Adverse Events of SARS-CoV-2 Therapy: A Pharmacovigilance Study of the FAERS Database.

BACKGROUND: Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical trial to lower COVID-19-related death or hospitalization at day 28 when compared with placebo. OBJECTIVE: Our study's aim was to explore the reported adverse events (AEs) associated with nirmatrelvir/ritonavir use for COVID-19. METHOD: We conducted a retrospective analysis using the FDA Adverse Event Reporting System (FAERS) database for AEs, listing nirmatrelvir/ritonavir as the primary drug between January and June 2022. The primary outcome was the incidence of reported AEs associated with nirmatrelvir/ritonavir. The OpenFDA database was queried using Python 3.10 to collect the AEs and Stata 17 was used to analyze the database. Adverse events were analyzed by associated medication, with "Covid-19" excluded. RESULTS: A total of 8098 reports were identified between January and June 2022. Most reported complaints in the AE system were COVID-19 and disease recurrence. The most common symptomatic AEs were dysgeusia, diarrhea, cough, fatigue, and headache. Event rates significantly rose between April and May. Disease recurrence and dysgeusia were the most commonly reported complaints for the top 8 concomitant drugs identified. Cardiac arrest, tremor, akathisia, and death were reported in 1, 3, 67, and 5 cases, respectively. CONCLUSIONS AND RELEVANCE: This is the first retrospective study done on reported AEs associated with nirmatrelvir/ritonavir use for COVID-19. COVID-19 and disease recurrence were the most reported AEs. Further monitoring of the FAERS database is warranted to periodically reassess the safety profile of this medication.

Acute Kidney Injury Associated with Severe SARS-CoV-2 Infection: Risk Factors for Morbidity and Mortality and a Potential Benefit of Combined Therapy with Tocilizumab and Corticosteroids.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients with severe COVID-19. METHODS: We retrospectively reviewed 249 patients admitted to an intensive care unit (ICU) during the first wave of the pandemic to determine risk factors for AKI. Demographics, comorbidities, and clinical and outcome variables were obtained from electronic medical records. RESULTS: Univariate analysis revealed older age, higher admission serum creatinine, elevated Sequential Organ Failure Assessment (SOFA) score, elevated admission D-Dimer, elevated CRP on day 2, mechanical ventilation, vasopressor requirement, and azithromycin usage as significant risk factors for AKI. Multivariate analysis demonstrated that higher admission creatinine (p = 0.0001, OR = 2.41, 95% CI = 1.56-3.70), vasopressor requirement (p = 0.0001, OR = 3.20, 95% CI = 1.69-5.98), elevated admission D-Dimer (p = 0.008, OR = 1.0001, 95% CI = 1.000-1.001), and elevated C-reactive protein (CRP) on day 2 (p = 0.033, OR = 1.0001, 95% CI = 1.004-1.009) were independent risk factors. Conversely, the combined use of Tocilizumab and corticosteroids was independently associated with reduced AKI risk (p = 0.0009, OR = 0.437, 95% CI = 0.23-0.81). CONCLUSION: This study confirms the high rate of AKI and associated mortality among COVID-19 patients admitted to ICUs and suggests a role for inflammation and/or coagulopathy in AKI development. One should consider the possibility that early administration of anti-inflammatory agents, as is now routinely conducted in the management of COVID-19-associated acute respiratory distress syndrome, may improve clinical outcomes in patients with AKI.

Triple Jeopardy: Rapidly Progressive Glomerulonephritis Induced by Triple Seropositive Disease-A Rare Case.

