Casirivimab/Imdevimab: First Approval

Luo

et al. 2022

Preprint

Neutralizing antibodies (NAbs) can prevent and treat infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, continuously emerging variants, such as Omicron, have significantly reduced the potency of most known NAbs. The selection of NAbs with broad neutralizing activities and the identification of conserved critical epitopes are still urgently needed. Here, we identified an extremely potent antibody (55A8) by single B-cell sorting from convalescent SARS-CoV-2-infected patients that recognized the receptor-binding domain (RBD) in the SARS-CoV-2 spike (S) protein. 55A8 could bind to wild-type SARS-CoV-2, Omicron BA.1 and Omicron BA.2 simultaneously with 58G6, a NAb previously identified by our group. Importantly, an antibody cocktail containing 55A8 and 58G6 (2-cocktail) showed synergetic neutralizing activity with a half-maximal inhibitory concentration (IC50) in the picomolar range in vitro and prophylactic efficacy in hamsters challenged with Omicron (BA.1) through intranasal delivery at an extraordinarily low dosage (25 μg of each antibody daily) at 3 days post-infection. Structural analysis by cryo-electron microscopy (cryo-EM) revealed that 55A8 is a Class III NAb that recognizes a highly conserved epitope. It could block angiotensin-converting enzyme 2 (ACE2) binding to the RBD in the S protein trimer via steric hindrance. The epitopes in the RBD recognized by 55A8 and 58G6 were found to be different and complementary, which could explain the synergetic mechanism of these two NAbs. Our findings not only provide a potential antibody cocktail for clinical use against infection with current SARS-CoV-2 strains and future variants but also identify critical epitope information for the development of better antiviral agents.

Section: Discussionmentioning

confidence: 99%

A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2

Luo

et al. 2022

Preprint

“…In mid-October 2021, during the very peak of the fourth COVID-19 wave in Romania, mAbs were introduced into clinical practice based on the European Medicines Agency’s (EMA) emergency use authorization, for patients at high risk of progressing to severe COVID-19 [ 8 ]. We have reported the first administration of mAbs in Romania in a patient with CF who had moderate COVID-19 at the time of initial evaluation.…”

Section: Discussionmentioning

confidence: 99%

First Case of COVID-19 Treated with Monoclonal Anti-Spike Antibodies in a Patient with Cystic Fibrosis in Romania

et al. 2022

Patients with chronic lung conditions, including cystic fibrosis, may be prone to severe COVID-19. Therefore, therapeutic intervention should be prompt and tailored to all associated comorbidities. We report the case of a 17-year-old male adolescent with cystic fibrosis and multiple chronic conditions (bronchiectasis, exocrine pancreatic insufficiency, chronic multidrug resistant Pseudomonas aeruginosa colonization, nasal polyposis, chronic sinusitis, ventricular extrasystoles and multiple drug allergies), who presented with an acute episode of productive cough, and was confirmed with moderate COVID-19 based on positive RT-PCR for SARS-CoV-2 and lung imaging showing isolated foci of interstitial pneumonia. Intravenous treatment with the monoclonal antibody cocktail casirivimab and imdevimab was administered. The evolution was favorable, with rapid remission of the inflammatory syndrome and gradual decrease of cough, without progression to severe or critical COVID-19, but with complications such as repeated hemoptysis, which was due to the patient’s underlying conditions, and which required close monitoring for timely adjustment of the patient’s chronic treatment.

Journal of Family Medicine and Primary Care

“…Likewise, in the appropriate clinical setting, early use of monoclonal antibodies will be life-saving in the case of COVID-19. [ 39 ] The challenge before the primary physician will be to distinguish between the two, early in the illness itself.…”

Section: Discussionmentioning

confidence: 99%

Covid-19 and leptospirosis, pulmonary involvement and response to steroids

Ittyachen¹,

Xavier²,

Baby³

et al. 2022

Background: COVID-19 is an emerging infectious disease with a global outreach. Leptospirosis is a zoonotic disease mainly confined to tropical areas. In both cases, most of those affected are asymptomatic or have only mild respiratory disease. Those who turn critical develop acute respiratory distress syndrome (ARDS) and/or multiple-organ failure occurs rapidly, with high fatality. Methodology: This is a retrospective observational study from 2020 involving COVID-19 and leptospirosis patients. The data were collected using a semi-structured proforma, and analysis was performed using Easy R (EZR) software. Results: There were five patients with COVIDC-19 and four patients with leptospirosis; with pulmonary involvement. All the patients were males. There was no significant difference in age, the onset of pulmonary involvement, time of initiation of steroids, duration of steroids, and outcome between the two groups. However, in the case of COVID-19, it took a longer period for clearing of infiltrates. Conclusion: Though COVID-19 and leptospirosis are two different diseases, both of them show a similar life-saving response to steroids, the common factor in the pathogenesis being cytokine storm. Primary care physicians in tropical areas of the world should be aware of the similarities between these two diseases, especially the initial clinical presentation, the pathogenesis, and the response to steroids.