Antiviral Therapy of COVID-19.

Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19.

Vaccination of patients with allergic disease against novel coronavirus infection: Position paper of the russian association of allergology and clinical immunology

One of the key tasks of the previous year is to stop the spread of coronavirus disease (COVID-19), which became a pandemic that led to the deaths of more than 4 million people worldwide and more than 140 thousand deaths in Russia. COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (2019-nCoV) virus of the coro-navirus family. Vaccination plays a leading role in ending the pandemic. Currently, five vaccines against COVID-19 have been registered in Russia, namely, Sputnik V, Sputnik light, EpiVacCorona, EpiVacCorona-H, and SoviVak. The short follow-up period and absence of randomized placebo-controlled trials of COVID-19 vaccines in certain patients with chronic diseases lead to several questions about the effectiveness/safety of vaccination in these patients. Given the wide spread of allergic diseases and the heterogeneity of patients with allergopathology, experts of the Russian Association of Allergology and Clinical Immunology have developed and approved a position paper on vaccination of patients with allergopathology.Copyright © 2020 Pharmarus Print Media.

Vaccination against covid-19 for patients with primary immunodefi ciency and hereditary angioedema: The position paper of the Russian association of allergology, clinical immunology, and the national association of experts in primary immunodefi ciencies.

Since the end of 2019, the whole world has been suff ering from the Corona virus-19 (COVID-19) pandemic due to the potentially severe acute respiratory infection caused by the SARS-CoV-2 virus. To date, the infection has led to more than 4 million deaths worldwide, and>140 thousand deaths in Russia. Vaccination against COVID-19 plays a key role in stopping the pandemic. According to the existing experience in infection prevention, mass vaccination will reduce the virus's expansion and the risk of vaccine-resistant strains developing. In the context of COVID-19, the question of the feasibility and safety of vaccination for patients with primary immunodefi ciency and hereditary angioedema arises. The Russian Association of Allergists, Clinical Immunologists, and the National Association of Experts in Primary Immunodefi ciencies have developed and approved a position paper on the vaccination for patients with primary immunodefi ciency and hereditary angioedema against COVID-19. This position paper provides answers to key questions regarding vaccination for patients with these diseases.Copyright © 2020 Pharmarus Print Media License.

Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell®.

The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to develop and characterize a SARS-CoV-2 vaccine targeting the highly conserved nucleocapsid (N) protein. Recombinant N protein was expressed in Escherichia coli, purified to homogeneity by chromatography and characterized by SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering and differential scanning calorimetry. The vaccine, formulated as a squalane-based emulsion, was used to immunize Balb/c mice and NOD SCID gamma (NSG) mice engrafted with human PBMCs, rabbits and marmoset monkeys. Safety and immunogenicity of the vaccine was assessed via ELISA, cytokine titer assays and CFSE dilution assays. The protective effect of the vaccine was studied in SARS-CoV-2-infected Syrian hamsters. Immunization induced sustainable N-specific IgG responses and an N-specific mixed Th1/Th2 cytokine response. In marmoset monkeys, an N-specific CD4+/CD8+ T cell response was observed. Vaccinated Syrian hamsters showed reduced lung histopathology, lower virus proliferation, lower lung weight relative to the body, and faster body weight recovery. Convacell® thus is shown to be effective and may augment the existing armamentarium of vaccines against COVID-19.

Dissection of Antibody Responses of Gam-COVID-Vac-Vaccinated Subjects Suggests Involvement of Epitopes Outside RBD in SARS-CoV-2 Neutralization.

