ABSTRACT
SARS-CoV-2 is a new coronavirus that is the cause of COVID-19 pandemic. To enter the cell, the virus interacts via its surface S protein with angiotensin-converting enzyme 2 (ACE2), the main entry receptor on the cell membrane. Most of protective antibodies, including those induced by vaccinations, target the S protein, preventing its interaction with the ACE2 receptor. We have evaluated an alternative strategy for blocking the S-ACE2 interaction using new antipeptide antibodies to the N-terminus of the ACE2 molecule. These antibodies allow detection of human ACE2 in vitro and ex vivo.
Subject(s)
Angiotensin-Converting Enzyme 2/immunology , COVID-19 , Pandemics , Angiotensins/metabolism , Humans , Pandemics/prevention & control , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, CoronavirusABSTRACT
Background: By 11/03/2020, the WHO had declared the COVID-19 outbreak a pandemic. At 25/05/2020 Russia ranked third by the incidence of COVID-19 and the number of confirmed cases was 344,481 with 3,541(1%) deaths. Aim: To describe the epidemiological characteristics and survival of patients with hematological diseases (HD) and COVID-19. Patients: Between 20/04/2020-25/05/2020, all hospitalized patients at NRCH were tested for COVID-19 before hospitalization and with once-weekly follow-up (or in case of fever). Nasal swab samples were studied by RT-PCR. The study population included 46 patients (pts) with HD and confirmed SARS-CoV-2. All pts were observed at ten departments. 15 pts who shared the same wards (3-4 patients in one ward) at one department were infected. Ten infected pts resided in single-bed wards and 21 pts were observed at the outpatient department. All pts with positive SARS-CoV-2 were treated either in COVID-19-specialized centers (29 (63%) pts) or at home (17 (37%) pts). Results: The most common symptom at the onset of illness was fever (26 (57%) pts), the other pts were asymptomatic. Pneumonia was diagnosed in 27 pts. All 17 pts who were treated at home recovered. Out of 8 pts who required treatment at the ICU, 5 pts died. Thirty-eight pts were treated without ICU (1 pt died due to sudden death). As of 25/05/2020, 10 out of 29 pts were still hospitalized. Totally, 13 pts were discharged, and 6 pts died. Out of the 8 pts who were admitted to the ICU, 1 pt was still at the ICU, 1 pt was discharged and returned home, 1 pt was transferred to the general wards, and 5 pts died. Six (13%) of 46 pts required IMV;of them, 5 pts died and 1 pt still remains. Conclusion: In this single-center analysis of 46 pts with HD and confirmed SARS-CoV-2, 1-month OS was 82%, the median follow-up was 18 days, and mortality was 13%. Compared to the general population with COVID-19 in Russia, the mortality in patients with HD was higher (13% vs 1%) with the comparable median age (40 vs 45 years). The COVID-19 pandemic dictates new epidemiological conditions for the management of pts with HD: mandatory SARS-CoV-19 testing in all pts before hospitalization followed by weekly testing, treatment in single-room wards and compliance with strict epidemiological measures.
ABSTRACT
Determination of T-cell immune response to SARS-CoV-2 is important both for diagnosis of the disease in symptomatic patients, and for determination of the total number of people who have had the disease, including its asymptomatic form. In addition, these assays are efficient for assessing the immune response after vaccination, as well as immunity levels in risk groups and in convalescent patients. The most promising method of T-cell immune response assessment is an ELISPOT-based assay measuring the release of interferon-gamma (IGRA) after stimulation with coronavirus-specific antigens. The present review analyses the prospects for using the ELISPOT technological platform in the clinical laboratory setting when dealing with the new coronavirus infection COVID-19, given specific aspects of the immune response. The review summarises data from articles published in peer-reviewed journals, preprints of articles available at arXiv resources, and information that some leading immunologists shared with the authors during private discussions. It has been shown that the introduction of B- and T-cell ELISPOT assays will make it possible to monitor the immunological status of patients, select a treatment strategy, identify the most vulnerable populations, carry out comprehensive assessment of vaccines during the development, clinical trials and implementation stages. The paper discusses the issues of maintaining T-cell immunity in the blood of people who have had HCoV, SARS, MERS, and COVID-19 coronavirus infections. It also discusses the advantages of the T-cell ELISPOT assay over serological tests as regards epidemiological assessment of the prevalence of the new coronavirus infection, and clinical trials of COVID-19 vaccines. Biotechnology companies have a ready-made technological platform for the development and industrial-scale production of ELISPOT kits, and this platform is easily adaptable to specific types of assays and pathogens. The paper supports the need to develop vaccines that would stimulate both cellular and humoral immune responses, and raises the question of the protective potential of cross-immunity acquired before the COVID-19 pandemic.