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1.
J Biomol Struct Dyn ; : 1-18, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2106892

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron is currently the most prevalent SARS-CoV-2 variant worldwide. Herein, we calculated molecular dynamics simulations of the trimeric spikeWT and SpikeBA.1 for 300 ns. Our results show that SpikeBA.1 has more conformational flexibility than SpikeWT. Our principal component analysis (PCA) allowed us to observe a broader spectrum of different conformations for SpikeBA.1, mainly at N-terminal domain (NTD) and receptor-binding domain (RBD). Such increased flexibility could contribute to decreased neutralizing antibody recognition of this variant. Our molecular dynamics data show that the RBDBA.1 easily visits an up-conformational state and the prevalent D614G mutation is pivotal to explain molecular dynamics results for this variant because to lost hydrogen bonding interactions between the residue pairs K854SC/D614SC, Y837MC/D614MC, K835SC/D614SC, T859SC/D614SC. In addition, SpikeBA.1 residues near the furin cleavage site are more flexible than in SpikeWT, probably due to P681H and D614G substitutions. Finally, dynamical cross-correlation matrix (DCCM) analysis reveals that D614G and P681H may allosterically affect the cleavage site S1/S2. Conversely, S2' site may be influenced by residues located between NTD and RBD of a neighboring protomer of the SpikeWT. Such communication may be lost in SpikeBA.1, explaining the changes of the cell tropism in the viral infection. In addition, the movements of the NTDWT and NTDBA.1 may modulate the RBD conformation through allosteric effects. Taken together, our results explain how the structural aspects may explain the observed gains in infectivity, immune system evasion and transmissibility of the Omicron variant.Communicated by Ramaswamy H. Sarma.

2.
Epidemiol Infect ; 150: e177, 2022 Oct 19.
Article in English | MEDLINE | ID: covidwho-2106269

ABSTRACT

Limited prospective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data in children regarding the impact of Omicron variant in seropositivity have been reported. We investigated SARS-CoV-2 seropositivity in children between 1 September 2021 and 30 April 2022, representing Delta and Omicron predominance periods. Serum samples from children admitted to the major tertiary Greek paediatric hospital for any cause, except for COVID-19, were randomly collected and tested for SARS-CoV-2 natural infection antibodies against nucleocapsid antigen (Elecsys® Anti-SARS-CoV-2 reagent). A total of 506/1312 (38.6%) seropositive children (0-16 years) were detected (males: 261/506(51.6%); median age (IQR): 95.2 months(24-144)). Seropositivity rates (%) increased from Delta to Omicron period from 29.7% to 48.5% (P-value<0.0001). Seropositivity increased for all age groups, except for the age group of 0-1 year (P-value:0.914). The highest seropositivity rate was detected in April 2022 (52.6%) and reached 73.9% specifically for the age group 12-16 years. No significant differences were detected in seropositivity with respect to gender, origin, or hospitalisation status. Median (IQR) antibody titres were higher in the Omicron vs. Delta period in all age groups, especially in 12-16 years [32.2 COI (7-77.1) vs. 11.4 COI(2.8-50.2), P-value:0.009). During Omicron variant period increased SARS-CoV-2 seropositivity was detected in paediatric population, especially in adolescents, implicating either increased transmissibility or reinfection rates.


Subject(s)
COVID-19 , SARS-CoV-2 , Adolescent , Child , Humans , Infant , Infant, Newborn , Male , Antibodies, Viral , COVID-19/epidemiology , Enzyme-Linked Immunosorbent Assay/methods , Prospective Studies , Seroepidemiologic Studies , Female , Child, Preschool
3.
Jpn J Infect Dis ; 75(4): 411-414, 2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-2100391

