Unmasking Bartonella henselae infection in the shadows of long COVID thanks to clinical metagenomics.

The diagnosis of long COVID often relies on symptoms post-COVID-19, occasionally lacking biological evidence. This case study illustrates how investigating long COVID uncovered an underlying bartonellosis through clinical metagenomics. Following mild COVID-19, a 26-year-old woman experienced persistent symptoms during 5 months, including axillary adenopathy. Pathological examination, 16 S rRNA PCR, and clinical metagenomic analysis were done on an adenopathy biopsy. The latter revealed Bartonella henselae DNA and RNA. Treatment with clarithromycin improved symptoms. This case underscores the relevance of clinical metagenomics in diagnosing hidden infections. Post-COVID symptoms warrant thorough investigation, and bartonellosis should be considered in polyadenopathy cases, regardless of a recent history of cat or flea exposures.

Reactivation of Epstein-Barr virus among intensive care patients: a prospective observational study.

PURPOSE: Herpesvirus reactivation has been documented among patients in the intensive care unit (ICU) and is associated with increased morbidity and mortality, particularly for cytomegalovirus (CMV). Epstein-Barr virus (EBV) has been poorly studied despite >95% of the population being seropositive. Our preliminary study suggested an association between EBV reactivation and increased morbidity and mortality. This study aimed to investigate this association among patients admitted to the ICU. METHODS: In this multicenter prospective study, polymerase chain reaction was performed to quantify EBV in patients upon ICU admission and then twice a week during their stay. Follow-up was 90 days. RESULTS: The study included 129 patients; 70 (54.3%) had EBV reactivation. On day 90, there was no difference in mortality rates between patients with and without reactivation (25.7% vs 15.3%, p = 0.22). Patients with EBV reactivation at admission had increased mortality compared with those without reactivation and those with later reactivation. EBV reactivation was associated with increased morbidity. Patients with EBV reactivation had fewer ventilator-free days at day 28 than those without reactivation (18 [1-22] vs. 21 days [5-26], p = 0.037) and a higher incidence of acute respiratory distress syndrome (34.3% vs. 17%, p = 0.04), infections (92.9% vs. 78%, p = 0.03), and septic shock (58.6% vs. 32.2%, p = 0.004). More patients with EBV reactivation required renal replacement therapy (30% vs. 11.9%, p = 0.02). EBV reactivation was also associated with a more inflammatory immune profile. CONCLUSION: While EBV reactivation was not associated with increased 90-day mortality, it was associated with significantly increased morbidity.

[Interests of clinical metagenomic in infectious diseases]. / Intérêts de la métagénomique clinique en infectiologie.

INTERESTS OF CLINICAL METAGENOMICS IN INFECTIOUS DISEASES. Clinical metagenomics (CM) is a cutting-edge molecular biology technique that is now a valuable diagnostic tool for microbiologists. It enables the detection of all microorganisms present in a sample, without any prior assumption or bias. The CM approach can be applied to various types of samples and involves multiple steps, such as extraction, library preparation, Next Generation Sequencing, and bioinformatics analysis. CM has been implemented in the diagnosis of various conditions, including infections of the central nervous system, respiratory, digestive, ocular, skin infection, and sepsis. Moreover, CM provides a comprehensive analysis of the microbiome present in the sample, microbial transcripts, and the host response in a single analysis. However, further studies are necessary to determine its place in the diagnostic algorithm. Besides diagnosis, CM has proven useful in identifying resistance to antimicrobial treatments and in epidemiology. Although the cost of CM is still higher than conventional methods, the emergence of more affordable sequencers and commercial tests will enable its implementation in a larger number of laboratories in the future.

