The relative prevalence of the Omicron variant within SARS-CoV-2 infected cohorts in different countries: A systematic review.

The Omicron variant of SARS-CoV-2 was detected in October 2021 and exhibited high transmissibility, immune evasion, and reduced severity when compared to the earlier variants. The lesser vaccine effectiveness against Omicron and its reduced severity created vaccination hesitancy among the public. This review compiled data reporting the relative prevalence of Omicron as compared to the early variants to give an insight into the existing variants, which may shape the decisions regarding the targets of the newly developed vaccines. Complied data revealed more than 90% prevalence within the infected cohorts in some countries. The BA.1 subvariant predominated over the BA.2 during the early stages of the Omicron wave. Moreover, BA.4/BA.5 subvariants were detected in South Africa, USA and Italy between October 2021 and April 2022. It is therefore important to develop vaccines that protect against Omicron as well as the early variants, which are known to cause more severe complications.

Evolution of SARS-CoV-2 variants of concern over a period of Delta and Omicron cocirculation, among patients hospitalized for COVID-19 in an Italian reference hospital: Impact on clinical outcomes.

Despite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS-CoV-2. This study, enrolling all COVID-19 adults admitted to a reference hospital who underwent both the S-gene-target-failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in-hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid-February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid-March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10-day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28-day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID-19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant.

Reinfection by SARS-CoV-2 by divergent Omicron sublineages, 16 days apart.

Since the beginning of the SARS-CoV-2 pandemic, studies on the variants and sublineages stand out, mainly in the cases of reinfection in a short period. In this study, we describe a case of infection by BA.1.1 sublineage in an individual from Southern Brazil. The same patient acquired reinfection with sublineage BA.2 within 16 days after the first detection. The viral extraction and RT-qPCR were performed on the samples LMM72045 (collected in May 2022) and LMM72044 (collected in June 2022). After the confirmation of SARS-CoV-2 infection, we conducted the sequencing and viral genome analysis. This case of reinfection affected a 52-year-old male patient, without comorbidities, with three doses of vaccines against COVID-19, showing symptoms on May 19. These symptoms lasted for approximately six days. The patient returned to work activities on May 30. However, on June 4, the patient felt a new round of clinical signs that lasted for approximately seven days. Analysis of the viral genomes recovered from patients' clinical samples revealed that the two COVID-19 episodes were related to two divergent VOC Omicron sublineages, namely, BA.1.1 for the first round of symptoms and BA.2 for the second infection. Based on our findings, we can say that the present case of reinfection is the shortest described so far.

Changes within the P681 residue of spike dictate cell fusion and syncytia formation of Delta and Omicron variants of SARS-CoV-2 with no effects on neutralization or infectivity.

The rapid spread and dominance of the Omicron SARS-CoV-2 lineages have posed severe health challenges worldwide. While extensive research on the role of the Receptor Binding Domain (RBD) in promoting viral infectivity and vaccine sensitivity has been well documented, the functional significance of the 681PRRAR/SV687 polybasic motif of the viral spike is less clear. In this work, we monitored the infectivity levels and neutralization potential of the wild-type human coronavirus 2019 (hCoV-19), Delta, and Omicron SARS-CoV-2 pseudoviruses against sera samples drawn four months post administration of a third dose of the BNT162b2 mRNA vaccine. Our findings show that in comparison to hCoV-19 and Delta SARS-CoV-2, Omicron lineages BA.1 and BA.2 exhibit enhanced infectivity and a sharp decline in their sensitivity to vaccine-induced neutralizing antibodies. Interestingly, P681 mutations within the viral spike do not play a role in the neutralization potential or infectivity of SARS Cov-2 pseudoviruses carrying mutations in this position. The P681 residue however, dictates the ability of the spike protein to promote fusion and syncytia formation between infected cells. While spike from hCoV-19 (P681) and Omicron (H681) promote only modest cell fusion and formation of syncytia between cells that express the spike-protein, Delta spike (R681) displays enhanced fusogenic activity and promotes syncytia formation. Additional analysis shows that a single P681R mutation within the hCoV-19 spike, or H681R within the Omicron spike, restores fusion potential to similar levels observed for the Delta R681 spike. Conversely, R681P point mutation within the spike of Delta pseudovirus abolishes efficient fusion and syncytia formation. Our investigation also demonstrates that spike proteins from hCoV-19 and Delta SARS-CoV-2 are efficiently incorporated into viral particles relative to the spike of Omicron lineages. We conclude that the third dose of the Pfizer-BNT162b2 provides appreciable protection against the newly emerged Omicron sub-lineages. However, the neutralization sensitivity of these new variants is diminished relative to that of the hCoV-19 or Delta SARS-CoV-2. We further show that the P681 residue within spike dictates cell fusion and syncytia formation with no effects on the infectivity of the specific viral variant and on its sensitivity to vaccine-mediated neutralization.

