Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020.

BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Molecular detection of dengue and chikungunya viruses in surveillance of wild-caught Aedes mosquitoes in Punjab, North India.

BACKGROUND: Dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses are transmitted mainly by Aedes mosquitoes and are responsible for a significant global healthcare burden. The current study aimed to detect arboviruses in the Aedes mosquitoes in close proximity of patients during the transmission season. METHODS: Both immature and adult mosquitoes were collected from in and around the patients' houses. Mosquito pools were homogenized and extracted RNA was subjected to reverse transcription polymerase chain reaction for arboviral detection. Transovarian transmission (TOT) was assessed by screening F0 adults. Mosquito positivity was correlated with the aetiological agents identified in patients. RESULTS: Of 46 pools, 19 consisted of wild Aedes, with arboviral positivity in 53% (10/19) of pools. Among wild A. aegypti pools, positivity of DENV mono-infection, CHIKV mono-infection and DENV+CHIKV co-infection was noted in four, two and three pools, respectively. One wild pool of Aedes albopictus was positive for DENV-1. Similarly, A. aegypti F0 (adult Aedes developed from immatures) pools showed 59.2% (16/27) positivity for arboviruses. F0 Aedes showed positivity in three, six and seven pools for DENV-2, CHIKV and DENV+CHIKV, respectively, suggestive of TOT. DENV serotypes and CHIKV from 24 patients' serum samples were matched with strains isolated from Aedes and correlation was observed in four instances. CONCLUSIONS: The study detected DENV and CHIKV from wild-caught Aedes and found evidence of DENV and CHIKV TOT in F0 adults.

Relamorelin in Gastroparesis and Diabetic Gastroparesis: A Meta-Analysis on Its Efficacy and Safety.

This meta-analysis aimed to evaluate the efficacy and safety of relamorelin, a synthetic ghrelin receptor agonist, for the treatment of gastroparesis and diabetic gastroparesis. A total of 1,033 participants from five randomized controlled trials were included. The primary outcome was the mean change in gastric emptying time from baseline. Relamorelin demonstrated a statistically significant improvement in gastric emptying time with a mean difference of -11.40 minutes compared to the placebo group. Furthermore, a significant improvement was observed specifically in diabetic gastroparesis patients, with a mean difference of -8.43 minutes. However, adverse effects, such as headaches, dizziness, and gastrointestinal symptoms, were more prevalent in the relamorelin group. Despite these adverse effects, the study concludes that relamorelin offers a promising avenue for gastroparesis treatment, especially given the limited existing therapeutic options. This comprehensive meta-analysis synthesizes existing evidence to inform clinical practice and guides future research in this domain.

The impact of aspirin use on outcomes in patients with inflammatory bowel disease: Insights from a national database.

BACKGROUND: Inflammatory bowel disease (IBD) is an inflammatory disorder that can increase the risk of mortality. Aspirin is an anti-inflammatory drug used for primary prevention of cardiovascular events. A single center analysis previously reported that aspirin use did not impact major outcomes in IBD. In this study, we aim to assess the impact of aspirin use on mortality and other outcomes in patients with IBD using national data. METHODS: National inpatient sample (NIS) 2016-2020 was used to identify adult patients with IBD. Data were collected on patient demographics, hospital characteristics, and comorbidities. The outcomes studied were in-hospital mortality, sepsis, shock, Intensive Care Unit (ICU) admission, and need for surgery. Multivariate logistic regression analysis was performed. RESULTS: A total of 1,524,820 IBD hospitalizations were included. Of these, 137,430 (9%) were long-term aspirin users. The majority of the patients in the aspirin group were aged > 65 years (34.11%), female (56.37%), White (78.83%) and had Medicare insurance (36.77%). Aspirin users had a lower incidence of in-hospital mortality (1.6% vs 1.4%, P = 0.06), sepsis (2.5% vs 2.9%, P < 0.001), shock (2.9% vs 3.4%, P < 0.001), ICU admission (2.6% vs 2.9%, P < 0.001), need for surgery (2.1% vs 4.2%, P < 0.001). After adjusting for confounders, aspirin was associated with a reduction in mortality (adjusted odds ratio: 0.49, 95%CI 0.45-0.55, P < 0.001). CONCLUSION: Our study reports that aspirin use among patients with IBD was associated with a lower risk of death, sepsis, and shock. Aspirin use may have a protective effect in patients with IBD. Further studies are needed to confirm these results.

