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To the Editor: Zika virus (ZIKV), an emerging flavivirus, generally causes mild infection in humans but is associated with severe neurologic complications and adverse fetal outcomes. ZIKV is transmitted to humans primarily by aedes mosquitoes. However, there is some evidence of sexual transmission. 1 , 2 Two studies have shown the presence of infectious ZIKV in semen. 3 A recent article described detection of ZIKV RNA in semen 62 days after the onset of illness, but infectious virus was not cultured. 4 We report a case of ZIKV infection in a previously healthy 24-year-old woman (Patient 1) who was living in Paris and in . . .

On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020. In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done. The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020. We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies. REACTing (Research & Action Emerging Infectious Diseases).

A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein-specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.

Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease. MAIT cell frequency is strongly reduced in blood. They display a strong activated and cytotoxic phenotype that is more pronounced in lungs. Blood MAIT cell alterations positively correlate with the activation of other innate cells, proinflammatory cytokines, notably interleukin (IL)-18, and with the severity and mortality of severe acute respiratory syndrome coronavirus 2 infection. We also identified a monocyte/macrophage interferon (IFN)-α–IL-18 cytokine shift and the ability of infected macrophages to induce the cytotoxicity of MAIT cells in an MR1-dependent manner. Together, our results suggest that altered MAIT cell functions due to IFN-α–IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation. Severe COVID-19 is characterized by hyperinflammation, and there is a need for accurate predictive biomarkers of progression. Lehuen et al. demonstrate that patients with severe COVID-19 show a dramatic loss of MAIT cells, and those that do remain are in a highly activated state.

COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13 low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DR low downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.

Empirical social contact patterns are essential to understand the spread of infectious diseases. To date, no such data existed for France. Although infectious diseases are frequently seasonal, the temporal variation of contact patterns has not been documented hitherto. COMES-F is the first French large-scale population survey, carried out over 3 different periods (February-March, April, April-May) with some participants common to the first and the last period. Participants described their contacts for 2 consecutive days, and reported separately on professional contacts when typically over 20 per day. 2033 participants reported 38 881 contacts (weighted median [first quartile-third quartile]: 8[5-14] per day), and 54 378 contacts with supplementary professional contacts (9[5-17]). Contrary to age, gender, household size, holidays, weekend and occupation, period of the year had little influence on the number of contacts or the mixing patterns. Contact patterns were highly assortative with age, irrespective of the location of the contact, and gender, with women having 8% more contacts than men. Although most contacts occurred at home and at school, the inclusion of professional contacts modified the structure of the mixing patterns. Holidays and weekends reduced dramatically the number of contacts, and as proxies for school closure, reduced R0 by 33% and 28%, respectively. Thus, school closures could have an important impact on the spread of close contact infections in France. Despite no clear evidence for temporal variation, trends suggest that more studies are needed. Age and gender were found important determinants of the mixing patterns. Gender differences in mixing patterns might help explain gender differences in the epidemiology of infectious diseases.

Infections after Smallpox Vaccination against MpoxVaccination has emerged as an important tool to prevent mpox infection. In this report, breakthrough infections after postexposure receipt of a smallpox vaccine are evaluated.

Background Funding for health research is intrinsically limited; therefore, priority-setting is necessary to optimise investments. Prioritisation is particularly important for epidemic and pandemic pathogens, as preparedness needs for hypothetical threats can be difficult to assess, and response during outbreaks requires accelerated decision-making. Exercises which prioritise epidemic and pandemic pathogens have been published; however, to our knowledge, there has been no systematic analysis of how, why and by whom these exercises are conducted. Guidelines and good practices for prioritisation exist, but whether these are followed for pathogen prioritisation and the consequences on the quality and impact of results has not yet been analysed. Methods We undertook a scoping review to investigate processes and methods of analysis reported across pathogen priority-setting exercises. We ran a grey literature search on Overton and Google to identify relevant resources published since 2018. The resources were screened by independent reviewers and extracted data were analysed using descriptive statistics and narrative synthesis. Results The identified pathogen prioritisation exercises varied in geographical scope and included exercises focusing on specific threats such as antimicrobial resistance, as well as all-hazard prioritisation activities. We identified differences in the types of participants involved and their roles in priority-setting processes. While a diversity of processes and methods of analysis exist, there were common practices and steps, notably identifying candidate priority pathogens and developing assessment criteria, and then scoring the former against the latter to reach a final priority list. There were commonalities in the criteria themes used to score pathogens, such as severity of disease, transmissibility, prevalence, impact and mitigation measures. Rabies and influenza A were the two most reported priority list pathogens. Our ability to synthesise a meaningful ordered priority list across publications was limited by discrepancies in taxonomy and scope. Conclusions This study provides the first examination of priority setting exercises identifying high-consequence infectious pathogens. The review reveals important elements of commonality and variability between priority-setting exercises, highlighting areas for improvement to increase the comparability and quality of future efforts and their implementation.

Background Partner notification interventions are complex and assessing their effectiveness is challenging. By reviewing the literature on the effectiveness of partner notification interventions, our aim was to evaluate the choice, collection, and interpretation of outcomes and their impact on study findings. Methods We conducted a systematic review of individual-level randomised controlled trials evaluating the effectiveness of partner notification interventions for bacterial STIs, HIV or sexually transmitted HCV in high-income countries since 2000. Partner notification interventions included assisted patient referral interventions and expedited treatment. The content analysis was carried out through a narrative review. Results In the 9 studies that met the inclusion criteria, 16 different outcomes were found. In most studies, one or two outcomes assessing partner notification practices were associated with an outcome reflecting STI circulation through index case reinfections. These outcomes assessed the main expected effects of partner notification interventions. However, partner notification is composed of a succession of actions between the intervention on the index case and the testing and/or treatment of the notified partners. Intermediate outcomes were missing so as to better understand levers and barriers throughout the process. Potential changes in participants’ sexual behaviour after partner notification, e.g. condom use, were outcomes reported in only two studies assessing interventions including counselling. Most outcomes were collected through interviews, some weeks after the intervention, which might lead to desirability and attrition biases, respectively. Assessment of the effectiveness of partner notification interventions on partner testing/treatment was limited by the collection of data from index cases. Few data describing index cases and their partners were provided in the studies. Additional data on the number and type of exposed partners and the proportion of partners already aware of their infection before being notified would help to interpret the results. Conclusions These insights would help to understand why and under what conditions the intervention is considered effective and therefore can be replicated or adapted to other populations and contexts.