Second Boost of Omicron SARS-CoV-2 S1 Subunit Vaccine Induced Broad Humoral Immune Responses in Elderly Mice (preprint)

Currently approved COVID-19 vaccines prevent symptomatic infection, hospitalization, and death from the disease. However, repeated homologous boosters, while considered a solution for severe forms of the disease caused by new SARS-CoV-2 variants in elderly individuals and immunocompromised patients, cannot provide complete protection against breakthrough infections. This highlights the need for alternative platforms for booster vaccines. In our previous study, we assessed the boost effect of the SARS-CoV-2 Beta S1 recombinant protein subunit vaccine (rS1Beta) in aged mice primed with an adenovirus-based vaccine expressing SARS-CoV-2-S1 (Ad5.S1) via subcutaneous injection or intranasal delivery, which induced robust humoral immune responses (1). In this follow-up study, we demonstrated that a second booster dose of a non-adjuvanted recombinant Omicron (BA.1) S1 subunit vaccine with Toll-like receptor 4 (TLR4) agonist RS09 (rS1RS09OM) was effective in stimulating strong S1-specific immune responses and inducing significantly high neutralizing antibodies against the Wuhan, Delta, and Omicron variants in 100-week-old mice. Importantly, the second booster dose elicits cross-reactive antibody responses, resulting in ACE2 binding inhibition against the spike protein of SARS-CoV-2 variants, including Omicron (BA.1) and its subvariants. Interestingly, the levels of IgG and neutralizing antibodies correlated with the level of ACE2 inhibition in the booster serum samples, although Omicron S1-specific IgG level showed a weaker correlation compared to Wuhan S1-specific IgG level. Furthermore, we compared the immunogenic properties of the rS1 subunit vaccine in young, middle-aged, and elderly mice, resulting in reduced immunogenicity with age, especially an impaired Th1-biased immune response in aged mice. Our findings demonstrate that the new variant of concern (VOC) rS1 subunit vaccine as a second booster has the potential to offer cross-neutralization against a broad range of variants and to improve vaccine effectiveness against newly emerging breakthrough SARS-CoV-2 variants in elderly individuals who were previously primed with the authorized vaccines.

Fourth dose of Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Elicits Robust Long-lasting Humoral Responses in mice (preprint)

The COVID-19 pandemic has underscored the pressing need for safe and effective booster vaccines, particularly in considering the emergence of new SARS-CoV-2 variants and addressing vaccine distribution inequalities. Dissolving microneedle array patches (MAP) offer a promising delivery method, enhancing immunogenicity and improving accessibility through the skin's immune potential. In this study, we evaluated a microneedle array patch-based S1 subunit protein COVID-19 vaccine candidate, which comprised a bivalent formulation targeting the Wuhan and Beta variant alongside a monovalent Delta variant spike proteins in a murine model. Notably, the second boost of homologous bivalent MAP-S1(WU+Beta) induced a 15.7-fold increase in IgG endpoint titer, while the third boost of heterologous MAP-S1RS09Delta yielded a more modest 1.6-fold increase. Importantly, this study demonstrated that the administration of four doses of the MAP vaccine induced robust and long-lasting immune responses, persisting for at least 80 weeks. These immune responses encompassed various IgG isotypes and remained statistically significant for one year. Furthermore, neutralizing antibodies against multiple SARS-CoV-2 variants were generated, with comparable responses observed against the Omicron variant. Overall, these findings emphasize the potential of MAP-based vaccines as a promising strategy to combat the evolving landscape of COVID-19 and to deliver a safe and effective booster vaccine worldwide.

Association of d-dimer levels with in-hospital outcomes among COVID-19 positive patients: a developing country multicenter retrospective cohort.