Artificial Intelligence in the Detection of Barrett's Esophagus: A Systematic Review.

Barrett's esophagus (BE) remains a significant precursor to esophageal adenocarcinoma, requiring accurate and efficient diagnosis and management. The increasing application of machine learning (ML) technologies presents a transformative opportunity for diagnosing and treating BE. This systematic review evaluates the effectiveness and accuracy of machine learning technologies in BE diagnosis and management by conducting a comprehensive search across PubMed, Scopus, and Web of Science databases up to the year 2023. The studies were organized into five categories: computer-aided systems, natural language processing and text-based systems, deep learning on histology and biopsy images, real-time and video analysis, and miscellaneous studies. Results indicate high sensitivity and specificity across machine learning applications. Specifically, computer-aided systems showed sensitivities ranging from 84% to 100% and specificities from 64% to 90.7%. Natural language processing and text-based systems achieved an accuracy as high as 98.7%. Deep learning techniques applied to histology and biopsy images displayed sensitivities up to greater than 90% and a specificity of 100%. Furthermore, real-time and video analysis technologies demonstrated high performance with assessment speeds of up to 48 frames per second (fps) and a mean average precision of 75.3%. Overall, the reviewed literature underscores the growing capability and efficiency of machine learning technologies in diagnosing and managing Barrett's esophagus, often outperforming traditional diagnostic methods. These findings highlight the promising future role of machine learning in enhancing clinical practice and improving patient care for Barrett's esophagus.

Mapping the stability of febrile illness hotspots in Punjab from 2012 to 2019- a spatial clustering and regression analysis.

INTRODUCTION: Febrile illnesses (FI) represent a typical spectrum of diseases in low-resource settings, either in isolation or with other common symptoms. They contribute substantially to morbidity and mortality in India. The primary objective was to study the burden of FI based on Integrated Disease Surveillance Programme (IDSP) data in Punjab, analyze geospatial and temporal trends and patterns, and identify the potential hotspots for effective intervention. METHODS: A retrospective ecological study used the district-level IDSP reports between 2012 and 2019. Diseases responsible for FI on a large scale, like Dengue, Chikungunya, Malaria (Plasmodium Falciparum, P. Vivax), Enteric fever, and Pyrexia of Unknown Origin (PUO), were included in the analysis. The digital map of Punjab was obtained from GitHub. Spatial autocorrelation and cluster analysis were done using Moran's I and Getis-Ord G* to determine hotspots of FI using the incidence and crude disease numbers reported under IDSP. Further, negative binomial regression was used to determine the association between Spatio-temporal and population variables per the census 2011. Stable hotspots were depicted using heat maps generated from district-wise yearly data. RESULTS: PUO was the highest reported FI. We observed a rising trend in the incidence of Dengue, Chikungunya, and Enteric fever, which depicted occasional spikes during the study period. FI expressed significant inter-district variations and clustering during the start of the study period, with more dispersion in the latter part of the study period. P.Vivax malaria depicted stable hotspots in southern districts of Punjab. In contrast, P. Falciparum malaria, Chikungunya, and PUO expressed no spatial patterns. Enteric Fever incidence was high in central and northeastern districts but depicted no stable spatial patterns. Certain districts were common incidence hotspots for multiple diseases. The number of cases in each district has shown over-dispersion for each disease and has little dependence on population, gender, or residence as per regression analysis. CONCLUSIONS: The study demonstrates that information obtained through IDSP can describe the spatial epidemiology of FI at crude spatial scales and drive concerted efforts against FI by identifying actionable points.

