Antiviral therapy for COVID-19 virus: A narrative review and bibliometric analysis.

The COVID-19 epidemic has become a major international health emergency. Millions of people have died as a result of this phenomenon since it began. Has there been any successful pharmacological treatment for COVID-19 since the initial report on the virus? How many searches are undertaken to address the impact of the infection? What is the number of drugs that have undergone investigation? What are the mechanisms of action and adverse effects associated with the investigated pharmaceuticals used to treat COVID-19? Has the Food and Drug Administration (FDA) approved any medication to treat COVID-19? To date, our understanding is based on a restricted corpus of published investigations into the treatment of COVID-19. It is important to note that no single study comprehensively encompasses all pharmacological interventions for COVID-19. This paper provides an introductory summary of a bibliometric analysis conducted on the data about COVID-19, sourced explicitly from two platforms, namely PubMed and ScienceDirect. The analysis encompasses the period spanning from 2019 to 2022. Furthermore, this study examines the published literature about the pharmacological interventions for the novel coronavirus disease 2019 (COVID-19), explicitly focusing on the safety and effectiveness of different medications such as Remdesivir (marketed as Veklury®), Lopinavir/Ritonavir (commercially known as Kaletra® or Aluvia®), Ribavirin, Favipiravir (marketed as Avigan®), Ivermectin, Casirivimab and Imdevimab (branded as Ronapreve®), Sotrovimab (marketed as Xevudy®), Anakinra, Molnupiravir, Nirmatrelvir/Ritonavir (marketed as Paxlovid®), and Galidesivir. Findings indicate that while Remdesivir and Nirmatrelvir/Ritonavir show significant efficacy in reducing hospitalization and severe outcomes, drugs like Lopinavir/Ritonavir and Ivermectin have inconsistent results. Our insights suggest a multifaceted approach incorporating these therapies can significantly improve patient outcomes. Repurposing drugs has been critical in rapidly responding to COVID-19, allowing existing medications to be used in new ways to combat the virus. Combination therapies and further research are essential to optimize treatment strategies.

Design and Evaluation of Microemulsion-Based Drug Delivery Systems for Biofilm-Based Infection in Burns.

Normal skin is the first line of defense in the human body. A burn injury makes the skin susceptible to bacterial infection, thereby delaying wound healing and ultimately leading to sepsis. The chances of biofilm formation are high in burn wounds due to the presence of avascular necrotic tissue. The most common pathogen to cause burn infection and biofilm is Pseudomonas aeruginosa. The purpose of this study was to create a microemulsion (ME) formulation for topical application to treat bacterial burn infection. In the present study, tea tree oil was used as the oil phase, Tween 80 and transcutol were used as surfactants, and water served as the aqueous phase. Pseudo ternary phase diagrams were used to determine the design space. The ranges of components as suggested by the design were chosen, optimization of the microemulsion was performed, and in vitro drug release was assessed. Based on the characterization studies performed, it was found that the microemulsion were formulated properly, and the particle size obtained was within the desired microemulsion range of 10 to 300 nm. The I release study showed that the microemulsion followed an immediate release profile. The formulation was further tested based on its ability to inhibit biofilm formation and bacterial growth. The prepared microemulsion was capable of inhibiting biofilm formation.

Linezolid-resistant Enterococcus faecium clinical isolates from Pakistan: a genomic analysis.

BACKGROUND: Linezolid-resistant Enterococcus faecium (LRE) is a global priority pathogen. Thirteen LRE were reported from clinical specimens between November 2021 and April 2023 at two laboratories in Karachi, Pakistan. We aimed to investigate the strain types and genes associated with linezolid resistance among these isolates. Whole genome sequencing (WGS) was performed and analyzed by multilocus sequence typing (MLST). The presence of linezolid resistance genes was identified using ResFinder v4.1.11 and the LRE-finder tool. RESULTS: Twelve isolates belonged to clonal complex 17 (CC17); ST80 (n = 10), ST612 (n = 1) and ST1380 (n = 1). Six isolates showed the presence of optrA gene and G2576T mutations in the 23S rRNA gene, while six showed poxtA and cfr(D) genes. One isolate showed the combination of optrA, cfr(D) and poxtA genes. CONCLUSION: Our findings show the circulation of CC17 sequence types with a known outbreak potential and we identified molecular mechanisms of resistance that were not previously reported from Pakistan.