The double-positive disease is the co-occurrence of antiglomerular basement membrane (anti-GBM) disease and antineutrophil cytoplasmic antibodies (ANCAs) and is an uncommon cause of renal failure. Our case of triple-positive disease is an even rarer cause of isolated renal failure, as it includes anti-GBM, antimyeloperoxidase (MPO), and antiproteinase 3 (PR3). We present a case of a 62-year-old Caucasian male with a history of multiple comorbidities, who presented to the emergency department (ED) with worsening dyspnea on exertion that started about one month prior to admission. He was found to be in renal failure secondary to triple-positive disease. We believe that the likely mechanism of our patient's triple-positive disease was a drug-induced ANCA vasculitis overlapping with Goodpasture's syndrome. We believe our case to be a valuable addition to the literature as it is a rare overlap syndrome without a previously established disease course or etiology.

COVID-19 Infection Presenting With Severe Hydrocephalus and Acute Stroke: A Case Report.

Hydrocephalus is the accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles and is considered an emergency in acute presentation. Hydrocephalus typically presents with symptoms of headache, nausea, vomiting, lethargy, vision changes and seizure; furthermore, narrowing down the underlying etiology of hydrocephalus can aid in treatment and management options. We present a rare case of a patient that presented with a recent diagnosis of COVID-19 and was found to have acute hydrocephalus and stroke. The aim of this case report is to explore the link between COVID-19 and the development of hydrocephalus and stroke by delineating the underlying pathophysiology of COVID-19 as well as the etiologies of hydrocephalus and possible management strategies. We hope to highlight the importance of keeping an open differential for presentations of headaches and also emphasize the potential complications of COVID-19 infection to help better patient outcomes.

A Case of Angioimmunoblastic T-cell Lymphoma Hidden in Plain Sight: A Delay in Diagnosis and Management.

Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon type of cluster of differentiation (CD)4 T-cell peripheral lymphoma. The varied clinical presentations of AITL present a challenge for accurate diagnosis. We present a case of a 57-year-old female with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, who presented to the hospital in the summer of 2021 with shortness of breath for 3 months. She underwent an extensive workup for lymphadenopathy while in Canada involving multiple core lymph node biopsies, which were inconclusive. Here in our institution, several tests for infectious diseases were unremarkable. Imaging tests revealed bilateral pleural effusion, lymphadenopathies, and rectal thickening. Results from rectal biopsy and excisional cervical lymph node biopsy revealed findings typical of AITL. Due to worsening hypoxia with pleural fluid accumulation, bilateral chest tubes (PleurX catheter) were placed. Steroids and chemotherapy were started. She was discharged in stable condition to follow-up care. An integrated and persistent approach comprising clinical, morphologic, excisional biopsy, immunophenotyping, and molecular tests is essential in reaching a correct diagnosis of AITL. Through our consistent effort to obtain further imaging and tissue biopsies, we came to the diagnosis which allowed her to begin appropriate life-saving treatments.

Catastrophic Thromboembolic Syndrome During the COVID-19 Pandemic.

Since March 2020, the SARS-CoV-2 virus known to cause COVID-19 has presented in many ways and it seems to affect almost all organ systems. One of its detrimental effects is on the coagulation system. Disruption of the coagulation pathway or hypercoagulability has been reported extensively in many articles and studies. It seems there is no specific pattern or location of the coagulopathy. The coagulopathy can present as part of the respiratory disease process or as an isolated phenomenon. Many articles had reported that the thrombus can be a venous thromboembolic phenomenon such as deep venous thrombosis (DVT), portal vein thrombosis, pulmonary embolism (PE), or as arterial thrombosis, for instance, coronary artery thrombosis, cerebrovascular thromboembolic disease (i.e., stroke), or an aortic thrombus. One of the disastrous presentations is what is called "catastrophic thrombosis syndrome." This syndrome is characterized by multiple thromboses that take place in different parts of the vascular system at different parts of the body at the same time. In many studies, D-dimer levels have been shown to predict the risk of increased thromboembolism in SARS-CoV-2. However, an appropriate anticoagulation agent, dosage, and duration are yet to be determined. We are presenting an interesting case of a female who suffered catastrophic thrombosis syndrome despite being on prophylactic anticoagulation. She presented with leg pain and was found to have extensive multiple thrombi starting from the ascending/descending aorta and extending to the distal peroneal arteries.