Computational design of medicinal compounds to inhibit RBD-hACE2 interaction in the Omicron variant: unveiling a vulnerable target site.

The COVID-19 pandemic, caused by SARS-CoV-2, has globally affected both human health and economy. Several variants with a high potential for reinfection and the ability to evade immunity were detected shortly after the initial reported case of COVID-19. A total of 30 mutations in the spike protein (S) have been reported in the SARS-CoV-2 (BA.2) variant in India and South Africa, while half of these mutations are in the receptor-binding domain and have spread rapidly throughout the world. Drug repurposing offers potential advantages over the discovery of novel drugs, and one is that it can be delivered quickly without lengthy assessments and time-consuming clinical trials. In this study, computational drug design, such as pharmacophore-based virtual screening and MD simulation has been concentrated, in order to find a novel small molecular inhibitor that prevents hACE2 from binding to the receptor binding domain (RBD). three medicinal compound databases: North-East African, North African, and East African were screened and carried out a multi-step screening approach that identified three compounds, which are thymoquinol 2-O-beta-glucopyranoside (C1), lanneaflavonol (C2), and naringenin-4'-methoxy-7-O-Alpha-L-rhamnoside (C3), with excellent anti-viral properties against the RBD of the omicron variant. Furthermore, PAIN assay interference, computation bioactivity prediction, binding free energy, and dissociation constant were used to validate the top hits, which indicated good antiviral activity. The three compounds that were found may be useful against COVID-19, though more research is required. These findings could aid the development of novel therapeutic drugs against the emerging Omicron variant of SARS-CoV-2.

HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor via intranasal administration.

The continuously emerging SARS-CoV-2 variants pose a great challenge to the efficacy of current drugs, this necessitates the development of broad-spectrum antiviral drugs. In the previous study, we designed a recombinant protein, heptad repeat (HR) 121, as a variant-proof vaccine. Here, we found it can act as a fusion inhibitor and demonstrated broadly neutralizing activities against SARS-CoV-2 and its main variants. Structure analysis suggested that HR121 targets the HR2 domain in SARS-CoV-2 spike (S) 2 subunit to block virus-cell fusion. Functional experiments demonstrated that HR121 can bind HR2 at serological-pH and endosomal-pH, highlighting its inhibition capacity when SARS-CoV-2 enters via either cellular membrane fusion or endosomal route. Importantly, HR121 can effectively inhibit SARS-CoV-2 and Omicron variant pseudoviruses entering the cells, as well as block authentic SARS-CoV-2 and Omicron BA.2 replications in human pulmonary alveolar epithelial cells. After intranasal administration to Syrian golden hamsters, it can protect hamsters from SARS-CoV-2 and Omicron BA.2 infection. Together, our results suggest that HR121 is a potent drug candidate with broadly neutralizing activities against SARS-CoV-2 and its variants.

