Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

Effects of post-COVID-19 vaccination in oral cavity: a systematic review.

OBJECTIVES: SARS-CoV-2 virus and its variants continue to be on a rampage worldwide. Several vaccines are being marketed to control their spread and reduce severity of symptoms in the affected. Various adverse events are being reported following the vaccine administration and therefore this systematic review investigated the oral adverse events post-COVID-19 vaccination. MATERIALS AND METHODS: A systematic search of five databases was conducted. Case reports, case series and observational studies describing oral lesions/oral adverse effects (outcome) following anti-SARS-CoV-2 vaccination (exposure) in humans were included. Quality assessment of the studies was done using Joanna Briggs Institute Critical Appraisal tools. A working classification was developed from reported final diagnosis. RESULTS: The systematic review included 18 individual cases. Majority of oral lesions occurred following BNT162b2 vaccination with average age of occurrence at 59.94 years. 67% of the affected individuals were female, with hypertension being the most common comorbidity. DISCUSSION: Immune-mediated oral events have a propensity of occurrence following COVID-19 vaccination. mRNA-based vaccinations may have an affinity for causing oral adverse effects. It might be due to the immune dysregulation caused by these vaccinations. CONCLUSION: The female, geriatric population and older individuals with co-morbidities might have an increased affinity to develop oral lesions post-COVID-19 vaccination.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting.

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (≤ or ≥60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants - ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post-omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months.

A Three-Dimensional Scale for the Qualitative and Quantitative Assessments of Secondary Alveolar Bone Grafting (SABG) in Unilateral Cleft Lip and Palate Patients Using Cone-Beam Computed Tomography (CBCT).

Background The objective of our study was to derive an objective assessment scale for three-dimensional (3D) qualitative and quantitative evaluation of secondary alveolar bone grafting (SABG) using cone-bone computed tomography (CBCT) in patients with unilateral cleft lip and palate (UCLP). Methods CBCT scans for pre- and 3-month post-SABG were reviewed for bone volume, height, width, and density of the bony bridge formed in the cleft defect in 20 patients with UCLP. Basic descriptive and principal component analysis was used to extract the various sub-components of the scale. Spearman's correlation was used to check the validity of the scale, and intra-class coefficient (ICC) and Cronbach's α were calculated to establish the reliability and retest applicability of the scale. Results Each CBCT scan was assessed in five areas: cementoenamel junction (CEJ), root apex, root midpoint, 3 and 6 mm below CEJ, and tabulated in percentiles of 20, 25, 40, 50, 60, and 75 for all the parameters (bone volume, density, and width). These scores were validated when correlated to the scale given by Kamperos et al. Cronbach's α for the domains demonstrated acceptable to excellent internal consistency. The ICC showed good test-retest reliability having a range of scores from 0.89 to 0.94. Conclusion The proposed scale for the 3D assessment of SABG in patients with UCLP provides gradation for the objective assessment of the bony bridge. This gradation enables the qualitative and quantitative assessments of the bony bridge, thus allowing each clinician to judge SABG more conclusively.

Evaluation of Alt-RAMEC With Facemask in Patients With Unilateral Cleft lip and Palate (UCLP) Using Cone Beam Computed Tomography (CBCT) and Finite Element Modeling-A Clinical Prospective Study.