Knowledge and Perceptions of Cerebral Venous Thrombosis Among the Adult Population: A Nationwide Cross-Sectional Study in Saudi Arabia.

Background: The current annual incidence of cerebral venous thrombosis (CVT) is 3-4 cases per one million population. CVT manifests itself with varying degrees of clinical presentation that may cause vital or morbid consequences if not treated and managed promptly. Studies have suggested varied levels of CVT public awareness. Aim: To assess the level of knowledge and public perception of CVT across the different socio-economic strata of the Saudi Adult population. Methods: A descriptive cross-sectional study was conducted using a mixed-method approach (an electronic questionnaire and phone interviews) for collecting the data. A validated questionnaire was distributed to consenting study participants and filled out to the best of their ability. The study setting was a nationwide survey conducted in Saudi Arabia and involved a representative portion of the study population. Results: A total of 1912 participants were included in this study. Overall, the majority of study participants (67.2%) had a low knowledge level of CVT on assessment, and only 2.6% had a high knowledge level of CVT. Younger age, female gender, working adults, higher education level, marital status, Saudi nationals, and place of residency were significantly associated with knowledge of CTV (p < 0.001). Conclusion: This study indicates a lower index of knowledge of CVT which offers an opportunity for much improvement in public perception and awareness of CVT in the study population. Our results can be utilized to target the demographics with the lowest knowledge via the most popular ways to gain information.

Pharmaceutical chitosan hydrogels: A review on its design and applications.

Chitosan (CS) has become a focal point of extensive research in the pharmaceutical industry due to its remarkable biodegradability, biocompatibility and sustainability. Chitosan hydrogels (CS HGs) are characterized by their viscoelasticity, flexibility and softness. The polar surfaces exhibit properties that mitigate interfacial tension between the hydrogel and body fluids. The inherent compatibility of CS HGs with body tissues and fluids positions them as outstanding polymers for delivering therapeutic proteins, peptides, DNA, siRNA, and vaccines. Designed to release drugs through mechanisms such as swelling-based diffusion, bioerosion, and responsiveness to stimuli, CS HGs offer a versatile platform for drug delivery. CS HGs play pivotal roles in serving purposes such as prolonging the duration of preprogrammed drug delivery, enabling stimuli-responsive smart delivery to target sites, protecting encapsulated drugs within the mesh network from adverse environments, and facilitating mucoadhesion and penetration through cell membranes. This review comprehensively outlines various novel preparation methods of CS HGs, delving into the parameters influencing drug delivery system design, providing a rationale for CS HG utilization in drug delivery, and presenting diverse applications across the pharmaceutical landscape. In synthesizing these facets, the review seeks to contribute to a nuanced understanding of the multifaceted role that CS HGs play in advancing drug delivery methodologies.

Titanium Oxide and Chitosan Nanoparticles Loaded in Methylene Blue Activated by Photodynamic Therapy on Caries Affected Dentin Disinfection, Bond Strength, and Smear Layer Removal Efficacy.

