Low neutralizing antibody titers against the Mu variant of SARS-CoV-2 in BNT162b2 vaccinated individuals (preprint)

Summary Background Global surveillance programs for the virus that causes COVID-19 are showing the emergence of variants with mutations in the Spike protein, including the Mu variant, recently declared a Variant of Interest (VOI) by the World Health Organization. Genomic and laboratory surveillance is important in these types of variants because they may be more infectious or less susceptible to antiviral treatments and vaccine-induced antibodies. Objectives To evaluate the sensitivity of the Mu variant (B.1.621) to neutralizing antibodies induced by the BNT162b2 vaccine. Study design Three of the most predominant SARS-CoV-2 variants in Colombia during the epidemiological peaks of 2021 were isolated. Microneutralization assays were performed by incubating 120 TCDI 50 of each SARS-CoV-2 isolate with five 2-fold serial dilutions of sera from 14 BNT162b2 vaccinated volunteers. The MN 50 titer was calculated by the Reed-Muench formula Results The three isolated variants were Mu, a Variant of Interest (VOI), Gamma, a variant of concern (VOC), and B.1.111 that lacks genetic markers associated with greater virulence. At the end of August, the Mu and Gamma variants were widely distributed in Colombia. Mu was predominant (49%), followed by Gamma (25%). In contrast, B.1.111 became almost undetectable. The evaluation of neutralizing antibodies suggests that patients vaccinated with BNT162-2 generate neutralizing antibody titers against the Mu variant at significantly lower concentrations relative to B.1.111 and Gamma. Conclusions This study shows the importance of continuing with surveillance programs of emerging variants as well as the need to evaluate the neutralizing antibody response induced by other vaccines circulating in the country against Mu and other variants with high epidemiological impact. Highlights Mu and Gamma variants represented 49% and 25% of cases in Colombia by August 2021. Increased proportion of SARS-COV-2 cases were mostly associated with Mu variant, despite being detected simultaneously with the VOC Gamma The Mu variant remarkably escapes from neutralizing antibodies elicited by the BNT162b2-vaccine Laboratory studies of neutralizing antibodies are useful to determine the efficacy of SARS-CoV-2 vaccines against VOC and VOI.

La construcción social del riesgo. Claves analíticas para comprender la pandemia de Covid-19 en México: el caso de la Jornada Nacional de Sana Distancia

El objetivo de este artículo es plantear claves analíticas de la sociología del riesgo para tratar de comprender el fenómeno de la pandemia por Covid-19 en México. Lo anterior se explica a través de la constitución de diferentes formas de asunción, apropiación y significación de la pandemia, a partir de visibilizar el carácter multidimensional de la construcción social del riesgo. En su sección teórica, se trazan los postulados de la sociología del riesgo, en sus "clásicos" y en sus perspectivas contemporáneas. En la sección analítica, se establecen modelos teóricos a partir de conceptos vistos como "herramientas" para aproximarse a la pandemia por Covid-19. En la última sección, se propone operar analíticamente el caso de la Jornada Nacional de Sana Distancia en México, la cual evidencia formas de la construcción del riesgo. Este acontecimiento marca temporalida des y categorizaciones analíticas específicas que darán cuenta de la complejidad de la configuración del riesgo en la pandemia en México.Alternate abstract:The aim of this particle is to present analytical sociological keys of risk assessment in order to attempt to understand the phenomenon of the Covid-19 pandemic in Mexico. This is achieved through the various forms of assumption, appropriation and signification of the pandemic by the visibilization of the multidimensional nature of the social construction of risk. Its theoretical section outlines the postulates of both classic and contemporary risk sociology. Its analytical section establishes theoretical models using concepts such as "tools" for approaching the Covid-19 pandemic. Its final section intends to analyze the Jornada Nacional de Sana Distancia in Mexico, which displayed different forms of risk construction. This evinces specific analytical categorizations and temporalities that will account for the complexity of risk configuration in the pandemic in Mexico.

High efficacy of therapeutic equine hyperimmune antibodies against SARS CoV-2 variants of concern (preprint)

SARS-CoV-2 variants of concern (VoC) show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies. We tested therapeutic equine polyclonal antibodies (pAbs) against four VoC (alpha, beta, epsilon and gamma). We show that equine pAbs efficiently neutralize VoC, suggesting they are an effective, broad coverage, low-cost and a scalable COVID-19 treatment.

Reduced macular vessel density in COVID-19 patients with and without associated thrombotic events using optical coherence tomography angiography.