Millions of people have been vaccinated with Gam-COVID-Vac but fine specificities of induced antibodies have not been fully studied. Plasma from 12 naïve and 10 coronavirus disease 2019 (COVID-19) convalescent subjects was obtained before and after two immunizations with Gam-COVID-Vac. Antibody reactivity in the plasma samples (n = 44) was studied on a panel of micro-arrayed recombinant folded and unfolded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and 46 peptides spanning the spike protein (S) and by immunoglobulin G (IgG) subclass enzyme-linked immunosorbent assay (ELISA). The ability of Gam-COVID-Vac-induced antibodies to inhibit binding of the receptor-binding domain (RBD) to its receptor angiotensin converting enzyme 2 (ACE2) was investigated in a molecular interaction assay (MIA). The virus-neutralizing capacity of antibodies was studied by the pseudo-typed virus neutralization test (pVNT) for Wuhan-Hu-1 and Omicron. We found that Gam-COVID-Vac vaccination induced significant increases of IgG1 but not of other IgG subclasses against folded S, spike protein subunit 1 (S1), spike protein subunit 2 (S2), and RBD in a comparable manner in naïve and convalescent subjects. Virus neutralization was highly correlated with vaccination-induced antibodies specific for folded RBD and a novel peptide (i.e., peptide 12). Peptide 12 was located close to RBD in the N-terminal part of S1 and may potentially be involved in the transition of the pre- to post-fusion conformation of the spike protein. In summary, Gam-COVID-Vac vaccination induced S-specific IgG1 antibodies in naive and convalescent subjects in a comparable manner. Besides the antibodies specific for RBD, the antibodies induced against a peptide close to the N-terminus of RBD were also associated with virus-neutralization.

Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation.

BACKGROUND: Severe acute respiratory syndrome corona virus (SARS-CoV-2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate safety and efficacy of a SARS-CoV-2-specific siRNA-peptide dendrimer formulation MIR 19® (siR-7-EM/KK-46) targeting a conserved sequence in known SARS-CoV-2 variants for treatment of COVID-19. METHODS: We conducted an open-label, randomized, controlled multicenter phase II trial (NCT05184127) evaluating safety and efficacy of inhaled siR-7-EM/KK-46 (3.7 mg and 11.1 mg/day: low and high dose, respectively) in comparison with standard etiotropic drug treatment (control group) in patients hospitalized with moderate COVID-19 (N = 52 for each group). The primary endpoint was the time to clinical improvement according to predefined criteria within 14 days of randomization. RESULTS: Patients from the low-dose group achieved the primary endpoint defined by simultaneous achievement of relief of fever, normalization of respiratory rate, reduction of coughing, and oxygen saturation of >95% for 48 h significantly earlier (median 6 days; 95% confidence interval [CI]: 5-7, HR 1.75, p = .0005) than patients from the control group (8 days; 95% CI: 7-10). No significant clinical efficacy was observed for the high-dose group. Adverse events were reported in 26 (50.00%), 25 (48.08%), and 28 (53.85%) patients from the low-, high-dose and control group, respectively. None of them were associated with siR-7-EM/KK-46. CONCLUSIONS: siR-7-EM/KK-46, a SARS-CoV-2-specific siRNA-peptide dendrimer formulation is safe, well tolerated and significantly reduces time to clinical improvement in patients hospitalized with moderate COVID-19 compared to standard therapy in a randomized controlled trial.

Delayed Pulmonary Tuberculosis (PTB) Diagnosis During the COVID-19 Pandemic: A Case Series

