Abnormal Blood Coagulation and Kidney Damage in Aged Hamsters Infected with Severe Acute Respiratory Syndrome Coronavirus 2.

Marumi Ohno,Toshiki Sekiya,Yasuko Orba,Masashi Shingai,Yasuhiko Suzuki,Michihito Sasaki,Osamu Ichii,Hiroshi Kida,Tatsuya Sawamura,Md Abdul Masum,Hirofumi Sawa,Akemi Kakino

doi:10.3390/v13112137

Marumi Ohno, Toshiki Sekiya + Show 10 more

Open Access

https://doi.org/10.3390/v13112137

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Journal: Viruses	Publication Date: Oct 22, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Hokkaido University, Shinshu University

Abstract

Systemic symptoms have often been observed in patients with coronavirus disease 2019 (COVID-19) in addition to pneumonia, however, the details are still unclear due to the lack of an appropriate animal model. In this study, we investigated and compared blood coagulation abnormalities and tissue damage between male Syrian hamsters of 9 (young) and over 36 (aged) weeks old after intranasal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite similar levels of viral replication and inflammatory responses in the lungs of both age groups, aged but not young hamsters showed significant prolongation of prothrombin time and prominent acute kidney damage. Moreover, aged hamsters demonstrated increased intravascular coagulation time-dependently in the lungs, suggesting that consumption of coagulation factors causes prothrombin time prolongation. Furthermore, proximal urinary tract damage and mesangial matrix expansion were observed in the kidneys of the aged hamsters at early and later disease stages, respectively. Given that the severity and mortality of COVID-19 are higher in elderly human patients, the effect of aging on pathogenesis needs to be understood and should be considered for the selection of animal models. We, thus, propose that the aged hamster is a good small animal model for COVID-19 research.

Highlights

Since the end of 2019, coronavirus disease 2019 (COVID-19) has been a serious threat worldwide
Abnormal blood coagulation parameters and acute kidney damage were observed only in aged hamsters after the infection, body weight loss and virus titers in the lungs were similar between the two age groups of animals. These findings indicate that age-related host factors may determine the severity of COVID-19 and emphasize the need for appropriate models, such as the use of aged animals, to understand disease pathogenesis
Since coagulopathy has been reported in human patients with severe COVID-19 [2,3], the international normalized ratio of prothrombin time (PT) (PTINR), a clinical index of the duration of blood coagulation, was evaluated

Summary

Introduction

Since the end of 2019, coronavirus disease 2019 (COVID-19) has been a serious threat worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen for COVID-19. Given previous findings on sepsis-induced organ dysfunction [1], microvascular thrombosis is considered to contribute to tissue injury and multiple organ dysfunction syndrome in COVID-19. Hypercoagulable states demonstrated by increased D-dimer, elevated concentrations of fibrinogen and fibrinogen degradation products, and prolonged prothrombin time (PT) have been observed in patients with severe COVID-19, and the development of microthrombi in the small vessels of the lungs has been reported [2,3,4,5]. Systemic symptoms, such as kidney and liver dysfunction, have been reported to be associated with lethal outcomes in patients with. The mechanisms of coagulation abnormalities and systemic symptoms in COVID-19 should be elucidated to better understand the pathogenesis of COVID-19

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