Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.

No abstract

IntroductionMost data on de-escalation of empirical antimicrobial therapy has focused on ventilator-associated pneumonia. In this retrospective monocentric study, we evaluated de-escalation as part of a global strategy of empiric antibiotherapy management irrespective of the location and the severity of the infection. The goal of this trial was to assess the application of a de-escalation strategy and the impact in terms of re-escalation, recurrent infection and to identify variables associated with de-escalation.MethodsAll consecutive patients treated with empiric antibiotic therapy and hospitalized in the intensive care unit for at least 72 hours within a period of 16 months were included. We compared the characteristics and outcome of patients who have experienced de-escalation therapy with those who have not.ResultsA total of 116 patients were studied corresponding to 133 infections. Antibiotic therapy was de-escalated in 60 cases (45%). De-escalation, primarily accomplished by a reduction in the number of antibiotics used, was observed in 52% of severe sepsis or septic shock patients. Adequate empiric antibiotic and use of aminoglycoside were independently linked with de-escalation. De-escalation therapy was associated with a significant reduction of recurrent infection (19% vs 5% P = 0.01). Mortality was not changed by de-escalation.ConclusionsAs part of a global management of empiric antibiotherapy in an intensive care unit, de-escalation might be safe and feasible in a large proportion of patients.

In sports medicine, there is increasing interest in quantifying the elastic properties of skeletal muscle, especially during extreme muscular stimulation, to improve our understanding of the impact of alterations in skeletal muscle stiffness on resulting pain or injuries, as well as the mechanisms underlying the relationships between these parameters. Our main objective was to determine whether real-time shear-wave elastography (SWE) can monitor changes in quadriceps muscle elasticity during an extreme mountain ultra-marathon, a powerful mechanical stress model. Our study involved 50 volunteers participating in an extreme mountain marathon (distance: 330 km, elevation: +24,000 m). Quantitative SWE velocity and shear modulus measurements were performed in most superficial quadriceps muscle heads at the following 4 time points: before the race, halfway through the race, upon finishing the race and after recovery (+48 h). Blood biomarker levels were also measured. A significant decrease in the quadriceps shear modulus was observed upon finishing the race (3.31±0.61 kPa) (p<0.001) compared to baseline (3.56±0.63 kPa), followed by a partial recovery +48 h after the race (3.45±0.6 kPa) (p = 0.002) across all muscle heads, as well as for each of the following three muscle heads: the rectus femoris (p = 0.003), the vastus medialis (p = 0.033) and the vastus lateralis (p = 0.001). Our study is the first to assess changes in muscle stiffness during prolonged extreme physical endurance exercises based on shear modulus measurements using non-invasive SWE. We concluded that decreases in stiffness, which may have resulted from quadriceps overuse in the setting of supra-physiological stress caused by the extreme distance and unique elevation of the race, may have been responsible for the development of inflammation and muscle swelling. SWE may hence represent a promising tool for monitoring physiologic or pathological variations in muscle stiffness and may be useful for diagnosing and monitoring muscle changes.