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).

[Parasite screening for immunosuppressed traveler]. / Dépistage parasitaire chez le voyageur immunosupprimé.

Before starting immunosuppressive therapy, it is important to screen for latent tuberculosis and, in case of particular exposures (e.g. travel, origin,…), for parasitosis such as amoebiasis, echinococcosis, strongyloidiasis and American trypanosomiasis. The Division of Tropical and Humanitarian Medicine of the Geneva University Hospitals has developed an algorithm to identify which screening is recommended according to exposure. Analysis of this practice shows that the most frequently detected latent disease is tuberculosis, followed by strongyloidiasis. For the latter, as the sensitivity of the serological test is reduced due to immunosuppression, the algorithm combine antibody testing with parasitological (Baermann and culture) and molecular (PCR) stool testing.

Avant le début d'un traitement immunosuppresseur, il est important d'effectuer un dépistage pour la tuberculose latente et, en cas d'expositions particulières (par exemple, voyage, origine…), de parasitoses comme l'amibiase, l'échinococcose, la strongyloïdiase et la trypanosomiase américaine. Le service de médecine tropicale et humanitaire des HUG a développé un algorithme pour identifier quel dépistage est recommandé en fonction de l'exposition. L'analyse de cette pratique montre que la maladie latente la plus fréquemment détectée est la tuberculose, suivie de la strongyloïdiase. Pour cette dernière, la sensibilité du test sérologique étant amoindrie à cause de l'immunosuppression, l'algorithme combine la recherche d'anticorps avec un test parasitologique (Baermann et culture) et moléculaire (PCR) des selles.

A Practical Approach to Screening for Strongyloides stercoralis.

Strongyloides stercoralis, causative agent of a neglected tropical disease, is a soil-transmitted helminth which may cause lifelong persisting infection due to continuous autoinfection. In the case of immunosuppression, life-threatening hyperinfection and disseminated strongyloidiasis can develop. We propose a pragmatic screening algorithm for latent strongyloidiasis based on epidemiologic exposure and immunosuppression status that can be applied for any kind of immunosuppressive therapy. The algorithm allows the diagnosis of latent strongyloidiasis with optimal accuracy in a well-equipped setting, while for endemic settings where the complete testing array is unavailable, an empiric treatment is generally recommended. Accurate diagnosis and extensive empiric treatment will both contribute to decreasing the current neglect of strongyloidiasis.

Screening for Parasitic Infection and Tuberculosis in Immunosuppressed and Pre-Immunosuppressed Patients: An Observational Study.

Reactivation of latent tuberculosis infection (LTBI) or latent parasitic infection (LPI) during drug-induced immunosuppression can have serious consequences. The Division of tropical and humanitarian medicine of the Geneva University Hospitals runs a specific consultation for parasitic screening of immunosuppressed or pre-immunosuppressed patients. We sought to determine the seroprevalence of LTBI and LPI in such patients and explore its relationship with country of origin or previous travel in a retrospective, single-centre observational study from 2016 to 2019. Demographic data, travel history, ongoing treatments and results of the parasitological (Strongyloides stercoralis, Trypanosoma cruzi, Echinococcus multilocularis, Entamoeba histolytica and Leishmania spp.) and TB screening were collected to calculate LPI or LTBI prevalence. Risk factors for LTBI and strongyloidiasis were analysed using Poisson regression with robust variance. Among 406 eligible patients, 24/353 (6.8%) had LTBI, 8/368 (2.2%) were positive for Strongyloides stercoralis infection, 1/32 (3.1%) was positive for Entamoeba histolytica and 1/299 (0.3%) was positive for Leishmaniasis. No cases of Trypanosoma cruzi (0/274) or Echinococcus multilocularis (0/56) infection were detected. Previous travel to or originating from high-prevalence countries was a risk factor for LTBI (PR = 3.4, CI 95%: 1.4-8.2 and 4.0, CI 95%: 1.8-8.9, respectively). The prevalence of serological Strongyloidiasis in immunosuppressed patients is lower in comparison to those without immunosuppression (PR = 0.1, CI 95%: 0.01-0.8). In conclusion, screening before immunosuppression needs to be individualized, and LTBI and LPI need to be ruled out in patients who originate from or have travelled to high-prevalence countries. The sensitivity of strongyloidiasis serology is reduced following immunosuppression, so an algorithm combining different tests or presumptive treatment should be considered.

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.

[COVID-19 Diagnosis]. / Diagnostic du Covid-19 en milieu ambulatoire.

The 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 outpatients 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 post-infectious phase.

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.

[SARS-CoV-2 screening in travelers: what approach to assess transmission risk ?] / Dépistage de l'infection à SARS-CoV-2 chez les voyageurs - Quelle approche pour évaluer le risque de transmis.