A Methodical Review on Omicron -a New Variant as a Drug Developer

In mid-November 2021, the new OMICRON variety was first discovered in South Africa. As of today, the OMICRON version already appeared on December 15, 2021. Around 77 countries are affected, with the bulk of cases originating in the United States, India, the United Kingdom, and South Africa. OMICRON-positive instances were also reported. The first mortality associated with the novel COVID-19 mutation was reported in the United Kingdom. Recently, a sister variant of OMICRON, 21L or BA.2, has also been discovered. Due to its enormously high number of mutations, viewed enhancement in immune evasion and transmissibility, OMICRON was developed as a new variant of concern (VOC) by the WHO on 26 November 2021. On a global pandemic scale, positive selection of SARSCoV-2 mutations appears to have begun in late 2020. Since then, the virus has been evolving on two fronts: immune evasion and enhanced transmissibility, as expressed by Delta. This review elaborates the effects of drugs in the management of OMICRON.Copyright © 2023 Society of Pharmaceutical Sciences and Research. All rights reserved.

Clinical virology and effect of Covid-19 vaccination and monoclonal antibodies against highly infectious SARS- CoV-2 omicron sub variant BF.7 (BA.5.2.1.7): A systematic review.

Over time, the SARS-CoV-2 virus has acquired several genetic mutations, particularly on the receptor-binding domain (RBD) spike glycoprotein. The Omicron variant is highly infectious, with enhanced immune escape activity, and has given rise to various sub-lineages due to mutations. However, there has been a sudden increase in COVID-19 reports of the Omicron subvariant BF.7 (BA.2.75.2), which has the highest number of reported cases, accounting for 76.2% of all cases worldwide. Hence, the present systematic review aimed to understand the viral mutations and factors associated with the increase in the reports of COVID-19 cases and to assess the effectiveness of vaccines and mAbs against the novel Omicron variant BF.7. The R346T mutation on the spike glycoprotein RBD might be associated with increased infection rates, severity, and resistance to vaccines and mAbs. Booster doses of COVID-19 vaccination with bivalent mRNA booster vaccine shots are effective in curtailing infections and decreasing the severity and mortality by enhancing the neutralizing antibodies (Abs) against the emerging Omicron subvariants of SARS-CoV-2, including BF.7 and future VOCs.

MRI of fatal course of acute hemorrhagic leukoencephalitis in a child with SARS-CoV-2 omicron BA 2.0 infection.

We present a pediatric case of acute hemorrhagic leukoencephalitis associated with SARS-CoV-2 Omicron BA 2.0 infection. A previously healthy girl presented with ataxia and diplopia three weeks after the COVID-19 confirmation from a nasopharyngeal swab. Acute and symmetrical motor weakness and drowsiness ensued within the following 3 days. She then became spastic tetraplegic. MRI revealed multifocal lesions in the cerebral white matter, basal ganglia, and brainstem, with hemorrhagic changes confirmed with T1-hyperintensity and hypointensity on susceptibility-weighted images. Peripheral areas of decreased diffusion, increased blood flow, and rim contrast enhancement were noted in the majority of lesions. She was treated with a combination of intravenous immunoglobulin and methylprednisolone pulse therapy. Neurological deterioration ensued with coma, ataxic respiratory pattern and decerebrate posture. Repeated MRI performed on day 31 revealed progression of abnormalities, hemorrhages and brain herniation. Despite the administration of plasma exchange, she died two months after admission.

Clinical characteristics and high-resolution computed tomography findings of 805 patients with mild or moderate infection from SARS-CoV-2 Omicron subvariant BA.2.

