Age, COVID-19-like symptoms and SARS-CoV-2 seropositivity profiles after the first wave of the pandemic in France.

BACKGROUND: The interplay between age and symptoms intensity on antibody response to SARS-CoV-2 infection has not been studied in a general population setting. METHODS: We explored the serologic profile of anti-SARS-CoV-2 antibodies after the first wave of the pandemic, by assessing IgG against the spike protein (ELISA-S), IgG against the nucleocapsid protein (ELISA-NP) and neutralizing antibodies (SN) in 82,126 adults from a French population-based multi-cohort study. RESULTS: ELISA-S positivity was increased in 30- to 49-year-old adults (8.5%) compared to other age groups (5.6% in 20- to 29-year-olds, 2.8% in ≥ 50-year-olds). In the 3681 ELISA-S positive participants, ELISA-NP and SN positivity exhibited a U-shaped relationship with age, with a lower rate in 30- to 49-year-old adults, and was strongly associated with COVID-19-like symptoms. CONCLUSION: Our study confirms the independent role of age and symptoms on the serologic profile of anti-SARS-CoV-2 antibodies, but the non-linear relationship with age deserves further investigation.

Epidemiological and clinical insights from SARS-CoV-2 RT-PCR crossing threshold values, France, January to November 2020.

BackgroundThe COVID-19 pandemic has led to an unprecedented daily use of RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of quantification cycles (Cq), is debated because of strong potential biases.AimWe explored the possibility to use Cq values from SARS-CoV-2 screening tests to better understand the spread of an epidemic and to better understand the biology of the infection.MethodsWe used linear regression models to analyse a large database of 793,479 Cq values from tests performed on more than 2 million samples between 21 January and 30 November 2020, i.e. the first two pandemic waves. We performed time series analysis using autoregressive integrated moving average (ARIMA) models to estimate whether Cq data information improves short-term predictions of epidemiological dynamics.ResultsAlthough we found that the Cq values varied depending on the testing laboratory or the assay used, we detected strong significant trends associated with patient age, number of days after symptoms onset or the state of the epidemic (the temporal reproduction number) at the time of the test. Furthermore, knowing the quartiles of the Cq distribution greatly reduced the error in predicting the temporal reproduction number of the COVID-19 epidemic.ConclusionOur results suggest that Cq values of screening tests performed in the general population generate testable hypotheses and help improve short-term predictions for epidemic surveillance.

Circulation of enterovirus A71 during 2019-2020, Marseille, France.

Enteroviruses A71 (EVs-A71) are known to cause serious neurological infections, especially in the pediatric population. We report here eight cases of EV-A71 infection diagnosed in Marseille over the past 2 years (seven cases in 2019 and one case in 2020). Only children under 5 years of age were affected, including one case of acute flaccid paralysis. Viral RNA was detected by RT-PCR in peripheral samples for all cases (feces and upper respiratory samples). Phylogenetic analyses based on VP1 and 2C3C coding regions revealed that all these cases of EV-A71 infection were caused by viruses belonging to the subgenogroup C1 that currently circulates in Europe and that these viruses are genetically closed to other EVs-A71 recently detected in European countries. These data therefore reinforce the usefulness of the enterovirus surveillance network and the need for systematic screening for EV-A71 in case of an enteroviral infection. This study therefore suggests that the systematic screening for EV-A71 in case of enteroviral infection could provide additional data for enterovirus surveillance networks.

Fatal underhanded chronic enterovirus infection associated with anti-CD20 monotherapy for central nervous system demyelinating disease.

We report a fatal case of coxsackievirus B4 chronic infection in a 30-year-old woman with a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disorder controlled by rituximab monotherapy for 3 years. Initially presenting as self-limited meningitis, the infection remained silent for 8 months before the sudden onset of fulminant myocarditis. Analysis of the complete genome showed that the same virus was responsible for both episodes.