Before a trip, a screening for SARS-CoV-2 infection by RT-PCR is often required and raises the problem of detection of residual viral RNA at distance from the acute infection (post-Covid). At the University Hospital of Geneva, we developed an expertise to distinguish acute from post-Covid infections. Between October and December 2020, 30% of the people tested positive were able to travel because the result corresponded to post-Covid and 65% were put in isolation because of an acute infection with a risk of transmission. To overcome the detection of residual viral RNA by RT-PCR, a rapid antigenic test would be an interesting and less expensive alternative. It could also be performed a few hours before departure.

Avant un voyage, un dépistage de l'infection à SARS-CoV-2 par RT-PCR est souvent exigé et soulève le problème de la détection d'ARN viral résiduel chez une personne à distance de l'infection aiguë (post-Covid). Aux HUG, nous avons développé une expertise permettant de distinguer les infections aiguës des post-Covid. Entre octobre et décembre 2020, 30 % des personnes dépistées positives ont pu voyager car le résultat correspondait à des post-Covid et 65 % ont été mises en isolement en raison d'une infection aiguë avec risque de transmission. Pour pallier la détection de l'ARN viral résiduel par la RT-PCR, un test rapide antigénique serait une alternative intéressante et moins chère. Il pourrait également être effectué juste avant le départ.

Rabies vaccination and multiple sclerosis relapse: A retrospective cohort study.

BACKGROUND: No studies assessing rabies vaccine (RV) tolerability in persons with multiple sclerosis (MS) have been conducted. Given the lack of safety data, RV is recommended essentially only for post-exposure prophylaxis, which is difficult to administer effectively in many rabies-endemic countries. We sought to determine whether RV administration as pre-exposure prophylaxis was associated with MS relapse. METHODS: This retrospective cohort study compared the clinical courses of MS patients in the year before and after rabies vaccination. The year before vaccination was defined as the pre-exposure risk period, the three months thereafter as the exposure-risk period, and the following nine months as the post-risk period. All adult MS patients immunized with RV between 2014 and 2018 and with available medical records in the two-year window were included. The primary outcome was the incidence of symptomatic MS relapse in the exposure-risk period versus the pre-exposure period. RESULTS: Fifty-five patients received at least one dose of RV. Most (38/55, 69%) were female; mean age was 38.5 years (SD ±9.2). While 21 (38%) patients experienced 24 relapses in the year before vaccination, only three (5%) experienced one relapse each in the post-vaccination exposure-risk period; three others (5%) experienced a total of four relapses in the subsequent post-risk period. The annualized relapse rates in the pre-exposure, exposure-risk, and post-risk periods were 0.44, 0.22, and 0.10, respectively (rate ratio for exposure-risk to pre-exposure periods, 0.509 [95% CI 0.098-1.677]). CONCLUSIONS: In this cohort, rabies vaccination was not associated with clinical MS relapse. Larger, prospective studies are needed to confirm these results.

Risk of MS relapse after yellow fever vaccination: A self-controlled case series.

OBJECTIVE: To determine whether live-attenuated yellow fever vaccine (YFV) was associated with MS relapse, we evaluated the clinical courses of 23 patients in the year before and the year after immunization at the university hospital of Geneva, Switzerland. METHODS: This self-controlled retrospective cohort included adult patients with MS receiving YFV between 2014 and 2018 and defined the year before vaccination, the 3 months thereafter, and the 9 months following as the pre-exposure (PEP), exposure-risk (ERP), and postrisk (PRP) periods, respectively. The primary outcome was the relative incidence of relapse in the ERP vs the PEP. Secondary end points included the presence of new T2-weighted (T2) or T1-weighted gadolinium-positive (T1Gd+) MRI lesions. RESULTS: Of 23 patients with MS receiving YFV (20 relapsing MS and 3 primary progressive MS), 17 (74%) were women; mean age was 34 years (SD ±10); and 10 of 23 (40%) were treated with disease-modifying therapies (DMTs). Although 9 patients experienced 12 relapses in the PEP, only one experienced a relapse in the ERP; 3 other patients experienced one relapse each in the PRP. None of the 8 patients receiving natalizumab at the time of vaccination experienced relapse thereafter. In the PEP, ERP, and PRP, 18, 2, and 9 patients had new brain and/or spinal cord lesions on T2 or T1Gd + MRI, respectively. CONCLUSIONS: In this cohort, YF vaccination was associated with neither an increase in MS relapse nor emergence of brain and/or spinal lesions. Further studies are warranted to confirm these findings. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for persons with MS, YFV may not increase relapse risk.

First reported case of Rothia dentocariosa spondylodiscitis in an immunocompetent patient.

Rothia dentocariosa is part of the normal human oropharyngeal microflora and is frequently associated with dental caries and periodontal disease. Invasive disease has been described essentially in immunocompromised hosts and/or patients with underlying conditions as predisposing factors. We present a case of an otherwise healthy 46-years old male with spondylodiscitis caused by this pathogen. Treatment with ceftriaxone and rifampin was successful. To our knowledge, this is the first R. dentocariosa spondylodiscitis reported in an immunocompetent patient, and the second one in the literature overall.