ABSTRACT

The World Health Organization designated Omicron (B.1.1.529 lineage) of SARS-CoV-2 as a new variant of concern on November 26, 2021. The risk to public health conferred by the Omicron variant is still not completely clear, although its numerous gene mutations have raised concerns regarding its potential for increased transmissibility and immune escape. In this study, we describe the development of two single-nucleotide polymorphism genotyping assays targeting the G339D or T547K mutations of the spike protein to screen for the Omicron variant. A specificity test revealed that the two assays successfully discriminated the Omicron variant from the Delta and Alpha variants, each with a single nucleotide mismatch. In addition, a sensitivity test showed that the G339D and T547K assays detected at least 2.60 and 3.36 RNA copies of the Omicron variant, respectively, and 1.59 RNA copies of the Delta variant. These results demonstrate that both assays could be useful for detecting and discriminating the Omicron variant from other strains. In addition, because of the rapid and unpredictable evolution of SARS-CoV-2, combining our assays with previously developed assays for detecting other mutations may lead to a more accurate diagnostic system.


Subject(s)
COVID-19 , Genotyping Techniques , Humans , COVID-19/diagnosis , COVID-19/virology , Genotype , RNA , RNA, Viral/genetics , Polymorphism, Single Nucleotide
4.
BMC Pediatr ; 22(1): 625, 2022 11 03.
Article in English | MEDLINE | ID: covidwho-2098326

ABSTRACT

BACKGROUND: Research of coronavirus disease (COVID-19) effects on newborns is ongoing. But the research of specific variant's effects is none. This study analyzed the effects of the Omicron variant on the perinatal outcomes of full-term newborns during the Omicron wave period.  METHODS: Between December 2021 and April 2022, this study was conducted on all newborns who visited a single center. We investigated due to the Omicron maternal infection maternal pregnancy complications, delivery methods, birth week, Apgar scores, neonatal resuscitation program requirement, whether respiratory support was required until 12 h after childbirth, suspicious infectious status, and mortality depending on maternal Omicron infection. RESULTS: A total of 127 neonates were enrolled, and 12 were excluded based on exclusion criteria. Sixteen neonates were born to mothers with a history of Omicron COVID-19, and 99 were born to non-infectious mothers. All infected mothers became infected in the 3rd trimester. Of the 16 mothers, seven were symptomatic, and four met the isolation criteria, according to Korean guidelines. The birth weight of newborns to mothers with a history of COVID and those without was 2.958 ± 0.272 kg and 3.064 ± 0.461 kg (p = 0.049), respectively. The 5-min Apgar score at childbirth was 9.29 ± 0.756 and 9.78 ± 0.460 for neonates born to symptomatic and asymptomatic mothers (p = 0.019), respectively. When compared with or without maternal self-isolation, neonates requiring respiratory support 12 h after birth demonstrated a significant difference (p = 0.014; OR, 10.275). Additionally, the presence or absence of transient tachypnea of the newborn showed a significant value (p = 0.010; OR 11.929). CONCLUSIONS: Owing to Omicron COVID-19, newborns were born with lower birth weight, low 5-min Apgar scores, and required respiratory support until 12 h after birth.


Subject(s)
COVID-19 , Infant, Newborn, Diseases , Pregnancy Complications, Infectious , Pregnancy Complications , Pregnancy , Female , Infant, Newborn , Humans , SARS-CoV-2 , Infectious Disease Transmission, Vertical , Resuscitation , Birth Weight
5.
J Biomol Struct Dyn ; : 1-9, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2097035

ABSTRACT

In the years since the rapid invasion of SARS-CoV-2, the world community has fully understood the extent of the danger of this new pathogen. And also the speed with which he is able to adapt both to humans as a species and to the means of combat that are introduced. However, this has already resulted in millions of lost lives and this situation may worsen in the future, due to the further inevitable evolution of the virus. Accordingly, the need for effective drugs is urgent. In this work, using an iterative approach, we de novo designed a molecule that revealed significant affinity to four variants of SARS-CoV-2 - Wuhan, Omicron, Delta and Cluster 5. More precisely, to their receptor-binding domain of S-glycoprotein, in particular, to the site that is directly involved in the recognition of human ACE2.What is confirmed in particular by the ΔGbind of the complexes of RBD of all four SARS-CoV-2 variants with a potential inhibitor: it is in significantly negative values. Along with this, the calculated ADMET parameters can generally be considered acceptable. Accordingly, we believe that the molecule we have designed has a high potential for further development as an effective drug against SARS-CoV-2. However, it currently requires further in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.