BACKGROUND: COVID-19 is a global pandemic. Currently, the predominant strain is SARS-CoV-2 Omicron subvariant BA.2 in many countries. Understanding its infection characteristics can facilitate clinical management. OBJECTIVES: This study aimed to characterize the clinical, laboratory, and high-resolution computed tomography (HRCT) findings in patients with mild or moderate infection from SARS-CoV-2 Omicron subvariant BA.2. METHODS: We performed a retrospective study on patients infected with SARS-CoV-2 Omicron subvariant BA.2 between April 4th and April 17th, 2022. The clinical characteristics, laboratory features, and HRCT images were reviewed. RESULTS: A total of 805 patients were included (411 males and 394 females, median age 33 years old). The infection was mild, moderate, severe, and asymptomatic in 490 (60.9%), 37 (4.6%), 0 (0.0%), and 278 (34.5%) patients, respectively. Notably, 186 (23.1%), 96 (11.9%), 265 (32.9%), 11 (3.4%), 7 (0.9%), and 398 (49.4%) patients had fever, cough, throat discomfort, stuffy or runny nose, fatigue, and no complaint, respectively. Furthermore, 162 (20.1%), 332 (41.2%), and 289 (35.9%) patients had decreased white blood cell counts, reduced lymphocytes, and elevated C-reactive protein levels, respectively. HRCT revealed pneumonia in 53 (6.6%) patients. The majority of the lung involvements were ground-glass opacity (50, 94.3%) mostly in the subpleural area. The grade of lung injury was mainly mild (90.6%). Short-term follow-ups showed that most patients with pneumonia recovered. CONCLUSION: Most patients with mild or moderate infection from SARS-CoV-2 Omicron subvariant BA.2 were adults, with fever and upper respiratory symptoms as the main clinical presentations. Lower respiratory infection was mild, with ground-glass opacity in the subpleural area as the main finding.

Omicron BA.1 and BA.2 sub-lineages show reduced pathogenicity and transmission potential than the early SARS-CoV-2 D614G variant in Syrian hamsters.

BACKGROUND: The epidemiological advantage of Omicron variant is evidenced by its rapid spread and the ability to outcompete prior variants. Among Omicron sub-lineages, early outbreaks were dominated by BA.1 while BA.2 has gained dominance since February 2022. The relative pathogenicity and transmissibility of BA.1 and BA.2 have not been fully defined. METHODS: We compared viral loads and clinical signs in Syrian hamsters after infection with BA.1, BA.2, or D614G variant. A competitive transmission model and next generation sequencing were used to compare the relative transmission potential of BA.1 and BA.2. RESULTS: BA.1 and BA.2 caused no apparent clinical signs while D614G caused more than 10% weight loss. Higher viral loads were detected from the nasal washes, nasal turbinate and lungs of BA.1 than BA.2 inoculated hamsters. No aerosol transmission was observed for BA.1 or BA.2 under the experimental condition that D614G transmitted efficiently. BA.1 and BA.2 were able to transmit among hamsters via direct contact; however, BA.1 transmitted more efficiently than BA.2 under the competitive transmission model. No recombination was detected from direct contacts exposed simultaneously to BA.1 and BA.2. CONCLUSIONS: Omicron BA.1 and BA.2 demonstrated attenuated pathogenicity and reduced transmission potential in hamsters when compared to early SARS-CoV-2 strains.

SARS-CoV-2 Omicron subvariant spike N405 unlikely to rapidly deamidate.

The RGD motif on the SARS-CoV-2 spike protein has been suggested to interact with RGD-binding integrins αVß3 and α5ß1 to enhance viral cell entry and alter downstream signaling cascades. The D405N mutation on the Omicron subvariant spike proteins, resulting in an RGN motif, has recently been shown to inhibit binding to integrin αVß3. Deamidation of asparagines in protein ligand RGN motifs has been demonstrated to generate RGD and RGisoD motifs that permit binding to RGD-binding integrins. Two asparagines, N481 and N501, on the Wild-type spike receptor-binding domain have been previously shown to have deamidation half-lives of 16.5 and 123 days, respectively, which may occur during the viral life cycle. Deamidation of Omicron subvariant N405 may recover the ability to interact with RGD-binding integrins. Thus, herein, all-atom molecular dynamics simulations of the Wild-type and Omicron subvariant spike protein receptor-binding domains were conducted to investigate the potential for asparagines, the Omicron subvariant N405 in particular, to assume the optimized geometry for deamidation to occur. In summary, the Omicron subvariant N405 was primarily found to be stabilized in a state unfavourable for deamidation after hydrogen bonding with downstream E406. Nevertheless, a small number of RGD or RGisoD motifs on the Omicron subvariant spike proteins may restore the ability to interact with RGD-binding integrins. The simulations also provided structural clarification regarding the deamidation rates of Wild-type N481 and N501 and highlighted the utility of tertiary structure dynamics information in predicting asparagine deamidation. Further work is needed to characterize the effects of deamidation on spike-integrin interactions.

