Nirmatrelvir plus ritonavir in COVID-19: a profile of its use

Oral nirmatrelvir plus ritonavir (Paxlovid™) is an effective treatment option for coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nirmatrelvir inhibits the main protease of SARS-CoV-2, with ritonavir acting as a pharmacokinetic booster. In the phase II/III EPIC-HR trial, nirmatrelvir plus ritonavir reduced the risk of progression to severe COVID-19 in symptomatic, unvaccinated, non-hospitalized adults with mild-to-moderate COVID-19 at high risk for progression to severe disease. The incidence of COVID-19-related hospitalization or death through day 28 was significantly lower with nirmatrelvir plus ritonavir than with placebo. The efficacy of nirmatrelvir plus ritonavir has also been demonstrated in the real-world setting. Nirmatrelvir plus ritonavir is generally well tolerated, with most adverse events being of mild or moderate severity.

Metapneumovirus Infections are Uncommon in Infants Younger than 60 Days of Age Admitted for Sepsis Evaluation

The epidemiology and clinical manifestations of human metapneumovirus are not well studied in infants younger than 60 days of age. In this retrospective review of infants admitted for sepsis evaluation, we identified HMPV less frequently than other viral etiologies via nasopharyngeal multiplex polymerase chain reaction testing;in only 16 (1.9%) infants. Two infants had apneic episodes, but none had wheezing. © 2023 Lippincott Williams and Wilkins. All rights reserved.

The Effect of Carriage of CYP3A5*3 and CYP3A4*22 Polymorphic Variants on the Safety of Remdesivir Therapy in Patients with COVID-19

The aim of the study was to assess the association of polymorphic variants CYP3A5*3 6986 A>G rs776746 and CYP3A4*22 rs35599367 C>T with the safety parameters of remdesivir therapy in patients with COVID-19. Material and methods. The study included 156 patients admitted to the City Clinical Hospital No. 15 of the Moscow Health Department with COVID-19 diagnosis, who received remdesivir as an antiviral drug. The frequency of adverse reactions (bradycardia, dyspeptic disorders), as well as various laboratory parameters (ALT, AST, creatinine, ferritin, interleukin-6, and d-dimer levels) were compared between the carriers of wild-type and polymorphic variants of the studied genes. Results. Carriers of CYP3A5*3 polymorphic variants (GA+AA) had higher ALT levels after the treatment with remdesivir than carriers of the wild variant (GG). When comparing the level of interleukin-6 after therapy with remdesivir, carriers of the polymorphic variant of the CYP3A4*22 (CT) gene had a significantly higher level of this cytokine. Conclusion. An association between the carriage of polymorphic variants of CYP3A5*3 and an increase in the level of liver enzymes was found. Polymorphic variants of CYP3A4*22 were associated with higher levels of interleukin-6. Additional pharmacogenetic studies are required to assess the possibilities of personalizing antiviral therapy for COVID-19.

It's not the shunt: an atypical cause of fever in an infant with hydrocephalus

Case Report:We present a 5-year-old male with two days of fever, cough, vomiting, and loose stools. His history is significant for premature birth (35 weeks gestational age) and shunted hydrocephalus. A ventriculoperitoneal (VP) shunt was placed 6 days prior to presentation. Parental report included episodes of post-tussive, nonbloody, non-bilious emesis, poor oral intake, tachypnea, and increased work of breathing. Physical examination demonstrated a dehydrated infant with sunken fontanelles. He had no notable rash, no lymphadenopathy, and clear conjunctiva. His VP shunt site appeared normal without swelling or erythema. Initial evaluation showed elevated inflammatory markers -ESR 51 and CRP 12.32 mg/dL. A viral respiratory PCR panel returned positive for coronavirus (not SARS-CoV-2). A head CT scan and shunt radiography series showed no abnormalities with his shunt. The following morning, Radiology reported an incidental retropharyngeal fluid collection on a re-read of the patient's initial CT scan. A neck CT was obtained and demonstrated a fluid pocket with secondary mass effect in addition to bilateral cervical lymphadenopathy. Screening blood cultures were negative. The patient remained febrile (tmax 103.6F) and developed a transaminitis (ALT 264.9, AST 654), elevated fibrinogen 476, elevated INR 1.4, and low albumin 2.1. Abdominal ultrasound showed a normal the liver and biliary tract. His transaminitis resolved without treatment. The next day, the patient developed lip erythema and conjunctival injection. An echocardiogram showed a dilated right coronary artery (z-score of 3.59) and his inflammatory markers (ESR 26, CRP 9.63) remained elevated. Treatment was initiated with IVIG and moderate-dose aspirin. The patient defervesced, and he remained afebrile for over 48 hours prior to discharge. A repeat echocardiogram 2 days later showed a slight reduction in coronary artery dilatation (z-score 3.39). Hewas discharged on lowdose aspirin, and followed up with cardiology as an outpatient. Kawasaki's Disease (KD) is most common in children from ages 1 to 4 years and is classically characterized by persistent fever with a constellation of symptoms including limbal sparing conjunctivitis, cervical lymphadenopathy, polymorphous rash, strawberry tongue, oral changes, and extremity changes. Our patient presented at a younger age with a concurrent diagnosis of coronavirus upper respiratory tract infection. His atypical hospital course and incidental finding of retropharyngeal edema and transaminitis increased the clinical suspicion for KD. His symptoms rapidly improved after administration of IVIG. Younger patients are at an increased risk for severe complications of KD including coronary aneurysm. KD has been shown in the literature to have an association with coronavirus infection as well as presentation with retropharyngeal edema. Clinicians should consider KD in their differential even if patients do not meet all criteria for diagnosis on initial presentation. Copyright © 2023 Southern Society for Clinical Investigation.

COVID-19 associated Mucormycosis (CAM): Implications for perioperative physicians - A narrative review

Mucormycosis once considered a rare disease with an incidence of 0.005 to 1.7 per million, has become one of the greatest menaces during the coronavirus disease (COVID-19) pandemic. India alone has contributed to nearly 70% of the global caseload of COVID-associated mucormycosis (CAM) and it had even been declared as a notifiable disease. Second wave of COVID-19 pandemic saw a steep rise in the incidence of mucormycosis and these patients have been presenting to anesthesiologists for various surgical procedures due to its primary or secondary sequelae. Rhino-orbito-cerebral mucormycosis (ROCM) is the commonest manifestation and is caused by Rhizopus arrhizus. Injudicious use of corticosteroids in vulnerable patients could have been a major contributing factor to the sudden rise in ROCM during the pandemic. Concerns related to anesthetic management include COVID-19 infection and post COVID sequalae, common presence of uncontrolled diabetes mellitus, possibility of difficult mask-ventilation and/or intubation, various drug therapy-associated adverse effects, and interaction of these drugs with anesthetic agents. Thorough preoperative optimization, multidisciplinary involvement, perioperative care, and vigilance go a long way in improving overall outcomes in these patients. Copyright © 2022 Saudi Journal of Anesthesia Published by Wolters Kluwer - Medknow.