pWCP is a widely distributed and highly conserved Wolbachia plasmid in Culex pipiens and Culex quinquefasciatus mosquitoes worldwide.

Mosquitoes represent the most important pathogen vectors and are responsible for the spread of a wide variety of poorly treatable diseases. Wolbachia are obligate intracellular bacteria that are widely distributed among arthropods and collectively represents one of the most promising solutions for vector control. In particular, Wolbachia has been shown to limit the transmission of pathogens, and to dramatically affect the reproductive behavior of their host through its phage WO. While much research has focused on deciphering and exploring the biocontrol applications of these WO-related phenotypes, the extent and potential impact of the Wolbachia mobilome remain poorly appreciated. Notably, several Wolbachia plasmids, carrying WO-like genes and Insertion Sequences (IS), thus possibly interrelated to other genetic units of the endosymbiont, have been recently discovered. Here we investigated the diversity and biogeography of the first described plasmid of Wolbachia in Culex pipiens (pWCP) in several islands and continental countries around the world-including Cambodia, Guadeloupe, Martinique, Thailand, and Mexico-together with mosquito strains from colonies that evolved for 2 to 30 years in the laboratory. We used PCR and qPCR to determine the presence and copy number of pWCP in individual mosquitoes, and highly accurate Sanger sequencing to evaluate potential variations. Together with earlier observation, our results show that pWCP is omnipresent and strikingly conserved among Wolbachia populations within mosquitoes from distant geographies and environmental conditions. These data suggest a critical role for the plasmid in Wolbachia ecology and evolution, and the potential of a great tool for further genetic dissection and possible manipulation of this endosymbiont.

Severity of self-reported symptoms and psychological burden 6-months after hospital admission for COVID-19: a prospective cohort study.

OBJECTIVES: Few studies have reported clinical COVID-19 sequelae six months (M6) after hospital discharge, but none has studied symptom severity. METHODS: Prevalence and severity of 7 symptoms were estimated until M6 using the self-administered influenza severity scale in COVID-19 hospitalized patients enrolled in the French COVID cohort. Factors associated with severity were assessed by logistic regression. Anxiety, depression and health-related quality of life (HRQL) were also assessed. RESULTS: At M6, among the 324 patients (median age 61 years, 63% men, 19% admitted to intensive care during the acute phase), 187/324 (58%) reported at least one symptom, mostly fatigue (47%) and myalgia (23%). Symptom severity was scored, at most, mild in 125 (67%), moderate in 44 (23%) and severe in 18 (10%). Female gender was the sole factor associated with moderate/severe symptom reporting (OR = 1.98, 95%CI=1.13-3.47). Among the 225 patients with psychological assessment, 24 (11%) had anxiety, 18 (8%) depressive symptoms, and their physical HRQL was significantly poorer than the general population (p=0.0005). CONCLUSION: Even if 58% of patients reported ≥1 symptom at M6, less than 7% rated any symptom as severe. Assessing symptoms severity could be helpful to identify patients requiring appropriate medical care. Women may require special attention.

Investigation of Coagulation Biomarkers to Assess Clinical Deterioration in SARS-CoV-2 Infection.

Since December 2019, a pandemic caused by a new coronavirus has spread to more than 170 countries around the world. Worsening infected patients requiring intensive care unit (ICU) admission associated with 30% of mortality. A part of worsening is induced by hemostasis deregulation. The aim of this study was to investigate the association of coagulation activation in COVID-19 progression. Thirty-five of the 99 patients got clinically worse. The final model of the logistic regression analysis revealed that O2 requirement (RR = 7.27 [1.50-19.31]), monocytes below 0.2G/L (RR = 2.88 [1.67-3.19]), fibrinogen levels (RR = 1.45 [1.17-1.82] per g/L increase), prothrombin fragments 1+2 higher than 290 pM (RR = 2.39 [1.20-3.30]), and thrombin peak (RR = 1.28 [1.03-1.59] per 50 nM increase) were associated with an increased risk of clinical worsening. A fibrinogen level threshold of 5.5 g/L, a thrombin peak measurement threshold of 99 pM, and O2 requirement associated with clinical outcome in more than 80% of our cohort. In conclusion, we identified fibrinogen and thrombin peak at admission as coagulation biomarkers associated with an increased risk of ICU admission or death. This finding allows initiating steroids and triage for worsening patients. Our results should therefore be considered as exploratory and deserve confirmation.

Chronic use of renin-angiotensin-aldosterone system blockers and mortality in COVID-19: A multicenter prospective cohort and literature review.

AIMS: The role of renin-angiotensin-aldosterone system (RAAS) blockers on the course of coronavirus disease 2019 (COVID-19) is debated. We assessed the association between chronic use of RAAS blockers and mortality among inpatients with COVID-19 and explored reasons for discrepancies in the literature. METHODS AND RESULTS: We included adult hypertensive patients from a prospective nationwide cohort of 3512 inpatients with COVID-19 up to June 30, 2020. Cox proportional hazard models with various adjustment or propensity weighting methods were used to estimate the hazard ratios (HR) of 30-day mortality for chronic users versus non-users of RAAS blockers. We analyzed data of 1160 hypertensive patients: 719 (62%) were male and 777 (67%) were older than 65 years. The main comorbidities were diabetes (n = 416, 36%), chronic cardiac disease (n = 401, 35%), and obesity (n = 340, 29%); 705 (61%) received oxygen therapy. We recorded 135 (11.6%) deaths within 30 days of diagnosis. We found no association between chronic use of RAAS blockers and mortality (unadjusted HR = 1.13, 95% CI [0.8-1.6]; propensity inverse probability treatment weighted HR = 1.09 [0.86-1.39]; propensity standardized mortality ratio weighted HR = 1.08 [0.79-1.47]). Our comprehensive review of previous studies highlighted that significant associations were mostly found in unrestricted populations with inappropriate adjustment, or with biased in-hospital exposure measurement. CONCLUSION: Our results do not support previous concerns regarding these drugs, nor a potential protective effect as reported in previous poorly designed studies and meta-analyses. RAAS blockers should not be discontinued during the pandemic, while in-hospital management of these drugs will be clarified by randomized trials. NCT04262921.

Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort.

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10-4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10-3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.