6.
Mol Ther Nucleic Acids ; 30: 465-476, 2022 Dec 13.
Article in English | MEDLINE | ID: covidwho-2095867

ABSTRACT

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the effectiveness of currently approved mRNA vaccines. To achieve wider coverage of VOCs, we first constructed a cohort of mRNAs harboring a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). The mutation abolished the cleavage between the S1 and S2 subunits. Systematic evaluation in vaccinated mice discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. In particular, the neutralizing antibodies (nAb) produced by immunization with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs. However, neither mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original Omicron variant and some sublineages. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we engineered an mRNA-based chimeric immunogen by introducing the receptor-binding domain of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA induced potent and broadly nAbs against Omicron and Delta, which paves the way to developing new vaccine candidates to target emerging variants in the future.

7.
Journal of the Chilean Chemical Society ; JOUR(3):5562-5570, 67.
Article in English | Web of Science | ID: covidwho-2092766

ABSTRACT

The aim of this work was identifying the physico-chemical properties of some medicinal plants which are applied in front of the Omicron Variant (Covid-19 variant B.1.1.529) symptoms. In this paper, seven medicinal ingredients for the most frequently symptoms of Omicron disease containing cough, sore throat, fever, short-breath, anorexia, muscle-joint pain, headache and Nausea-vomiting related to the fidelity level index has been run. In fact, coronaviruses (CoVs) is able to infect people and multiple types of animals through enteric, respiratory, and central nervous system maladied with considerable agents for designing anti-Omicron conjunction. In this investigation, it has been discussed the compounds of thymol, gingerol, salvinorina A, cynnamil, curcumin, pulegone and rosmarinic acid as a probable anti pandemic Omicron receptor derived from medicinal plants and herbs of thyme, ginger, salvia divinorum, cinnamon leaves, curcuma longa (turmeric), mentha pulegium (pennyroyal) and rosemary, respectively. Anti-Omicron through the H-bonding employing the physical and chemical characteristics containing heat of formation, Gibbs free energy, electronic energy, charge distribution of active parts in the hydrogen bonding, NMR estimation of medicinal ingredients jointed to the database amino acids fragment of Tyr-Met-His as the selective zone of the Omicron, positive frequency and intensity of different normal modes of these structures have been measured. On the other hand, the simulated computations were accomplished at different steps of theory to get the more real equilibrium geometrical coordination, and IR spectral data for each of the complex proposed drugs of N-terminal or O-terminal auto-cleavage substrate were individually identified to represent the structural flexibility and substrate binding of these natural plants embedded to active site of Omicron molecule. Finally, a comparison of these structures with two configurations prepares new outlooks for modeling the substrate-based anti-targeting Omicron. This issue exhibits a feasible model for simulating a wide-spectrum of anti-Omicron medications. The structure-based optimization of these molecules has resulted two more efficacious lead materials, nitrogen and oxygen elements through producing the hydrogen bonding (H-bonding) with a rich anti-Omicron Variant (Covid-19 variant B.1.1.529).

