Non-Human Primate “SARS-COV-2” Animal Model Study (2020)

Since no animal model fully reproduces every aspect of COVID-19, it is necessary to weigh the strengths and weaknesses of each according to the goals of the study.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023231/#__ffn_sectitle

The above statement from a June 2021 article on the status of animal models for “SARS-COV-2” showcases the giant glaring elephant in the room: to date, they can not reproduce “Covid-19” in animals. This admission should make anyone believing the official narrative take pause. If virologists are unable to recreate the same disease in animals that is seen in humans, there is no proof of pathogenicity. Showing that the disease can be recreated in animals should have been clearly established before there were ever any claims of the existence of a new “virus.” This proof of pathogenicity can not be done.

To get around this fact, virologists try to either transgenically alter animals such as mice in order to make them sick or they attempt to mimic one or two of the numerous symptoms associated with “Covid-19” in an animal and call it a win. There honestly isn’t much reason to even entertain these animal studies as they never work with purified/isolated “virus” particles and they never expose the animals to any “virus” in a natural way. They never factor into the equation that the stress from the experiments alone is enough to make animals sick. All you really need to debunk any of these studies is to read the methods section and it’s game over from there.

Regardless, this non-human primate study from August 2020 is interesting for a few reasons. One, it showcases the ridiculous methods used to claim that the NHP’s succumbed to “Covid.” And two, in order to prop up their own animal model, they tear down all of the others. Highlights below:

Comparison of nonhuman primates identified the suitable model for COVID-19

Abstract

Identification of a suitable nonhuman primate (NHP) model of COVID-19 remains challenging. Here, we characterized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in three NHP species: Old World monkeys Macaca mulatta (M. mulatta) and Macaca fascicularis (M. fascicularis) and New World monkey Callithrix jacchus (C. jacchus). Infected M. mulatta and M. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. Viral genomes were detected in swab and blood samples from all animals. Viral load was detected in the pulmonary tissues of M. mulatta and M. fascicularis but not C. jacchus. Furthermore, among the three animal species, M. mulatta showed the strongest response to SARS-CoV-2, including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues. Collectively, these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M. mulatta as the most suitable for modeling COVID-19.

“However, some challenging and critical questions, including the roles of cytokine storm,4 SARS-CoV-2 tropism,5 and virus–host interaction,6 remain unanswered, and antiviral drugs and vaccines have not been developed,7 which requires an animal model that can recapitulate the important features of COVID-19 in patients.8 In fact, several animal models of COVID-19 were recently reported; these models include hACE2-transgenic mouse models,5,9 a non-transgenic mouse model,10 a golden hamster model,11 a ferret model12 and nonhuman primate (NHP) models.13,14,15 However, in addition to the different genetic backgrounds of the experimental animals, the use of different viral strains, dosages and routes of challenge in these models resulted in different and even controversial conclusions. Therefore, in this study, three species of NHPs were challenged with the same strain of SARS-CoV-2 to identify the suitability of NHP models of COVID-19.”

Clinical signs in SARS-CoV-2-infected monkeys

First, a rise in body temperature, one of the clinical signs of SARS-CoV-2 infection, was assessed. Increases in body temperature of more than 0.5 °C were observed in 11 out of 14 Macaca mulatta (HHH-1–HHH-14), 4 out of 6 Macaca fascicularis (SXH-1–SXH-6) and 3 out of 6 Callithrix jacchus (RH-1–RH-6) (Fig. 1b). Notably, M. fascicularis SXH-6 showed a continuously high body temperature over the 21-day experimental period. The loss of body weight (BW) was noticed at 10 days post inoculation (dpi), when 11 out of 13 M. mulatta showed a decrease in BW by 5.88–28.57%. Five out of six M. fascicularis showed a decrease in BW by 2.17–10.51% (Supplementary Table 2), suggesting more severe loss of BW in M. mulatta than in M. fascicularis.

Next, the effects of SARS-CoV-2 infection on the lung were evaluated on the basis of chest radiographs using a four-pattern approach.17 We observed lung abnormalities in the form of nodules, masses, and interstitial patterns in both M. mulatta and M. fascicularis at 12 dpi. In particular, aged M. mulatta showed more interstitial patterning than young or adult M. mulatta (Fig. 1c). Importantly, overall comparison of the chest radiographs showed that the pulmonary abnormalities were more severe in M. mulatta than in M. fascicularis, suggesting that M. mulatta are more susceptible to SARS-CoV-2 infection than M. fascicularis. However, no other respiratory symptoms were observed in any of the three monkey species during this study.”