INTÉRÊTS DE LA MÉTAGÉNOMIQUE CLINIQUE EN INFECTIOLOGIE. La métagénomique clinique (MgC) est un nouvel outil de biologie moléculaire dans l'arsenal diagnostique des microbiologistes. Elle permet de détecter sans a priori tous les micro-organismes présents. Utilisable sur tous types de prélèvements, elle nécessite plusieurs étapes (extraction, préparation des banques, séquençage par next generation sequencing, analyses bio-informatiques). Son utilisation en diagnostic a été décrite dans différentes pathologies (infections du système nerveux central, infections respiratoires, digestives, oculaires, cutanées et en cas de sepsis). En une seule analyse, la MgC permet également d'étudier le microbiome présent dans le prélèvement, d'analyser les transcrits microbiens et d'étudier la réponse de l'hôte. Sa place dans l'algorithme diagnostique doit faire l'objet d'études supplémentaires. En sus du diagnostic, la MgC a démontré son utilité dans la recherche de résistance aux traitements antimicrobiens, mais également en épidémiologie. Malgré les progrès visant à réduire les coûts, la MgC reste encore à l'heure actuelle plus coûteuse que les méthodes conventionnelles. La mise sur le marché de séquenceurs plus accessibles ainsi que le développement de tests commerciaux permettront l'utilisation de la MgC dans un plus grand nombre de laboratoires dans les années futures.

Neutralizing Antibody Levels as a Correlate of Protection Against SARS-CoV-2 Infection: A Modeling Analysis.

Although anti-severe acute respiratory syndrome-coronavirus 2 antibody kinetics have been described in large populations of vaccinated individuals, we still poorly understand how they evolve during a natural infection and how this impacts viral clearance. For that purpose, we analyzed the kinetics of both viral load and neutralizing antibody levels in a prospective cohort of individuals during acute infection with alpha variant. Using a mathematical model, we show that the progressive increase in neutralizing antibodies leads to a shortening of the half-life of both infected cells and infectious viral particles. We estimated that the neutralizing activity reached 90% of its maximal level within 11 days after symptom onset and could reduce the half-life of both infected cells and circulating virus by a 6-fold factor, thus playing a key role to achieve rapid viral clearance. Using this model, we conducted a simulation study to predict in a more general context the protection conferred by pre-existing neutralization titers, due to either vaccination or prior infection. We predicted that a neutralizing activity, as measured by 50% effective dose > 103 , could reduce by 46% the risk of having viral load detectable by standard polymerase chain reaction assays and by 98% the risk of having viral load above the threshold of infectiousness. Our model shows that neutralizing activity could be used to define correlates of protection against infection and transmission.

The clinical and epidemiological impacts of whole genomic sequencing on bacterial and virological agents.

Whole Genome Sequencing (WGS) is a molecular biology tool consisting in the sequencing of the entire genome of a given organism. Due to its ability to provide the finest available resolution of bacterial and virological genetics, it is used at several levels in the field of infectiology. On an individual scale and through application of a single technique, it enables the typological identification and characterization of strains, the characterization of plasmids, and enhanced search for resistance genes and virulence factors. On a collective scale, it enables the characterization of strains and the determination of phylogenetic links between different microorganisms during community outbreaks and healthcare-associated epidemics. The information provided by WGS enables real-time monitoring of strain-level epidemiology on a worldwide scale, and facilitates surveillance of the resistance dissemination and the introduction or emergence of pathogenic variants in humans or their environment. There are several possible approaches to completion of an entire genome. The choice of one method rather than another is essentially dictated by the matrix, either a clinical sample or a culture isolate, and the clinical objective. WGS is an advanced technology that remains costly despite a gradual decrease in its expenses, potentially hindering its implementation in certain laboratories and thus its use in routine microbiology. Even though WGS is making steady inroads as a reference method, efforts remain needed in view of so harmonizing its interpretations and decreasing the time to generation of conclusive results.

A randomised controlled trial to study the transmission of SARS-CoV-2 and other respiratory viruses during indoor clubbing events (ANRS0066s ITOC study).