OBJECTIVE: Evaluate the effects of alternate rapid maxillary expansion and constriction (Alt-RAMEC) protocol on patients with unilateral cleft lip and palate (UCLP) along with maxillary protraction using cone beam computed tomography (CBCT) records and a finite element modeling (FEM) model. MATERIALS AND METHODS: Twenty-five patients (aged 9-13 years) with UCLP having a GOSLON score 3 were selected for this prospective single-arm cohort study after obtaining necessary informed consent. A 9-week Alt-RAMEC protocol using a custom-made fan-shaped expansion screw was initiated, which was followed by 6-month facemask wear. Pre (T1) and posttreatment (T2) records including CBCT were taken and were evaluated for treatment changes in all 3 dimensions using paired t test. Additionally, a FEM model (ANSYS 15.0) using the Alt-RAMEC protocol was also analyzed for the displacement and stress on various craniofacial structures. RESULTS: Significant forward movement of the maxilla along with clockwise rotation of mandible along with statistically significant increase in lower molar height and upper incisor proclination (P < .05) was observed. CBCT evaluation showed a statistical significant decrease in buccal alveolar bone thickness and increase in molar inclination (P < .05). Finite element modeling analysis highlighted that the maximum displacement occurred at the anterior region with stresses radiating till the anterior nasal spine, zygomatic arch, and sphenoid bone. CONCLUSION: Alt- RAMEC protocol combined with facemask protraction can lead to significant maxillary advancement, with some transient decrease in buccal bone thickness noted thereby warranting long-term studies to further assess its effect on the dentofacial apparatus.

A New Frame for Orienting Infants With Cleft Lip and Palate During 3-Dimensional Facial Scanning.

BACKGROUND: Nonradiographic 3-D assessment of soft tissue facial structures is an ideal tool to measure 3-D facial change and smartphone apps like Bellus 3D have brought these technologies to our doorsteps. Although this app works well for adults, it doesn't do so well with infants as their stabilization is difficult thus proper alignment becomes problematic often leading to distortion. This seriously hampers the repeatability and reliability of the whole process. MATERIAL AND METHOD: A stainless steel rod of 150-cm length is curved into a semicircle of a radius of 42.5 cm. Bases are fabricated at both the ends to firmly hold the stand on the table. A Teflon ring of one inch is made for adjusting the diameter of the camera holder. A camera holder is then attached to the Teflon ring. The mobile holder mounted is free to move within the arc. A 3-D facial scan of a single patient was carried out with the camera mounted on the frame and once without the frame. The same was compared using side-by-side comparison and superimposition of the .STL files from the frontal, profile, and worm's eye view. RESULT AND CONCLUSION: It was found that considerable distortion was noted around the nasal and paranasal areas when the scan was performed without the frame as compared to the one that was taken with the frame. This technique avoided distortion and the difficulty in turning the baby's head to record the lateral portion of the face.

A comparative evaluation of presurgical infant orthopedics of modified Grayson's technique with clear aligners incorporating a nasal elevator in patients with unilateral cleft lip and palate.

OBJECTIVE: To assess the differences between 2 methods of presurgical infant orthopedics: the modified Grayson's technique and a new technique using clear aligners in patients with complete unilateral cleft lip and palate. METHODS: For this prospective comparative cohort study, 30 patients were divided into 2 groups: group A (modified Grayson technique) and group B (clear aligner trays), with 15 patients each. Scanned cast measurements were taken before and after treatment and evaluated using an appropriate 3-dimensional software assessing treatment changes in the alveolus (eg, reduction of width between major and minor segment, angulation change of each respective segment [intragroup and intergroup, respectively]). This was supplemented with standardized anterioposterior, Worms-eye view, and profile photographs assessing changes in columellar angle, nostril width, height, nasolabial angle, and soft-tissue cleft gap. Furthermore, the number of visits for each patient group was also tabulated and assessed. The differences were compared using the independent t test and Mann-Whitney U test for the respective parameters. RESULTS: Groups A and B showed similar posttreatment changes, with no overt significant differences. However, there was a statistically significant difference in the number of visits (P <0.05), with group B having much lower visits to the center than group A. The posttreatment values matched previously established growth reference values. The analysis of photographic measurements showed improved nasal asymmetry in both groups without any significant difference. CONCLUSIONS: Because there was no difference in the treatment results between the 2 methods and a reduction in the number of required patient visits, presurgical infant orthopedics via clear aligners could pave the way for a more patient-efficient approach.

Comparative Study of Presurgical Infant Orthopedics by Modified Grayson Method and Dynacleft With Nasal Elevators in Patients With Unilateral Cleft Lip and Palate-A Clinical Prospective Study.