AIM: Effect of nanoparticles (NPs) loaded methylene blue (MB) mediated photodynamic therapy (PDT) on caries-affected dentin (CAD) against S.mutans, smear layer (SL) elimination, and shear bond strength (SBS) of single bottle 7th generation adhesive. METHODOLOGY: Sixty human molars with carious lesions were selected. Samples were randomly allocated into four groups, based on the disinfection regime (n=11) Group 1-(CHX), Group 2-(MB-PDT), Group 3-(MB-CNPs-PDT), and Group 4-(MB-TiO2NPs-PDT). Following disinfection S.Mutans' survival rate was assessed using the pour plate method. Five specimens from each disinfection group were subjected to SL removal assessment using a scanning electron microscope (SEM). Bonding of 7th generation adhesive and composite restoration was performed on ten samples from each group. Artificial aging of the bonded samples was performed followed by SBS and failure mode analysis using a universal testing machine and stereomicroscope respectively. One-way analysis of variance (ANOVA) and Tukey post hoc test were used to analyze the data. RESULTS: Group 3 (MB-CNPs-PDT) treated CAD surface unveiled the lowest survival rate (0.12 ± 0.02 CFU/mL) of tested bacteria, maximum SL removal (1.21±0.35), and highest bond strength (13.42 ± 1.05). However, Group 1 (CHX) treated specimens displayed the highest survival rate (0.53 ± 0.11 CFU/mL) with the lowest SL removal (2.24±0.30) and SBS (8.88± 0.73 MPa). CONCLUSION: MB-CNPs-PDT appears to be a suitable alternative to CHX for CAD disinfection as it displayed better antibacterial efficacy, SL removal, and SBS with 7th generation single bottle adhesive.

Disparities in age and gender-specific SARS-CoV-2 diagnostic testing trends: a retrospective study from Pakistan.

BACKGROUND: Pakistan reported 1.57 million COVID-19 cases between 2020 and 2022, based on approximately 30.6 million SARS-CoV-2 RT-PCR (reverse-transcription polymerase chain reaction) tests conducted. This study utilized data from one of the largest in-country testing facilities, Aga Khan University Hospital (AKUH) in Karachi, Pakistan, to explore gender and age-related in RT-PCR testing patterns. METHODS: We conducted a retrospective review of SARS-CoV-2 RT-PCR test data extracted from AKUH clinical laboratory records between February 2020 and February 2022. Gender and age distributions were examined in the context of testing patterns across the period. Multivariate regression models assessed independent associations between COVID-19 positivity and key variables. RESULTS: We reviewed 470,249 RT-PCR tests, finding that most tests were in those aged 21-40 years (48.1%). Overall, COVID-19 test positivity was 20.6%. In all, 57.7% were performed for males, predominant amongst those tested across all age groups and waves. Females had significantly lower odds of testing positive for COVID-19 (OR: 0.9; 95% CI: 0.9-1.0). However, when adjusted for gender, age and pandemic phases, the positivity rates between males and females were the same. The odds of a positive result increased significantly with age; individuals aged > 80 years had 2.5 times higher odds of testing positive than those aged 0-10 years (aOR 2.5, 95% CI 2.3-2.7). CONCLUSIONS: The analysis indicates a consistent male dominance in COVID-19 testing, with higher positivity rates in older age groups. Our study highlight the importance of examining demographic characteristics in disease associated data especially, representation of females amongst cohorts.

Risk factors for mortality in hospitalized COVID-19 patients across five waves in Pakistan.