Association between time of onset and Omicron BA.2 RNA clearance time in children: a retrospective cohort study.

Background: The association between the time of onset [time from the date of detection of a positive real-time reverse-transcription polymerase chain reaction (RT-PCR) to the date of detection of a positive RT-PCR in the first child] and viral RNA clearance time (time from first positive RT-PCR to two consecutive negative RT-PCR) remains unclear. Our study aimed to evaluate their association. That can provide a reference for the number of nucleic acid tests. Methods: We conducted a retrospective analysis of children diagnosed with Omicron BA.2 infection at Fujian Medical University Affiliated First Quanzhou Hospital between March 14, 2022 (date the first child in the outbreak was found positive for RT-PCR) and April 9, 2022 (date the last child was found positive for RT-PCR). We used the electronic medical record to extract demographic data, symptoms, radiology and laboratory findings, treatments, and viral RNA clearance time. The 282 children were divided equally into 3 groups according to the time of onset. We calculated the factors affecting viral RNA clearance time by univariate and multivariate analysis. We used the generalized additive model to investigate the relationship between the time of onset and viral RNA clearance time. Results: 46.45% of children were female. Fever (62.06%) and cough (15.60%) were the dominant onset symptoms. We found no serious cases and all children were cured. The median time to viral RNA clearance was 14 days (IQR 12-17 days), with a range of 5 to 35 days. After adjustment for potential confounders, the viral RNA clearance time was reduced by 2.45 (95% CI: 0.85, 4.04) days in the 7-10 days group and by 4.62 (95% CI: 2.38, 6.14) days in > 10 days group compared to the ≤6 days group. There was a non-linear association between the time of onset and viral RNA clearance time. Conclusions: Time of onset was non-linearly associated with Omicron BA.2 RNA clearance time. During the first 10 days of the outbreak, viral RNA clearance time decreased with increasing onset date. After 10 days of the outbreak, viral RNA clearance time did not decrease with increasing onset date.

Conclusion and Suggestions

The world is engulfed in a global health emergency that is taxing enormous medical, social, and economic tolls upon humanity since early 2020 and lasting early 2022. Despite medical advances, COVID-19 took a toll of more than 6, 132, 461 globally around 0.9 million in USA alone. US is number one in total COVID-19 mortality as of March 30, 2022, followed by Brazil, India, and Russian Federation. In the US, COVID-19 cases are rising modestly in the Northeast, Philadelphia has reinstituted an indoor mask mandate, and some colleges are requiring masks during the final days of the spring semester (CNN in Is COVID endemic yet? Experts aren't so sure, 2022). © TheEditor(s) (ifapplicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2021, 2022.

Protection probability against SARS-CoV-2 Omicron variant BA.1, BA.2 and BA.5 in asympto- matic infection caused by prototype strain

