Paxlovid ( Nirmatrelvir/Ritonavir ) and Cyclosporin in a Kidney Transplant Patient with Covid-19 Infection

Introduction: COVID-19 infection causes high morbidity,mortality and burden to the healthcare system.Solid organ transplant patients with COVID-19 have been reported to have between 13-30% rate of mortality.Over the past 2 years,treatment of COVID-19 has evolved with new drugs being introduce such as Molnupiravir which reported to reduce death and hospitalization up to 50%.Recently a new novel drug Paxlovid (Nirmatrelvir/Ritonavir) develop by Pfizer has shed much hope in terms of managing COVID-19 patient especially in those with solid organ transplant.However,there is not much data in using Paxlovid for kidney transplant with COVID-19.Paxlovid is known to have drug-drug interaction with medication that is highly dependent on CYP3A4 which is a member of Cytochrome P450 enzyme for clearance.It is advice to withhold certain calcineurin inhibitor drugs if on Paxlovid.However,there was no mention on withholding cyclosporin which is one of the drugs in in kidney transplant patient.We've reported the first case in literature of a kidney transplant patient on cyclosporin diagnose with COVID 19 on Paxlovid. Method(s): Our patient is a End Stage Renal Disease on regular hemodialysis for a year.He subsequently had a living related renal transplant.He was vaccinated and boosted with SARS-CoV-2 Vaccine from Pfizer BioNTech.Baseline creatinine level was 126 umol/L.Immunosuppressants are Cyclosporin 50mg BD,Prednisolone 7.5mg OD and Azathioprine 50mg OD.Baseline cyclosporin trough level was 113ng/ml.He was well until SARS-CoV-2 Rapid Test Kit was positive on day four of illness.Serum Creatinine level was 137 umol/L.His estimated Glomerular Filtration Rate was 53 ml/min/1.73m2.Chest Radiograph shows ground glass opacity on both lower zone.Patient was treated for COVID-19 Pneumonia Category 3A.In view eGFR was 53 ml/min/1.73m2,Paxlovid was started at adjusted dose (Nirmatrelvir 150mg/Ritonavir 100mg BD).Patient had four doses of Paxlovid before we were able to send cyclosporin level on day three of his admission due to logistic problem.Cyclosporin trough level was 737 ng/ml and we withheld his cyclosporin.Paxlovid was continued and there was improvement in terms of his symptoms.Serial chest radiographs showed improvement as in Figure 1.We were able to monitor his cyclosporin trough level and serum creatinine on daily basis as shown in Figure 2 and Figure 3 respectively.He completed five days of Paxlovid.On day seven of admission,cyclosporin was restarted back at 25mg BD. [Formula presented] [Formula presented] [Formula presented] Results: He was discharged well with cyclosporin dose being adjusted back to his old dose.We followed him up as outpatient and monitor his cyclosporin level which was stable and continued on his old immunosuppressant regime. Conclusion(s): This case highlights the potential treatment with Paxlovid in patients with kidney transplant on cyclosporin diagnosed to have COVID-19 infection.Drug-drug interaction between cyclosporin and Paxlovid needs to be taken into account.Moving forward in the endemic era,there will be increase usage of Paxlovid that can help to reduce severity,hospital admission and mortality in solid organ transplant with COVID-19 infection.Close monitoring of cyclosporin level,proper mitigation strategy,adjustment of immunosuppressants and safe prescription of Paxlovid will be beneficial for kidney transplant patient infected with COVID-19.This can help in reducing morbidity and mortality in our kidney transplant patients. No conflict of interestCopyright © 2023

Quantitative Analysis of Academic Performance in Electronic Engineering Students Under the Virtual Modality During the COVID-19 Pandemic

The context of this work lies in the higher education institutions current situation in the Dominican Republic and the efforts carried out by the main actors and their effort to continue teaching virtually as a measure due to universities lockdownd due to COVID-19 pandemic. For this study, the subject of electronics II, from the Electronic Engineering Major at a university in the northern region of the country, has been selected. This subject covers theoretical content on a wide variety of electronic devices, and is complemented by laboratory classes that allow the use and practical experimentation of these devices. In this work we have hypothesized "that the academic performance of the students on this subject improves and that the withdrawal rate decreases under the virtual modality". Correlation and independent t-tests were performed for quantitative analysis between students' performance and the rate of withdrawals according to the teaching modality. Results show that both student performance and the withdrawal rate are affected, decreasing for performance and increasing for the withdrawal rate respectively. Future works are recommended to explore the factors that lead to these results. © 2022 Latin American and Caribbean Consortium of Engineering Institutions. All rights reserved.