BACKGROUND: In the context of the circulation of the SARS-CoV-2 B.1.617.2 (Delta) variant, vaccination re-authorised mass indoor gatherings. The "Indoor Transmission of COVID-19" (ITOC) trial (ClinicalTrials.gov, NCT05311865) aimed to assess the risk of transmission of SARS-CoV-2 and other respiratory viruses during an indoor clubbing event among participants fully-vaccinated against COVID-19. METHODS: ITOC, a randomised, controlled trial in the Paris region (France), enrolled healthy volunteers aged 18-49 years, fully-vaccinated against COVID-19, with no co-morbidities or symptoms, randomised 1:1 to be interventional group "attendees" or control "non-attendees". The intervention, a 7-hour indoor event in a nightclub at full capacity, with no masking, prior SARS-CoV-2 test result or social distancing required. The primary-outcome measure was the numbers of RT-PCR-determined SARS-CoV-2-positive subjects on self-collected saliva 7 days post-gathering in the per-protocol population. Secondary endpoints focused on 20 other respiratory viruses. RESULTS: Healthy participants (n = 1,216) randomised 2:1 by blocks up to 10, 815 attendees and 401 non-attendees, yielding 529 and 287 subjects, respectively, with day-7 saliva samples. One day-7 sample from each group was positive. Looking at all respiratory viruses together, the clubbing event was associated with an increased risk of infection of 1.59 [95% CI 1.04-2.61]. CONCLUSIONS: In the context of low Delta-VOC circulation, no evidence of SARS-CoV-2 transmission among asymptomatic and vaccinated participants was found, but the risk of other respiratory virus transmission was higher.

Multiplex Polymerase Chain Reaction Assay to Detect Nasopharyngeal Viruses in Immunocompromised Patients With Acute Respiratory Failure.

BACKGROUND: In immunocompromised patients with acute respiratory failure (ARF), the clinical significance of respiratory virus detection in the nasopharynx remains uncertain. RESEARCH QUESTION: Is viral detection in nasopharyngeal swabs associated with causes and outcomes of ARF in immunocompromised patients? STUDY DESIGN AND METHODS: This preplanned post hoc analysis of a randomized controlled trial enrolled immunocompromised patients admitted to 32 ICUs for ARF between May 2016 and December 2017. Nasopharyngeal swabs sampled at inclusion were assessed for 23 respiratory pathogens using multiplex polymerase chain reaction (PCR) assay. Causes of ARF were established by managing physicians and were reviewed by three expert investigators masked to the multiplex PCR assay results. Associations between virus detection in nasopharyngeal swabs, causes of ARF, and composite outcome of day 28 mortality, invasive mechanical ventilation (IMV), or both were assessed. RESULTS: Among the 510 sampled patients, the multiplex PCR assay results were positive in 103 patients (20.2%), and a virus was detected in 102 samples: rhinoviruses or enteroviruses in 35.5%, coronaviruses in 10.9%, and flu-like viruses (influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus) in 52.7%. The cause of ARF varied significantly according to the results of the multiplex PCR assay, especially the proportion of viral pneumonia: 50.0% with flu-like viruses, 14.0% with other viruses, and 3.6% when no virus was detected (P < .001). No difference was found in the composite outcome of day 28 mortality, IMV, or both according to positive assay findings (54.9% vs 54.7%; P = .965). In a pre-established subgroup analysis, flu-like virus detection was associated with a higher rate of day 28 mortality, IMV, or both among recipients of allogeneic hematopoietic stem cell transplantation compared with those without detected virus. INTERPRETATION: In immunocompromised patients with ARF, the results of nasopharyngeal multiplex PCR assays are not associated with IMV or mortality. A final diagnosis of viral pneumonia is retained in one-third of patients with positive assay results and in one-half of the patients with a flu-like virus.

Circulating T cell profiles associate with enterotype signatures underlying hematological malignancy relapses.

