Corpus overview


MeSH Disease

Human Phenotype

Hepatitis (1)

Meningitis (1)

Fever (1)


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    Equine hyperimmune globulin raised against the SARS-CoV-2 spike glycoprotein has extremely high neutralizing titers

    Authors: Luis Eduardo R. Cunha; Adilson A. Stolet; Marcelo A. Strauch; Victor A. R. Pereira; Carlos H. Dumard; Patricia N. C. Souza; Juliana G. Fonseca; Francisco E. Pontes; Leonardo G. R. Meirelles; Jose W. M. Albuquerque; Carolina Q. Sacramento; Natalia Fintelman-Rodrigues; Tulio M. Lima; Renata G. F. Alvim; Russolina Zingali; Guilherme A. P. Oliveira; Thiago M. L. Souza; AMILCAR TANURI; Andre M. O. Gomes; Andrea C. Oliveira; Herbert L. M. Guedes; Leda R. Castilho; Jerson L. Silva; Scott Hensley

    doi:10.1101/2020.08.17.254375 Date: 2020-08-18 Source: bioRxiv

    COVID-19 pandemic caused approximately 750,000 deaths MESHD and over 20 million confirmed cases TRANS of infection MESHD by SARS-CoV-2 within 8 months since the emergence of the virus. While there are no vaccines approved and considering the difficulty in meeting the large vaccination demand worldwide, the potential use of passive immunization should be considered based on existing successful therapies against many diseases. Here we demonstrate that hyperimmune globulin preparations raised in horses against the recombinant trimeric spike (S) glycoprotein of SARS-CoV-2 in the prefusion conformation provide very high ELISA SERO titers as well as highly potent neutralizing activity against SARS-CoV-2. Five horses were subcutaneously inoculated for 6 weeks with the recombinant S protein (ectodomain, residues 1-1208). Four out of the 5 horses presented a strong immune response. Considering the average of all 5 horses, ELISA SERO titers above 1:1,000,000 and neutralizing titers (PRNT90) reaching 1:14,604 were observed. When compared with the plasma SERO of three convalescent COVID-19 patients, sera of immunized horses displayed approximately 140-fold higher neutralizing titers measured as PRNT90. To prevent eventual side effects caused by horse antiserum, IgG was digested with pepsin and purified by fractional salt precipitation to eliminate Fc fragments, a process that is industrially used for the production of passive immunization F(ab)2 concentrates against rabies, tetanus MESHD and snake venoms. The high neutralizing titers against SARS-CoV-2 obtained for the unprocessed sera were confirmed for the F(ab)2 fragments and were 150-fold higher than the PRNT90 neutralizing titers of plasma SERO of three COVID-19 convalescent patients. The great advantage of using the recombinant trimeric S glycoprotein is that it is safe and provides quick adaptive immunity in horses. Our data show the perspective of using hyperimmune anti-SARS-CoV-2 F(ab)2 preparations as a passive immunization therapy in humans, similar to therapies that have been safely used for decades against rabies, tetanus MESHD and snake venoms.

    Benefit-risk analysis of health benefits of routine childhood immunisation against the excess risk of SARS-CoV-2 infections MESHD during the Covid-19 pandemic in Africa

    Authors: Kaja Abbas; Simon R Procter; Kevin van Zandvoort; Andrew Clark; Sebastian Funk; - LSHTM CMMID Covid-19 Working Group; Tewodaj Mengistu; Dan Hogan; Emily Dansereau; Mark Jit; Stefan Flasche

    doi:10.1101/2020.05.19.20106278 Date: 2020-05-26 Source: medRxiv

    Background: National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. Our aim is to compare the health benefits of sustaining routine childhood immunisation in Africa against the risk of acquiring SARS-CoV-2 infections MESHD through visiting routine vaccination service delivery points. Methods: We used two scenarios to approximate the child TRANS deaths that may be caused by immunisation coverage reductions during COVID-19 outbreaks. First, we used previously reported country-specific child TRANS mortality impact estimates of childhood immunisation for diphtheria, tetanus MESHD, pertussis, hepatitis HP hepatitis MESHD B, Haemophilus influenzae type b, pneumococcal MESHD, rotavirus MESHD, measles, meningitis HP meningitis MESHD A, rubella MESHD, and yellow fever MESHD fever HP (DTP3, HepB3, Hib3, PCV3, RotaC, MCV1, MCV2, MenA, RCV, YFV) to approximate the future deaths averted before completing five years of age TRANS by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. Second, we analysed an alternative scenario that approximates the health benefits of sustaining routine childhood immunisation to only the child TRANS deaths averted from measles outbreaks during the COVID-19 risk period. The excess number of infections MESHD due to additional SARS-CoV-2 exposure during immunisation visits assumes that contact reducing interventions flatten the outbreak curve during the COVID-19 risk period, that 60% of the population will have been infected by the end of that period, that children TRANS can be infected by either vaccinators or during transport and that upon child TRANS infection the whole household would be infected. Country specific household age TRANS structure estimates and age TRANS dependent infection fatality rates are then applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation alongside 95% uncertainty range estimates from probabilistic sensitivity SERO analysis. Findings: For every one excess COVID-19 death attributable to SARS-CoV-2 infections MESHD acquired during routine vaccination clinic visits, there could be 84 (14-267) deaths in children TRANS prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children TRANS, siblings, parents TRANS or adult TRANS care-givers, and older adults TRANS in the households of vaccinated children TRANS are 85,000 (4,900 - 546,000), 75,000 (4,400 - 483,000), 769 (148 - 2,700), and 96 (14 - 307) respectively. In the alternative scenario that approximates the health benefits to only the child TRANS deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children TRANS is 3 (0 - 10) under these highly conservative assumptions and if the risk to only the vaccinated children TRANS is considered, the benefit-risk ratio is 3,000 (182 - 21,000). Interpretation: Our analysis suggests that the health benefits of deaths prevented by sustaining routine childhood immunisation in Africa far outweighs the excess risk of COVID-19 deaths associated with vaccination clinic visits, especially for the vaccinated children TRANS. However, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in African countries during the COVID-19 pandemic. These include logistical constraints of vaccine supply chain problems caused by the COVID-19 pandemic, reallocation of immunisation providers to other prioritised health services, healthcare staff shortages caused by SARS-CoV-2 infections MESHD among the staff, decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting SARS-CoV-2 infections MESHD, and infection risk TRANS infection risk TRANS to healthcare staff providing immunisation services as well as to their households and onward SARS-CoV-2 transmission TRANS into the wider community.

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MeSH Disease
Human Phenotype

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