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Review
. 2022 Sep 7;18(9):e1010741.
doi: 10.1371/journal.ppat.1010741. eCollection 2022 Sep.

After the virus has cleared-Can preclinical models be employed for Long COVID research?

Ethan B Jansen  1   2 , Spencer N Orvold  3 , Cynthia L Swan  1 , Anthony Yourkowski  1   2 , Brittany M Thivierge  1 , Magen E Francis  1   2 , Anni Ge  4 , Melissa Rioux  4 , Joseph Darbellay  1 , John G Howland  3 , Alyson A Kelvin  1
Affiliations
Review

After the virus has cleared-Can preclinical models be employed for Long COVID research?

Ethan B Jansen et al. PLoS Pathog. .

Abstract

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) can cause the life-threatening acute respiratory disease called COVID-19 (Coronavirus Disease 2019) as well as debilitating multiorgan dysfunction that persists after the initial viral phase has resolved. Long COVID or Post-Acute Sequelae of COVID-19 (PASC) is manifested by a variety of symptoms, including fatigue, dyspnea, arthralgia, myalgia, heart palpitations, and memory issues sometimes affecting between 30% and 75% of recovering COVID-19 patients. However, little is known about the mechanisms causing Long COVID and there are no widely accepted treatments or therapeutics. After introducing the clinical aspects of acute COVID-19 and Long COVID in humans, we summarize the work in animals (mice, Syrian hamsters, ferrets, and nonhuman primates (NHPs)) to model human COVID-19. The virology, pathology, immune responses, and multiorgan involvement are explored. Additionally, any studies investigating time points longer than 14 days post infection (pi) are highlighted for insight into possible long-term disease characteristics. Finally, we discuss how the models can be leveraged for treatment evaluation, including pharmacological agents that are currently in human clinical trials for treating Long COVID. The establishment of a recognized Long COVID preclinical model representing the human condition would allow the identification of mechanisms causing disease as well as serve as a vehicle for evaluating potential therapeutics.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Time course and symptoms of COVID-19 and PASC.
Acute COVID-19 includes symptoms present up to 4 weeks. Live virus is typically present in the respiratory tract for 1-week pso, with variability among individuals. Common symptoms of acute COVID-19 are summarized that include pulmonary and systemic manifestations. Long COVID or PASC includes persistent symptoms present 4 weeks post-acute infection. The diverse range of multiorgan complications of PASC are summarized. COVID-19, Coronavirus Disease 2019; PASC, Post-Acute Sequelae of COVID-19; pso, post-symptom onset.
Fig 2
Fig 2. Potential animal models of post-acute sequelae of COVID-19 (PASC) manifestations.
The 4 main groups of animal models (hamsters, mice, ferrets, and NHPs) are outlined with corresponding human manifestations of PASC. COVID-19, Coronavirus Disease 2019; NHP, nonhuman primate; PASC, Post-Acute Sequelae of COVID-19.
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