Early administration of azithromycin after allogeneic hematopoietic stem cell transplantation was shown to increase the relapse of hematological malignancies. To determine the impact of azithromycin on the post-transplant gut ecosystem and its influence on relapse, we characterized overtime gut bacteriome, virome, and metabolome of 55 patients treated with azithromycin or a placebo. We describe four enterotypes and the network of associated bacteriophage species and metabolic pathways. One enterotype associates with sustained remission. One taxon from Bacteroides specifically associates with relapse, while two from Bacteroides and Prevotella correlate with complete remission. These taxa are associated with lipid, pentose, and branched-chain amino acid metabolic pathways and several bacteriophage species. Enterotypes and taxa associate with exhausted T cells and the functional status of circulating immune cells. These results illustrate how an antibiotic influences a complex network of gut bacteria, viruses, and metabolites and may promote cancer relapse through modifications of immune cells.

Adenovirus F41 infection and liver cytolysis in adult hematopoietic stem cell transplant recipients.

Human adenoviruses (HAdVs) of the F species are commonly responsible for acute gastroenteritis. A few cases of systemic infections have been described in adults or children who have received a hematopoietic stem cell transplant (HSCT), but with no report of liver cytolysis. Since January 2022, several countries have reported an increase in cases of acute hepatitis of unknown cause in children. Adenovirus species F type 41 (HAdV-F41) infection was predominantly identified. The objective of this study is to describe HAdV-F41 infections diagnosed since January 2022 in adult HSCT recipients in two French hospitals. All four patients had diarrhea and liver cytolysis at the time of diagnosis of infection. HAdV viremia was observed in three patients (#1, #3, and #4), but no disseminated disease was reported. HAdV whole genome sequencing and metagenomics characterization were performed on stool and blood samples. The complete HAdV-F41 genome sequence was obtained for three patients and phylogenetic analysis showed that the strains consisted of similar lineage (2b). We did not identify any new HAdV-F41 strains. Metagenomics analysis found adeno-associated virus 2 and torque-teno virus infection in patient #1 and Epstein-Barr virus in patient #4. This is the first case series reporting liver cytolysis during HAdV-F41 infection in adult HSCT patients.

Higher convergence of human-great ape enteric eukaryotic viromes in central African forest than in a European zoo: a One Health analysis.

Human-animal pathogenic transmissions threaten both human and animal health, and the processes catalyzing zoonotic spillover and spillback are complex. Prior field studies offer partial insight into these processes but overlook animal ecologies and human perceptions and practices facilitating human-animal contact. Conducted in Cameroon and a European zoo, this integrative study elucidates these processes, incorporating metagenomic, historical, anthropological and great ape ecological analyses, and real-time evaluation of human-great ape contact types and frequencies. We find more enteric eukaryotic virome sharing between Cameroonian humans and great apes than in the zoo, virome convergence between Cameroonian humans and gorillas, and adenovirus and enterovirus taxa as most frequently shared between Cameroonian humans and great apes. Together with physical contact from hunting, meat handling and fecal exposure, overlapping human cultivation and gorilla pillaging in forest gardens help explain these findings. Our multidisciplinary study identifies environmental co-use as a complementary mechanism for viral sharing.

Bronchiolitis obliterans syndrome following SARS-CoV-2 infection in an allogeneic hematopoietic stem cell recipient.

Peripheral allogeneic hematopoietic stem cell transplant recipients are the most vulnerable patients to community-acquired respiratory viruses such as respiratory syncytial virus, influenza virus, or others. These patients are likely to develop severe acute viral infections; community-acquired respiratory viruses have also been identified as triggers of bronchiolitis obliterans (BO). BO is a manifestation of pulmonary graft-versus-host disease, most often leading to irreversible ventilatory impairment. To date, there are no data on whether Severe acute respiratory syndrome â€‹coronavirus 2 (SARS-CoV-2) could be a trigger for BO. Here, we report the first report of a case of bronchiolitis obliterans syndrome following SARS-CoV-2 infection occurring 10 months after allogeneic hematopoietic stem cell transplant with a flare of underlying extra thoracic graft-versus-host disease. This observation provides a new perspective and should be of particular interest to clinicians, suggesting the need for close monitoring of pulmonary function test (PFTs) after SARS-CoV-2 infection. The mechanisms leading to bronchiolitis obliterans syndrome after SARS-CoV-2 infection require further investigation.

