“Acute Respiratory Distress and Cytokine Storm in Aged, SARS-CoV-2 Infected African Green Monkeys, but not in Rhesus Macaques”
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Abstract
SARS-CoV-2 induces a wide range of disease severity ranging from asymptomatic infection, to a life-threating illness, particularly in the elderly and persons with comorbid conditions. Among those persons with serious COVID-19 disease, acute respiratory distress syndrome (ARDS) is a common and often fatal presentation. Animal models of SARS-CoV-2 infection that manifest severe disease are needed to investigate the pathogenesis of COVID-19 induced ARDS and evaluate therapeutic strategies. Here we report ARDS in two aged African green monkeys (AGMs) infected with SARS-CoV-2 that demonstrated pathological lesions and disease similar to severe COVID-19 in humans. We also report a comparatively mild COVID-19 phenotype characterized by minor clinical, radiographic and histopathologic changes in the two surviving, aged AGMs and four rhesus macaques (RMs) infected with SARS-CoV-2. We found dramatic increases in circulating cytokines in three of four infected, aged AGMs but not in infected RMs. All of the AGMs showed increased levels of plasma IL-6 compared to baseline, a predictive marker and presumptive therapeutic target in humans infected with SARS-CoV-2 infection. Together, our results show that both RM and AGM are capable of modeling SARS-CoV-2 infection and suggest that aged AGMs may be useful for modeling severe disease manifestations including ARDS.
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SciScore for 10.1101/2020.06.18.157933: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Study approval: The Institutional Animal Care and Use Committee of Tulane University reviewed and approved all the procedures for this experiment. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Tissues were blocked with 10% normal goat serum (NGS) for 40 minutes, followed by a 60-minute incubation with the primary antibodies (SARS-CoV-2 nucleoprotein, mouse IgG1 (Sino Biological, cat#40143-MM08); ACE2, rabbit polyclonal (Millipore, cat# HPA000288); SARS-CoV-2 nucleoprotein , mouse IgG1suggested: Nonemousesugge…SciScore for 10.1101/2020.06.18.157933: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Study approval: The Institutional Animal Care and Use Committee of Tulane University reviewed and approved all the procedures for this experiment. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Tissues were blocked with 10% normal goat serum (NGS) for 40 minutes, followed by a 60-minute incubation with the primary antibodies (SARS-CoV-2 nucleoprotein, mouse IgG1 (Sino Biological, cat#40143-MM08); ACE2, rabbit polyclonal (Millipore, cat# HPA000288); SARS-CoV-2 nucleoprotein , mouse IgG1suggested: Nonemousesuggested: (Sino Biological Cat# 40143-MM08, RRID:AB_2827978)ACE2suggested: (GenWay Biotech Inc. Cat# 18-661-15169-0.1 mg, RRID:AB_514759)Detection of binding IgG antibody in plasma: Serum samples collected at preinfection and at necropsy were tested for binding IgG antibodies against SARS-CoV-2 S1/S2 proteins using an ELISA kit from XpressBio (cat# SP864C). binding IgGsuggested: NoneSamples collected at preinfection and weekly post-infection until necropsy were tested for detection of binding IgG antibodies against SARS-CoV-2 nucleoprotein (NP) by MFIA COVID-Plex from Charles River Laboratories. SARS-CoV-2 nucleoprotein ( NPsuggested: NoneExperimental Models: Cell Lines Sentences Resources Plaque assays were performed in Vero E6 cells. Vero E6suggested: RRID:CVCL_XD71)The 4 animals (AGM1, AGM4, RM3, RM4) were exposed by aerosol and received an inhaled dose of approximately 2×103 TCID50. AGM1suggested: NoneRM3suggested: NoneSoftware and Algorithms Sentences Resources Plates were read on a Bio-Plex® 200 System (Bio-Rad Laboratories, Hercules, CA) Bio-Rad Laboratoriessuggested: (Bio-Rad Laboratories, RRID:SCR_008426)MFIA scores were calculated using Bio-Plex Manager™ Software v6.2 (Bio-Rad) as indicated by Charles River Laboratories. Bio-Plexsuggested: NoneManager™suggested: (?Manager, RRID:SCR_016865)Statistics: Statistical tests were performed with Graphpad prism v8.4.3. Graphpad prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your data.
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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