Summary of radiological scoring.

All thorax radiographs were scored blinded by a veterinary radiologist, with scores of 0 to 3 assigned to each of the 7 lung lobes. For each time point, the total score of all lung lobes was tabulated. Thus, the maximum score per time point is 21. (DOCX)</p

Multivariable correlation analysis.

(A). Spearman r correlation matrix in heatmap format. For this analysis, lung pathology scores are the interstitial cellularity scores (from Fig 7). Lung ISH are the in situ hybridization data of Fig 6. Peak NT50 represents the peak neutralizing antibody titers up to day 5 (i.e., prior to possible de novo antibody responses). VITROS anti-spike total Ig represents the peak value for each animal (i.e., day 2; Fig 2). Nasal, oropharyngeal and BAL sgRNA values are based on AUC of the data in S7 Fig. Clinical scores (sedated and cage-side) are the tabulated scores of each animal over the 7-day observation period (Fig 3C and 3F). (B) Correlation between neutralizing antibody peak NT50 values and lung pathology scores (Spearman r = -0.87; p < 0.0005). The labels next to each symbol indicate the individual animal.</p

Lack of effect of convalescent plasma on sgRNA kinetics in nasal and oropharyngeal swabs and BAL of SARS-CoV-2 infected macaques.

A weighted average analysis was performed on the sgRNA data from nasal and oropharyngeal swabs and BAL (S7 Fig.) to calculate the relative decline of viral RNA (relative to cellular mRNA in the sample) from day 1 to day 7. For each animal, the AUC of relative sgRNA per cellular mRNA over time was tabulated using day 1 as baseline value, and then divided by 6 days to get the weighted average in the decline of sgRNA over the 6-day time period. Lines indicate mean values. On panel C, animal CCP-2 was excluded, as it had no detectable viral RNA in the BAL sample, which precluded this analysis. Statistical analysis revealed no effects between the control and CCP groups (panel A, p = 0.29; panel B: p = 0.30; panel C, p = 0.88; unpaired t-test). (TIFF)</p

Quantitation of SARS-CoV-2 RNA-positive cells in lung sections.

In situ hybridization (RNAScope) was used to detect viral RNA in lung sections. (A) For each animal, the number of positive cells was counted in approximately 20 fields of right caudal lung lobe. Lines indicate median values. There were no differences between both study groups (p = 0.89, Mann Whitney test). (B) Example of lung section of animal CCP-2, with the arrows indicating RNA-positive cells.</p

Time course of additional cytokines and chemokines in plasma of SARS-CoV-2 inoculated animals.

Cytokines and chemokines presented in this panel were ones that did not show consistent changes among animals. The legend is the same as that of S4 Fig. (TIFF)</p

Animal demographics.

(DOCX)</p

Innate and adaptive immune responses following infection.

(A) Representative gating strategy for innate immune cells in whole blood. Fluorochromes used: CD66:APC, CD20/CD3/Dead: APC-Cy7, Ki67:AF488, CD14:AF700, CD123:BV421, CD16:BV605, HLA-DR:BV786, CD11c:PE-Cy7. Kinetics of circulating neutrophils, proinflammatory monocytes, mDCs, and pDCs measured at 0,1,3,5, and 7 days post SARS-CoV-2 infection. (B) Representative T cell gating strategy from whole blood. Fluorochromes used: CD25: APC, CD20/Dead: APC-Cy7, Ki67:AF488, CD3:AF700, CD95:BUV737, CD8:BUV805, CD4:BV650, CD69:BV711, CD28:PECF594, PD-1:PE-Cy7. Kinetics of circulating naïve, central memory, effector memory populations, and Ki67+PD-1+ memory cells of CD4 T cell. Kinetics of circulating naïve, central memory, effector memory, and CD69+ effector memory CD8 T cells. Significance was calculated using one tailed paired t test comparing pooled convalescent plasma and normal plasma animals against Day 0 *p = 0.05, **p = 0.01, ***p = 0.001. Statistical analysis yielded no significant different between convalescent and normal plasma groups. (PDF)</p

Time course of cytokines and chemokines in plasma of SARS-CoV-2 inoculated animals.

Cytokines and chemokines were measured in plasma using established Luminex-based methodology (see Materials and methods section). Red and black arrows indicate time of virus inoculation and plasma administration on days 0 and 1, respectively. Markers on this figure represent ones that showed the most visible changes after infection. For other markers, see S5 Fig. Using mixed-model analyses, there were no statistically significant differences between the 2 treatment groups after correction for the false discovery rate. (TIFF)</p

Time course of serum chemistry markers in SARS-CoV-2 inoculated animals.

Biochemistry analysis on serum samples was performed using Piccolo® BioChemistry Plus disks. (A) through (C) present C-reactive protein (CRP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), which showed transient changes during the early stages of infection regardless of the study group. Other markers in the panel did not show any obvious changes. Red and black arrows indicate time of virus inoculation and plasma administration on days 0 and 1, respectively. Using mixed-model analyses, there were no statistically significant differences between the 2 treatment groups after correction for the false discovery rate. (TIFF)</p

Multivariable correlation analysis on CCP-treated animals.

Multivariate analysis was performed on the 8 CCP-treated animals only. (A). Spearman r correlation matrix in heatmap format. For this analysis, the markers used are the same ones as in Fig 8. (B) Correlation between neutralizing antibody peak NT50 values and clinical scores based on cage-side observations (Spearman r = -0.77; p = 0.04). (TIFF)</p