Background. The COVID-19 pandemic has been associated with underreporting of pulmonary tuberculosis (PTB). Overlapping risk factors, clinical features, and chronicity of post COVID-19 sequelae can lead to attribution of respiratory disease solely to COVID-19 and result in delayed recognition of PTB. Methods. Identification of inpatients with both sputum (spu) culture (clt) positive TB and SARS-CoV-2 + PCR was achieved using data extraction tool Slicer Dicer Epic system during 3/2020-1/2022 followed by a retrospective review of electronic medical records. We defined COVID-PTB as a patient (pt) who had positive spu clt for TB <= 12 months (mos) following a COVID-19 diagnosis. Results. 8 pts had both PTB and COVID-19. Two had PTB > 5 mos prior to, and one had PTB > 12 mos after COVID-19. 3/8 were promptly suspected to have PTB [1 with right upper lobe (RUL) infiltrate;1 RUL cavitary infiltrate;1 with miliary nodules and cavities];in these 3, spu was tested for MTB <= 48 hours (h) (hrs) of presentation. 5/8 had COVID-PTB. All 5 had fever and/or respiratory symptoms and >= 1 risk factors for TB identified at the time of presentation with COVID-19. Spu was tested for MTB in 48 hs in 1 with RUL cavitary infiltrate, and 5 days after chest CT findings of apical densities and scattered nodules in another. In the remaining 3, spu testing was delayed a median of 36 days (range, 8-133) after initial TB consistent CT findings (LUL opacity and nodular densities in 1;RLL cavitary infiltrate in 1;and clustered RML nodules in 1) and despite immigration from high burden TB countries in all 3;known LTBI in 2;diabetes in 1, and immunosuppressive therapies in 2. Conclusion. We observed a delay in sputum collection after COVID-19 diagnosis in the presence of epidemiological risk factors for TB disease and clinical features consistent with PTB. Lack of familiarity with the range radiological TB features, a diagnostic bias towards more typical radiographic (e.g., cavities, miliary patterns) and COVID-19 anchoring bias may have contributed to delayed PTB diagnosis. PTB should be considered, when clinically appropriate, in the setting of COVID-19 or apparent post COVID-19 sequelae.

Sorrelation between age and the intensity of the post-vaccination humoral immune response in individuals passed COVID-19

Introduction. Despite widespread vaccination against COVID-19 worldwide, the epidemiological situation remains insufficient. The appearance of mutant forms of SARS-CoV-2 with increased virulence causes new waves of COVID-19 morbidity. The virus variability can cause the reduction of the vaccination effectiveness. In this regard, it is important to study the dynamics of post-vaccination immunity, its features in various population groups, as well as the relationship between post-infectious and post-vaccination immunity. The study continues a series of researches of the features of SARS-CoV-2-specific immunity in COVID-19 convalescents and recipients of the <<Sputnik V>> vaccine. The aim of the study - assessment of the intensity of the SARS-CoV-2-specific immune response in different age groups of people passed COVID-19 and subsequently vaccinated with <<Sputnik V>>. Material and methods. With the help of EIA, the level of IgG antibodies to S-antigen and N-antigen of SARS-CoV-2 was studied in 155 samples of blood sera of individuals (men and women) aged 18 to 70 years who passed COVID-19 and after 6 month of recovery underwent a full course of vaccination with <<Sputnik V>>. Samples from individuals of the following age groups were examined: from 18 to 35, from 35 to 45, from 45 to 55, from 55 to 65, from 65 to 70 years. Results. In all the examined age groups of individuals passed COVID-19 and then vaccinated with <<Sputnik V>>, there was a high level of IgG antibodies to SARS-CoV-2 S-protein (positivity coefficient 8.1 and higher). The level of IgG antibodies to the N-protein in more than half of the cases was lower than positive values among all the subjects. Conclusion. The study showed that individuals passed COVID-19 and then vaccinated with <<Sputnik V>>, regardless of age, have intense post-vaccination humoral immunity. Copyright © 2022 Meditsina Publishers. All rights reserved.

N PROTEIN BASED VACCINE AGAINST SARS-COV-2 PRODUCES A STRONG T CELL IMMUNE RESPONSE TO N PROTEIN OF NOVEL STRAINS

The second generation COVID-19 vaccines should produce the long-term protective immune response to the existing and novel strains of SARS-CoV-2. The Convacell® vaccine was designed to produce such immune response by using N protein as an antigen. N-protein is not susceptible to fast accumulation of mutations and is highly homologous to nucleocapsid proteins of other β-coronaviruses. The study was aimed to perform in vitro assessment of the Convacell® vaccine ability to produce immune response to the Wuhan, Delta, and Omicron strains. Mononuclear cells of vaccinated volunteers and survivors were subjected to N protein stimulation. After that specific activation of the cells was assessed by flow cytometry. The results showed that a sibstantial percentage of CD4 and CD8 cells produced IFNγ and IL2 in response to stimulation. No significant reduction of the response to strains Delta and Omicron compared to the Wuhan strain was revealed. The findings support the direction of the N protein based vaccine design towards creation of the universal vaccine. © 2022 Federal Medical Biological Agency Publishing Group. All Rights Reserved.

Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation (preprint)

BACKGROUND Severe acute respiratory syndrome corona virus (SARS-CoV-2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate safety and efficacy of a SARS-CoV-2-specific siRNA-peptide dendrimer formulation (MIR 19 ®) targeting a conserved sequence in known SARS-CoV-2 variants for treatment of COVID-19. METHODS We conducted an open-label, randomized controlled multicenter phase II trial (NCT05184127) evaluating safety and efficacy of inhaled MIR 19 ® (3.7mg and 11.1 mg/day: groups 1 and 2, respectively) in comparison with standard etiotropic drug treatment (group 3) in patients hospitalized with moderate COVID-19. The primary endpoint was the time to clinical improvement according to predefined criteria within 14 days of randomization. RESULTS Patients from group1 had a significantly reduced (median 6 days (95% confidence interval [CI]: 5-7, HR 1.75, P=0.0005) time to clinical improvement compared to patients from group 3 (8 days (95% CI: 7-10). Normalized oxygen saturation (SpO >94%) occurred quicker in the group 1 (median 5 days (95% CI: 4–5, HR 1.59, P=0.0033) than in the group 3 (6 days, 95% CI: 5–8). Treatment with MIR 19® was well tolerated and safe. CONCLUSIONS MIR 19 ®, a SARS-CoV-2-specific siRNA-peptide dendrimer formulation is safe and significantly reduces time to clinical improvement in hospitalized moderate COVID-19 patients compared to standard therapy in a randomized controlled trial. MIR 19 ® treatment targets a sequence which is identical in all SARS-CoV-2 variants known so far and hence should be applicable for all of them.

Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global COVID-19 pandemic. One possibility to control the pandemic is to induce sterilizing immunity through the induction and maintenance of neutralizing antibodies preventing SARS-CoV-2 from entering human cells to replicate in. METHODS: We report the construction and in vitro and in vivo characterization of a SARS-CoV-2 subunit vaccine (PreS-RBD) based on a structurally folded recombinant fusion protein consisting of two SARS-CoV-2 Spike protein receptor-binding domains (RBD) fused to the N- and C-terminus of hepatitis B virus (HBV) surface antigen PreS to enable the two unrelated proteins serving as immunologic carriers for each other. RESULTS: PreS-RBD, but not RBD alone, induced a robust and uniform RBD-specific IgG response in rabbits. Currently available genetic SARS-CoV-2 vaccines induce mainly transient IgG1 responses in vaccinated subjects whereas the PreS-RBD vaccine induced RBD-specific IgG antibodies consisting of an early IgG1 and sustained IgG4 antibody response in a SARS-CoV-2 naive subject. PreS-RBD-specific IgG antibodies were detected in serum and mucosal secretions, reacted with SARS-CoV-2 variants, including the omicron variant of concern and the HBV receptor-binding sites on PreS of currently known HBV genotypes. PreS-RBD-specific antibodies of the immunized subject more potently inhibited the interaction of RBD with its human receptor ACE2 and their virus-neutralizing titers (VNTs) were higher than median VNTs in a random sample of healthy subjects fully immunized with registered SARS-CoV-2 vaccines or in COVID-19 convalescent subjects. CONCLUSION: The PreS-RBD vaccine has the potential to serve as a combination vaccine for inducing sterilizing immunity against SARS-CoV-2 and HBV by stopping viral replication through the inhibition of cellular virus entry.