OBJECTIVE: To compare the effects of presurgical infant orthopedics using 2 different methods, that is, the Dynacleft with Nasal elevator system versus the modified Grayson's technique in patients with complete unilateral cleft lip and palate. DESIGN: Prospective comparative cohort study. MATERIALS AND METHODS: Twenty-eight patients were divided into 2 groups, that is, Group A consisting of 14 patients who underwent correction with DynaCleft with Nasal elevator system and Group B consisting of 14 patients undergoing correction using the modified Grayson technique. Maxillary cast measurements were taken at 2-time intervals (pre- and posttreatment) to assess various parameters using a laser scanning machine (C500 Solutionix) and 3D software (GOM Inspect). Similarly, standardized anterior-posterior and worm's-eye view photographs using a custom box were taken and imported to Adobe Photoshop CS6 for measurements. Paired t test and independent t test were used to compare intra- and intergroup changes, respectively. RESULTS: The analysis of cast (primary outcome) and photographic (secondary outcome) measurements showed improved nasal asymmetry and alveolar correction in both groups which showed no significant intergroup difference when assessed using the independent t test (P > .05). Group A showed higher chances (42.8%) of causing a T-shaped defect (due to excessive mesial-inward rotation of the minor segment) when compared to the Group B possibly due to a more controlled molding vector (P < .05). CONCLUSION: Both methods proved effective in improving the nasal asymmetry, reducing the alveolar cleft gap, and approximating the lips together; but care must be taken when applying the alveolar molding vector in the Dynacleft system.

A comparative assessment of transfer accuracy of two indirect bonding techniques in patients undergoing fixed mechanotherapy: A randomised clinical trial.

OBJECTIVES: To assess the transfer accuracy of three-dimensional (3D) printed transfer trays and compare them with transfer trays made up of polyvinyl siloxane (PVS) for use in indirect bonding. DESIGN: This was a two-arm parallel prospective randomised controlled trial. SETTING: The trial was undertaken at the outpatient department of a dental college. PARTICIPANTS: A total of 30 patients (18 men, 12 women) were randomly allocated to two groups. METHODS: The inclusion criteria included patients with permanent and fully erupted dentition (age range = 17-24 years), Angles class I malocclusion with crowding <3 mm requiring non-extraction treatment, good oral hygiene and no previous history of orthodontic treatment. Blinding was applicable only for outcome assessment. Indirect bonding was performed by the primary investigator for both the groups. Digital images of the pre-transfer and post-transfer brackets were obtained by means of an intra-oral scanner and compared using software. Superimpositions of pre- and post-transfer images were done to determine the transfer error for linear and angular variables for all tooth types. RESULTS: A total of 600 teeth were bonded, 300 each for both groups. Statistically significant differences were observed in all dimension between the two groups, with 3D-printed trays being more accurate than PVS trays except in the vertical dimension (P < 0.05). The prevalence of clinically unacceptable transfer errors revealed that most of the transfer errors were in the vertical dimensions for 3D-printed trays. CONCLUSION: 3D-printed trays are more accurate than PVS trays except for transfers in vertical dimension.

OrthoAligner "NAM": A Case Series of Presurgical Infant Orthopedics (PSIO) Using Clear Aligners.

Presurgical infant orthopedics (PSIO) is done to reduce the size of the cleft defect along with improving the arch alignment and nasolabial aesthetics in patients with cleft lip and palate, leading to an improvement of nasolabial aesthetics allowing for a tidier and more aesthetic reparative procedure and postsurgical scar. Since the 2000s, clear aligners have slowly and steadily treaded their way as an acceptable orthodontic modality, with their usage and acceptability increasing considerably over the past decade. Thus, from the knowledge gathered in its 10 years working with 3-dimensional (3-D) diagnosis, treatment planning, and 3-D Printing services, Compass 3D (Belo Horizonte, Brazil) developed the OrthoAligner NAM system. This case series highlights one of the world's first documented cases of PSIO treated with a series of clear aligners.

Aesthetic perceptions and psychosocial impact of malocclusion: comparison between cleft and non-cleft patients and their parents.