D-dimer levels, which originate from the lysis of cross-linked fibrin, are serially measured during coronavirus disease 2019 illness to rule out hypercoagulability as well as a septic marker. Methods: This multicenter retrospective study was carried out in two tertiary care hospitals in Karachi, Pakistan. The study included adult patients admitted with a laboratory-confirmed coronavirus disease 2019 infection, with at least one measured d-dimer within 24 h following admission. Discharged patients were compared with the mortality group for survival analysis. Results: The study population of 813 patients had 68.5% males, with a median age of 57.0 years and 14.0 days of illness. The largest d-dimer elevation was between 0.51-2.00 mcg/ml (tertile 2) observed in 332 patients (40.8%), followed by 236 patients (29.2%) having values greater than 5.00 mcg/ml (tertile 4). Within 45 days of hospital stay, 230 patients (28.3%) died, with the majority in the ICU (53.9%). On multivariable logistic regression between d-dimer and mortality, the unadjusted (Model 1) had a higher d-dimer category (tertile 3 and tertile 4) associated with a higher risk of death (OR: 2.15; 95% CI: 1.02-4.54, P=0.044) and (OR: 4.74; 95% CI: 2.38-9.46, P<0.001). Adjustment for age, sex, and BMI (Model 2) yields only tertile 4 being significant (OR: 4.27; 95% CI: 2.06-8.86, P<0.001). Conclusion: Higher d-dimer levels were independently associated with a high risk of mortality. The added value of d-dimer in risk stratifying patients for mortality was not affected by invasive ventilation, ICU stays, length of hospital stays, or comorbidities.

Adverse events following COVID‐19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia

Background and Objectives Since publishing successful clinical trial results of mRNA coronavirus disease 2019 (COVID‐19) vaccines in December 2020, multiple reports have arisen about cardiovascular complications following the mRNA vaccination. This study provides an in‐depth account of various cardiovascular adverse events reported after the mRNA vaccines' first or second dose including pericarditis/myopericarditis, myocarditis, hypotension, hypertension, arrhythmia, cardiogenic shock, stroke, myocardial infarction/STEMI, intracranial hemorrhage, thrombosis (deep vein thrombosis, cerebral venous thrombosis, arterial or venous thrombotic events, portal vein thrombosis, coronary thrombosis, microvascular small bowel thrombosis), and pulmonary embolism. Methods A systematic review of original studies reporting confirmed cardiovascular manifestations post‐mRNA COVID‐19 vaccination was performed. Following the PRISMA guidelines, electronic databases (PubMed, PMC NCBI, and Cochrane Library) were searched until January 2022. Baseline characteristics of patients and disease outcomes were extracted from relevant studies. Results A total of 81 articles analyzed confirmed cardiovascular complications post‐COVID‐19 mRNA vaccines in 17,636 individuals and reported 284 deaths with any mRNA vaccine. Of 17,636 cardiovascular events with any mRNA vaccine, 17,192 were observed with the BNT162b2 (Pfizer−BioNTech) vaccine, 444 events with mRNA‐1273 (Moderna). Thrombosis was frequently reported with any mRNA vaccine (n = 13,936), followed by stroke (n = 758), myocarditis (n = 511), myocardial infarction (n = 377), pulmonary embolism (n = 301), and arrhythmia (n = 254). Stratifying the results by vaccine type showed that thrombosis (80.8%) was common in the BNT162b2 cohort, while stroke (39.9%) was common with mRNA‐1273 for any dose. The time between the vaccination dosage and the first symptom onset averaged 5.6 and 4.8 days with the mRNA‐1273 vaccine and BNT162b2, respectively. The mRNA‐1273 cohort reported 56 deaths compared to the 228 with BNT162b2, while the rest were discharged or transferred to the ICU. Conclusion Available literature includes more studies with the BNT162b2 vaccine than mRNA‐1273. Future studies must report mortality and adverse cardiovascular events by vaccine types. We aim to summarize the events of cardiac complications following the mRNA coronavirus disease 2019 vaccine, providing an in‐depth analysis of their occurrences, and their implications. The review includes 69 case reports/case series, 4 studies with data obtained from electronic medical records (hospital surveillance data, national database, VAERS/VigiBase), and 8 observational studies including prospective/retrospective cohort.

Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia.

BACKGROUND AND OBJECTIVES: Since publishing successful clinical trial results of mRNA coronavirus disease 2019 (COVID-19) vaccines in December 2020, multiple reports have arisen about cardiovascular complications following the mRNA vaccination. This study provides an in-depth account of various cardiovascular adverse events reported after the mRNA vaccines' first or second dose including pericarditis/myopericarditis, myocarditis, hypotension, hypertension, arrhythmia, cardiogenic shock, stroke, myocardial infarction/STEMI, intracranial hemorrhage, thrombosis (deep vein thrombosis, cerebral venous thrombosis, arterial or venous thrombotic events, portal vein thrombosis, coronary thrombosis, microvascular small bowel thrombosis), and pulmonary embolism. METHODS: A systematic review of original studies reporting confirmed cardiovascular manifestations post-mRNA COVID-19 vaccination was performed. Following the PRISMA guidelines, electronic databases (PubMed, PMC NCBI, and Cochrane Library) were searched until January 2022. Baseline characteristics of patients and disease outcomes were extracted from relevant studies. RESULTS: A total of 81 articles analyzed confirmed cardiovascular complications post-COVID-19 mRNA vaccines in 17,636 individuals and reported 284 deaths with any mRNA vaccine. Of 17,636 cardiovascular events with any mRNA vaccine, 17,192 were observed with the BNT162b2 (Pfizer-BioNTech) vaccine, 444 events with mRNA-1273 (Moderna). Thrombosis was frequently reported with any mRNA vaccine (n = 13,936), followed by stroke (n = 758), myocarditis (n = 511), myocardial infarction (n = 377), pulmonary embolism (n = 301), and arrhythmia (n = 254). Stratifying the results by vaccine type showed that thrombosis (80.8%) was common in the BNT162b2 cohort, while stroke (39.9%) was common with mRNA-1273 for any dose. The time between the vaccination dosage and the first symptom onset averaged 5.6 and 4.8 days with the mRNA-1273 vaccine and BNT162b2, respectively. The mRNA-1273 cohort reported 56 deaths compared to the 228 with BNT162b2, while the rest were discharged or transferred to the ICU. CONCLUSION: Available literature includes more studies with the BNT162b2 vaccine than mRNA-1273. Future studies must report mortality and adverse cardiovascular events by vaccine types.

Tetravalent SARS-CoV-2 S1 Subunit Protein Vaccination Elicits Robust Humoral and Cellular Immune Responses in SIV-Infected Rhesus Macaque Controllers (preprint)

The COVID-19 pandemic has highlighted the need for safe and effective vaccines to be rapidly developed and distributed worldwide, especially considering the emergence of new SARS-CoV-2 variants. Protein subunit vaccines have emerged as a promising approach due to their proven safety record and ability to elicit robust immune responses. In this study, we evaluated the immunogenicity and efficacy of an adjuvanted tetravalent S1 subunit protein COVID-19 vaccine candidate composed of the Wuhan, B.1.1.7 variant, B.1.351 variant, and P.1 variant spike proteins in a nonhuman primate model with controlled SIVsab infection. The vaccine candidate induced both humoral and cellular immune responses, with T- and B cell responses mainly peaking post-boost immunization. The vaccine also elicited neutralizing and cross-reactive antibodies, ACE2 blocking antibodies, and T-cell responses, including spike specific CD4+ T cells. Importantly, the vaccine candidate was able to generate Omicron variant spike binding and ACE2 blocking antibodies without specifically vaccinating with Omicron, suggesting potential broad protection against emerging variants. The tetravalent composition of the vaccine candidate has significant implications for COVID-19 vaccine development and implementation, providing broad antibody responses against numerous SARS-CoV-2 variants.

