Characteristics and outcomes of COVID-19 patients during the BA.5 omicron wave in Tehran, Iran: a prospective observational study.

BACKGROUND: Omicron (B.1.1.529) is the fifth variant of concern of SARS-CoV-2, which has several subvariants. Clinical features of BA.1 and BA.2 infections have been described in the literature, but we have limited information about the clinical profile of BA.5, which caused the seventh wave in Iran. METHODS: A prospective observational study was conducted on the BA.5 confirmed patients referred to Imam Khomeini Hospital Complex, Tehran, Iran, from 11th to 31st August 2022. The patients were divided into the two groups of outpatients and hospitalized patients, and their clinical, radiological, and laboratory data and outcomes were recorded and analyzed. RESULTS: We included 193 patients with confirmed BA.5 infection, of whom 48 patients (24·8%) were hospitalized. The mean age of the patients was 45·3 ± 16·5 years, and 113 patients (58·5%) were female. The mean number of days patients had symptoms was 6·8 ± 2·4 days. The most common symptoms were weakness (69·9%), sore throat (67·4%), myalgia (66·3%), hoarseness (63·7%), headache (55·4%), fatigue (54·9%), and dry cough (50·3%). Fever and dyspnea were significantly more observed in the hospitalized patients (p < 0·0001). The COVID-19 vaccination rate was significantly lower in hospitalized patients than in outpatients (35/48-72·9% vs. 140/145 - 96·6%, p < 0·0001). The most common underlying diseases were hypertension (16·1%), diabetes mellitus (9·8%), and cardiovascular diseases (9·8%), all of which were significantly more common in hospitalized patients. Lung opacities were observed in 81·2% of hospitalized patients. By the end of our study, 1·5% of patients died despite receiving critical care services. CONCLUSIONS: Our findings suggested that BA.5 symptoms are more non-respiratory and usually improve within 7 days. Although the proportion of hospitalized patients is still significant, very few patients require intensive care. COVID-19 vaccination is effective in reducing the hospitalization rate. TRIAL REGISTRATION: Not applicable. This study is not a clinical trial.

The protection quest is a primary key to sharing the neutralizing antibody response to cover against all emerging VOCs based on BIV1-CovIran studies

Over time, the antigenic evolution of emerging variants of SARS-CoV-2 has demanded the development of potential protective vaccines. Administration of additional doses of current vaccines based on the WT spike protein may boost immunity, but their effectiveness has dwindled for patients with more recent variants. Here, we studied the neutralization activity of post-WT strain-based vaccination and a structural simulation in-silico based on the interactions of the RBD-hACE2 as the key to initiating infection among the VOCs of SARS-CoV-2. Our data display shows that WT sera showed a markedly greater reduction in Delta and Omicron, suggesting that the Wuhan-based vaccines may be more susceptible to breakthrough and new VOCs. According to the MD simulation, mutations of Omicron result in a significant change in the variant charge distribution throughout the binding interface that consequently alters the critical interface electrostatic potential in comparison to other variants. This observation provides new insights into immunization policy and next-generation vaccine development. Graphical abstract Image 1

Intranasal administration of cold-adapted live-attenuated SARS-CoV-2 candidate vaccine confers protection against SARS-CoV-2.

With the COVID-19 pandemic globally, the ongoing threat of new challenges of mucosal infections was once again reminded human beings. Hence, access to the next-generation vaccine to elicit mucosal immunity is required to reduce virus shedding. SARS-CoV-2 retains a unique polybasic cleavage motif in its spike protein, recognized by the host furin protease. The proteolytic furin cleavage site at the junction of S1/S2 glycoprotein plays a key role in the pathogenesis of SARS-CoV-2. Here, we examined the protective immunity of a double-deleted PRRA/GTNGTKR motifs cold-adapted live-attenuated candidate vaccines as a called "KaraVac." using a hamster animal model of infected attenuated SARS-CoV-2. The KaraVac vaccinated hamsters were challenged against the wild-type (WT) SARS-CoV-2. No apparent bodyweight loss and histopathological lesions were observed in the hamsters. The establishment of sterilizing immunity was induced via stimulating a robust neutralizing antibody (NAb) response in a hamster model. Consequently, deletions in the spike sequence and inoculation into hamsters provide resistance to the subsequent challenge with WT SARS-CoV-2. We have suggested that deletion of the furin cleavage site and GTNGTKR motifs in the spike sequence attenuates the virus from the parental strain and can be used as a potent immunogen.