8.
Science ; JOUR(6617):233-233, 378.
Article in English | Academic Search Complete | ID: covidwho-2092084

ABSTRACT

The article discusses Twitter exploded with outrage about a study in which scientists engineered the spike protein of Omicron the fast-spreading but relatively mild variant of SARS-CoV-2 that's pervasive into a deadlier strain of the coronavirus found in Washington state early in the pandemic.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(10): 1085-1091, 2022 Oct 15.
Article in Chinese | MEDLINE | ID: covidwho-2090828

ABSTRACT

OBJECTIVES: To study the clinical features and prognosis of children and their family members with family clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection under the admission mode of parent-child ward. METHODS: A retrospective analysis was performed on the medical data of 190 children and 190 family members with SARS-CoV-2 Omicron variant infection who were admitted to Shanghai Sixth People's Hospital, the designated hospital for coronavirus disease 2019 (COVID-19), April 8 to May 10, 2022. RESULTS: Both the child and adult groups were mainly mild COVID-19, and the proportion of mild cases in the child group was higher than that in the adult group (P<0.05). Respiratory symptoms were the main clinical manifestations in both groups. Compared with the adult group, the child group had higher incidence rates of fever, abdominal pain, diarrhea, and wheezing (P<0.05) and lower incidence rates of nasal obstruction, runny nose, cough, dry throat, throat itching, and throat pain (P<0.05). Compared with the child group, the adult group had higher rates of use of Chinese patent drugs, traditional Chinese medicine decoction, recombinant interferon spray, cough-relieving and phlegm-eliminating drugs, and nirmatrelvir/ritonavir tablets (P<0.05). Compared with the adult group, the child group had a lower vaccination rate of SARS-CoV-2 vaccine (30.5% vs 71.1%, P<0.001) and a shorter duration of positive SARS-CoV-2 nucleic acid (P<0.05). The patients with mild COVID-19 had a shorter duration of positive SARS-CoV-2 nucleic acid than those with common COVID-19 in both groups (P<0.05). The patients with underlying diseases had a longer duration of positive SARS-CoV-2 nucleic acid than those without such diseases in both groups (P<0.05). CONCLUSIONS: Both children and adults with family clusters of SARS-CoV-2 Omicron variant infection manifest mainly mild COVID-19. Despite lower vaccination rate of SARS-CoV-2 vaccine in children, they have rapid disease recovery, with a shorter duration of positive SARS-CoV-2 nucleic acid than adults, under the admission mode of parent-child ward.


Subject(s)
COVID-19 , Nucleic Acids , Adult , Humans , COVID-19/epidemiology , SARS-CoV-2 , Cough , Retrospective Studies , COVID-19 Vaccines , China/epidemiology , Family
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(10): 1092-1097, 2022 Oct 15.
Article in Chinese | MEDLINE | ID: covidwho-2090827

ABSTRACT

OBJECTIVES: To study the clinical features of children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The medical data of 19 children who were diagnosed with SARS-CoV-2 Omicron variant infection from January 28 to March 3, 2022 in Hangzhou were retrospectively reviewed. RESULTS: Among the 19 children, there were 7 boys (37%) and 12 girls (63%), and their age ranged from 6 months to 16 years, with a median age of 2 years and 1 month. Most of these children were infants and young children (aged ≤3 years, accounting for 53%). Among these children, 11 (58%) were unvaccinated with SARS-CoV-2 vaccine and 8 (42%) were vaccinated with SARS-CoV-2 vaccine, and 3 children (16%) had a history of underlying diseases. All 19 children had a clear history of close contact with persons infected with SARS-CoV-2, and 10 children (53%) were involved in the cluster outbreak in a maternal and infant care center. In terms of clinical classification, 13 children (68%) had mild coronavirus disease 2019 (COVID-19) and 6 (32%) had common COVID-19, with no severe cases of COVID-19. The most common clinical symptoms were cough (100%) and fever (63%). The children with a normal peripheral white blood cell count accounted for 84%, and those with a normal lymphocyte count accounted for 68%. There were no significant abnormalities in platelet count, procalcitonin, liver function parameters (alanine aminotransferase and aspartate aminotransferase), and renal function parameters (creatinine and urea). Six children (32%) had obvious signs of pneumonia on chest CT. All 19 children were given symptomatic treatment, and 12 children (63%) were given aerosol inhalation of interferon α. All children were cured and discharged. CONCLUSIONS: Children infected with Omicron variant strains are more common in infants and young children, with mild symptoms and good prognosis. Most of the children have a history of close contact with persons infected with SARS-CoV-2, and epidemic prevention and control should be strengthened in places with many infants and children, such as maternal and infant care centers.