Outcomes of COVID-19 patients with acute kidney injury and longitudinal analysis of laboratory markers during the hospital stay: A multi-center retrospective cohort experience from Pakistan

The frequency of acute kidney injury (AKI) in COVID-19 patients can be varied and related to worse outcomes in the disease population. AKI is common among hospitalized patients with COVID-19, particularly the ones needing critical care. This study was conducted in order to determine the outcomes of hospitalized patients with prolonged hospital stays who suffered from COVID-19 associated AKI. It was conducted as a multi-centered, retrospective, cohort study, and including all patients who were diagnosed on COVID-19 PCR. End-stage renal disease patients on hemodialysis were excluded. The cohort included 1069 patients, with 68% males, mean age of 56.21 years, and majority within 50 to 75 years age group (60%). Mean disease onset was 14.43 ± 7.44 days and hospital stay was 7.01 ± 5.78 days. About 62% of patients stayed in intensive care and 18% of them were on invasive ventilation. The mortality rate was 27%. Frequency of AKI was 42%, around 14% of them were resolving during hospital stay and other 28% worsened. The mortality rate was significantly higher with AKI (OR: 4.7, P < .001). Alongside AKI, concomitant liver dysfunction was also significantly contributing to mortality (OR: 2.5), apart from ICU stay (OR: 2.9), invasive ventilation (OR: 9.2), and renal replacement therapy (OR: 2.4). Certain laboratory markers were associated with AKI throughout in-hospital stay.

Impact of the COVID-19 pandemic on knowledge, perceptions, and effects of telemedicine among the general population of Pakistan: A national survey.

Background: Telemedicine is the provision of healthcare services through information and communication technology with the potential to mobilize all facets of the health sector to prevent the spread of COVID-19, provide quality healthcare, protect patients, doctors, and the public from exposure to disease, and reduce the burden on the healthcare system. This study aims to identify knowledge, perceptions, willingness to use, and the impact of the COVID-19 pandemic on telemedicine awareness. Methods: A cross-sectional study was conducted from 27 May 2020 to 17 June 2020 using the convenient sampling technique in the general population of Pakistan. Data were collected by designing an online questionnaire consisting of demographic information, knowledge, attitude perceptions, barriers, utilization, and the impact of the COVID-19 pandemic on telemedicine. Results: Of the 602 participants included in the study, 70.1% had heard about telemedicine, 54.3% had a good understanding of the definition of "telemedicine," 81.4% had not used telemedicine in the past, 29.9% did not know that telemedicine was available before the COVID-19 pandemic, and 70.4% responded that the COVID-19 pandemic had changed their attitudes toward telemedicine. Gender (p = 0.017) and family income (p = 0.027) had a significant association with the perception of the benefits of telemedicine. Conclusion: The knowledge and usage of telemedicine are lacking due to inadequate awareness and technology. The need of the hour is to maximize the application of telemedicine to overcome the deficiencies of the healthcare system. Hence, it is essential to increase awareness through various means and develop an appropriate infrastructure to attain maximum benefits from telehealth services.

Outcomes of COVID-19 patients with acute kidney injury and longitudinal analysis of laboratory markers during the hospital stay: A multi-center retrospective cohort experience from Pakistan.

The frequency of acute kidney injury (AKI) in COVID-19 patients can be varied and related to worse outcomes in the disease population. AKI is common among hospitalized patients with COVID-19, particularly the ones needing critical care. This study was conducted in order to determine the outcomes of hospitalized patients with prolonged hospital stays who suffered from COVID-19 associated AKI. It was conducted as a multi-centered, retrospective, cohort study, and including all patients who were diagnosed on COVID-19 PCR. End-stage renal disease patients on hemodialysis were excluded. The cohort included 1069 patients, with 68% males, mean age of 56.21 years, and majority within 50 to 75 years age group (60%). Mean disease onset was 14.43 ± 7.44 days and hospital stay was 7.01 ± 5.78 days. About 62% of patients stayed in intensive care and 18% of them were on invasive ventilation. The mortality rate was 27%. Frequency of AKI was 42%, around 14% of them were resolving during hospital stay and other 28% worsened. The mortality rate was significantly higher with AKI (OR: 4.7, P < .001). Alongside AKI, concomitant liver dysfunction was also significantly contributing to mortality (OR: 2.5), apart from ICU stay (OR: 2.9), invasive ventilation (OR: 9.2), and renal replacement therapy (OR: 2.4). Certain laboratory markers were associated with AKI throughout in-hospital stay.