Gastrointestinal symptoms and the acquisition of enteric pathogens in Hajj pilgrims: a 3-year prospective cohort study.

The acquisition of enteric pathogens and risk factors for Hajj-associated diarrhea in Hajj pilgrims is poorly documented. Pilgrims from Marseille participating in the Hajj in 2016-2018 underwent successive systematic rectal swabbing before and after their travel. Carriage of the main enteric pathogens was assessed by real-time PCR. Baseline demographics, adherence to individual preventive measures, gastrointestinal symptoms, and treatments were recorded. A total of 376 pilgrims were included. The median age was 62.0 years. During the Hajj, 18.6% presented at least one gastrointestinal symptom, 13.8% had diarrhea, and 36.4% had acquired at least one enteric pathogen. Enteropathogenic Escherichia coli (EPEC) and Enteroaggregative E. coli (EAEC) were the pathogens most frequently acquired by pilgrims (17.6% and 14.4%, respectively). Being female was associated with increased frequency of gastrointestinal symptoms during the pilgrimage (aOR = 2.38, p = 0.004). Enterohemorrhagic Escherichia coli (EHEC) acquisition was associated with a four-fold higher risk of reporting at least one gastrointestinal symptom and diarrhea (aOR = 3.68 and p = 0.01 and aOR = 3.96 and p = 0.01, respectively). Pilgrims who suffered from diarrhea were more likely to wash their hands more often (aOR = 2.07, p = 0.03) and to be either overweight (aOR = 2.71, p = 0.03) or obese (aOR = 2.51, p = 0.05). Enteric bacteria such as E. coli that are frequently associated with traveler's diarrhea due to the consumption of contaminated food and drink were frequently found in pilgrims. Respecting strict measures regarding food and water quality during the Hajj and adherence to preventive measures such as good personal hygiene and environmental management will help reduce the burden of gastrointestinal infections at the event.

Dengue Virus Type 1 Infection in Traveler Returning from Benin to France, 2019.

We investigated a case of dengue virus type 1 infection acquired in Benin. Phylogenetic analysis revealed the strain belongs to genotype V but clusters with Asian, rather than with known African, strains. Our finding suggests the introduction of Asian dengue virus in West Africa.

Point-of-care multiplexed diagnosis of meningitis using the FilmArray® ME panel technology.

Infectious meningitis is a medical urgency and rapid detection of the causative pathogen into the cerebrospinal fluid (CSF) is mandatory to guide the management of patients. We compared the performances of the multiplexed PCR FilmArray® ME panel with standard microbiological analyses, for rapid diagnosis of infectious meningitis. All the CSF samples received in our routine laboratory for the diagnosis of infectious meningitis were prospectively analyzed by the FilmArray® ME panel for the detection of fourteen targets in parallel to standard routine real-time PCR assays and bacterial culture. We reviewed clinical and biological records of patients for whom a discrepant result was obtained to achieve a definite diagnosis. Among 1124 CSF samples tested over a 43-week period, 113 (10.1%) and 87 (7.74%) were positive using the FilmArray® ME panel and the standard techniques, respectively. Among 40 CSF samples which yielded discrepant results, 34 were positive only using the FilmArray® ME panel and 6 were positive only using standard techniques. A total of 16/34 (47.1%) FilmArray® ME panel-positive CSF, and 6/6 (100%) of standard technique-positive CSF were interpreted as true positive. We were able to estimate the sensitivity, the specificity, the positive predictive value, and the negative predictive value of the FilmArray® ME panel at 94.2%, 98.2%, 84.3%, and 99.4%, respectively. The FilmArray® ME panel is an efficient tool for the rapid diagnosis of infectious meningitis at the point-of-care. Its higher sensitivity compared with that of standard molecular biology and culture techniques yields an increase of true positive diagnosis.

Children account for a small proportion of diagnoses of SARS-CoV-2 infection and do not exhibit greater viral loads than adults.