Characteristics of circulating KSHV-infected viroblasts during active KSHV+ multicentric Castleman disease.

Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8-associated multicentric Castleman disease (MCD) is a polyclonal B-cell lymphoproliferative disorder that mainly occurs in immunocompromised hosts. The diagnosis relies on lymph node biopsy demonstrating KSHV-infected cells located in the mantle zone with a marked interfollicular plasma cell infiltration. Infected cells are large cells positive for immunoglobulin M (IgM), λ light chain, and CD38, described initially as infected plasmablasts. We show that IgM+λ+CD38high cells were also detectable in the peripheral blood of 14 out of 18 (78%) patients with active KSHV-MCD and absent in 40 controls. Using immunofluorescence and flow-fluorescence in situ hybridization, we demonstrate that these cells are KSHV infected and express both latent and lytic KSHV transcripts. These KSHV-infected viroblasts (KIVs) harbor a distinct phenotype compared with conventional plasmablasts. We also identified several putative mechanisms of immune escape used by KSHV, because KIVs displayed an overall decrease of costimulatory molecules, with a remarkable lack of CD40 expression and are interleukin-10-producing cells. The identification of this specific and easily accessible KSHV+ circulating population brings new elements to the understanding of KSHV-MCD but also raises new questions that need to be clarified.

Impact of the COVID-19 pandemic on antiviral drug development for other community-acquired respiratory viruses' infections.

The coronavirus disease 2019 (COVID-19) pandemic indirectly resulted in missed therapeutic opportunities for many diseases. Here we focus on community-acquired respiratory viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) [respiratory syncytial virus, parainfluenza and influenza A], and highlight the pandemics impact on clinical trials to develop novel therapies for other severe respiratory viral infections. We retrospectively reviewed inclusion rates within respiratory antiviral clinical trials in comparison with all other clinical trials in our clinical investigations center, before and during the COVID-19 pandemic. As opposed to the remaining clinical trials developed within our unit, respiratory antiviral trials inclusion rates did not recover after the initial recruitment decrease observed across all trials during the first pandemic wave. These results were discussed in the context of non-COVID-19 respiratory viral infection rates within our center, showing a general decline in seasonal respiratory viruses spread since the COVID-19 pandemic onset. Virus epidemiology changes upon the wide SARS-CoV-2 expansion as well as the lifestyle changes globally adopted to prevent SARS-CoV-2 transmission could have therefore contributed to the negative impact of the COVID-19 pandemic on antiviral drug development. Our study highlights the peculiarity of respiratory antiviral drug development during the COVID-19 pandemic era and describes potential explanations for such drug development halting.

Detection of SARS-CoV-2 in Saliva and Nasopharyngeal Swabs According to Viral Variants.

The genome of the Omicron variant of concern (VOC) contains more than 50 mutations, many of which have been associated with increased transmissibility, differing disease severity, and the potential to elute immune responses acquired after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection with previous VOCs. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs (NPS). Our objective was to compare the SARS-CoV-2 levels in saliva fluid and NPS to estimated Ct values, according to the main SARS-CoV-2 variants circulating in France since the beginning of 2021. We analyzed 1,289 positive reverse transcription-polymerase chain reaction (RT-PCR) results during the three major waves: Alpha, Delta, and Omicron. NPS and saliva sampling were performed for 909 (71%) and 380 (29%) cases, respectively. The Ct values were significantly lower in the NPS samples than in the saliva samples for the three main VOCs. Still, the difference was less pronounced with the Omicron variant than for the Alpha and Delta variants. In contrast, in the saliva samples, Ct values were significantly lower for the Omicron variant than for the Delta (difference of -2.7 Ct) and the Alpha (difference of -3.0 Ct) variants, confirming a higher viral load in saliva. To conclude, the higher viral load in saliva was evidenced for the Omicron variant, compared to the Alpha and Delta variants, suggesting that established diagnostic methods might require revalidation with the emergence of novel variants. IMPORTANCE Established methods for SARS-CoV-2 diagnostics might require revalidation with the emergence of novel variants. This is important for screening strategy programs and for the investigation of the characteristics of new variants in terms of tropism modification and increased viral burden leading to its spread. SARS-CoV-2 RT-PCR screening on saliva samples reported lower but acceptable performance, compared to nasopharyngeal samples. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs. Our study analyzed 1,289 positive RT-PCR results during the three major waves in France: Alpha, Delta, and Omicron. Our findings also showed a higher viral load in saliva for the Omicron variant, compared to the Alpha and Delta variants.