Subject(s)
COVID-19 , SARS-CoV-2 , Child , Infant , Male , Female , Humans , Child, Preschool , Retrospective Studies , COVID-19 Vaccines , China/epidemiology
11.
Yonsei Med J ; 63(11): 977-983, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2089803

ABSTRACT

As soon as the first case of the omicron variant of severe acute respiratory syndrome coronavirus 2 was reported in November 2021, it quickly spread worldwide with the emergence of several subvariants. Compared to previous variants, omicron was heavily mutated, especially for those in the Spike (S) protein and its receptor-binding domain. These mutations allowed the viruses to evade immune responses (i.e., previous infections and vaccine-elicited) and increase in transmissibility. Although vaccine effectiveness is decreased for omicron, boosters remain effective for protecting against severe diseases. Also, bivalent vaccines have been developed to increase vaccine effectiveness. Interestingly, although omicron is highly infectious, it has less morbidity and mortality compared to previously identified variants, such as delta. Additionally, the mutations that allow the virus to evade immune responses also allow it to evade many of the monoclonal antibodies developed at the beginning of the pandemic for treatment. Here, we reviewed the omicron variant's epidemiology, genetics, transmissibility, disease severity, and responsiveness to vaccine and treatments.


Subject(s)
COVID-19 , Viral Vaccines , Humans , Antibodies, Viral , SARS-CoV-2/genetics
12.
Virus Evol ; 8(2): veac089, 2022.
Article in English | MEDLINE | ID: covidwho-2087850

ABSTRACT

New variants of SARS-CoV-2 show remarkable heterogeneity in their relative fitness over both time and space. In this paper we extend the tools available for estimating the selection strength for new SARS-CoV-2 variants to a hierarchical, mixed-effects, renewal equation model. This formulation allows us to estimate selection effects at the global level while incorporating both measured and unmeasured heterogeneity among countries. Applying this model to the spread of Omicron in forty countries, we find evidence for very strong but very heterogeneous selection effects. To test whether this heterogeneity is explained by differences in the immune landscape, we considered several measures of vaccination rates and recent population-level infection as covariates, finding moderately strong, statistically significant effects. We also found a significant positive correlation between the selection advantage of Delta and Omicron at the country level, suggesting that other region-specific explanatory variables of fitness differences do exist. Our method is implemented in the Stan programming language, can be run on standard consumer-grade computing resources, and will be straightforward to apply to future variants.

13.
chemRxiv;
Preprint in English | ChemRxiv | ID: ppcovidwho-346175

ABSTRACT

Mutations in spike (S) protein epitopes allow SARS-CoV-2 variants to evade antibody responses induced by infection and/or vaccination. In contrast, glycosylation sites in the S protein are conserved across SARS-CoV-2 variants, making glycans a potential robust target for developing antivirals. However, this target has not been adequately exploited for SARS-CoV-2, mostly due to intrinsically weak monovalent protein-glycan inter-actions. We hypothesize that polyvalent nano-lectins with flexibly linked carbohydrate-recognition-domains (CRDs) can adjust their relative positions and bind multivalently to S protein glycans, potentially exerting potent antiviral activity. Herein, we displayed the CRDs of DC-SIGN, a dendritic cell lectin known to bind to diverse viruses, polyvalently onto 13 nm gold nanoparticles (named as G13-CRD). G13-CRD bound strongly and specifically to target glycan-coated quantum dots with sub-nM Kd. Moreover, G13-CRD neutralized particles pseudo-typed with the S proteins of Wuhan Hu-1, B1, Delta variant and Omicron subvariant BA.1 with low nM EC50. In contrast, natural tetrameric DC-SIGN and its G13 conjugate were ineffective. Further, G13-CRD potently and completely inhibited authentic SARS-CoV-2 Wuhan Hu-1 and BA.1, with <10 pM and <10 nM EC50, respectively. These results identify G13-CRD as a polyvalent nano-lectin with broad activity against SARS-CoV-2 variants that merits further exploration as a novel approach to antiviral therapy.