First detection and genetic identification of Rickettsia spp. from ticks collected from rodents in north India.

BACKGROUND: Changing climatic conditions and invasion of ticks in urban areas have led to a greater number of cases of tick-borne diseases, thus, becoming a matter of increasing concern. Tick borne rickettsioses are one of the important emerging diseases worldwide. Knowledge of epidemiology of the vector and pathogen in the community is essential in order to understand and prevent the transmission of the disease to healthy population. METHODS: In our present study, we trapped rodents in selected areas of Chandigarh and Punjab in north India. The rodents were screened for the presence of ticks which were further screened for the presence of rickettsial agents. PCRs targeting 17 â€‹kDa and gltA genes were carried out followed by Sanger sequencing of the positive amplicons followed by phylogenetic analysis of the sequences. RESULTS: A total of 17 ticks were collected out of which one (Rhipicephalus sanguineus) was found to be harboring a Rickettsia sp. PCR targeting gltA and 17 â€‹kDa genes of rickettsia were put up and Sanger sequencing was performed. Phylogenetic analysis revealed the sequences to be closely related to Rickettsia rhipicephali. CONCLUSION: The current study establishes the presence of rickettsial agents in the community. Although Rickettsia rhipicephali is a non-pathogenic agent, the study encourages more vigorous community surveillance should be carried out in order to determine the exact burden of rickettsial agents in our community. To our knowledge, this is the first study reporting Rickettsia rhipicephali in India.

Acute Delirium Post-inguinal Hernia Mesh Repair in a 40-Year-Old Male: An Unusual Case of Cystocerebral Syndrome.

Acute urinary retention is a known complication of inguinal hernia repair. However, the development of severe agitation and delirium as a result of acute urinary retention following inguinal hernia repair is less commonly reported. Here, we present the case of a 40-year-old male with no relevant medical history who underwent open mesh hernia repair for an uncomplicated left-sided indirect inguinal hernia. Postoperatively, the patient became hypertensive, delirious, and violent. He was found to have urinary retention on a bladder scan. Urgent intervention with catheterization and bladder decompression resulted in the prompt resolution of the patient's symptoms. The patient regained his senses and did not remember the events that led to it. This case highlights the importance of recognizing and managing acute urinary retention to prevent the development of severe agitation and delirium following spinal anesthesia. Further research and awareness are necessary to better understand the underlying neurovisceral mechanisms and optimize preventive strategies.

Right Atrial Thrombus and Submassive Pulmonary Embolism in a COVID-19-Infected Patient: A Case Report.

Coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, but it undoubtedly results in systemic illness that affects multiple systems. The high incidence of thromboembolic events is one distinctive clinical characteristic of COVID-19. This case report is about a unique clinical presentation of a 40-year-old homeless female with polysubstance abuse, who was diagnosed with a right atrial thrombus, sub-massive pulmonary embolism, and COVID-19 infection. The patient presented with shortness of breath, subjective fevers, generalized swelling, and chest and upper abdominal pain. Initially, she was treated with tissue plasminogen activator (TPA) and heparin drip for her thrombi, and she was managed conservatively when hemoptysis ensued post-TPA. She was later sent to a higher level of care for surgical embolectomy. In most cases, severe pulmonary parenchymal disease secondary to COVID-19 correlates with the severity of thromboembolic complications, however, in our case report, there was a right atrial thrombus and pulmonary embolism in the absence of COVID pneumonia. This highlights how notorious COVID-19 infections can be.