Objective: To evaluate the influence of dentofacial attractiveness using the 'Psychosocial Impact of Dental Aesthetics Questionnaire' (PIDAQ), Satisfaction with Life Scale (SWLS) and Aesthetic Component (AC) of the Index of Orthodontic Treatment Need (IOTN) in patients with cleft lip/palate (CLP), and non-cleft orthodontic patients (Non-CLP) and their parents. Materials and methods: Eighty patients (aged 11-19 years) comprising 40 CLP and 40 non-CLP were administered the PIDAQ and SWLS questionnaires to be rated individually by the patients, along with IOTN-AC rated by the patients and their parents, respectively. The subjects were also sub-divided according to their age, i.e. pre-adolescent and adolescent. Results: The PIDAQ subpart scores for aesthetic concern differed between the two groups, with a significantly (P < 0.02) lower scoring for the CLP group. The adolescent CLP group scored more negatively than the pre-adolescent group in the dental self-confidence and social impact sub-parts of PIDAQ. No significant differences were observed for satisfaction with life. The parents' IOTN-AC score for both groups was significant (P < 0.05) greater than the patient's score, especially for adolescent subjects. Limitations: Non-condition specific questionnaires with restrictive sampling sizing and non-inclusion of parameters like stress coping mechanism etc. Conclusion: The parents rated the malocclusion of their child more critically than the child itself. A majority of the CLP group had a problem in identifying themselves using the IOTN-AC as no photo existed depicting a Class III or edge-to-edge malocclusion. Attitudes, especially perceptions of the aesthetics of front teeth, are crucial factors influencing patient's psychological self-concept, social confidence, and treatment need in CLP patients and non-CLP patients, having more relevance as the patient matures towards adolescence and adulthood.

Comparison of rate of tooth movement and pain perception during accelerated tooth movement associated with conventional fixed appliances with micro-osteoperforations - a randomised controlled trial.

OBJECTIVES: To investigate the influence of micro-osteoperforation (MOP) on rate of orthodontic tooth movement and pain perception with fixed appliances. DESIGN: 2 arm parallel randomized controlled trial with an allocation ratio of 1:1. SETTING: The outpatient department of a dental college. PARTICIPANTS: 105 patients were screened, out of which 60 met the inclusion criteria and consented to participate; consisting of 33 females and 27 males requiring en-masse retraction following first premolar extractions. METHODS: The experimental group consisted of patients bonded with a fixed appliance (Gemini 3M) who received MOP distal to canines throughout the period of retraction every 28 days. These were compared with a control group treated with identical brackets without MOP and were assessed for rate of tooth movement (canine retraction) and pain perception using a Visual Analogue Scale (VAS) of 10 mm. RESULTS: Prior to commencement, all baseline parameters were matched between the two groups (p>0.05). A statistically significant increase in rate of tooth movement in the MOP group (p<0.05). CONCLUSION: MOP appears to enhance the rate of tooth movement with no differences in pain perception.

Comparative assessment of facemask therapy with and without skeletal anchorage in growing Class III patients with unilateral cleft lip and palate (UCLP): A single-center, prospective randomized clinical trial.

OBJECTIVE: The purpose of this study was to evaluate the maxillary protraction effect of facemask therapy with and without skeletal anchorage in growing Class III patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: Thirty patients (aged 9-13 years) with UCLP having a GOSLON score 3 were selected for this prospective clinical study. The patients were allocated into two groups using computer generated random number table. Group I (facemask therapy along with two I shaped miniplates, FM + MP) and Group II (facemask mask along with tooth-anchored appliance, FM). Skeletal and dental parameters were evaluated on pre- and post-treatment lateral cephalograms and pharyngeal airway on cone-beam computed tomography systems (CBCT) for assessment of the treatment changes. RESULTS: Both methods proved to be effective with statistically significant improvements in skeletal and dental parameters (p < .05). Skeletal parameters (e.g., SNA, convexity-point A, ANB) with the FM + MP group showed greater change compared to those with FM group (SNA, 2.56°; convexity-point A, 1.22°; ANB, 0.35°). Significant proclination of maxillary incisors was observed in the FM group as compared to FM + MP group (U1 to NA, 5.4°; 3.37 mm). A statistically significant increase in pharyngeal airway volume was noted in both groups (p < .05). CONCLUSION: While both therapies are effective in protracting the maxilla in growing patients with UCLP, the FM + MP allows for a greater skeletal correction, minimizing the dental side effects seen with FM therapy alone. Thus, FM + MP appears to be a promising adjunct in reducing the severity of Class III skeletal correction needed in patients with cleft lip and palate (CLP).