14.
Front Immunol ; 13: 1004045, 2022.
Article in English | MEDLINE | ID: covidwho-2080154

ABSTRACT

Haemodialysis patients respond poorly to vaccination and continue to be at-risk for severe COVID-19. Therefore, dialysis patients were among the first for which a fourth COVID-19 vaccination was recommended. However, targeted information on how to best maintain immune protection after SARS-CoV-2 vaccinations in at-risk groups for severe COVID-19 remains limited. We provide, to the best of our knowledge, for the first time longitudinal vaccination response data in dialysis patients and controls after a triple BNT162b2 vaccination and in the latter after a subsequent fourth full-dose of mRNA-1273. We analysed systemic and mucosal humoral IgG responses against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron and Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell responses by interferon γ release assay. After triple BNT162b2 vaccination, anti-RBD B.1 IgG and ACE2 binding inhibition reached peak levels in dialysis patients, but remained inferior compared to controls. Whilst we detected B.1-specific ACE2 binding inhibition in 84% of dialysis patients after three BNT162b2 doses, binding inhibition towards the Omicron variant was only detectable in 38% of samples and declining to 16% before the fourth vaccination. By using mRNA-1273 as fourth dose, humoral immunity against all SARS-CoV-2 variants tested was strongly augmented with 80% of dialysis patients having Omicron-specific ACE2 binding inhibition. Modest declines in T-cell responses in dialysis patients and controls after the second vaccination were restored by the third BNT162b2 dose and significantly increased by the fourth vaccination. Our data support current advice for a four-dose COVID-19 immunisation scheme for at-risk individuals such as haemodialysis patients. We conclude that administration of a fourth full-dose of mRNA-1273 as part of a mixed mRNA vaccination scheme to boost immunity and to prevent severe COVID-19 could also be beneficial in other immune impaired individuals. Additionally, strategic application of such mixed vaccine regimens may be an immediate response against SARS-CoV-2 variants with increased immune evasion potential.


Subject(s)
COVID-19 , Viral Vaccines , Mice , Animals , Humans , Immunity, Humoral , SARS-CoV-2 , 2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19/prevention & control , Angiotensin-Converting Enzyme 2 , COVID-19 Vaccines , Mice, Inbred BALB C , Vaccination , Immunoglobulin G , Renal Dialysis , RNA, Messenger
15.
Front Immunol ; 13: 961198, 2022.
Article in English | MEDLINE | ID: covidwho-2080141

ABSTRACT

In December 2019, an outbreak emerged of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which leads to coronavirus disease 2019 (COVID-19). The World Health Organisation announced the outbreak a global health emergency on 30 January 2020 and by 11 March 2020 it was declared a pandemic. The spread and severity of the outbreak took a heavy toll and overburdening of the global health system, particularly since there were no available drugs against SARS-CoV-2. With an immediate worldwide effort, communication, and sharing of data, large amounts of funding, researchers and pharmaceutical companies immediately fast-tracked vaccine development in order to prevent severe disease, hospitalizations and death. A number of vaccines were quickly approved for emergency use, and worldwide vaccination rollouts were immediately put in place. However, due to several individuals being hesitant to vaccinations and many poorer countries not having access to vaccines, multiple SARS-CoV-2 variants quickly emerged that were distinct from the original variant. Uncertainties related to the effectiveness of the various vaccines against the new variants as well as vaccine specific-side effects have remained a concern. Despite these uncertainties, fast-track vaccine approval, manufacturing at large scale, and the effective distribution of COVID-19 vaccines remain the topmost priorities around the world. Unprecedented efforts made by vaccine developers/researchers as well as healthcare staff, played a major role in distributing vaccine shots that provided protection and/or reduced disease severity, and deaths, even with the delta and omicron variants. Fortunately, even for those who become infected, vaccination appears to protect against major disease, hospitalisation, and fatality from COVID-19. Herein, we analyse ongoing vaccination studies and vaccine platforms that have saved many deaths from the pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19 Vaccines , COVID-19/prevention & control , Pharmaceutical Preparations
16.
Acta Paediatr ; 2022 Oct 19.
Article in English | MEDLINE | ID: covidwho-2078332