Frequency of COVID-19 vaccine side effects and its associated factors among the vaccinated population of Pakistan: A cross-sectional study.

Background: Coronavirus disease 2019 (COVID-19) vaccine side effects have an important role in the hesitancy of the general population toward vaccine administration. Therefore, this study was conducted to document the COVID-19 vaccine side effects in our population. Materials and Methods: An online survey-based, cross-sectional study was carried out from September 1, 2021, to October 1, 2021, to document the side effects of the COVID-19 vaccine among the general public. The questionnaire included participants' sociodemographic data, type of vaccine, comorbidities, previous COVID-19 infection, and assessment of side effects reported by them. Results: The majority of the participants were <20 years of age (62.2%), females (74.9%), belonged to the educational sector (58.1%), residents of Sindh (65.7%), and were previously unaffected by COVID-19 infection (73.3%). Sinovac (38.7%) followed by Sinopharm (30.4%) and Moderna (18.4%) were administered more frequently. Commonly reported side effects were injection site pain (82%), myalgia (55%), headache (46%), fatigue/malaise (45%), and fever (41%). Vaccine side effects were more likely to be reported with the first dose as compared to the second dose. On regression analysis, factors associated with occurrence of side effects included younger age (odds ratio [OR]: 6.000 [2.065-17.431], p < 0.001), female gender (OR: 2.373 [1.146-4.914], p = 0.020), marital status (OR: 0.217 [0.085-0.556], p < 0.001), graduate level of education (OR: 0.353 [0.153-0.816], p = 0.015), and occupation being either retired, freelancers, or social workers (OR: 0.310 [0.106-0.909]), p = 0.033). Previous infection with COVID-19 (p = 0.458) and comorbidities were found unrelated (p = 0.707) to the occurrence of side effects. Conclusion: The overall prevalence of local side effects was quite higher than the systemic ones. Further large-scale studies on vaccine safety are required to strengthen public confidence in the vaccination drive.

Frequency of COVID‐19 vaccine side effects and its associated factors among the vaccinated population of Pakistan: A cross‐sectional study

Background Coronavirus disease 2019 (COVID‐19) vaccine side effects have an important role in the hesitancy of the general population toward vaccine administration. Therefore, this study was conducted to document the COVID‐19 vaccine side effects in our population. Materials and Methods An online survey‐based, cross‐sectional study was carried out from September 1, 2021, to October 1, 2021, to document the side effects of the COVID‐19 vaccine among the general public. The questionnaire included participants' sociodemographic data, type of vaccine, comorbidities, previous COVID‐19 infection, and assessment of side effects reported by them. Results The majority of the participants were <20 years of age (62.2%), females (74.9%), belonged to the educational sector (58.1%), residents of Sindh (65.7%), and were previously unaffected by COVID‐19 infection (73.3%). Sinovac (38.7%) followed by Sinopharm (30.4%) and Moderna (18.4%) were administered more frequently. Commonly reported side effects were injection site pain (82%), myalgia (55%), headache (46%), fatigue/malaise (45%), and fever (41%). Vaccine side effects were more likely to be reported with the first dose as compared to the second dose. On regression analysis, factors associated with occurrence of side effects included younger age (odds ratio [OR]: 6.000 [2.065–17.431], p < 0.001), female gender (OR: 2.373 [1.146–4.914], p = 0.020), marital status (OR: 0.217 [0.085–0.556], p < 0.001), graduate level of education (OR: 0.353 [0.153–0.816], p = 0.015), and occupation being either retired, freelancers, or social workers (OR: 0.310 [0.106–0.909]), p = 0.033). Previous infection with COVID‐19 (p = 0.458) and comorbidities were found unrelated (p = 0.707) to the occurrence of side effects. Conclusion The overall prevalence of local side effects was quite higher than the systemic ones. Further large‐scale studies on vaccine safety are required to strengthen public confidence in the vaccination drive.

