Background The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike protein than any previous variant, especially in the receptor-binding domain (RBD). We analyzed the binding of the Omicron RBD to the human angiotensin-converting enzyme-2 receptor (ACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta, or Delta RBD variants. Methods All RBDs were produced in insect cells. RBD binding to ACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 81 vaccinated individuals, and 34 booster recipients were titrated by ELISA on RBDs from the original Wuhan strain, Beta, Delta, and Omicron VOCs. In addition, the neutralization efficacy of authentic SARS-CoV-2 wild type (D614G), Delta, and Omicron by sera from 2× or 3× BNT162b2-vaccinated persons was analyzed. Results Surprisingly, the Omicron RBD showed a somewhat weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. A 2.6× reduction in Omicron RBD binding was observed for serum of 2× BNT162b2-vaccinated persons. Neutralization of Omicron SARS-CoV-2 was completely diminished in our setup. Conclusion These results indicate an immune escape focused on neutralizing antibodies. Nevertheless, a boost vaccination increased the level of anti-RBD antibodies against Omicron, and neutralization of authentic Omicron SARS-CoV-2 was at least partially restored. This study adds evidence that current vaccination protocols may be less efficient against the Omicron variant.
BackgroundThe ongoing COVID-19 pandemic is caused by the beta coronavirus SARS-CoV-2. COVID-19 manifests itself from mild or even asymptomatic infections to severe forms of life-threatening pneumonia. At the end of November 2021, yet another novel SARS-CoV-2 variant named B.1.1.529 or Omicron was discovered and classified as a variant of concern (VoC) by the WHO. Omicron shows significantly more mutations in the amino acid (aa) sequence of its spike protein than any previous variant, with the majority of those concentrated in the receptor binding domain (RBD). In this work, the binding of the Omicron RBD to the human ACE2 receptor was experimentally analyzed in comparison to the original Wuhan SARS-CoV-2 virus, and the Beta and Delta variants. Moreover, we compared the ability of human sera from COVID-19 convalescent donors and persons fully vaccinated with BNT162b2 (Corminaty) or Ad26.COV2.S (Janssen COVID-19 vaccine) as well as individuals who had boost vaccine doses with BNT162b2 or mRNA-1273 (Spikevax) to bind the different RBDs variants.MethodsThe Omicron RBD with 15 aa mutations compared to the original Wuhan strain was produced baculovirus-free in insect cells. Binding of the produced Omicron RBD to hACE was analyzed by ELISA. Sera from 27 COVID-19 patients, of whom 21 were fully vaccinated and 16 booster recipients were titrated on the original Wuhan strain, Beta, Delta and Omicron RBD and compared to the first WHO Integrnational Standard for anti-SARS-CoV-2 immunoglobulin (human) using the original Wuhan strain as reference.ResultsThe Omicron RBD showed a slightly reduced binding to ACE2 compared to the other RBDs. The serum of COVID-19 patients, BNT162b2 vaccinated and boost vaccinated persons showed a reduced binding to Omicron RBD in comparison to the original Wuhan strain, Beta und Delta RBDs. In this assay, the boost vaccination did not improve the RBD binding when compared to the BNT162b2 fully vaccinated group. The RBD binding of the Ad26.COV2.S serum group was lower at all compared to the other groups.ConclusionsThe reduced binding of human sera to Omicron RBD provides first hints that the current vaccinations using BNT162b2, mRNA-1273 and Ad26.COV2.S may be less efficient in preventing infections with the Omicron variant.
C‑reactive protein (CRP) and albumin are inflammation sensitive parameters that are regulated by interleukin‑6 inflammatory pathways. The CRP to albumin ratio (CAR) integrates these two into a potent clinical parameter whose clinical and prognostic association in the context of coronavirus disease 2019 (COVID-19) have not been well defined. We aimed to investigate the clinical and prognostic significance of CAR in the context of COVID-19 infection. We retrospectively analyzed 2309 consecutive COVID-19 patients hospitalized at a tertiary level hospital in the period from March 2020 to March 2021 who had baseline data for a CAR assessment. Findings were validated in an independent cohort of 1155 patients hospitalized from March 2021 to June 2021. The majority of patients (85.8%) had severe or critical COVID-19 on admission. Median CRP, albumin and CAR levels were 91 mg/L, 32 g/L and 2.92, respectively. Higher CAR was associated with a tendency for respiratory deterioration during hospitalization, increased requirement of high-flow oxygen treatment and mechanical ventilation, higher occurrence of bacteriemia, higher occurrence of deep venous thrombosis, lower occurrence of myocardial infarction, higher 30-day mortality and higher postdischarge mortality rates. We defined and validated four CAR prognostic categories (< 1.0, 1.0–2.9, 3.0–5.9 and ≥ 6.0) with distinct 30-day survival. In the series of multivariate Cox regression models we could demonstrate robust prognostic properties of CAR that was associated with inferior 30-day survival independently of COVID-19 severity, age and comorbidities and additionally independently of COVID-19 severity, CURB-65 and VACO index in both development and validation cohorts. The CAR seems to have a good potential to improve prognostication of hospitalized COVID-19 patients. Supplementary Information The online version of this article (10.1007/s00508-021-01999-5) contains supplementary material, which is available to authorized users.
In the framework of green materials, in recent years, natural fiber composites attracted great attention of academia and industry. Their mechanical and tribological characteristics, such as high strength, elasticity, friction, and wear resistance, make them suitable for a wide range of industrial applications in which issues regarding a large amount of disposal are to be considered since their environmental friendliness gives them an advantage over conventional synthetic materials. Based on the recent and relevant investigations found in the scientific literature, an overview focused on the tribological characteristics of composite materials reinforced with different types of natural fibers is presented. The aim is to introduce the reader to the issues, exploring the actual knowledge of the friction and wear characteristics of the composites under the influence of different operating parameters, as well as the chemical treatment of fibers. The main experimental tribological techniques and the main used apparatus are also discussed, with the aim of highlighting the most appropriate future research directions to achieve a complete framework on the tribological behavior of many possible natural fiber composite materials.
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