Objective To estimate the protection probability against SARS-CoV-2 variant Omicron strains BA.1, BA.2 and BA.5 infection, symptomatic infection and severe disease outcomes in asymptomatic individuals infected with SARS-CoV-2 prototype strain previously. Methods Our previous study had shown that the dynamic change of neutralizing antibodies in asymptomatic individuals infected with the SARS-CoV-2 prototype strain. Based on our previous study, a peer–reviewed predictive model on the basis of logistic model was used to estimate the protection probability of asymptomatic individuals against Omicron strains BA.1, BA.2 and BA.5. We estimate the protection probability against infection, symptomatic infection and severe disease outcomes on 28, 51 and 261 days after confirmation. Results The protection probability against reinfection of Omicron variant strains BA.1, BA.2, and BA.5 on 28 days after confirmation were 30% (95% CI: 16%–52%) , 23% (95% CI: 15%–36%) and 8% (95% CI: 4%–16%) respectively, while decreased to 9% (95% CI: 3%–21%) , 6% (95% CI: 3%–12%) and 2% (95% CI: 1%–4%) on 261 days after confirmation. The protection probability against symptomatic infection of Omicron strains BA.1, BA.2, and BA.5 were 51% (95% CI: 28%–80%) , 42% (95% CI: 26%–67%) and 16% (95% CI: 7% – 40%) respectively on 28 days after confirmation, while decreased to 16% (95% CI: 7%–35%) , 12% (95% CI: 7% – 22%) and 3% (95% CI: 1% – 8%) on 261 days after confirmation. The protection probability against severe disease of Omicron strains BA.1, BA.2, and BA.5 were 91% (95% CI: 72%–98%) , 88% (95% CI: 70%–97%) and 66% (95% CI: 35%–90%) respectively on 28 days after confirmation, while decreased to 60% (95% CI: 35%–86%) , 51% (95% CI: 32%–75%) and 22% (95% CI: 10%–50%) on 261 days after confirmation. Conclusions Neutralizing antibodies induced in asymptomatic individuals infected with prototype strain could provide higher protection against Omicron strain BA.5 than Omicron strains BA.1 and BA.2. Among the three clinical outcomes, the protective probability against severe disease outcome was better, followed by symptomatic infection, and the protective probability against infection was poor. © 2023, Publication Centre of Anhui Medical University. All rights reserved.

Effect Analysis of Different Environmental Disinfection Methods on Reducing Contamination of Surfaces by the Omicron BA.2.2 Variant of SARS-CoV-2 and the Characteristics of Fomite Contamination in the Fever Clinic in the Out-Broken of Shanghai.

This study aimed to investigate the effect of different environmental disinfection methods on reducing contaminated surfaces (CSs) by the Omicron BA.2.2 variant of SARS-CoV-2 in the fever clinic between March 20 and May 30, 2022, and to analyze the influences and related factors of CSs. This study includes survey data from 389 positive patients (SPPs) and 204 CSs in the fever clinic, including the CS type, disinfection method, length of time spent in the clinic, cycle threshold (CT) value, name, age, weight, mask type, mask-wearing compliance, hand-mouth touch frequency and sex. Associations between study variables and specified outcomes were explored using univariate regression analyses. Mask-wearing compliance had a significant negative correlation with CSs (r = - 0.446, P = 0.037). Among the 389 SPPs, 22 SPPs (CRP, 5.66%) caused CSs in the separate isolation room. A total of 219 SPPs (56.30%) were male. The mean age of SPPs was 4.34 ± 3.92 years old, and the mean CT value was 12.44 ± 5.11. In total, 9952 samples with exposure history were taken, including 204 (2.05%) CSs. Among the CSs, the positive rate of flat surfaces was the highest in public areas (2.52%) and separate isolation rooms (4.75%). Disinfection methods of ultraviolet radiation + chemical irradiation significantly reduced the CSs in both the public area (0% vs. 4.56%) and the separate isolation room (0.76% vs. 2.64%) compared with the chemical method alone (P < 0.05). Compared with ordinary SPPs, CRPs were older (6.04 year vs. 4.23 year), and the male proportion was higher (72.73% vs. 55.31%). In particular, it was found that SPPs contaminated their surroundings and therefore imposed risks on other people. Environmental disinfection with ultraviolet radiation + chemical treatment should be emphasized. The findings may be useful to guide infection control practices for the Omicron BA.2.2 variant of SARS-CoV-2.

C-reactive protein to lymphocyte ratio is a significant predictive factor for poor short-term clinical outcomes of SARS-CoV-2 BA.2.2 patients.