Impact of the COVID-19 pandemic on knowledge, perceptions, and effects of telemedicine among the general population of Pakistan: A national survey

Background Telemedicine is the provision of healthcare services through information and communication technology with the potential to mobilize all facets of the health sector to prevent the spread of COVID-19, provide quality healthcare, protect patients, doctors, and the public from exposure to disease, and reduce the burden on the healthcare system. This study aims to identify knowledge, perceptions, willingness to use, and the impact of the COVID-19 pandemic on telemedicine awareness. Methods A cross-sectional study was conducted from 27 May 2020 to 17 June 2020 using the convenient sampling technique in the general population of Pakistan. Data were collected by designing an online questionnaire consisting of demographic information, knowledge, attitude perceptions, barriers, utilization, and the impact of the COVID-19 pandemic on telemedicine. Results Of the 602 participants included in the study, 70.1% had heard about telemedicine, 54.3% had a good understanding of the definition of "telemedicine,” 81.4% had not used telemedicine in the past, 29.9% did not know that telemedicine was available before the COVID-19 pandemic, and 70.4% responded that the COVID-19 pandemic had changed their attitudes toward telemedicine. Gender (p = 0.017) and family income (p = 0.027) had a significant association with the perception of the benefits of telemedicine. Conclusion The knowledge and usage of telemedicine are lacking due to inadequate awareness and technology. The need of the hour is to maximize the application of telemedicine to overcome the deficiencies of the healthcare system. Hence, it is essential to increase awareness through various means and develop an appropriate infrastructure to attain maximum benefits from telehealth services.

Non-alcoholic fatty liver disease and liver secretome.

Metabolism of carbohydrates and lipids and protein degradation occurs in the liver and contributes to the body's homeostasis by secreting a variety of mediators. Any imbalance in this homeostasis due to excess fat consumption and the pathologic events accompanying lipotoxicity, autophagy dysregulation, endoplasmic reticulum stress, and insulin resistance may cause disturbances in the secretion of the proteins from the liver and their physiologic modifications and interactions with others. Since the liver secretome plays a role in the regulation of fuel metabolism and inflammation not only in the liver per se but also in other organs, the proteins belong to the utmost targets for treating metabolic and inflammatory diseases (e.g., COVID-19), depending on the available and feasible approaches to controlling their biological effects. However, in this era, we still come across new liver-derived proteins but are yet unable to entirely understand the pathologic basis underlying disease progression. This review aims to provide an updated overview of liver secretome biology with explanatory mechanisms with regard to the progression of metabolic and inflammatory liver diseases.

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice (preprint)

This paper presents a novel approach for improving the efficacy of COVID-19 vaccines against emergent SARS-CoV-2 variants. We have evaluated the immunogenicity of unadjuvanted wild-type (WU S1-RS09cg) and variant-specific (Delta S1-RS09cg and OM S1-RS09cg) S1 subunit protein vaccines delivered either as a monovalent or a trivalent antigen in BALB/c mice. Our results show that a trivalent approach induced a broader humoral response with more coverage against antigenically distinct variants, especially when compared to monovalent Omicron-specific S1. This trivalent approach was also found to have increased or equivalent ACE2 binding inhibition, and increased S1 IgG endpoint titer at early timepoints, against SARS-CoV-2 spike variants when compared monovalent Wuhan, Delta, or Omicron S1. Our results demonstrate the utility of protein subunit vaccines against COVID-19 and provide insights into the impact of variant-specific COVID-19 vaccine approaches on the immune response in the current SARS-CoV-2 variant landscape. Particularly, our study provides insight into effects of further increasing valency of currently approved SARS-CoV-2 vaccines, a promising approach for improving protection to curtail emerging viral variants.