Post-vaccination and post-infection humoral immune response to the SARS-CoV-2 infection

Introduction. Mass vaccination of the population against SARS-CoV-2 in Russia and abroad has been going on for more than 2 years. Various types of vaccines are used for vaccination (vector vaccines, RNA vaccines, whole-virion vaccines). The first in the world was registered the Russian vector vaccine «Gam-COVID-Vac» («Sputnik V»), which is widely used in our country, as well as in many other countries of the world. An important area of research is the monitoring of the parameters of the vaccine-induced immune response their analysis in relation to the characteristics of the immune response caused by SARSCoV-2 infection/COVID-19. Such studies are important both for assessing the intensity and duration of post-vaccination immunity, and for improving strategies for immunoprophylaxis and immunotherapy of coronavirus infection. The article presents the results of a study of the humoral immune response in patients with COVID-19 and vaccinated with «Sputnik V» in the period from autumn 2020 till the present time. The aim of the work - a comparative study of the humoral immune response to SARSCoV-2 infection and vaccination against COVID-19. Material and methods. The content of antibodies against SARS-CoV-2 S- and N-proteins was studied in 449 blood serum samples of men and women (age 25-65 years). 5 groups of samples were formed: suffered from COVID-19 of mild and moderate severity, at different times after recovery (262 samples);immunized with the «Sputnik V» vaccine, at different times after injection of the 2nd component of «Sputnik V» (104 samples);suffered from COVID-19 of mild and moderate severity, and then vaccinated with «Sputnik V» (53 samples);vaccinated with «Sputnik V», and then suffered with COVID-19 (12 samples);revaccinated with the vaccine «Sputnik Light» (18 samples). Results. To assess the content of IgG antibodies to S-protein and to N-protein of SARSCoV-2 in human blood sera, an EIA diagnostic system was developed further certified by the Ministry of Health of Russian Federation. In people suffered COVID-19 in 90 % of cases the positive levels of IgG antibodies to SARS-CoV-2 S-protein persist 9 months after recovery, while the proportion of potential plasma donors and material for obtaining intravenous immunoglobulin with a high content of IgG antibodies to S-protein 1 month after the disease is 20 %. In 76 % of people vaccinated with «Sputnik V» high levels of IgG antibodies to S-protein are detected within 6 months after the course of vaccination. The content of IgG antibodies to S-protein in the blood sera of persons suffered COVID-19, and then 6 months after recovery vaccinated with the 1st component of the vaccine «Sputnik V» in 100 % of cases was high with a positivity coefficient above 8.1, regardless of the initial value, already on 7 and 21 days after injection. In persons vaccinated with «Sputnik V» and then passed COVID-19, a high content of S-specific IgG antibodies is observed in 100 % of cases. The examination of vaccinated persons who underwent revaccination with «Sputnik Light» showed a 100 % high level of antibodies against S-protein. Conclusion. The developed test system may be suitable for assessing the content of IgG antibodies to SARS-CoV-2 antigens in COVID-19 patients, vaccinated and revaccinated. The performed study demonstrated that there is a intensive post-vaccination immunity for 6 months and post-infectious immunity for 9 months.

Early versus delayed ileocolic resection for complicated Crohn's disease: is "cooling off" necessary?

BACKGROUND: Ileal Crohn's disease (CD) complicated by intraabdominal abscess, phlegmon, fistula, and/or microperforation is commonly treated with antibiotics, bowel rest, and percutaneous drainage followed by interval ileocolic resection (ICR). This "cool off" strategy is intended to facilitate the safe completion of a one-stage resection using a minimally invasive approach and minimize perioperative complications. There is limited data evaluating the benefits of delayed versus early resection. METHODS: A retrospective review of a prospectively maintained inflammatory bowel disease (IBD) database at a tertiary center was queried from 2013-2020 to identify patients who underwent ICR for complicated ileal CD confirmed on preoperative imaging. ICR cohorts were classified as early (≤ 7 days) vs delayed (> 7 days) based on the interval from diagnostic imaging to surgery. Operative approach and 30-day postoperative morbidity were analyzed. RESULTS: Out of 474 patients who underwent ICR over the 7-year period, 112 patients had complicated ileal CD including 99 patients (88%) with intraabdominal abscess. Early ICR was performed in 52 patients (46%) at a median of 3 days (IQR 2, 5) from diagnostic imaging. Delayed ICR was performed in 60 patients (54%) following a median "cool off" period of 23 days of non-operative treatment (IQR 14, 44), including preoperative percutaneous abscess drainage in 17 patients (28%). A higher proportion of patients with intraabdominal abscess underwent delayed vs early ICR (57% vs 43%, p = 0.19). Overall, there were no significant differences in the rate of laparoscopy (96% vs 90%), conversion to open surgery (12% vs 17%), rates of extended bowel resection (8% vs 13%), additional concurrent procedures (44% vs 52%), or fecal diversion (10% vs 2%) in the early vs delayed ICR groups. The median postoperative length of stay was 5 days in both groups with an overall 25% vs 17% (p = 0.39) 30-day postoperative complication rate and a 6% vs 5% 30-day readmission rate in early vs delayed ICR groups, respectively. Overall median follow-up time was 14.3 months (IQR 1.2, 24.1) with no difference in the rate of subsequent CD-related intestinal resection (4% vs 5%) between the two groups. CONCLUSIONS: In this contemporary series, at a high-volume tertiary referral center, a "cool off" delayed resectional approach was not found to reduce perioperative complications in patients undergoing ICR for complicated ileal Crohn's disease. Laparoscopic ICR can be performed within one week of diagnosis with low rates of conversion and postoperative complications.

