Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice
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Abstract
Improving the standard of clinical care for individuals infected with SARS-CoV-2 variants is a global health priority. Small molecule antivirals like remdesivir (RDV) and biologics such as human monoclonal antibodies (mAb) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of COVID-19. However, it is not known if combination RDV/mAb will improve outcomes over single agent therapies or whether antibody therapies will remain efficacious against variants. In kinetic studies in a mouse-adapted model of ancestral SARS-CoV-2 pathogenesis, we show that a combination of two mAbs in clinical trials, C144 and C135, have potent antiviral effects against even when initiated 48 hours after infection. The same antibody combination was also effective in prevention and therapy against the B.1.351 variant of concern (VOC). Combining RDV and antibodies provided a modest improvement in outcomes compared to single agents. These data support the continued use of RDV to treat SARS-CoV-2 infections and support the continued clinical development of the C144 and C135 antibody combination to treat patients infected with SARS-CoV-2 variants.
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SciScore for 10.1101/2021.01.27.428478: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Biocontainment and biosafety: Studies were approved by the UNC Institutional Biosafety Committee approved by animal and experimental protocols in the Baric laboratory. Randomization In a blinded manner, three random fields of lung tissue were chosen and scored for the following: (A) neutrophils in the alveolar space (none = 0, 1–5 cells = 1, > 5 cells = 2), (B) neutrophils in the interstitial septae (none = 0, 1–5 cells = 1, > 5 cells = 2), (C) hyaline membranes (none = 0, one membrane = 1, > 1 membrane = 2), (D) Proteinaceous debris in air spaces (none = 0, one instance = 1, > 1 instance = 2), (E) alveolar septal thickening (< 2x mock thickness = 0, 2–4x … SciScore for 10.1101/2021.01.27.428478: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Biocontainment and biosafety: Studies were approved by the UNC Institutional Biosafety Committee approved by animal and experimental protocols in the Baric laboratory. Randomization In a blinded manner, three random fields of lung tissue were chosen and scored for the following: (A) neutrophils in the alveolar space (none = 0, 1–5 cells = 1, > 5 cells = 2), (B) neutrophils in the interstitial septae (none = 0, 1–5 cells = 1, > 5 cells = 2), (C) hyaline membranes (none = 0, one membrane = 1, > 1 membrane = 2), (D) Proteinaceous debris in air spaces (none = 0, one instance = 1, > 1 instance = 2), (E) alveolar septal thickening (< 2x mock thickness = 0, 2–4x mock thickness = 1, > 4x mock thickness = 2). Blinding Analyses and scoring were performed by a Board Certified Veterinary Pathologist who was blinded to the treatment groups as described previously (Sheahan et al., 2020a). Power Analysis not detected. Sex as a biological variable Study design and treatment groups: For the RDV experiment, a total of N=40, ~20-week-old male and female mice were divided into four groups each with N=10 mice with equal numbers of females and males in each group. Table 2: Resources
Antibodies Sentences Resources Groups of N=20 female mice (N=5 mice treated with C144 + C135, N=5 mice treated with C144, N=5 mice treated with C135, and N=5 mice treated with 3BNC117 + 10-1074) were administered antibody 12 hours before infection, N=20 female mice (N=5 mice treated with C144 + C135, N=5 mice treated with C144, N=5 mice treated with C135, and N=5 mice treated with 3BNC117 + 10-1074) were administered antibody 12hpi (early therapeutic group), N=20 female mice (N=5 mice treated with C144 + C135, N=5 mice treated with C144, N=5 mice treated with C135, and N=5 mice treated with 3BNC117 + 10-1074) were administered antibody 24hpi (mid-late therapeutic group), and N=20 female mice (N=5 mice treated with C144 + C135, N=5 mice treated with C144, N=5 mice treated with C135, and N=5 mice treated with 3BNC117 + 10-1074) were administered antibody 48hpi (late therapeutic group). C135suggested: NoneSoftware and Algorithms Sentences Resources Statistics: All statistical analyses were performed using GraphPad Prism 9. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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