Assessment of BIV1-CovIran inactivated vaccine-elicited neutralizing antibody against the emerging SARS-CoV-2 variants of concern.

OBJECTIVES: The BIV1-CovIran vaccine is highly effective against COVID-19. The neutralizing potency of all SARS-CoV-2 vaccines seems to be decreased against variants of concern. We assessed the sensitivity of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants to neutralizing antibodies (NAbs) present in sera from individuals who had received the BIV1-CovIran candidate vaccine compared with an original Wuhan-related strain. METHODS: The ability of vaccine serum to neutralize the variants was measured using the conventional virus neutralization test. The correlation of spike (S) protein antibody and anti-receptor binding domain with neutralizing activity was investigated. RESULTS: The current study demonstrated that 29 of 32 (90.6%; 95% CI: 75.0-98.0) of the vaccinees developed NAbs against a Wuhan-related strain. It is noteworthy that 28 (87.50%) and 24 of 32 (75%) of the recipients were able to produce NAbs against Alpha, Beta, and Delta variants, respectively. Serum virus-neutralizing titres for different SARS-CoV-2 strains were weakly correlated with anti-receptor binding domain antibodies (Spearman r = 36-42, p < 0.05), but not S-binding antibodies (p > 0.05). DISCUSSION: Although there was a reduction in neutralization titres against the Alpha, Beta, and Delta variants compared with the Wuhan strain, BIV1-CovIran still exhibited potent neutralizing activity against the SARS-CoV-2 variants of concern.

SARS-CoV-2: Current trends in emerging variants, pathogenesis, immune responses, potential therapeutic, and vaccine development strategies.

More than a year after the SARS-CoV-2 pandemic, the Coronavirus disease 19 (COVID-19) is still a major global challenge for scientists to understand the different dimensions of infection and find ways to prevent, treat, and develop a vaccine. On January 30, 2020, the world health organization (WHO) officially announced this new virus as an international health emergency. While many biological and mechanisms of pathogenicity of this virus are still unclear, it seems that cytokine storm resulting from an immune response against the virus is considered the main culprit of the severity of the disease. Despite many global efforts to control the SARS-CoV-2, several problems and challenges have been posed in controlling the COVID-19 infection. These problems include the various mutations, the emergence of variants with high transmissibility, the short period of immunity against the virus, the possibility of reinfection in people improved, lack of specific drugs, and problems in the development of highly sensitive and specific vaccines. In this review, we summarized the results of the current trend and the latest research studies on the characteristics of the structure and genome of the SARS-CoV- 2, new mutations and variants of SARS-CoV-2, pathogenicity, immune response, virus diagnostic tests, potential treatment, and vaccine candidate.

Safety and potency of BIV1-CovIran inactivated vaccine candidate for SARS-CoV-2: A preclinical study.

The development of effective and safe COVID-19 vaccines is a major move forward in our global effort to control the SARS-CoV-2 pandemic. The aims of this study were (1) to develop an inactivated whole-virus SARS-CoV-2 candidate vaccine named BIV1-CovIran and (2) to determine the safety and potency of BIV1-CovIran inactivated vaccine candidate against SARS-CoV-2. Infectious virus was isolated from nasopharyngeal swab specimen and propagated in Vero cells with clear cytopathic effects in a biosafety level-3 facility using the World Health Organization's laboratory biosafety guidance related to COVID-19. After characterisation of viral seed stocks, the virus working seed was scaled-up in Vero cells. After chemical inactivation and purification, it was formulated with alum adjuvant. Finally, different animal species were used to determine the toxicity and immunogenicity of the vaccine candidate. The study showed the safety profile in studied animals including guinea pig, rabbit, mice and monkeys. Immunisation at two different doses (3 or 5 µg per dose) elicited a high level of SARS-CoV-2 specific and neutralising antibodies in mice, rabbits and nonhuman primates. Rhesus macaques were immunised with the two-dose schedule of 5 or 3 µg of the BIV1-CovIran vaccine and showed highly efficient protection against 104 TCID50 of SARS-CoV-2 intratracheal challenge compared with the control group. These results highlight the BIV1-CovIran vaccine as a potential candidate to induce a strong and potent immune response that may be a promising and feasible vaccine to protect against SARS-CoV-2 infection.