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.

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.

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.

The Menace of Candida auris Epidemic Amidst the COVID-19 Pandemic: A Systematic Review.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent for the Coronavirus Disease 2019 (COVID-19) pandemic, has sparked a medical emergency worldwide. With the rise in COVID-19 infections and an eventual increase in hospitalized critically ill patients, a trend of bacterial, fungal, and viral superinfection has been noted. One important agent of co-infection identified is Candida auris. Due to its multidrug-resistant nature and easy transmissibility, C. auris is difficult to manage in COVID-positive patients. Patients with comorbidities, immunosuppressive states, intubated and on ventilators are more likely to contract the fungal infection. Therefore, it is essential to the first screen, diagnose, and isolate patients with C. auris infection and manage and treat them while preventing the spread of the disease. Failure to recognize and prevent its spread may lead to an eventual epidemic or even a pandemic during the current COVID-pandemic, which the exhausted healthcare system can most definitely not handle. This systematic review investigates the prevalence of C. auris, its pathophysiology, diagnosis, prevention, and treatment during the COVID-19 pandemic.

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.

Willingness and Perceptions Regarding COVID-19 Vaccine Booster Dose in Pakistani Vaccinated Population: A Cross-Sectional Survey

Objectives This study was conducted to evaluate COVID-19 vaccine booster dose willingness and identify predictors and factors of willingness and hesitance in the vaccinated population of Pakistan. Methods A cross-sectional web-based survey was undertaken between January and February 2022 to highlight the public perceptions regarding the COVID-19 booster dose and evaluate the willingness to get the additional dose. Demographic information and booster dose willingness were recorded through the questionnaire. Additionally, a 5-point Likert scale was employed to explore fears and beliefs regarding COVID-19 vaccinations. Univariate and multivariate regression was performed to identify booster dose willingness and hesitance factors. Results Of the 787 respondents, 69.6% were females, 75.3% fell in the 18–30 years age group, 53.5% were university students or had a Bachelor's degree. Overall, a 77.8% booster dose willingness was reported. Participants showed absence or low fear levels associated with a booster dose (47.3%). 60.1% agreed it was safe to receive an additional vaccine dose, with 44.1% agreeing that boosters are effective against coronavirus variants. Independent predictors of willingness included the absence of comorbidities, whereas not being willing to pay for the booster dose was a predictor of hesitance. Conclusion This study showed a suboptimal willingness level of booster dose uptake among the vaccinated Pakistani population. Public health policymakers must undertake necessary awareness campaigns to strategize vaccination drives and dispel myths.

Safety and efficacy of colchicine in COVID-19 patients: A systematic review and meta-analysis of randomized control trials.

BACKGROUND: Colchicine has been used an effective anti-inflammatory drug to treat gout diseases. Owing to its pharmacodynamic of inhibiting interleukins, it has been repurposed to target the cytokine storm post-SARS-CoV-2 invasion. The goal of this meta-analysis was to evaluate the safety profile of colchicine in COVID-19 patients using the gold-standard randomised-control trials. METHODS: Electronic databases (Pubmed, Google Scholar, and Cochrane) were systematically searched until June 2021 and RCTs were extracted. Outcomes of interest included all-cause mortality, COVID-19 severity, mechanical ventilation, C-reactive protein and D-dimer levels. Using a random-effects model, dichotomous outcomes were pooled using odds ratios (OR) through the generic inverse variance formula while weighted mean differences were calculated using the Wan's method. P-values < 0.05 were considered statistically significant for all outcomes. RESULTS: A total population of 16,048 from five RCTs were included in the analysis. Of this, 7957 were randomized to colchicine, and 8091 received standard care, with an average age of 60.67 years. Colchicine was observed to significantly reduce COVID-19 severity (OR: 0.41, 95% CI [0.22, 0.76]; p = 0.005), and CRP levels (WMD: -19.99, 95% CI [-32.09, -7.89]; p = 0.001). However, there was no significant difference in D-dimer levels (WMD: 0.31, 95% CI [-0.61, 1.23]; p = 0.51), mechanical ventilation (OR: 0.42, 95% CI [0.17, 1.03]; p = 0.06; I2 = 74%) and all-cause mortality (OR: 0.98, 95% CI [0.83, 1.16]; p = 0.84) among patients receiving colchicine or standard care. CONCLUSION: Colchicine treatment decreased CRP levels and COVID-19 severity, with dimer levels, all-cause mortality and mechanical ventilation remaining seemingly unaffected. Thus, clinical trials need to be carried out that allow effective evaluation of colchicine in COVID-19 patients.