Peculiarities of the T Cell Immune Response in COVID-19.

Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance, and control strategies for this disease. This review provides data from studies of the immune response in coronavirus infections. It describes general mechanisms of immunity, its T cell components, and presents a detailed scheme of the T cell response in SARS-CoV-2 infection, including from the standpoint of determining the most promising targets for assessing its level. In addition, we reviewed studies investigating post-vaccination immunity in the development of vaccines against COVID-19. This review also includes the peculiarities of immunity in different age and gender groups, and in the presence of a number of factors, for example, comorbidity or disease severity. This study summarizes the most informative methods for assessing the immune response to SARS-CoV-2 infection.

Vaccination of patients with allergic disease against novel coronavirus infection: Position paper of the russian association of allergology and clinical immunology

One of the key tasks of the previous year is to stop the spread of coronavirus disease (COVID-19), which became a pandemic that led to the deaths of more than 4 million people worldwide and more than 140 thousand deaths in Russia. COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (2019-nCoV) virus of the coro-navirus family. Vaccination plays a leading role in ending the pandemic. Currently, five vaccines against COVID-19 have been registered in Russia, namely, Sputnik V, Sputnik light, EpiVacCorona, EpiVacCorona-Н, and СoviVak. The short follow-up period and absence of randomized placebo-controlled trials of COVID-19 vaccines in certain patients with chronic diseases lead to several questions about the effectiveness/safety of vaccination in these patients. Given the wide spread of allergic diseases and the heterogeneity of patients with allergopathology, experts of the Russian Association of Allergology and Clinical Immunology have developed and approved a position paper on vaccination of patients with allergopathology. © 2020 Pharmarus Print Media.

Vaccination against covid-19 for patients with primary immunodefi ciency and hereditary angioedema: The position paper of the Russian association of allergology, clinical immunology, and the national association of experts in primary immunodefi ciencies

Since the end of 2019, the whole world has been suff ering from the Corona virus-19 (COVID-19) pandemic due to the potentially severe acute respiratory infection caused by the SARS-CoV-2 virus. To date, the infection has led to more than 4 million deaths worldwide, and>140 thousand deaths in Russia. Vaccination against COVID-19 plays a key role in stopping the pandemic. According to the existing experience in infection prevention, mass vaccination will reduce the virus’s expansion and the risk of vaccine-resistant strains developing. In the context of COVID-19, the question of the feasibility and safety of vaccination for patients with primary immunodefi ciency and hereditary angioedema arises. The Russian Association of Allergists, Clinical Immunologists, and the National Association of Experts in Primary Immunodefi ciencies have developed and approved a position paper on the vaccination for patients with primary immunodefi ciency and hereditary angioedema against COVID-19. This position paper provides answers to key questions regarding vaccination for patients with these diseases. © 2020 Pharmarus Print Media License.