Previous reports have suggested that children are less affected than adults by SARS-CoV-2. We analyzed SARS-CoV-2 diagnoses between February 27, 2020, and March 14, 2020, and mortality among positive patients in Marseille university hospitals. Of 4050 tested individuals, 228 were positive. Deaths occurred in 2/99 documented cases (both > 85 year-old). Children were majorly asymptomatic. Incidence increased by 7.4-fold between 1-5 and 45-65 years then decreased. It was significantly lower among 0-1 year- (0%) and 1-5 (1.1%) and 5-10 (3.6%)-year-old children than among subjects > 18 years (6.5%). Viral loads did not differ between children and adults. Children may not contribute significantly to virus circulation.

Correction to: Combination of ELISA screening and seroneutralisation tests to expedite Zika virus seroprevalence studies.

In the original publication of this article [1], Table 1 has some errors.

Combination of ELISA screening and seroneutralisation tests to expedite Zika virus seroprevalence studies.

Here we propose a strategy allowing implementing efficient and practicable large-scale seroepidemiological studies for Zika Virus (ZIKV). It combines screening by a commercial NS1 protein-based Zika IgG ELISA, and confirmation by a cytopathic effect-based virus neutralization test (CPE-based VNT). In post-epidemic samples from Martinique Island blood donors (a population with a dengue seroprevalence above 90%), this strategy allowed reaching specificity and sensitivity values over 98%. The CPE-based VNT consists of recording CPE directly under the optical microscope, which is easy to identify with ZIKV strain H/PF/2013 at day 5 pi. Overall, considered that CPE-based VNT is cost effective and widely automatable, the NS1 protein-based Zika IgG ELISA+CPE-based VNT combination strategy represents a convenient tool to expedite ZIKV seroprevalence studies.

The nasopharyngeal microbiota in patients with viral respiratory tract infections is enriched in bacterial pathogens.

The nasopharynx is the primary site of colonization by respiratory pathogen that constitutes the port of entrance in the respiratory tract. The role of mucosal respiratory microbiota in infection has been recently emphasized; therefore, we aimed to assess if a specific respiratory microbiota profile was associated with symptomatic infection and/or with presence of respiratory viruses. We performed a case-control study to characterize the healthy respiratory microbiota and its alteration during acute viral infections. Next-generation sequencing of the 16S rRNA gene was applied to 225 nasopharyngeal samples from 177 patients with viral respiratory infection and 48 matched healthy controls. We evidenced an important decrease of bacterial alpha-diversity in patients with symptomatic respiratory infection and a loss of the healthy core microbiota, specifically anaerobes and Prevotella spp. Moreover, eight respiratory pathogens were enriched in these patients, including Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Dol osigranulum pigrum and Corynebacterium propinquum/pseudodiphtheriticum, whose role in respiratory infection is unclear. The asymptomatic carrier of influenza harbors a microbiota similar to healthy subjects, suggesting a critical role of microbiota in the clinical expression of viruses. These data suggest that the commensal microbiota plays a significant role in susceptibility to viral infection. The frequent co-detection of virus and bacteria raises the question of a strategy to prevent bacterial disease, focusing on the prevention of nasopharyngeal colonization through effective antibiotic treatment. In addition to antibiotics, further studies should test preventive or therapeutic interventions for maintaining or restoring a healthy nasopharyngeal microbiota.

Identification of dengue type 2 virus in febrile travellers returning from Burkina Faso to France, related to an ongoing outbreak, October to November 2016.

Dengue fever is rarely reported in travellers returning from Africa. We report two cases of dengue fever in travellers returning from Burkina Faso to France. One of them presented a severe dengue fever with ALT > 1,000 IU/L and pericarditis. Serotype 2 was identified. The cases reflect a large ongoing outbreak with over 1,000 reported cases between August and November in the capital city. Clinicians should consider dengue fever in malaria-negative febrile travellers returning from Africa.