Postoperative Outcomes After Tympanoplasty for Active Versus Inactive Otitis Media Patients With Tympanic Membrane Perforation: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare postoperative tympanoplasty outcomes between active versus inactive otitis media (OM) patients with tympanic membrane perforation. DATABASES REVIEWED: Medline via PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar for studies published from inception to March 1, 2023. METHODS: Studies of 15- to 60-year-old patients undergoing microscopic/endoscopic myringoplasty using underlay/overlay technique with reported postoperative mean hearing gain and graft uptake were included. Studies requiring simultaneous surgical procedures, reporting patients with comorbidities and with non-English full text articles were excluded. Articles were independently screened by two researchers with data extracted according to a predetermined proforma in Microsoft Excel. Cochrane risk-of-bias assessment was used for risk of bias evaluation of randomized studies and Risk of Bias in Nonrandomized Studies of Interventions for nonrandomized studies. Similar studies were pooled for meta-analysis using the inverse variance random effects model to calculate the mean difference and corresponding 95% confidence interval (CI) for mean hearing gain and DerSimonian and Laird random effects model for graft uptake. RESULTS: Thirty-three studies comprising 2,373 patients met the inclusion/exclusion criteria, seven were pooled for meta-analysis. Included articles showed inactive OM patients have higher average postoperative mean hearing gain of 10.84 dB and graft uptake of 88.7% compared to active OM patients (9.15 dB and 84.2%). Meta-analysis of mean hearing gain (MD, -0.76 dB; 95% CI, -2.11 to 0.60; p = 0.27, moderate certainty) and graft uptake (OD, 0.61; 95% CI, 0.34-1.09; p = 0.10, moderate certainty) have an overall p value >0.05. CONCLUSION: There were no statistically significant differences in postoperative mean hearing gain and graft uptake between active and inactive OM patients undergoing tympanoplasty. Hence, tympanoplasty procedures should not be postponed solely because of patients' preoperative ear discharge status.

Pericardial Cyst in Birt-Hogg-Dubé Syndrome: An Unexpected Discovery.

Birt-Hogg-Dubé syndrome (BHD) is a genetic disorder typically characterized by pulmonary cysts, cutaneous fibrofolliculomas, and renal tumors. We report a case of an 87-year-old male patient with a known diagnosis of BHD and a large pericardial cyst who presented to the emergency room with chest pain. BHD is classically associated with pulmonary cysts and not pericardial cysts. In this report, we highlight the potential of pericardial cysts to independently cause retrosternal pain resembling angina, while also mentioning that BHD too can cause chest pain through the rupture of a pulmonary cyst leading to spontaneous pneumothorax. In our case, coronary angiography revealed non-obstructive coronary arteries, so the cause of chest pain was attributed to myocardial infarction with non-obstructive coronary arteries (MINOCA). Atypical causes of chest pain should be considered, especially in patients with diagnosed genetic syndromes.

Hepatopulmonary Syndrome in a Patient With Autoimmune Hepatitis and Chronic Hepatitis C: A Case Report Highlighting Typical Echo Findings.

Hepatopulmonary syndrome (HPS) is a rare complication of liver disease characterized by intrapulmonary vascular dilatations leading to arterial hypoxemia. We present the case of a 59-year-old female with a past medical history of bilateral breast cancer status post mastectomy who presented with progressive dyspnea on exertion and fatigue. A comprehensive diagnostic workup was conducted to exclude other cardiac, pulmonary, and systemic etiologies. She was diagnosed with autoimmune hepatitis along with chronic hepatitis C. Echocardiography revealed characteristic findings of intrapulmonary shunting characteristic of HPS. The patient showed improvement in pulmonary symptoms and oxygenation status following the initiation of steroid therapy. Although corticosteroids are not the definitive treatment for HPS, they were considered a supportive measure in this case. However, it is important to note that liver transplantation remains the definitive treatment for HPS. This case underscores the importance of echocardiography and the potential role of supportive measures, like corticosteroids, in managing HPS-related symptoms, particularly in patients with autoimmune hepatitis, as a bridging therapy while awaiting liver transplantation.

Ectopic Liver Tissue Encountered Incidentally During a Laparoscopic Cholecystectomy: A Case Report.