Host responses to SARS-CoV-2 infection

“Finally, host responses to SARS-CoV-2 infection were evaluated by assessments of the production of virus-specific antibodies and secretion of inflammatory cytokines, hematology, and histopathology. We found that SARS-CoV-2 infection induced the production of virus-specific antibodies in the majority of monkeys, with these antibodies becoming detectable at 4 dpi (Fig. 3a, b). Overall, antibody levels in old and adult M. mulatta were higher than those in young M. mulatta. Consistent with the results of virus monitoring, we did not detect virus-specific antibodies in serum samples from infected C. jacchus. Neutralization assays revealed that virus-specific antibodies from most of the animals had neutralizing activity against SARS-CoV-2, with the highest viral titer (1:256) observed in M. fascicularis at 21 dpi (Supplementary Table 4).”

Discussion

“SARS-CoV-2, which remains enigmatic, has rapidly spread worldwide, leading to high economic losses and threats to public health. Within 6 months after SARS-CoV-2 was first reported, five kinds of animals were developed into models in which to study COVID-19: the mouse, ferret, tree shrew, golden hamster, and a NHP species. Murine models of COVID-19 were developed by genetic manipulation of human ACE2 through transgene expression,9 CRISPR-cas9 editing,5 and the transient overexpression of ACE2,18 which makes mice susceptible to SARS-CoV-2 infection. However, due to the many differences in their genetics, anatomy and physiology, these murine models of COVID-19 are not suitable for studies of COVID-19 pathogenesis. The ferret and golden hamster are naturally susceptible to SARS-CoV-2 infection.11,12 However, they are also genetically different from humans and are not ideal animal models for studies of vaccines and pathogenesis. The tree shrew is relatively genetically close to primates and can act as an alternative experimental animal to NHPs.19 Unfortunately, our recent study showed that the tree shrew is not susceptible to SARS-CoV-2 infection and may instead be an asymptomatic carrier.20

NHPs are widely recognized as ideal animal models for emerging and re-emerging diseases, including SARS16,21,22 and Middle East respiratory syndrome.23 To date, there have been four reports of NHP (Old World monkeys) models of COVID-1914,15,24,25 that recapitulate different aspects of COVID-19, but these models have also raised some debate, probably due to differences in animal species (M. mulatta and M. fascicularis), virus strain, challenge route, and methods of evaluation. Using comparative analysis, our study revealed that M. mulatta is a more susceptible species to SARS-CoV-2 infection than M. fascicularis and C. jacchus.”

“The NHP model in this study recapitulates several clinical features of COVID-19. First, the increased body temperature and abnormal chest radiograph of our model simulate two typical clinical signs in COVID-19 patients, fever and pneumonia, respectively.”

“In conclusion, we have established a NHP model of COVID-19 through comparative analysis of the clinical symptoms, viral replication and tissue tropism, and host responses to SARS-CoV-2 infection among three species from two families of NHPs in one system. Ultimately, this study identified M. mulatta as suitable for the study of SARS-CoV-2 infection, as it most closely recapitulated human-like conditions.”

Materials and methods

“Referencing a NHP model of SARS,16 we inoculated adult and aged Old world monkeys with a total of 4.75 ml of 106 pfu/ml SARS-CoV-2 intratracheally (4 ml), intranasally (0.5 ml) and on the conjunctiva (0.25 ml), and a half-dose of the virus was administered to young monkeys. New World monkeys were intranasally challenged with 1.0 ml of the same virus due to their small body size. After viral inoculation, animals were checked daily for clinical signs. Then, we anesthetized the animals with ketamine (6 mg/kg) and performed the following experimental procedures: body temperature and weight monitoring, sample collection, chest radiography, and necropsies at the indicated stages (Fig. 1a).”

https://www.nature.com/articles/s41392-020-00269-6

In Summary:

  • Identification of a suitable nonhuman primate (NHP) model of “COVID-19” remains challenging
  • Infected M. mulatta and M. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight
  • Several animal models of “COVID-19” were recently reported; these models include hACE2-transgenic mouse models, a non-transgenic mouse model, a golden hamster model, a ferret model and nonhuman primate (NHP) models
  • However, in addition to the different genetic backgrounds of the experimental animals, the use of different “viral” strains, dosages and routes of challenge in these models resulted in different and even controversial conclusions
  • In this current NHP study, increases in body temperature of more than 0.5 °C were observed in 11 out of 14 Macaca mulatta, 4 out of 6 Macaca fascicularis and 3 out of 6 Callithrix jacchus
  • They next looked for loss of body weight (BW) which was noticed at 10 days post inoculation (dpi)
  • The effects of “SARS-CoV-2” infection on the lung were evaluated on the basis of chest radiographs
  • In particular, aged M. mulatta showed more interstitial patterning than young or adult M. mulatta
  • No other respiratory symptoms were observed in any of the three monkey species during this study
  • They did not detect “virus-specific” antibodies in serum samples from infected C. jacchus
  • Within 6 months after “SARS-CoV-2” was first reported, five kinds of animals were developed into models in which to study “COVID-19:” the mouse, ferret, tree shrew, golden hamster, and a NHP species
  • Due to the many differences in their genetics, anatomy and physiology, the murine models of “COVID-19” are not suitable for studies of “COVID-19” pathogenesis
  • Ferrets and golden hamsters are also genetically different from humans and are not ideal animal models for studies of vaccines and pathogenesis
  • The tree shrew is not susceptible to “SARS-CoV-2” infection and may instead be an “asymptomatic carrier”
  • To date, there have been four reports of NHP (Old World monkeys) models of “COVID-19” that recapitulate different aspects of “COVID-19,” but these models have also raised some debate
  • The authors claim the increased body temperature and abnormal chest radiograph of their model simulates two typical clinical signs in “COVID-19” patients, fever and pneumonia, respectively
  • They identified M. mulatta as suitable for the study of “SARS-CoV-2” infection, as it most closely recapitulated human-like conditions
  • They inoculated adult and aged Old world monkeys with a total of 4.75 ml of 10 pfu/ml “SARS-CoV-2” intratracheally (in the throat), intranasally (in the nose), and on the conjunctiva (on the eye)
  • New World monkeys were intranasally challenged with 1.0 ml of the same “virus” due to their small body size

As can be seen, the researchers tear down the murine, ferret, golden hamster, tree shrew, and even some NHP animal models. They state that these animals are not genetically related to humans and they do not experience the exact same disease. However, through their own study in which they injected monkeys with toxic cell culture goo not once (throat), not twice (nose), but three times (eyes), the researchers claim that they were able to recreate fever and pneumonia in rhesus macaques. In their own words, rhesus macaques were the “most likely” to recapitulate “human-like conditions.” They also claim that the older macaques had more interstitial patterning on their lungs than the younger macaques. Obviously, this could just be due to their advanced age but that didn’t stop the researchers from implying that “Covid” infected the older macaques more severely than the younger macaques. They make this distinction even though they admit no other respiratory symptoms were observed during the experiments.

The good news is that since this study is from August 2020, we have hindsight as we can look to see what other researchers think of this NHP animal model:

From a review published April 2021:

Animal models for SARS-Cov2/Covid19 research-A commentary

“A comprehensive review was recently published by Ehaideb et al., [10][24][25] that surveyed publications that reported data on SARS CoV-2 infections in a variety of animals. These included hamsters, non-human primates (macaques), mice, rats, ferrets, rabbits, and cats. All supported viral replication in the lung with mild disease ensuing as assessed by tissue pathology. No animals developed the severe symptoms seen in humans although a transient inflammation was observed inconsistently in non-human primates, hamsters and mice (see below). No cytokine stormscoagulopathy, hypoxemic respiratory failure, multiple organ failure or death were reported.”

https://www.sciencedirect.com/science/article/pii/S0006295221001398

No animals, not even the rhesus macaques, developed severe “Covid” seen in humans. There were:

In other words, there was no “Covid” in any of these animals including the rhesus macaques. The macaques had no respiratory symptoms of disease beyond interstitial patterns from imaging taken after they were killed. Some macaques experienced fever and weight loss while others did not. All of this just goes to show that yet another animal model fails to produce the required evidence of pathogenicity. Without proof of pathogenicity, there can be no claim of any “virus.”

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