A prospective study of the protective effect of SARS-CoV-2-specific antibodies and T cells in Moscow residents (preprint)

BackgroundCoronavirus disease COVID-19 has spread worldwide extremely rapidly. Although many individuals have been infected and have cleared the virus, developing virus-specific antibodies and effector/memory T cells, an important question still to be answered is what levels of T cell and antibody responses are sufficient to protect from the infection. MethodsIn 5,340 Moscow residents, we evaluated the anti-SARS-CoV-2 IgM/IgG titers and the frequencies of the T cells specific to the nucleocapsid, membrane, and spike proteins of SARS-CoV-2, using IFN{gamma} ELISpot, and we also evaluated the fractions of virus-specific CD4+ and CD8+ T cells using intracellular staining of IFN{gamma} and IL2 followed by flow cytometry. Furthermore, we analyzed the post-inclusion COVID-19 rates as a function of the assessed antibody and T cell responses using the Kaplan-Meyer estimator method. ResultsWe showed that T cell and antibody responses are closely interconnected and commonly are induced concurrently. Individuals positive for both antibody and T cell immunities demonstrated the highest levels of protectivity against the SARS-CoV-2 infection, indistinguishably from individuals with antibody response only. Meanwhile, individuals with T cell response only demonstrated slightly higher protectivity than individuals without both types of immunity, as measured from N-protein-specific or CD4+IL2+ T cells. However, these individuals were characterized by higher IgG titers than individuals without any immunity, although the titers were below the seropositivity cut-off. ConclusionsThe results of the study indicated the advantage of serology testing over the analysis of T cell responses for the prediction of SARS-CoV-2 infection rates on a populational level.

Molecular immunological aspects of diagnostics, prevention and treatment of coronavirus infection

The rapid spread of the infection caused by the new coronavirus SARS-CoV-2, which in a short time covered almost the whole world and acquired the pandemic character, has become a serious challenge to the health care system. Unprecedented measures are being taken to organize medical care for infected people, carry out quarantine measures, develop drugs for treatment and prevention of infection. Over the past 2020 year a significant amount of scientific information has been accumulated about the pathogenesis of SARS-CoV-2 infection, the biology of the virus and its interaction with the human immune system. This made it possible to come close to the development of effective substances of countering the spread of a new coronavirus infection – the development of effective vaccines and innovative targeted antiviral drugs. This review is devoted to analysis of the latest advances in the diagnosis, immunoprophylactics and treatment of COVID-19, a disease caused by the novel SARS-CoV-2 coronavirus.

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA2 LEN consensus.

BACKGROUND: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. METHODS: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. RESULTS: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). CONCLUSIONS: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.

Silencing of SARS-CoV-2 with modified siRNA-peptide dendrimer formulation.

BACKGROUND: First vaccines for prevention of Coronavirus disease 2019 (COVID-19) are becoming available but there is a huge and unmet need for specific forms of treatment. In this study we aimed to evaluate the anti-SARS-CoV-2 effect of siRNA both in vitro and in vivo. METHODS: To identify the most effective molecule out of a panel of 15 in silico designed siRNAs, an in vitro screening system based on vectors expressing SARS-CoV-2 genes fused with the firefly luciferase reporter gene and SARS-CoV-2-infected cells was used. The most potent siRNA, siR-7, was modified by Locked nucleic acids (LNAs) to obtain siR-7-EM with increased stability and was formulated with the peptide dendrimer KK-46 for enhancing cellular uptake to allow topical application by inhalation of the final formulation - siR-7-EM/KK-46. Using the Syrian Hamster model for SARS-CoV-2 infection the antiviral capacity of siR-7-EM/KK-46 complex was evaluated. RESULTS: We identified the siRNA, siR-7, targeting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) as the most efficient siRNA inhibiting viral replication in vitro. Moreover, we showed that LNA-modification and complexation with the designed peptide dendrimer enhanced the antiviral capacity of siR-7 in vitro. We demonstrated significant reduction of virus titer and lung inflammation in animals exposed to inhalation of siR-7-EM/KK-46 in vivo. CONCLUSIONS: Thus, we developed a therapeutic strategy for COVID-19 based on inhalation of a modified siRNA-peptide dendrimer formulation. The developed medication is intended for inhalation treatment of COVID-19 patients.