A 60-year-old male patient who presented with right upper quadrant (RUQ) pain was diagnosed with acute cholecystitis after an ultrasound of the abdomen revealed multiple gallstones, gallbladder wall thickening, pericholecystic fluid, and a positive sonographic Murphy sign. The patient was admitted, administered IV fluids, antibiotics, and pain relief, and scheduled for laparoscopic cholecystectomy. During surgery, an incidental finding of ectopic liver tissue attached to the gallbladder was noted. Histopathology confirmed the presence of chronic cholecystitis and multifaceted cholesterol stones. Normal liver tissue was noted in the ectopic mass. Ectopic liver tissue is defined as liver tissue located outside the main liver parenchyma and is usually asymptomatic. They are usually detected at the time of autopsies, incidentally during surgeries, or during imaging done for other etiologies. They can occur at various sites in the body. Ectopic liver tissue can cause potential complications such as hepatocellular carcinoma and torsion, and in the event that they are incidentally detected, it is advised to remove them. The case report highlights the importance of dealing with incidental findings during laparoscopic cholecystectomy and creating awareness about it.

Malaria vector sibling species distribution in different endemic districts of Punjab, India.

BACKGROUND & OBJECTIVES: Malaria transmission in Punjab, India is mainly seasonal with variation in its endemicity that may be due to varying vector behaviour in different areas of the state, primarily attributed to the existence of sibling species complexes among the vector species. So far there is no report regarding the existence of malaria vectors sibling species in the state of Punjab, therefore, the present study was planned to investigate the status of sibling species of two main vectors of malaria viz. Anopheles culcifacies and Anopheles fluviatilis in different districts of Punjab. METHODS: Mosquito collections were made through hand catch in the morning hours. Malaria vector species An. culicifacies and An. fluviatilis were morphologically identified and man hour density was calculated. Both the vector species were subjected to molecular assays for sibling species identification through amplification of D3 domain of 28S ribosomal DNA by allele-specific PCR. RESULTS: Four sibling species of An. culicifacies, were identified viz. A, B, C and E. Species A was identified from Bhatinda district, species B, C and E from. S.A.S. Nagar and species C from Hoshiarpur. Two sibling species S and T of An. fluviatilis were identified from districts S.A.S. Nagar and Rupnagar. INTERPRETATION & CONCLUSION: Presence of four sibling species of An. culicifacies and two sibling species of An. fluviatilis in Punjab necessitates planning of longitudinal studies to ascertain their role in disease transmission so that appropriate interventions may be applied to achieve malaria elimination.

Herpes Simplex Virus Meningoencephalitis Masquerading as Acute Stroke With Broca's Aphasia: A Case Report.

This case report presents a rare and unique instance of a 70-year-old morbidly obese female with type 2 diabetes mellitus and bilateral lymphedema, who presented with fever and expressive aphasia, initially suspected to be a stroke. A negative CT scan prompted the performance of an MRI, which revealed suggestive imaging findings of herpes encephalitis. Following the MRI, the patient experienced seizures and required intubation in the intensive care unit. Subsequently, a lumbar puncture was performed, confirming the diagnosis of herpes simplex virus (HSV) meningoencephalitis. Prompt initiation of acyclovir therapy led to an improvement in aphasia, ultimately allowing for extubation and transfer to the general ward. The rarity of this case lies in the unusual manifestation of Broca's aphasia caused by HSV, which is not typically associated with this neurological deficit. This report highlights the importance of considering herpes encephalitis as a potential etiology in patients presenting with atypical neurological symptoms, even in the absence of typical radiological findings. Early diagnosis and appropriate management with acyclovir are crucial in improving outcomes in such cases.

Patient outcomes in public sector hepatitis C treatment programmes: a retrospective cohort analysis across five low- and middle-income countries.

