 vs 3.9×107, p<0.001), and were not able to drool saliva at the end of the sampling (p=0.002). VLs were significantly lower with saliva PCR than with NP RT-PCR (median 8.7 cp/ml x104; IQR 1.2×104-5.2×105; vs median 4.0×107cp/ml; IQR 8.6×105-1.x108; p<0.001).ConclusionSaliva PCR shows diagnostic performances close to NP RT-PCR for SARS-CoV2 detection in most symptomatic outpatient children and adolescents.

La nécessité de freiner la circulation du virus SARS-CoV-2 dans la communauté et diagnostiquer les personnes à risque de développer des complications implique de choisir le test approprié selon le contexte épidémiologique et clinique. Les tests antigéniques rapides, soit nasopharyngés, soit nasaux, ont l'avantage de mieux refléter la contagiosité que la PCR et de donner un résultat immédiat, raison pour laquelle ils sont utilisés en première intention pour le diagnostic et le dépistage communautaire. Un test rapide permet d'orienter tout de suite la prise en charge ambulatoire d'un•e patient•e et ne pas attribuer faussement un épisode aigu à une ancienne infection à SARS-CoV-2. La PCR, qu'elle soit nasopharyngée ou buccosalivaire, est utile pour la surveillance épidémiologique, notamment des nouveaux variants, ainsi que pour l'identification d'un Covid sévère dans la phase postinfectieuse. COVID-19 DiagnosisThe need to curb the circulation of SARS-CoV-2 virus in the community and to diagnose those at risk of developing complications implies that an appropriate test should be chosen according to the epidemiological and clinical context. Rapid antigen tests, either nasopharyngeal or nasal, have the advantage of reflecting contagiousness better than PCR and giving an immediate result, reason why they are used as first-line for community diagnosis and screening. A rapid test allows immediate management of out patients and does not falsely attribute the current acute episode to a previous SARS-CoV-2 infection. PCR, whether nasopharyngeal or buccosalivary, is useful for epidemiological surveillance, including that of new variants, as well as identification of severe COVID in the postinfectious phase.

BackgroundThe newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy or with a suspected allergic reaction after the first dose remains to be defined.MethodsIn this real-life study, we defined two cohorts of individuals: one pre-vaccination including 187 individuals with high-risk profiles for developing anaphylaxis and a second post-vaccination including 87 individuals with suspected allergic reactions after the COVID-19 mRNA vaccine. Upon negative skin test with an mRNA vaccine, a two-step (10–90%) vaccination protocol was performed. Positive skin tests were confirmed with the basophil activation test (BAT).ResultsAmong 604,267 doses of vaccine, 87 suspected allergic reactions (5 after the booster) were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% of the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced isolated asthmatic reactions during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism.ConclusionSensitization to SARS-CoV-2 mRNA vaccines can be detected with intradermal testing. Significantly more individuals were sensitized to mRNA vaccines in the post-vaccination cohort. A two-step 10–90%-vaccination protocol can be safely administered upon negative skin testing.