PURPOSE: Thrombotic events (TE) represent one of the major complications of SARS-CoV-2 infection. The objective is to evaluate vessel density (VD) and perfusion density (PD) by optical coherence tomography angiography (OCTA) in COVID-19 patients, and compare the findings with healthy controls. The secondary objective is to evaluate if there are differences in OCTA parameters between COVID-19 patients with and without associated TE. METHODS: Cross-sectional case-control study that included patients with laboratory-confirmed diagnosis of COVID-19 with and without TE related to the infection and age-matched healthy controls. Ophthalmological examination and OCTA were performed 12 weeks after diagnosis. Demographic data and medical history were collected. Macular OCTA parameters in the superficial retinal plexus were analyzed according to ETDRS sectors. RESULTS: Ninety patients were included, 19 (20%) COVID-19 patients with associated TE, 47 (49.5%) COVID-19 patients without TE, and 29 (30.5%) healthy controls. Fifty-three (55.7%) were male, mean age 54.4 (SD 10.2) years. COVID-19 patients presented significantly lower VD than healthy controls: central (p = 0.003), inner ring (p = 0.026), outer ring (p = 0.001). PD was also significantly decreased: outer ring (p = 0.003), full area (p = 0.001). No differences in OCTA parameters were found between COVID-19 patients with and without TE. CONCLUSIONS: OCTA represents a promising tool for the in vivo assessment of microvascular changes in COVID-19. Patients with SARS-CoV-2 infection show lower VD and PD compared to healthy controls. However, no differences were found between COVID-19 when considering TE. Prospective studies are required to further evaluate the retinal microvascular involvement of SARS-CoV-2 and its impact on the vasculature of other organs.

Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2 (preprint)

The SARS-CoV-2 genetic diversification has a potential impact in the virus escape from natural infection- or vaccine-elicited neutralizing antibodies and higher transmissibility. Here we report the emergence of novel B.1.621 variant of interest with the insertion 145N in the N-terminal domain and amino acid change N501Y, E484K, and P681H in the Receptor Binding Domain of the Spike protein. Further studies in vitro biological assays and epidemiologic analysis will allow evaluating the public health impact of B.1.621 variant.

Breast Cancer Management During COVID-19 Pandemic in Madrid: Surgical Strategy.

BACKGROUND: From the first case of SARS-CoV-2 infection in Wuhan (China), the infection spread all around the world causing a pandemic of coronavirus disease-2019 (COVID-19). Spain has been one of the most severely affected countries, and Madrid has reported a high number of cases and deaths. We discuss our strategies for optimal breast cancer management during COVID-19 pandemic. PATIENTS AND METHODS: This was a retrospective observational study at Clínico San Carlos Hospital to analyze the management of patients with breast cancer during the pandemic outbreak and the surgical strategy after the pandemic outbreak. We created a practical and dynamic tool based on a "traffic light" system for prioritizing surgical time. Every patient was contacted by telephone with a preoperative COVID-19 protocol. After surgical procedures, patient satisfaction was assessed using the European Organisation for Research and Treatment of Cancer in-patient satisfaction with cancer care questionnaire (EORTC IN-PATSAT32). RESULTS: Patients with breast cancer actively treated with surgical procedures were put on a waiting list and received systemic therapy. Telemedicine was used to evaluate any side effects and to avoid unnecessary hospital visits. Surgery was only considered after the pandemic outbreak, and then, only those procedures designed to minimize surgical complications and, therefore, reduce hospital stay. We also measured patients' satisfaction with medical and nursing scales that resulted in a "very good" evaluation tending to "excellent". CONCLUSION: It is necessary to adapt management of oncology treatment and surgical strategy to optimize resources during the COVID-19 pandemic. Patients' perception of care quality and the degree of patients' satisfaction with health services has potential relevance in the absence of outcome data.

Development and pre-clinical characterization of two therapeutic equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19 (preprint)

In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.

Impact of COVID-19 outbreak on ischemic stroke admissions and in-hospital mortality in North-West Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries heavily stricken by COVID-19. But this epidemic has not affected all regions equally. We analyzed the impact of the COVID-19 pandemic on hospital stroke admissions and in-hospital mortality in tertiary referral hospitals from North-West Spain. METHODS: Spanish multicenter retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. We recorded the number of patients admitted for ischemic stroke between 30 December 2019 and 3 May 2020, the number of IVT and EVT procedures, and in-hospital mortality. RESULTS: In the study period, 2737 patients were admitted with ischemic stroke. There was a decrease in the weekly mean admitted patients during the pandemic (124 vs. 173, p<0.001). In-hospital mortality of stroke patients increased significantly (9.9% vs. 6.5%, p = 0.003), but there were no differences in the proportion of IVT (17.3% vs. 16.1%, p = 0.405) or EVT (22% vs. 23%, p = 0.504). CONCLUSION: We found a decrease in the number of ischemic stroke admissions and an increase in in-hospital mortality during the COVID-19 epidemic in this large study from North-West Spain. There were regional changes within the network, not fully explained by the severity of the pandemic in different regions.