Metagenomic next-generation sequencing restores the diagnosis of a rare infectious complication of B cell depletion.

A 45-year-old female patient receiving rituximab for B cell non-Hodgkin follicular lymphoma presented unexplained recurrent fever, abdominal discomfort, and pollakiuria. We performed shotgun metagenomic sequencing from peri-kidney collection that identified a co-infection with Mycoplasma hominis and Ureaplasma urealyticum. The patient recovered with sequelae after appropriate antibiotic treatment was given.

[Aspects virologiques, diagnostic et variants du SARS-CoV-2]. / Virological aspects, diagnostic tools and variants of SARS-CoV-2.

VIROLOGICAL ASPECTS, DIAGNOSTIC TOOLS AND VARIANTS OF SARS-COV-2 SARS-CoV-2 is an enveloped non-segmented linear single-stranded positive RNA virus. The envelope carries the protein spike (S) which recognizes the ACE2 receptor on the target cell and allows entry of the virus. The numerous mutations on the S protein are at the origin of a great genetic diversity, involved in the species barrier and the escape from neutralizing antibodies. The main mode of transmission is respiratory. The virus replicates 24 hours after infection and the viral RNA is detected by direct diagnostic techniques as the reference technique is RT-PCR on a nasopharyngeal sample. To expand screening, RT-PCR on saliva samples and antigenic tests have been developed. The majority of patients develop specific antibodies within 10-15 days which are detectable by serological methods. It is recommended to combine the search for anti-N and anti-S antibodies. The viral genome has great plasticity and variants emerged from the summer of 2020. There are several classifications, including that of the WHO, which assigns each variant a Greek letter. Finally, Santé publique France has deployed an epidemiological surveillance system of variants using PCR screening and sequencing.

ASPECTS VIROLOGIQUES, DIAGNOSTIC ET VARIANTS DU SARS-COV-2 Le SARS-CoV-2 est un virus enveloppé à ARN monocaténaire linéaire non segmenté de polarité positive. L'enveloppe porte la protéine Spike (S) qui reconnaît le récepteur ACE2 sur la cellule cible et permet l'entrée du virus. Les nombreuses mutations sur la protéine S sont à l'origine d'une grande diversité génétique, impliquées dans le franchissement de la barrière d'espèce et l'échappement aux anticorps neutralisants. Le mode de transmission principal est respiratoire. Le virus réplique dès vingt-quatre heures après l'infection, et l'ARN viral est détecté par les techniques de diagnostic direct ; la technique de référence est la RT-PCR sur prélèvement nasopharyngé. Pour élargir le dépistage, la RT-PCR sur prélèvement salivaire et les tests antigéniques ont été développés. La majorité des patients développent des anticorps spécifiques en dix à quinze jours, qui sont détectables par les méthodes sérologiques ; il est recommandé de combiner la recherche des anticorps anti-N (nucléocapside) et anti-S. Le génome viral est doté d'une grande plasticité, et des variants ont émergé dès l'été 2020. Il en existe plusieurs classifications dont celle de l'Organisation mondiale de la santé qui attribue à chaque variant une lettre grecque. Enfin, Santé publique France a déployé un système de surveillance épidémiologique de ces variants à l'aide de techniques de criblage et de séquençage.

Humoral and cellular responses to SARS-CoV-2 BNT162b2 vaccination in allogeneic hematopoietic stem cell transplantation recipients.