OBJECTIVES: Given limited data on factors associated with hepatitis C virus (HCV) treatment discontinuation and failure in low- and middle-income countries, we aimed to describe patient populations treated for HCV in five countries and identify patient groups that may need additional support. DESIGN: Retrospective cohort analysis using routinely collected data. SETTING: Public sector HCV treatment programmes in India (Punjab), Indonesia, Myanmar, Nigeria (Nasarawa) and Vietnam. PARTICIPANTS: 104 957 patients who initiated treatment in 2016-2022 (89% from Punjab). PRIMARY OUTCOMES: Treatment completion and cure. RESULTS: Patient characteristics and factors associated with outcomes varied across countries and facilities. Across all patients, median age was 40 years (IQR: 29-52), 30.6% were female, 7.0% reported a history of injecting drugs, 18.2% were cirrhotic and 4.9% were coinfected with HIV. 79.8% were prescribed sofosbuvir+daclastasvir. Of patients with adequate follow-up, 90.6% (89,551) completed treatment. 77.5% (69,426) of those who completed treatment also completed sustained virological testing at 12 weeks (SVR12), and of those, 92.6% (64 305) were cured. In multivariable-adjusted models, in most countries, significantly lower treatment completion was observed among patients on 24-week regimens (vs 12-week regimens) and those initiated in later years of the programme. In several countries, males, younger patients <20 years and certain groups of cirrhotic patients were less likely to complete treatment or be cured. In Punjab, treatment completion was also lower in those with a family history of HCV and people who inject drugs (PWID); in other countries, outcomes were comparable for PWID. CONCLUSION: High proportions of patients completed treatment and were cured across patient groups and countries. SVR12 follow-up could be strengthened. Males, younger people and those with decompensated cirrhosis on longer regimens may require additional support to complete treatment and achieve cure. Adequate programme financing, minimal user fees and implementation of evidence-based policies will be critical to close gaps.

Surface-modified measles vaccines encoding oligomeric, fusion-stabilized SARS-CoV-2 spike glycoproteins bypass measles seropositivity, boosting neutralizing antibody responses to omicron and historical variants.

Serum titers of SARS-CoV-2 neutralizing antibodies (nAb) correlate well with protection from symptomatic COVID-19, but decay rapidly in the months following vaccination or infection. In contrast, measles-protective nAb titers are life-long after measles vaccination, possibly due to persistence of the live-attenuated virus in lymphoid tissues. We therefore sought to generate a live recombinant measles vaccine capable of driving high SARS-CoV-2 nAb responses. Since previous clinical testing of a live measles vaccine encoding a SARS-CoV-2 spike glycoprotein resulted in suboptimal anti-spike antibody titers, our new vectors were designed to encode prefusion-stabilized SARS-CoV-2 spike glycoproteins, trimerized via an inserted peptide domain and displayed on a dodecahedral miniferritin scaffold. Additionally, to circumvent the blunting of vaccine efficacy by preformed anti-measles antibodies, we extensively modified the measles surface glycoproteins. Comprehensive in vivo mouse testing demonstrated potent induction of high titer nAb in measles-immune mice and confirmed the significant incremental contributions to overall potency afforded by prefusion stabilization, trimerization, and miniferritin-display of the SARS-CoV-2 spike glycoprotein, and vaccine resurfacing. In animals primed and boosted with a MeV vaccine encoding the ancestral SARS-CoV-2 spike, high titer nAb responses against ancestral virus strains were only weakly cross-reactive with the omicron variant. However, in primed animals that were boosted with a MeV vaccine encoding the omicron BA.1 spike, antibody titers to both ancestral and omicron strains were robustly elevated and the passive transfer of serum from these animals protected K18-ACE2 mice from infection and morbidity after exposure to BA.1 and WA1/2020 strains. Our results demonstrate that antigen engineering can enable the development of potent measles-based SARS-CoV-2 vaccine candidates.

Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody to antigenically distinct omicron SARS-CoV-2 subvariants

The rapid evolution of SARS-CoV-2 Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identify S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) and derived from an individual previously infected with SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrates broad cross-neutralization of all dominant variants including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1). Furthermore, it protected hamsters against in vivo challenges with wildtype, Delta, and BA.1 viruses. Structural analysis reveals that this antibody targets a class 1 epitope via multiple hydrophobic and polar interactions with its CDR-H3, in addition to common class 1 motifs in CDR-H1/CDR-H2. Importantly, this epitope is more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared to diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential, and may inform target-driven vaccine design against future SARS-CoV-2 variants.