This retrospective cohort study aims to describe the clinical characteristics and outcomes and assess risk factors for mortality across the epidemic waves in hospitalized COVID-19 patients in a major tertiary-care center in Pakistan. A total of 5368 patients with COVID-19, hospitalized between March 2020 and April 2022 were included. The median age was 58 years (IQR: 44-69), 41% were females, and the overall mortality was 12%. Comparative analysis of COVID-19 waves showed that the proportion of patients aged ≥ 60 years was highest during the post-wave 4 period (61.4%) and Wave 4 (Delta) (50%) (p < 0.001). Male predominance decreased from 65.2% in Wave 2 to 44.2% in Wave 5 (Omicron) (p < 0.001). Mortality rate was lowest at 9.4% in wave 5 and highest at 21.6% in the post-wave 4 period (p = 0.041). In multivariable analysis for risk factors of mortality, acute respiratory distress syndrome (ARDS) was most strongly associated with mortality (aOR 22.98, 95% CI 15.28-34.55, p < 0.001), followed by need for mechanical ventilation (aOR 6.81, 95% CI 5.13-9.05, p < 0.001). Other significant risk factors included acute kidney injury (aOR 3.05, 95% CI 2.38-3.91, p < 0.001), stroke (aOR 2.40, 95% CI 1.26-4.60, p = 0.008), pulmonary embolism (OR 2.07, 95% CI 1.28-3.35, p = 0.003), and age ≥ 60 years (aOR 2.45, 95% CI 1.95-3.09, p < 0.001). Enoxaparin use was associated with lower mortality odds (aOR 0.45, 95% CI 0.35-0.60, p < 0.001. Patients hospitalized during Wave 4 (aOR 2.22, 95% CI 1.39-3.56, p < 0.001) and the post-wave 4 period (aOR 2.82, 95% CI 1.37-5.80, p = 0.005) had higher mortality odds compared to other waves. The study identifies higher mortality risk in patients admitted in Delta wave and post-wave, aged ≥ 60 years, and with respiratory and renal complications, and lower risk with anticoagulation during COVID-19 waves.

Formulation, Optimization, and Evaluation of Non-Propellent Foam-Based Formulation for Burn Wounds Treatment.

Burn injuries worldwide pose significant health risks due to frequent microbial infections, which worsen complications and increase mortality rates. The conventional antimicrobial formulations are available in the form of ointments and creams. These formulations are very greasy and stick to the clothes. The applications of these formulations by finger or applicator produce pain in the affected area and incur the possibility of microbial infection. To overcome these hurdles, authors developed a novel non-propellent foam (NPF) based formulation containing chlorhexidine for effective topical delivery. Initially, NPF containing Labrasol® (26.7%), sodium lauryl sulfate (1.2%), hydroxy propyl methyl cellulose (0.56%), butylated hydroxytoluene (0.1%), ethanol (1%), and distilled water was prepared and assessed for its consistency, and ability to form foam. The NPF was statistically optimized using the Box-Behnken design to determine the effect of polymer and surfactants on the critical foam properties. The optimized formulation showed a collapse time of 45 s with a unique nature of collapsing upon slight touch which is highly beneficial for burn patients with microbial infection. The diffusion study showed that more than 90% of the drug was released within 6 h. The skin permeation study showed that 23% of the total drug permeated through the skin after 6 h with 7.64 µg/cm2/h permeation flux. The developed formulation showed good antibacterial activity. The minimum inhibitory concentration of prepared NPF was found to be 2.5 µg/mL, 2.5 µg/mL, and 5.0 µg/mL against E. coli (MTCC-1687), P. aeruginosa (MTCC-1688), and S aureus (MTCC-737) respectively. The developed NPF formulation showed quick collapse time, excellent spreadability, good anti-bacterial activity, and a non-sticky nature representing a promising avenue for burn wound treatment without using any applicator.

Knowledge of Diabetes Mellitus and Practices Regarding Lifestyle Factors and Diabetes Management in a General Adult Population of Aseer Region, Saudi Arabia.