Structure and evaluation of preventive medicine residency programs' websites: A cross sectional analysis.

The goal of this study was to analyze the content availability and accessibility of preventive medicine residency program websites. In COVID-related travel restrictions, the information provided on program websites has become increasingly crucial for residency applicants. A cross-sectional study was conducted by extracting the list of preventive medicine residency programs on the Fellowship and Residency Electronic and Interactive Database (FRIEDA). A 40-point criterion was used for the quality evaluation of residency programs. The study was conducted and analyzed in 2021. 82 preventive medicine residency programs were identified, and listed on FRIEDA, out of which 65 program websites were accessible. The median number of 40-point criteria met by the preventive medicine residency website was 25. The criteria fulfilled by the greatest number of program websites was research opportunity/facilities (94%). The majority of the preventive medicine residency program websites were not up to the mark regarding accessibility and quality. An updated preventive medicine residency program website is essential for the applicants. Programs with relevant and precise information on their websites have higher chances of attracting potential candidates and better chances of finding the match between applicants and programs.

Assessment of knowledge and attitude of healthcare professionals regarding the use of telemedicine: A cross-sectional study from rural areas of Sindh, Pakistan.

Background: Telemedicine has proved its significance in the healthcare system, especially during the coronavirus disease 2019 (COVID-19) pandemic as it assists in the provision of early and effective healthcare to those in distant areas. This study aimed to assess the knowledge and attitude of healthcare professionals toward the use of telemedicine in the rural areas of Sindh, Pakistan. Materials and methods: The cross-sectional study was conducted with 212 healthcare professionals including physicians, consultants, surgeons, residents, dentists, and house officers working in public sector hospitals. The face-to-face method was used for data collection. Chi-square test and logistic regression analysis were applied to find the association between different variables and knowledge and practice of telemedicine using SPSS V 24. Results: The knowledge of participants regarding the usability of telemedicine and various tools used for the provision of medical services (video consultations, conferencing, use of applications, software, and online groups) was good. A total of 52.2% of participants showed agreement when they were questioned about being aware of online healthcare service provision. In this study, 52.8% of the participants practiced telemedicine by delivering healthcare services through online consultations. The majority of the participants were surgeons (25.9%), residents (23.1%), and physicians (18.9%). The internet (42.4%) and public media (25.9%) were the major sources of information for telemedicine. A total of 70.5% of participants suggested that strategies and efforts should be directed toward the enhanced implementation of telemedicine. Training in telemedicine as a source of information [OR = 13.02 (95% CI = 3.9-43.6), p < 0.001)] and awareness regarding the effect of telemedicine in healthcare quality [OR = 10.25 (95% CI = 2.9-35.4), p < 0.001)] remained the predicting factors for the practice of telemedicine among healthcare workers using multivariate regression analysis. Conclusion: Telemedicine has technologically revolutionized the medical sciences worldwide. The awareness level and usage of telemedicine were good among healthcare professionals in rural Sindh. Telemedicine should be utilized to provide quality healthcare in underprivileged areas by investing in infrastructure and education.

COVID-19 and myasthenia gravis: A review of neurological implications of the SARS-COV-2.

INTRODUCTION: This review highlights the potential mechanisms of neuromuscular manifestation of COVID-19, especially myasthenia gravis (MG). METHODS: An extensive literature search was conducted by two independent investigators using PubMed/MEDLINE and Google Scholar from its inception to December 2020. RESULTS: Exacerbations of clinical symptoms in patients of MG who were treated with some commonly used COVID-19 drugs has been reported, with updated recommendations of management of symptoms of neuromuscular disorders. Severe acute respiratory syndrome coronavirus 2 can induce the immune response to trigger autoimmune neurological disorders. CONCLUSIONS: Further clinical studies are warranted to indicate and rather confirm if MG in the setting of COVID-19 can pre-existent subclinically or develop as a new-onset disease.