Previous studies reporting the response to SARS-CoV-2 mRNA vaccination in alloHSCT recipients used serological and/or cellular assays, but no study has evaluated vaccine-induced neutralizing antibodies. We prospectively studied 28 alloHSCT recipients who received two BNT162b2 doses. Two patients groups were defined according to time from alloHSCT and immunosuppressive treatment, and had different baseline immunologic status. Study end-point was the evaluation of humoral and cellular responses one month after the second vaccine. All patients seroconverted. Anti-S IgG levels and neutralizing antibodies percentages were not significantly different between both groups. Using IFNγ ELISpot assay, five patients showed a strong increase, without correlation with the humoral response. Using flow cytometry lymphocyte proliferation assay, 14 patients exhibited responding T cells, without difference between both groups or correlation with anti-S IgG levels. A few low serological responders had a detectable CD4 + T cell proliferative response. This finding should be confirmed in a larger cohort.

Diagnostic accuracy of non-invasive detection of SARS-CoV-2 infection by canine olfaction.

BACKGROUND: Throughout the COVID-19 pandemic, testing individuals remains a key action. One approach to rapid testing is to consider the olfactory capacities of trained detection dogs. METHODS: Prospective cohort study in two community COVID-19 screening centers. Two nasopharyngeal swabs (NPS), one saliva and one sweat samples were simultaneously collected. The dog handlers (and the dogs…) were blinded with regards to the Covid status. The diagnostic accuracy of non-invasive detection of SARS-CoV-2 infection by canine olfaction was assessed as compared to nasopharyngeal RT-PCR as the reference standard, saliva RT-PCR and nasopharyngeal antigen testing. RESULTS: 335 ambulatory adults (143 symptomatic and 192 asymptomatic) were included. Overall, 109/335 participants tested positive on nasopharyngeal RT-PCR either in symptomatic (78/143) or in asymptomatic participants (31/192). The overall sensitivity of canine detection was 97% (95% CI, 92 to 99) and even reached 100% (95% CI, 89 to 100) in asymptomatic individuals compared to NPS RT-PCR. The specificity was 91% (95% CI, 72 to 91), reaching 94% (95% CI, 90 to 97) for asymptomatic individuals. The sensitivity of canine detection was higher than that of nasopharyngeal antigen testing (97% CI: 91 to 99 versus 84% CI: 74 to 90, p = 0.006), but the specificity was lower (90% CI: 84 to 95 versus 97% CI: 93 to 99, p = 0.016). CONCLUSIONS: Non-invasive detection of SARS-CoV-2 infection by canine olfaction could be one alternative to NPS RT-PCR when it is necessary to obtain a result very quickly according to the same indications as antigenic tests in the context of mass screening.

Incidence, risk factors and outcome of BK virus hemorrhagic cystitis following allogenic hematopoietic cell transplantation: a retrospective cohort study.

BK polyomavirus (BKPyV) can cause hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (allo-HCT). Recent evaluation of BKPyV HC (BKHC) incidence and risk factors are scarce. We conducted a retrospective single-center study on a recent allo-HCT cohort over 3 years in a referral academic hospital for hematological malignancies. Primary objective was to determine BKHC incidence using competitive risk analysis. Secondary objectives were the identification of HC risk factors using Fine and Gray models and the evaluation of mortality. Among 409 allo-HCT recipients (median age 47 years), 41 developed BKHC after a median delay of 41 [32-55] days. Incidence density of BKHC was 2.4 [1.8-3.1] events per 100 days post-allo-HCT. The proportion of BKHC after adjustment for time-dependent competing risk was 9.5 [9.5-9.6]% at 100 days. BK viremia was detected in 63 versus 20% in tested patients with and without BKHC, respectively. After adjustment for confounders, myeloablative conditioning regimen with and without cyclophosphamide and CMV seropositivity were independently associated with BKHC. Post-transplantation cyclophosphamide was not associated with BKHC. BKHC resolved in 90% of the patients. No difference in mortality was found between patients with or without BKHC. In parallel to the recent evolution of allo-HCT protocols, BKHC remains a frequent complication following allo-HCT.