Introduction: Many studies report a lack of public awareness of the risk factors and complications of Diabetes Mellitus. Adequate glycemic control is crucial in preventing or delaying the onset of type 2 diabetes complications, and medication adherence is one of the key factors in achieving this goal. This study aimed to measure the knowledge about diabetes mellitus and practices regarding lifestyle factors and diabetes management in the study population in the Aseer region, of Saudi Arabia. Material and Methods: A descriptive cross-sectional survey was conducted in Abha, a city in the Aseer region of Saudi Arabia. The general population of 18 years of age and above, who were residing in the study area during the period of study, ie, January 2023 to June 2023, were included. The questionnaire was distributed through social media and e-mail for data collection. The descriptive variables were presented using frequency, percentage, and graphs. Pearson's chi-square test was used at a 5% level of significance. Multivariate tests were applied to further explore the findings of univariate analysis. The data were analyzed using SPSS version 20.0. Results: Out of the total 348 participants, a higher proportion was males (56.3%). About 78.7% of the participants were ever diagnosed with diabetes mellitus and 21.3% were never diagnosed with diabetes mellitus. Nearly 31.6% knew that the major cause of diabetes mellitus was obesity and 31.3% knew that it was a hereditary disease. About 42.2% of respondents exercised regularly and 27.6% were smokers. Adherence to prescribed anti-diabetic medications was seen in 63.2% of the respondents. Self-alterations in the timing and dose of prescribed anti-diabetic drugs were seen in 36.5% and 34.8%, respectively. About 60.1% had a moderate level of self-rated knowledge about Diabetes Mellitus, and 27.6% and 12.4% had good and poor self-rated knowledge levels of Diabetes mellitus, respectively. On multivariate analysis, the age group 60-69 years had significant variations as compared to the other age groups on DM, bachelor's degree holders had significant variations as compared to other education variables, being married had significant differences as compared to those unmarried, those employed had significant variations as compared to the other occupation categories, and smokers had a significant impact on DM as compared to non-smokers. Conclusion: Findings indicated less number of respondents exercised regularly, low adherence to prescribed anti-diabetic medications and low levels of self-rated knowledge of diabetes mellitus. Enhancing the patients' knowledge of diabetes mellitus and improving their self-management and adherence to its medications is necessary through public health education.

Human Immunodeficiency Virus Type-1 Genetic Diversity and Drugs Resistance Mutations among People Living with HIV in Karachi, Pakistan.

The human immunodeficiency virus type-1 epidemic in Pakistan has significantly increased over the last two decades. In Karachi, Pakistan, there is a lack of updated information on the complexity of HIV-1 genetic diversity and the burden of drug resistance mutations (DRMs) that can contribute to ART failure and poor treatment outcomes. This study aimed to determine HIV-1 genetic diversity and identify drug-resistance mutations among people living with HIV in Karachi. A total of 364 HIV-positive individuals, with a median age of 36 years, were enrolled in the study. The HIV-1 partial pol gene was successfully sequenced from 268 individuals. The sequences were used to generate phylogenetic trees to determine clade diversity and also to assess the burden of DRMs. Based on the partial pol sequences, 13 distinct HIV-1 subtypes and recombinant forms were identified. Subtype A1 was the most common clade (40%), followed by CRF02_AG (33.2%). Acquired DRMs were found in 30.6% of the ART-experienced patients, of whom 70.7%, 20.7%, and 8.5% were associated with resistance to NNRTIs, NRTIs, and PIs, respectively. Transmitted DRMs were found in 5.6% of the ART-naïve patients, of whom 93% were associated with resistance against NNRTIs and 7% to PIs. The high prevalence of DRMs in ART-experienced patients poses significant challenges to the long-term benefits and sustainability of the ART program. This study emphasizes the importance of continuous HIV molecular epidemiology and drug resistance surveillance to support evidence-based HIV prevention, precise ART, and targeted AIDS care.

Gastric Non-Hodgkin Lymphoma in a Helicobacter pylori-Infected Patient.

Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is a rare gastric malignant neoplasm. While the association between Heliobacter pylori infection and gastric mucosa-assisted lymphoid tissue lymphoma is well established, data supporting its association with DLBCL are less robust. Here we present a rare case of PG-DLBCL diagnosed with H. pylori. An 82-year-old man presented to clinic with complaints of worsening epigastric pain. He underwent an endoscopy which revealed 1 large nonbleeding gastric ulcer. Histopathological and immunohistochemical analysis confirmed PG-DLBCL. He was started on H. pylori eradication (HPE) and subsequently completed 6 cycles of R-mini-CHOP chemotherapy. Since then, the patient maintained clinical and radiological remission for more than a year without recurrence. PG-DLBCL is an aggressive Non-hodgkin lymphoma (NHL) that usually presents late. It has been shown that HPE without chemotherapy in DLBCL codiagnosed with H. pylori is not an effective strategy. Thus, the standard of care for patients would be HPE and chemotherapy as in our patient. More research is needed to better understand association between H. pylori and DLBCL.