ABSTRACT

AIM: We examined the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children during the autumn and winter season from 1 September 2021 to 30 January 2022 and compared it with the same period in 2020-2021. METHODS: This study was carried out int the paediatric emergency department (PED) of a tertiary Italian hospital. We compared the clinical and demographical features of all children who presented during the two study periods and tested positive for SARS-CoV-2. RESULTS: During the 2021-2022 autumn and winter season 5813 children presented to the PED, 19.0% were tested for SARS-CoV-2 and 133 (12.0%) of those tested positive. In 2020-2021, 2914 presented to the PED, 12.3% were tested, and 30 (8.3%) of those tested positive. There were no statistically significant differences in clinical severity during the two study periods, despite a higher percentage of neurological symptoms in 2020-2021. Of the SARS-CoV-2-positive cases, 29/133 (21.8%) were hospitalised during the 2021-2022 season and 10/30 (33.3%) during the previous one. Only 3/163 children required intensive care. CONCLUSION: The greater spread of SARS-CoV-2 was probably due to the greater transmissibility of the Omicron variant, but the symptoms were mild and only 3 children required intensive care.

17.
Proc Natl Acad Sci U S A ; 119(44): e2206509119, 2022 11.
Article in English | MEDLINE | ID: covidwho-2077260

ABSTRACT

The sudden emergence and rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant has raised questions about its animal reservoir. Here, we investigated receptor recognition of the omicron's receptor-binding domain (RBD), focusing on four of its mutations (Q493R, Q498R, N501Y, and Y505H) surrounding two mutational hotspots. These mutations have variable effects on the RBD's affinity for human angiotensin-converting enzyme 2 (ACE2), but they all enhance the RBD's affinity for mouse ACE2. We further determined the crystal structure of omicron RBD complexed with mouse ACE2. The structure showed that all four mutations are viral adaptations to mouse ACE2: three of them (Q493R, Q498R, and Y505H) are uniquely adapted to mouse ACE2, whereas the other one (N501Y) is adapted to both human ACE2 and mouse ACE2. These data reveal that the omicron RBD was well adapted to mouse ACE2 before omicron started to infect humans, providing insight into the potential evolutionary origin of the omicron variant.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Animals , Humans , Mice , Angiotensin-Converting Enzyme 2/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism , Peptidyl-Dipeptidase A/metabolism , COVID-19/genetics , Protein Binding , Mutation
18.
World J Pediatr ; 2022 Oct 17.
Article in English | MEDLINE | ID: covidwho-2075688

ABSTRACT

BACKGROUND: The number of pediatric cases of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has increased. Here, we describe the clinical characteristics of children in a tertiary children's medical center in Shanghai. METHODS: A total of 676 pediatric coronavirus disease 2019 (COVID-19) cases caused by the Omicron variant who were admitted to the Shanghai Children's Medical Center from March 28 to April 30, 2022 were enrolled in this single-center, prospective, observational real-world study. Patient demographics and clinical characteristics, especially COVID-19 vaccine status, were assessed. RESULTS: Children of all ages appeared susceptible to the SARS-CoV-2 Omicron variant, with no significant difference between sexes. A high SARS-CoV-2 viral load upon admission was associated with leukocytopenia, neutropenia, and thrombocytopenia (P = 0.003, P = 0.021, and P = 0.017, respectively) but not with physical symptoms or radiographic chest abnormalities. Univariable linear regression models indicated that comorbidities (P = 0.001) were associated with a longer time until viral clearance, and increasing age (P < 0.001) and two doses of COVID-19 vaccine (P = 0.001) were associated with a shorter time to viral clearance. Multivariable analysis revealed an independent effect of comorbidities (P < 0.001) and age (P = 0.003). The interaction effect between age and comorbidity showed that the negative association between age and time to virus clearance remained significant only in patients without underlying diseases (P < 0.001). CONCLUSION: This study describes the clinical characteristics of children infected with the Omicron variant of SARS-CoV-2 and calls for additional studies to evaluate the effectiveness and safety of vaccination against COVID-19 in children.

