Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

Pneumonia is one of the major complications of drowning, but the optimal empirical antibiotic treatment is not clearly defined. Multidrug-resistant (MDR) bacteria and fungi have been identified in a recent series of freshwater drowning-associated pneumonia. However, microbial data in seawater drowning are scarce. The objective of the study is to describe the microorganisms isolated in early respiratory specimens obtained from seawater drowning-associated pneumonia and to provide their antibiotic susceptibility pattern. All patients admitted for seawater drowning between 2003 and 2013 to two intensive care units, from the region in France with the highest drowning rate, were retrospectively included. Demographics, antimicrobial therapy and microbiological data from respiratory samples collected within the first 48 h after admittance were analyzed. Seventy-four drowned patients were included, of which 36 (49%) were diagnosed by the clinician as having early pneumonia. Concerning the overall population, the median simplified acute physiology score (version 2) was 45 (30–65), and the mortality was 26%. Twenty-four respiratory samples from different patients were obtained within the first 48 h. Sixteen were positive. The main microorganisms found were Enterobacteriaceae (Enterobacter spp., Klebsiella spp. and Escherichia coli) and Gram-positive aerobic cocci (Streptococcus pneumonia and Staphylococcus aureus) with a low rate of antimicrobial resistance. No MDR bacteria or fungi were identified. However, among the positive respiratory samples collected, 5/16 (31%) grew bacteria with natural resistance to amoxicillin–clavulanate, the first-line antibiotic commonly used in our cohort. Resistance was only found among Gram-negative bacteria and from respiratory samples of patients with a higher drowning grade at admission (p = 0.01). This 10-year descriptive study, the largest cohort to date, provides early respiratory samples from seawater drowning patients. The microorganisms retrieved were either mostly part of the human oro-pharyngeal flora or Enterobacteriaceae and displayed low rates of antimicrobial resistance. Respiratory samples should nonetheless be collected at admittance to the ICU to avoid inappropriate treatment. Empiric use of cephalosporin could be restricted to severe patients or if Gram-negative bacilli are found after direct examination.

Background: Polymicrobial infections are complex infections associated with worse outcomes compared to monomicrobial infections. We need simple, fast, and cost-effective animal models to assess their still poorly known pathogenesis. Methods: We developed a Drosophila melanogaster polymicrobial infection model for opportunistic pathogens and assessed its capacity to discriminate the effects of bacterial mixtures taken from cases of human polymicrobial infections by Aeromonas strains. A systemic infection was obtained by needle pricking the dorsal thorax of the flies, and the fly survival was monitored over time. Different lineages of the flies were infected by a single strain or paired strains (strain ratio 1:1). Results: Individual strains killed more than 80% of the flies in 20 h. The course of infection could be altered with a microbial mix. The model could distinguish between the diverse effects (synergistic, antagonistic, and no difference) that resulted in a milder, more severe, or similar infection, depending on the paired strain considered. We then investigated the determinants of the effects. The effects were maintained in deficient fly lineages for the main signaling pathways (Toll deficient and IMD deficient), which suggests an active microbe/microbe/host interaction. Conclusion: These results indicate that the D. melanogaster systemic infection model is consistent with the study of polymicrobial infection.