Congenital Infection of Severe Acute Respiratory Syndrome Coronavirus 2 With Intrauterine Fetal Death: A Clinicopathological Study With Molecular Analysis.

BACKGROUND: Observations of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from mother to fetus have recently been described in the literature. However, the consequences of such transmission, whether fetal or neonatal, are poorly understood. METHODS: From a case of in utero fetal death at 24+2 weeks of gestation that occurred 7 days after the diagnosis of symptomatic SARS-CoV-2 infection in the mother, we isolated the incriminating virus by immunochemistry and molecular techniques in several fetal tissues, with a variant analysis of the SARS-CoV-2 genome. RESULTS: The fetal demise could be explained by the presence of placental histological lesions, such as histiocytic intervillositis and trophoblastic necrosis, in addition to fetal tissue damage. We observed mild fetal growth retardation and visceral damage to the liver, causing hepatocellular damage and hemosiderosis. To the best of our knowledge, this is the first report in the literature of fetal demise secondary to maternal-fetal transmission of SARSCoV- 2 with a congenital infection and a pathological description of placental and fetal tissue damage. CONCLUSIONS: SARS-CoV-2 was identified in both specimens using 3 independent techniques (immunochemistry, real-time quantitative polymerase chain reaction, and realtime digital polymerase chain reaction). Furthermore, the incriminating variant has been identified.

Screening of health workers exposed to SARS-CoV-2 in a university hospital in the south of France.

INTRODUCTION: SARS-CoV-2, which causes COVID-19, is a virus that has caused a global pandemic. Health workers (HWs) are major players in the fight against this infection and are occupationally exposed to the virus in the course of their work. In this context, this study presents surveillance data on 1714 workers in a hospital center in the south of France for the period from March 17 to April 20, 2020. MATERIALS AND METHODS: Symptomatic HWs, contact cases and those with high anxiety were tested. Diagnosis of COVID-19 was performed by RT-PCR after nasopharyngeal sampling. RESULTS: During this period, 30.4% of hospital staff received 3028 nasal swabs. Of these, 8.0% were infected with SARS-CoV-2. Among the SARS-CoV-2 positive HWs, 24.3% were asymptomatic. Among COVID unit and non COVID unit, the positive HWs for SARS-CoV-2 were, respectively, 5.8% and 8.2% (p = 0.2). HWs over 50 years of age were less likely to be positive for SARS-CoV-2 (3.8%) than other younger HWs (9.1%) (p < 0.001). No serious cases of COVID-19 were reported in our population during this period. DISCUSSION: Our study suggests that HWs who tested positive for COVID-19 are often asymptomatic. Therefore, PPE is pivotal to prevent HWs to patients and HWs to HWs transmission during workshifts. Contact tracing and screening is essential to limit the spread of the virus within the hospital. On the other hand, HWs working in COVID-19 units are not more often infected probably because they have a higher risk awareness than other HWs.

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.

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.

Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy.

BACKGROUND: The seroprevalence of human Parvovirus B19 (PVB19) is 70-85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy. METHODS: Cases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017-2018. RESULTS: The 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis. CONCLUSION: PVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.

Vector-borne transmission of Zika virus in Europe, southern France, August 2019.

On 1 October 2019, a locally-acquired Zika virus disease case was laboratory confirmed in Hyères, Var department. Active case finding identified two additional locally-acquired cases living within 90 m, with symptom onset 8 days before the index case. Extensive patient interviews did not yield information supporting transmission through sexual contact or substances of human origin. Vector-borne transmission by local Aedes albopictus mosquitoes is the most likely mode of transmission. Here we describe the public health response.

Emerging viral diseases in kidney transplant recipients.