Comparative analysis of neutrophil to lymphocyte ratio and derived neutrophil to lymphocyte ratio with respect to outcomes of in-hospital coronavirus disease 2019 patients: A retrospective study.

Introduction and objectives: In patients with coronavirus disease 2019 (COVID-19), several abnormal hematological biomarkers have been reported. The current study aimed to find out the association of neutrophil to lymphocyte ratio (NLR) and derived NLR (dNLR) with COVID-19. The objective was to compare the accuracy of both of these markers in predicting the severity of the disease. Materials and methods: The study was conducted in a single-center having patients with COVID-19 with a considerable hospital stay. NLR is easily calculated by dividing the absolute neutrophil count (ANC) with the absolute lymphocyte count (ALC) {ANC/ALC}, while dNLR is calculated by ANC divided by total leukocyte count minus ANC {ANC/(WBC-ANC)}. Medians and interquartile ranges (IQR) were represented by box plots. Multivariable logistic regression was performed obtaining an odds ratio (OR), 95% CI, and further adjusted to discover the independent predictors and risk factors associated with elevated NLR and dNLR. Results: A total of 1,000 patients with COVID-19 were included. The baseline NLR and dNLR were 5.00 (2.91-10.46) and 4.00 (2.33-6.14), respectively. A cut-off value of 4.23 for NLR and 2.63 for dNLR were set by receiver operating characteristic (ROC) analysis. Significant associations of NLR were obtained by binary logistic regression for dependent outcome variables as ICU stay (p < 0.001), death (p < 0.001), and invasive ventilation (p < 0.001) while that of dNLR with ICU stay (p = 0.002), death (p < 0.001), and invasive ventilation (p = 0.002) on multivariate analysis when adjusted for age, gender, and a wave of pandemics. Moreover, the indices were found correlating with other inflammatory markers such as C-reactive protein (CRP), D-dimer, and procalcitonin (PCT). Conclusion: Both markers are equally reliable and sensitive for predicting in-hospital outcomes of patients with COVID-19. Early detection and predictive analysis of these markers can allow physicians to risk assessment and prompt management of these patients.

Effects of SARS-CoV-2 infection and COVID-19 pandemic on menstrual health of women: A systematic review.

Background: The menstrual cycle in women is the main indicator of their reproductive health which is affected by the ongoing coronavirus disease 2019 (COVID-19) pandemic. This review aims to summarize the effects of the COVID-19 infection and the global pandemic on the menstrual health of women. Methods: The literature search was conducted in PubMed, Cochrane library, and Google Scholar using keywords "COVID-19," "Menstrual Cycle," "Menstrual Cycle Irregularities," "Amenorrhea," "Polymenorrhea," and "Dysmenorrhea." The articles were selected according to the following inclusion criteria: (i) cross-sectional studies, (ii) cohort studies, (iii) surveys, and (iv) other observational studies observing the effects of SARS-CoV-2 infection or COVID-19 pandemic on menstrual health of women. Exclusion criteria included: case reports, gray literature, and website articles regarding menstrual health. Results: A total of 30,510 articles were shortlisted after a comprehensive search. Sixteen articles were included out of which 13 studies investigated the effects of the COVID-19 pandemic on the menstrual cycle while 3 evaluated the possible effects of COVID-19 infection on the menstrual health of women. Menstrual disorders or irregularities were a more common finding during the pandemic as compared to before (p = 0.008). Women affected by pandemic-related stress were more prone to changes in the duration of their menses (p = 0.0008), reported heavier bleeding (p = 0.028), and increased incidence of painful periods (p < 0.0001). COVID-19 infected women also reported changes in their menstrual cycle including irregular menstruation, increased symptoms of premenstrual syndrome, and infrequent menstruation. Conclusions: Women suffering from COVID-19 infection or pandemic-associated stress and anxiety were more likely to experience irregular menstruation, dysmenorrhea, amenorrhea, and other menstrual abnormalities compared to those who were less exposed.