A quest for universal anti-SARS-CoV-2 T cell assay: systematic review, meta-analysis, and experimental validation.

Measuring SARS-CoV-2-specific T cell responses is crucial to understanding an individual's immunity to COVID-19. However, high inter- and intra-assay variability make it difficult to define T cells as a correlate of protection against COVID-19. To address this, we performed systematic review and meta-analysis of 495 datasets from 94 original articles evaluating SARS-CoV-2-specific T cell responses using three assays - Activation Induced Marker (AIM), Intracellular Cytokine Staining (ICS), and Enzyme-Linked Immunospot (ELISPOT), and defined each assay's quantitative range. We validated these ranges using samples from 193 SARS-CoV-2-exposed individuals. Although IFNγ ELISPOT was the preferred assay, our experimental validation suggested that it under-represented the SARS-CoV-2-specific T cell repertoire. Our data indicate that a combination of AIM and ICS or FluoroSpot assay would better represent the frequency, polyfunctionality, and compartmentalization of the antigen-specific T cell responses. Taken together, our results contribute to defining the ranges of antigen-specific T cell assays and propose a choice of assay that can be employed to better understand the cellular immune response against viral diseases.

An assessment of masticatory efficiency and occlusal load distribution in adolescent patients undergoing orthodontic treatment with functional jaw orthopedics: A prospective cohort study.

INTRODUCTION: Functional jaw orthopaedics, produces a radical change in the occlusal scheme and the masticatory apparatus, particularly in patients with Class II malocclusion. It remains to be seen how the changes brought about by a functional appliance alter the masticatory ability of a growing child, who needs the necessary nutrition to properly grow the craniofacial region. MATERIALS AND METHODS: Pretreatment and Post-treatment values of masticatory efficiency and the distribution of the occlusal load at centric occlusion were evaluated and compared for 20 patients with Class II division 1 malocclusion undergoing functional jaw orthopaedics. RESULTS: Significant increase in the masticatory efficiency was seen during and after treatment (p < 0.5) There was an increase in the anterior distribution of occlusal load associated with a concomitant decrease in the posterior region at centric occlusion. CONCLUSION: Improvement in the masticatory efficiency was observed after treatment of a retrognathic mandible with functional jaw orthopaedics in the adolescent participants with Class II malocclusion. This highlights the importance of treatment with functional jaw orthopaedics, which apart from providing esthetic and functional improvement also improves the ability of a growing child to extract proper nutrition from his/her diet.

Clinical and experimental evidence suggest omicron variant of SARS-CoV-2 is inherently less pathogenic than delta variant independent of previous immunity.

OBJECTIVES: To study clinical disease outcomes in both human and animal models to understand the pathogenicity of omicron compared to the delta variant. METHODS: In this cross-sectional observational study, clinical outcomes of adults who tested positive at 2 testing centres in Delhi National Capital Region between January 2022 and March 2022 (omicron-infected; N = 2998) were compared to a similar geographical cohort (delta-infected; N = 3292). In addition, disease course and outcomes were studied in SARS-CoV-2-infected golden Syrian hamsters and K-18 humanized ACE2 transgenic mice. RESULTS: Omicron variant infection was associated with a milder clinical course [83% (95% CI 61, 94) reduced risk of severity compared against delta] adjusting for vaccination, age, sex, prior infection and occupational risk. This correlated with lower disease index and vir comparing omicron with other variants in animal models. CONCLUSIONS: Infections caused by the omicron variant were milder compared to those caused by the delta variant independent of previous immunity.