Viruses are the most important cause of infections and a major source of mortality in Kidney Transplant Recipients (KTRs). These patients may acquire viral infections through exogenous routes including community exposure, donor organs, and blood products or by endogenous reactivation of latent viruses. Beside major opportunistic infections due to CMV and EBV and viral hepatitis B and C, several viral diseases have recently emerged in KTRs. New medical practices or technologies, implementation of new diagnostic tools, and improved medical information have contributed to the emergence of these viral diseases in this special population. The purpose of this review is to summarize the current knowledge on emerging viral diseases and newly discovered viruses in KTRs over the last two decades. We identified viruses in the field of KT that had shown the greatest increase in numbers of citations in the NCBI PubMed database. BKV was the most cited in the literature and linked to an emerging disease that represents a great clinical concern in KTRs. HHV-8, PVB19, WNV, JCV, H1N1 influenza virus A, HEV, and GB virus were the main other emerging viruses. Excluding HHV8, newly discovered viruses have been infrequently linked to clinical diseases in KTRs. Nonetheless, pathogenicity can emerge long after the discovery of the causative agent, as has been the case for BKV. Overall, antiviral treatments are very limited, and reducing immunosuppressive therapy remains the cornerstone of management.

Circulation of respiratory viruses among pilgrims during the 2012 Hajj pilgrimage.

BACKGROUND: The Hajj is the oldest and largest annual mass gathering in the world and may increase the risk of spread of respiratory viruses. METHODS: We performed a prospective survey among a cohort of pilgrims departing from Marseille, France, to Mecca in the Kingdom of Saudi Arabia (KSA) for the 2012 Hajj season. Nasal swabs were collected from participants and tested for 11 respiratory viruses by real-time reverse transcription polymerase chain reaction. RESULTS: Of 165 participants sampled before departing to the KSA, 8 (4.8%) were positive for at least 1 virus (5 rhinovirus, 1 influenza C, 1 adenovirus, and 1 enterovirus). Seventy symptomatic pilgrims underwent additional nasal swabs during their pilgrimage in the KSA, of which 27 (38.6%) were positive for at least 1 virus (19 rhinovirus, 6 influenza A, 1 influenza C, 1 respiratory syncytial virus B, 1 metapneumovirus, 1 adenovirus, and 1 enterovirus). This was significantly higher than the 4.8% who were positive before departing for the KSA (P < .001). Of 154 pilgrims sampled before leaving the KSA, 17 (11%) were positive for at least 1 virus (13 rhinovirus, 3 adenovirus, 2 influenza B, and 1 enterovirus), which was also significantly higher than the percentage of positive pilgrims (4.8%), before departing for the KSA (P = .040). CONCLUSIONS: This study suggests a rapid acquisition of respiratory viruses among pilgrims during their stay in the KSA, most notably rhinovirus, and highlights the potential of spreading these infections in the pilgrims' home countries upon their return.

Sheep-to-human transmission of Orf virus during Eid al-Adha religious practices, France.

Five persons in France were infected with Orf virus after skin wounds were exposed to infected sheep tissues during Eid al-Adha, the Muslim Feast of Sacrifice. Infections were confirmed by electron microscopy, PCR, and sequence analysis. Prevention and control of this underdiagnosed disease can be achieved by educating physicians, slaughterhouse workers, and persons participating in Eid al-Adha.

Interferon-γ production by natural killer cells and cytomegalovirus in critically ill patients.

OBJECTIVE: The mechanisms involved in cytomegalovirus reactivation in critically ill patients who were previously immunocompetent are still unknown. The current study was designed to evaluate the possible role of natural killer cells in the reactivation of cytomegalovirus in these patients. DESIGN: Prospective observational. SETTING: : A medical intensive care unit of a university hospital. PATIENTS: Fifty-one subjects, including 15 patients who experienced cytomegalovirus reactivation (cases) during their intensive care unit stay and 15 patients who matched intensive care unit controls, selected from a cohort of consecutive nonimmunocompromised intensive care unit patients, as well as healthy controls. INTERVENTIONS: Tests included weekly systematic immunomonitoring and routine screening for cytomegalovirus infection until discharge from the intensive care unit or death. The immunophenotype and functions of natural killer cells were performed by flow cytometry, and serum levels of pro- and anti-inflammatory cytokines were determined by enzyme-linked immunosorbent assay. MEASUREMENTS AND MAIN RESULTS: The overall occurrence of cytomegalovirus reactivation in the cohort was 27%. No differences of natural killer cell effector functions were observed at admission between cases and controls. Instead, before cytomegalovirus reactivation, the ability of natural killer cells to secrete interferon-γ was significantly reduced in cases as compared with controls upon stimulation with antibody-coated target cells (p = .029) and with K562 cell stimulation (p = .029). No phenotypic or quantitative differences were observed between cases and controls. Cases exhibited higher levels of interleukin 10 (p = .031) and interleukin 15 (p = .021) than controls before cytomegalovirus reactivation. CONCLUSIONS: Impaired natural killer cell function with reduced interferon-γ secretion precedes the occurrence of cytomegalovirus reactivation among previously immunocompetent critically ill patients.