Objective: The aim of the present study is to assess the utility of C-reactive protein to Lymphocyte Ratio (CLR) in predicting short-term clinical outcomes of patients infected by SARS-CoV-2 BA.2.2. Methods: This retrospective study was performed on 1,219 patients with laboratory-confirmed SARS-CoV-2 BA.2.2 to determine the association of CLR with short-term clinical outcomes. Independent Chi square test, Rank sum test, and binary logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aORs) with their 95% CI, respectively. Results: Over 8% of patients admitted due to SARS-CoV-2 BA.2.2. were critically ill. The best cut-off value of CLR was 21.25 in the ROC with a sensitivity of 72.3% and a specificity of 86%. After adjusting age, gender, and comorbidities, binary logistic regression analysis showed that elevated CLR was an independent risk factor for poor short-term clinical outcomes of COVID-19 patients. Conclusion: C-reactive protein to Lymphocyte Ratio is a significant predictive factor for poor short-term clinical outcomes of SARS-CoV-2 BA.2.2 inflicted patients.

Analysis of the ARTIC V4 and V4.1 SARS-CoV-2 primers and their impact on the detection of Omicron BA.1 and BA.2 lineage-defining mutations.

The ARTIC protocol uses a multiplexed PCR approach with two primer pools tiling the entire SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genome. Primer pool updates are necessary for accurate amplicon sequencing of evolving SARS-CoV-2 variants with novel mutations. The suitability of the ARTIC V4 and updated V4.1 primer scheme was assessed using whole genome sequencing of Omicron from clinical samples using Oxford Nanopore Technology. Analysis of Omicron BA.1 genomes revealed that 93.22 % of clinical samples generated improved genome coverage at 50× read depth with V4.1 primers when compared to V4 primers. Additionally, the V4.1 primers improved coverage of BA.1 across amplicons 76 and 88, which resulted in the detection of the variant-defining mutations G22898A, A26530G and C26577G. The Omicron BA.2 sub-variant (VUI-22JAN-01) replaced BA.1 as the dominant variant by March 2022, and analysis of 168 clinical samples showed reduced coverage across amplicons 15 and 75. Upon further interrogation of primer binding sites, a mutation at C4321T [present in 163/168 (97 %) of samples] was identified as a possible cause of complete dropout of amplicon 15. Furthermore, two mutations were identified within the primer binding regions for amplicon 75: A22786C (present in 90 % of samples) and C22792T (present in 12.5 % of samples). Together, these mutations may result in reduced coverage of amplicon 75, and further primer updates would allow the identification of the two BA.2-defining mutations present in amplicon 75: A22688G and T22679C. This work highlights the need for ongoing surveillance of primer matches as circulating variants evolve and change.

Novel pro-and eukaryotic expression plasmid expressing omicron antigens delivered via Salmonella elicited MHC class I and II based protective immunity.

The latest omicron variants are emerging with mutations in the receptor binding domain (RBD) that confer immune evasion and resistance against current vaccines. Such variants have raised the peril of future vaccine effectiveness, as leading vaccines target the spike protein. Type-IV hypersensitivity, and other ailments due to the dominant Th1 response by leading vaccines, is also to be resolved. Therefore, vaccine that target diverse SARS-CoV-2 proteins and provide broad-spectrum protection and a balanced Th1 and Th2 response is an indispensable armament against the pandemic. In that prospect, a novel dual expression plasmid pJHL270 was developed and demonstrated the expression of omicron antigens exogenously from Salmonella and endogenously in the host cells. The simultaneous activation of MHC class I and II molecules culminated in a balanced Th1 and Th2 response, which was evident through the upsurge of IgG, IgA antibodies, IgG2a/IgG1 ratio, cytokine responses and CD4+, CD8+ T-lymphocytes. The level of CD44+ cells showed the trigger for Th1 and Th2 balance and memory-cell activation for long-lasting immunity. The level of IFN-γ + cells and neutralizing antibodies signifies the anti-viral response. The vaccine protected the hamsters from BA.5 and BA.2.75 omicron viral-challenge, exhibited a significant reduction in lung viral-load and histopathological lesions. In addition to two-way antigen expression and bilateral immune elicitation, this Salmonella-based vaccine delivery system can be prospectively applied to humans and a broad range of animals as a convenient alternative to viral and chemical vaccine delivery approaches.