SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma

Deere, Jesse D.; Carroll, Timothy D.; Dutra, Joseph; Fritts, Linda; Sammak, Rebecca L.; Yee, JoAnn; Olstad, Katherine J.; Kistler, Amy; Kamm, Jack; Germanio, Clara Di; Lakshmanappa, Yashavanth Shaan; Elizaldi, Sonny R.; Roh, Jamin W.; Simmons, Graham; Watanabe, Jennifer; Pollard, Rachel E.; Usachenko, Jodie; Immareddy, Ramya; Schmidt, Brian; O’Connor, Shelby L.; DeRisi, Joseph L.; Busch, Michael P.; Iyer, Smita S.; Rompay, Koen K. A. Van; Hartigan-O’Connor, Dennis J.; Miller, Christopher J.

doi:10.1128/spectrum.01397-21

Cited by 19 publications

(20 citation statements)

References 52 publications

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“…As described earlier 19, 20 , all animals were SARS CoV-2 infected. No animals showed severe clinical signs (such as acute fever, weight loss, or respiratory distress) after infection.…”

Section: Resultsmentioning

confidence: 99%

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Inducible Bronchus-Associated Lymphoid Tissue in SARS-CoV-2 Infected Rhesus Macaques

Olstad

Rompay

et al. 2022

Preprint

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Pulmonary immunity against SARS-CoV-2 infection has not been well studied. This study investigated the distribution of immune cells int the lungs of 8 rhesus macaques experimentally infected with SARS-CoV-2, and euthanized 11-14 days later. Using immunohistochemistry, inducible bronchus-associated lymphoid tissue was found in all animals. The inducible bronchus-associated lymphoid tissues were composed of B cells, T cells, and follicular dendritic cells with evidence of lymphocyte priming and differentiation. This suggests local immunity plays an important role in the SARS-CoV-2 infection. Further study of local immunity in the lung would benefit our understanding of SARS-CoV-2 pathogenesis and could lead to new interventions to control the SARS-CoV-2 infection and disease.

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“…As described earlier 19, 20 , all animals were SARS CoV-2 infected. No animals showed severe clinical signs (such as acute fever, weight loss, or respiratory distress) after infection.…”

Section: Resultsmentioning

confidence: 99%

“…Animal information. Detailed information on the study's experimental design was reported earlier 19,20 . Briefly, this study included 5 males and 3 females colony-bred Indian origin rhesus macaques (Macaca mulatta) with ages ranging from 4 to 5 years old and weight ranging from 5.4 to 10.7 kg (median 8.6 kg).…”

Section: Methodsmentioning

confidence: 99%

Inducible Bronchus-Associated Lymphoid Tissue in SARS-CoV-2 Infected Rhesus Macaques

Olstad

Rompay

et al. 2022

Preprint

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“…Accordingly, lack of endogenous nAb at baseline has been associated with a higher risk of viremia, but Marconato et al showed that CCP recipients benefit from high-titer CCP even after adjusting for their endogenous nAb (14). Specific intact antibodies in CCP are expected to neutralize SARS-CoV-2 in the intravascular system and, in some patients, prevent progression from early to severe and life-threatening disease (as seen in animal models (15–17)). However, this antiviral therapy cannot be expected to reverse the inflammatory phase of the disease, nor neutralize infectious viruses invading the extravascular system.…”

Section: Resultsmentioning

confidence: 99%

COVID-19 convalescent plasma and randomized clinical trials: explaining conflicting outcomes and finding signals of efficacy

Focosi¹,

Franchini

Pirofski

et al. 2021

Preprint

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Convalescent plasma (CP) recurs as a frontline treatment in epidemics because it is available as soon as there are survivors. The COVID-19 pandemic represented the first large-scale opportunity to shed light into mechanisms of action, safety and efficacy of convalescent plasma using modern evidence-based medicine approaches. Studies ranging from observational case series to randomized controlled trials (RCT) have reported highly variable efficacy results for COVID-19 CP (CCP), resulting in more doubt than certainty. Reasons for CCP success and failure may be hidden in study details, which are usually difficult to explain to physicians and the public but provide fertile ground for designing next-generation studies. In this paper we analyzed variables associated with efficacy such as clinical settings, disease severity, CCP SARS-CoV-2 antibody levels and function, dose, timing of administration (variously defined as time from onset of symptoms, molecular diagnosis, diagnosis of pneumonia, or hospitalization, or by serostatus), outcomes (defined as hospitalization, requirement for ventilation, clinical improvement or mortality), CCP provenance and time for collection, and criteria for efficacy. Focusing only on the results from the 23 available RCT we noted that these were more likely to show signals of efficacy, including reductions in mortality, if the plasma neutralizing titer was ≥ 160 and the time to randomization was ≤ 9 days, consistent with passive antibody therapy efficacy requiring dosing with sufficient antibody. The fact that most studies revealed signals of efficacy despite variability in CCP and its use suggest robust therapeutic effects that become apparent despite the data noise.

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“…It might play a potential role in replication, transmissibility, and pathogenicity [ 217 , 219 ] a . It might not increase viral infectivity alone [ 217 , 222 ], but the cluster with N679K+P681H is associated with an increase in cell invasion and improved metastasis [ 223 ]. Also, it might relate to tissue culture adaptations [ 224 ], which also appeared in Rhesus Macaques treated with Normal plasma [ 225 ] - Immune: some evidence linking it to mAb evasion [ 224 , 226 ] a - Structural: decreased protein stability − 0.08 [ 120 ].…”

Section: The Spike Protein (S) Of Sars-cov-2: Clinical Interest and N...mentioning

confidence: 99%

Spike protein of SARS-CoV-2 variants: a brief review and practical implications

et al. 2022

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The scientific community has been alarmed by the possible immunological evasion, higher infectivity, and severity of disease caused by the newest variants of SARS-CoV-2. The spike protein has an important role in the cellular invasion of viruses and is the target of several vaccines and therapeutic resources, such as monoclonal antibodies. In addition, some of the most relevant mutations in the different variants are on the spike (S) protein gene sequence that leads to structural alterations in the predicted protein, thus causing concern about the protection mediated by vaccines against these new strains. The present review highlights the most recent knowledge about COVID-19 and vaccines, emphasizing the different spike protein structures of SARS-CoV-2 and updating the reader about the emerging viral variants and their classifications, the more common viral mutations described and their distribution in Brazil. It also compiles a table with the most recent knowledge about all of the Omicron spike mutations.

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SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma

Cited by 19 publications

References 52 publications

Inducible Bronchus-Associated Lymphoid Tissue in SARS-CoV-2 Infected Rhesus Macaques

Inducible Bronchus-Associated Lymphoid Tissue in SARS-CoV-2 Infected Rhesus Macaques

COVID-19 convalescent plasma and randomized clinical trials: explaining conflicting outcomes and finding signals of efficacy

Spike protein of SARS-CoV-2 variants: a brief review and practical implications

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