Combined endoscopic mucosal resection and full-thickness resection for large colorectal polyps: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Combined endoscopic mucosal resection (EMR) with endoscopic Full thickness resection (EFTR) is an emerging technique that has been developed to target colorectal polyps larger than 2 cm. We performed a systematic review and meta-analysis to evaluate this technique for the resection of large colorectal lesions. METHODS: We conducted a comprehensive search of multiple electronic databases from inception through August 2023, to identify studies that reported on hybrid FTR. A random-effects model was employed to calculate the overall pooled technical success, macroscopic complete resection, free vertical margins resection rate, adverse events, and recurrence on follow up. RESULTS: A total of 8 Study arms with 244 patients (30% women) were included in the analysis. The pooled technical success rate was 97% (95% CI 88%-100%, I2 = 79.93%). The pooled rate of macroscopic complete resection was achieved in 95% (95% CI 90%-99%, I2 = 49.98) with a free vertical margins resection rate 88% (95% CI, 78%-96%, I2 = 63.32). The overall adverse events rate was 2% (95% CI 0%-5%, I2 = 11.64) and recurrence rate of 6% (95% CI 2%-12%, I2=20.32). CONCLUSION: Combined EMR with EFTR is effective and safe for resecting large, and complex colorectal adenomas, offering a good alternative for high surgical risk patients. Regional heterogeneity was observed, indicating that outcomes may be impacted by differences in operator expertise and industry training certification across regions. Comparative studies that directly compare combined EMR with EFTR against alternative methods such as ESD and surgical resection are needed.

Exploring the burden of irritable bowel syndrome among university students in Saudi Arabia: A study on prevalence, psychological associations, and well-being.

Patients with irritable bowel syndrome (IBS) experience not only a detrimental impact on their physical health but also a significant influence on their psychological well-being. This study aimed to assess the prevalence of IBS among university students, investigating the sociodemographic and lifestyle factors influencing its onset. Furthermore, it explored the potential impact of psychological factors such as depression, anxiety, and overall well-being on the prevalence of IBS. A cross-sectional analytical study was conducted at Saudi Arabian universities in November and December 2023. To collect data, an anonymous, validated, predesigned questionnaire was used. The diagnosis of IBS was carried out using the validated Arabic version of the Rome IV questionnaire. We used the Arabic version of the World Health Organization Well-being Index to assess the participants' well-being. We used the Arabic version of the Hospital Anxiety and Depression Scale (HADS) to identify people who show clinically significant symptoms of anxiety and depression. Our study included a total of 379 university students, 46.7% were female 86.0% of participants resided in urban areas, and 7.2% had been previously diagnosed with IBS. The prevalence of IBS among participants was found to be 31.9%. We observed a significant association between marital status and IBS (χ2 = 3.95, P = .047). Furthermore, the highest prevalence of IBS was observed among students majoring in literary and scientific disciplines (χ2 = 0.952, P = .049). Individuals with IBS demonstrate a significantly higher prevalence of anxiety (71.90% vs 41.09%, P < .001) and depression (64.46% vs 42.64%, P < .001) compared to those without IBS. Furthermore, people with IBS had a slightly higher prevalence of poor well-being (38.84%) compared to those without IBS (33.72%), but this association was not statistically significant. In multivariate analysis, having a family history of IBS [OR = 1.75 (95% CI, 1.06-2.87), P = .029] having borderline anxiety [OR = 7.58, 95% CI (2.12-27.06), P = .012] and anxiety [OR = 16.07, 95% CI (4.57-56.52), P < .001], and depression [OR = 2.97, 95% CI (1.13-7.83), P = .010] were the main significant predictors of IBS among university students. The high prevalence of IBS among university students was associated with a family history of IBS as well as depression and anxiety. Increasing awareness, multidisciplinary support, and access to mental health services is required to ensure university students' well-being.