Stroke etiologies in patients with COVID-19: the svin COVID-19 multinational registry

Background and purpose: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology. Methods: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID- 19 from 31 hospitals in 4 countries (3/1/20-6/16/20). Results: Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60-79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p</=0.05 for all comparisons). In a multivariable backward stepwise regression model estimating the odds of in-hospital mortality, cryptogenic stroke mechanism was associated with a fivefold greater odds in-hospital mortality than strokes due to any other mechanism (adjusted OR 5.16, 95%CI 1.41-18.87, p=0.01). In that model, older age (aOR2.05 per decade, 95%CI 1.35-3.11, p<0.01) and higher baseline NIHSS (aOR 1.12, 95%CI 1.02-1.21, p=0.01) were also independently predictive of mortality. Conclusions: Our findings suggest that cryptogenic stroke among COVID-19 patients may berelated to more severe disease and carries a significant risk of early mortality.

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: the society of vascular and interventional neurology multinational registry

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. Aims: To summarize the findings of a multinational observational cohort of patients with SARS-CoV- 2 and cerebrovascular disease. Methods: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in 4 countries (2/1/2020 - 06/16/2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). Results: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort;1130/100,000 patients, 95%CI 970- 1320/100,000), 68/171 (40.5%) of whom were female and 96/172 (55.8%) were between the ages 60-79 years. Of these, 156 had acute ischemic stroke (1.08%;1080/100,000 95%CI 920- 1260/100,000), 28 ICH (0.19%;190/100,000 95%CI 130 - 280/100,000) and 3 with CVST (0.02%;20/100,000, 95%CI 4-60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline strokeseverity, and all predictors of in-hospital mortality found in univariate regression (p<0.1: male sex,tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, andintracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p<0.01), olderage (aOR 1.78, 95%CI 1.07-2.94, p=0.03), and lower lymphocyte count on admission (aOR 0.58,95%CI 0.34-0.98 p=0.04) were the only independent predictors of mortality among patients withstroke and COVID-19. Conclusions: COVID-19 is associated with a small but significant risk of clinically relevantcerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19associated cerebrovascular complications, therefore aggressive monitoring and early interventionshould be pursued to mitigate poor outcomes.

Acute stroke care during the COVID-19 pandemic: the society of vascular and interventional neurology collaboration

Background: We sought to evaluate whether the coronavirus disease 2019 (COVID-19) pandemic may have contributed to delays in acute stroke management at Comprehensive Stroke Centers (CSCs). Methods: Pooled clinical data of consecutive adult stroke patients from 12 U.S. CSCs (1/1/2019- 5/31/2020) were queried. The rate of thrombolysis for non-transferred patients within the Target: Stroke goal of 60min was compared between patients admitted 3/1/2019-5/31/2019 (pre-COVID-19) and 3/1/2020-5/31/2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed. Results: Of the 7906 patients included, 1319 were admitted pre-COVID-19 and 933 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. There was no difference in the rate of thrombolysis within 60min during COVID-19 (OR 0.88, 95%CI 0.42-1.86, p=0.74), despite adjustment for variables associated with earlier treatment (adjusted OR 0.82, 95%CI 0.38-1.76, p=0.61). There was no significant overall delay to thrombolysis during the COVID-19 period vs. pe- COVID-19 (p=0.42), even after multivariable adjustment (p=0.63) or after comparison across months leading to COVID-19 (Figure). The only independent predictor of delayed treatment time between periods was the use of emergency medical services (adjusted β=-6.93, 95%CI -12.83 -1.04, p=0.03). There was no significant delay from hospital arrival to imaging in all patients, or imaging to skin puncture in patients who underwent thrombectomy. Conclusions: There was no independent effect of the COVID-19 period on delays in acute care with respect to thrombolysis or thrombectomy in this multicenter observational cohort. Further studies are warranted to externally validate these findings, and determine if site volume or center accreditation may mediate a collateral effect of the pandemic on stroke care paradigms.