Early recovery of immunity after cord-blood transplantation in children: qualitative features and impact of cytomegalovirus infection.

This study investigated immune recovery and the effect of cytomegalovirus (CMV) infection on the early stages of T-lymphocyte recovery after cord-blood transplantation (CBT) from unrelated donors to 24 children. In addition, 15 children who were recipients of a bone-marrow transplant (BMT) were studied concomitantly. The main objectives of the study were whether lymphocytes from CBT recipients were capable of rapid qualitative differentiation in the effector memory (EM) stage, of regenerating de novo naïve cells and of responding to CMV infection. Results showed that CB lymphocytes were mainly differentiated into the EM stage at 3 months and into the naïve stage at 6 months. CMV infection induced a dramatic increase in CD8 but not CD4 T-cell counts, and differentiation into the EM stage with high perforin contents. Our data suggest that CB lymphocytes are capable of rapid differentiation in children, but stabilization of lymphocyte counts in children is associated with effective naïve subset regeneration at 6 months. Moreover, the T-cell repertoire is capable of rapid adjustment when CMV infection occurs.

Dynamics of community-acquired meningitis syndrome outbreaks in southern France.

In southern France, cases of community-acquired meningitis syndrome (CAM) are typically clustered as outbreaks with determinants which remain unknown. This 61-month retrospective investigation in Nîmes and Marseille university hospital laboratories, yielded 2,209/20,779 (10.63%) documented CAM cases caused by 62 different micro-organisms, represented by seasonal viral etiologies (78.8%), including Enterovirus, Herpes Simplex Virus (HSV), and Varicella-Zoster Virus (VZV; 1,620/2,209 = 73.4%). Multi correspondence analysis revealed an association of infection with age and sex, with the risk of infection being relatively higher in young men, as confirmed by Fisher's exact test (p < 10-3). Bacterial meningitis accounted for 20% of cases, mostly caused by Streptococcus pneumoniae (27.4% of cases), Neisseria meningitidis (12.5%), and Haemophilus influenzae (9.5%) with bacteria/virus coinfection (0.9%), and only six cases of documented fungal meningitis. In total, 62.6% of cases, of which 88.7% were undocumented, arose from 10 outbreaks. 33.2% of undocumented cases were aged >60 years compared to 19.2% of documented cases (p < 0.001), and viral infection was more common in the summer (87.5%) compared to other seasons (72.3%; p < 0.001). Outbreaks most often started in Nîmes and moved eastward toward Marseille at a speed of ~9 km/day, and these dynamics significantly correlated with atmospheric temperature, especially during summer outbreaks. In particular, the incidence of Enterovirus-driven outbreaks correlated with temperature, revealing correlation coefficients of 0.64 in Nîmes and 0.72 in Marseille, and its occurrence in Marseille lagged that in Nîmes by 1-2 weeks. Tracing the dynamics of CAM outbreak during this retrospective investigation in southern France yielded a speed of displacement that correlated with the variation in temperature between both cities, and these results provide clues for the next occurrence of undocumented outbreaks.

Direct Diagnosis of Echovirus 12 Meningitis Using Metagenomic Next Generation Sequencing.

The current point-of-care diagnosis of enterovirus meningitis does not identify the viral genotype, which is prognostic. In this case report, more than 81% of an Echovirus 12 genome were detected and identified by metagenomic next-generation sequencing, directly from the cerebrospinal fluid collected in a 6-month-old child with meningeal syndrome and meningitis: introducing Echovirus 12 as an etiological agent of acute meningitis in the pediatric population.