Fisetin from Dietary Supplement to a Drug Candidate: An Assessment of Potential

Fisetin is a bioactive compound found in numerous fruits and vegetables, including strawberries, apples, grapes, persimmon, cucumber, onion, etc. The compound is also wellknown for its neurotrophic, anti-inflammatory, anti-carcinogenic, anti-diabetic, and other healthpromoting properties. Although there is increasing agreement that it has therapeutic properties, but its poor water solubility, high lipophilicity, and lower oral bioavailability make it difficult to use clinically. Extensive research has attempted to overcome these restrictions by developing novel and superior delivery systems. Considering the diverse potential, this review is the first to summarise the available data on Fisetin to collate the information related to analytical methods, pharmacological action, their mechanisms, regulatory aspects, and toxicity profile. It also covers the marketed products, related clinical trials, and patent updates of the moiety. In addition, an endeavor has been attempted to discuss and assess the various drug delivery systems employed to increase the biological attributes of Fisetin. The presented manuscript is the first to present a compendium of up-to-date literature on all of the domains considered necessary for this type of natural molecule to carve down its path from being a mere dietary supplement to a promising therapeutic drug candidate. The manuscript is expected to benefit the researchers working on natural and bioactive compounds, industrial scientists, and the general population interested in Fesitin.

Hepatic Duct Adenoma Identified Using Direct Cholangioscopy.

Bile duct adenomas (BDAs) are rare benign tumors that can arise in the intra-hepatic or extra-hepatic biliary tree. We present a case of a 46-year-old female who presented with symptoms suggestive of choledocholithiasis. Direct cholangioscopy identified a 15 mm polypoid lesion in the common hepatic duct (CHD). Biopsy revealed a BDA. We present this case to highlight the role of direct cholangioscopy in the diagnosis and management of BDAs.

Shift in SARS-CoV-2 variants of concern from Delta to Omicron was associated with reduced hospitalizations, increased risk of breakthrough infections but lesser disease severity.

BACKGROUND: COVID-19 epidemiology changed with the emergence of SARS-CoV-2 variants of concern (VOC). Pakistan administered mostly inactivated vaccines. We investigated the association between VOC and breakthrough infections in a mixed-vaccination-status population of Karachi. METHODS: We investigated SARS-CoV-2 VOC tested in 392 respiratory specimens collected between May and December 2021. Data for age, sex, hospital admission, vaccinations, together with CT values of the diagnostic PCR test were analyzed. RESULTS: The median age of COVID-19 cases tested was 40 (27-57) years and 43.4% were female. Delta variants were most common (56.4%) followed by Alpha (15.9%), Omicron (12.2%), Beta/Gamma (11.3%), and others (4.3%). Eighteen percent of cases were hospitalized whereby, predominant VOC were Beta/Gamma (40.8%), Alpha (35.2%) and Delta (22.5%). Overall, 55.4% of individuals were fully vaccinated, 7.4% were partially vaccinated and 37.2% were unvaccinated. Most (74.6%) inpatients were unvaccinated. Vaccines comprised inactivated (85.34%), single-shot vector (8.62%), two-shot vector (3.02%) and mRNA (3.02%) types. Omicron variants showed lower viral loads as compared to Alpha, Beta/Gamma, and Delta (p = 0.017). The risk of infection with Delta and Omicron variants was higher, 8 weeks after vaccination. The majority of those with breakthrough infections after receiving inactivated vaccines acquired COVID-19 within 4 months of vaccination. CONCLUSION: Our data highlights the shifting of VOC from Delta to Omicron during 2021 and that COVID-19 vaccinations reduced both hospitalizations and viral transmission. It informs on the increased risk of breakthrough infection within 8 weeks of vaccination, indicating the need for booster vaccinations.