Self-Medication Practices in Medical Students During the COVID-19 Pandemic: A Cross-Sectional Analysis.

Background and Objectives: During the pandemic, the growing influence of social media, accessibility of over-the-counter medications, and fear of contracting the virus may have led to self-medication practices among the general public. Medical students are prone to such practices due to relevant background knowledge, and access to drugs. This study was carried out to determine and analyze the prevalence of self-medication practices among medical students in Pakistan. Materials and Methods: This descriptive, cross-sectional study was conducted online in which the participants were asked about the general demographics, their self-medication practices and the reasons to use. All participants were currently enrolled in a medical college pursuing medical or pharmacy degree. Non-probability sampling technique was used to recruit participants. Results: A total of 489 respondents were included in the final analysis. The response rate was 61%. Majority of the respondents were females and 18-20 years of age. Self-medication was quite prevalent in our study population with 406 out of 489 individuals (83.0%) were using any of the drugs since the start of pandemic. The most commonly utilized medications were Paracetamol (65.2%) and multivitamins (56.0%). The reasons reported for usage of these medications included cold/flu, or preventive measures for COVID-19. The common symptoms reported for self-medication included fever (67.9%), muscle pain (54.0%), fatigue (51.7%), sore throat (46.6%), and cough (44.4%). Paracetamol was the most commonly used drug for all symptoms. Female gender, being in 3rd year of medical studies, and individuals with good self-reported health were found more frequent users of self-medication practices. Conclusion: Our study revealed common self-medication practices among medical and pharmacy students. It is a significant health issue especially during the pandemic times, with high consumption reported as a prevention or treating symptoms of COVID-19.

COVID-19 Vaccine Hesitancy in the United States: A Systematic Review.

Vaccine hesitancy in the US throughout the pandemic has revealed inconsistent results. This systematic review has compared COVID-19 vaccine uptake across US and investigated predictors of vaccine hesitancy and acceptance across different groups. A search of PUBMED database was conducted till 17th July, 2021. Articles that met the inclusion criteria were screened and 65 studies were selected for a quantitative analysis. The overall vaccine acceptance rate ranged from 12 to 91.4%, the willingness of studies using the 10-point scale ranged from 3.58 to 5.12. Increased unwillingness toward COVID-19 vaccine and Black/African Americans were found to be correlated. Sex, race, age, education level, and income status were identified as determining factors of having a low or high COVID-19 vaccine uptake. A change in vaccine acceptance in the US population was observed in two studies, an increase of 10.8 and 7.4%, respectively, between 2020 and 2021. Our results confirm that hesitancy exists in the US population, highest in Black/African Americans, pregnant or breastfeeding women, and low in the male sex. It is imperative for regulatory bodies to acknowledge these statistics and consequently, exert efforts to mitigate the burden of unvaccinated individuals and revise vaccine delivery plans, according to different vulnerable subgroups, across the country.

COVID-19 Associated Mucormycosis: A Systematic Review from Diagnostic Challenges to Management.

The coronavirus disease 2019 (COVID-19) outbreak has caused significant destruction, claiming over three million lives worldwide. Post SARS-COV-2 invasion, immunosuppression with hyperglycemia and elevated ferritin levels along with steroidal treatment creates a perfect storm for opportunistic infections. There is increasing evidence of mucormycosis co-infection in COVID-19 patients, during or post-treatment. A worse prognosis, a late diagnosis, and limited guidelines of screening and management of COVID-19 associated mucormycosis have made healthcare professionals fear an epidemic alongside a pandemic. This review geographically reports cases of COVID-19 associated mucormycosis (CAM), evaluates characteristics, clinical manifestations, and outcomes of mucormycosis in COVID-19 active or recovered patients. It further describes preventive strategies and recommendations for optimal management therapy that can be adopted worldwide to curtail an impending threat to the healthcare system.