19.
Neurol Sci ; 2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2075443

ABSTRACT

INTRODUCTION: The Omicron variant of COVID-19 is highly transmissible, triggering unprecedented infection rates. The present study aimed to investigate the course of multiple sclerosis (MS) in the Omicron era among Iranian patients with MS. METHODS: This observational study was designed on MS patients of the national MS registry of Iran through a self-designed online questionnaire. A questionnaire was prepared as a Google Form for MS patients during the Omicron outbreak from 1 March to 30 April 2022. RESULTS: One hundred seventy-four patients with a mean age of 37.3 ± 9.04 were enrolled. Of the patients, 95.97% used DMT, the most common of which were rituximab and fingolimod. Of the patients, 77.58% were fully vaccinated for COVID-19. Regardless of the COVID-19 vaccination status, 76 patients developed COVID-19, which was mild to moderate. Except for recent corticosteroid therapy and secondary progressive MS (SPMS), other demographic and MS characteristics were not significantly associated with the severity of COVID-19. There was also a marginal association between the Expanded Disability Status Scale (EDSS) and the severity of COVID-19. In addition, 17.10% of patients reported MS relapse following COVID-19 leading to escalation therapy in eight patients. CONCLUSION: Our study demonstrated that in the Omicron era, most patients developed mild COVID-19. Although the predominant COVID-19 variant in this period was Omicron, we could not separate the pathogenic variants. The risk factors for COVID-19 during the Omicron era were not different from other pandemic waves. Our preliminary results revealed that the MS relapse following COVID-19 was higher than in previous waves.

20.
J Med Virol ; 2022 Oct 13.
Article in English | MEDLINE | ID: covidwho-2075075

ABSTRACT

In March 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surged during the Coronavirus Disease 2019 (COVID-19) pandemic in Shanghai, but over 90% of patients were mild. This study included 1139 COVID-19 patients mildly infected with the Omicron variant of SARS-CoV-2 in Shanghai from May 1 to 10, 2022, aiming to clarify the demographic characteristics and clinical symptoms of patients with mild Omicron infection. The clinical phenotypes of Omicron infection were identified by model-based cluster analysis to explore the features of different clusters. The median age of the patients was 41.0 years [IQR: 31.0-52.0 years] and 73.0% were male. The top three clinical manifestations are cough (57.5%), expectoration (48.3%), and nasal congestion and runny nose (43.4%). The prevalence of nasal congestion and runny nose varied significantly across the doses of vaccinations, with 23.1% in the unvaccinated population and 30%, 45.9%, and 44.3% in the 1-dose, 2-dose and 3-dose vaccinated populations, respectively. In addition, there were significant differences for fever (23.1%, 26.0%, 28.6%, 18.4%), head and body heaviness (15.4%, 14.0%, 26.7%, 22.4%), and loss of appetite (25.6%, 30.0%, 33.6%, 27.7%). The unvaccinated population had a lower incidence of symptoms than the vaccinated population. Cluster analysis revealed that all four clusters had multisystemic symptoms and were dominated by both general and respiratory symptoms. The more severe the degree of the symptoms was, the higher the prevalence of multisystemic symptoms will be. The Omicron variant produced a lower incidence of symptoms in mildly infected patients than previous SARS-CoV-2 variants, but the clinical symptoms caused by the Omicron variant are more complex, so that it needs to be differentiated from influenza.

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