Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques

Abstract

As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARS-CoV-2 infection model in Chinese rhesus macaques ( Macaca mulatta ) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b + and CD8 + cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b + cells, and persistent infiltration of CD8 + cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection.

SARS-CoV-2 vaccines in development

“…Several animal models for SARS-CoV-2 have been developed including mice expressing human ACE2, either via adenovirus transduction or by genetic engineering 61,62 , mouse models with mouse adapted SARS-CoV-2 strains [63][64][65][66][67] , ferrets [68][69][70] as well as hamsters [71][72][73] and nonhuman primates (especially rhesus macaques) 23,33,[74][75][76][77][78][79][80][81] . The hamster model can mimic severe disease as seen in a proportion of humans while the NHP model more reflects mild to moderate infection.…”

S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates

“…The animal model for SARS-CoV-2 challenge in rhesus macaques was conducted as previously described ( 41,42 ). Rhesus Macaques (3-6 years old) were randomized into 3 groups of 6 animals, and immunized intramuscularly with either PBS as a negative control, or 30 μg S-Trimer adjuvanted with 0.25 mL AS03, or 30 μg S-Trimer adjuvanted with 1.5 mg CpG 1018 plus 0.75 mg alum.…”

“…Lung tissue samples were homogenized, and total RNA was extracted for viral load analysis by qRT-PCR. For detection of SARS-CoV-2 genomic RNA, primers and probes used in this experiment included: forward primer 5’-GGGGAACTTCTCCTGCTAGAAT-3’, reverse primer 5’-CAGACATTTTGCTCTCAAGCTG-3’, and probe FAM-TTGCTGCTGCTTGACAGATT-TAMRA-3’, as previously described ( 41,42 ). Pathological examination by H&E staining and IHC staining with a mouse monoclonal antibody specific for S1 of SARS-CoV-2 (Clover Biopharma) were conducted.…”

Efficacy of Tocilizumab in Covid 19: A metanalysis of case series studies

“…The Centers for Disease Control and Prevention (CDC) also added new symptoms including new loss of taste or smell, repeated shaking with chills, and sore throat. A characteristic feature of COVID-19 during its progression in severity is the cytokine storm (via interleukin-6, IL-6) which is responsible for secondary acute respiratory distress syndrome (ARDS) [2][3] [4]. ARDS is the most devastating complication of SARSCoV-2 with a higher death toll [5] [6].…”