Abstract
The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation. Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans.
Highlights
Biomedical and clinical researchers have tried to define the different phases of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans from various perspectives [1,2,3,4]
To investigate factors leading to the different COVID-19 manifestations animal models are essential as the moment and site of infection can be controlled and the subsequent response can be monitored in detail
The study focused on the post-acute phase of the SARS-CoV-2 infection in rhesus and cynomolgus macaques, defined as the 3–4 week period following the disappearance of detectable virus from the nose and throat swab samples
Summary
Biomedical and clinical researchers have tried to define the different phases of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans from various perspectives [1,2,3,4]. The general consensus is that the initial phase of infection is viremia or the progressive state in which immune responses determine if the person remains healthy or not. This phase, which takes about a week, is followed by the pneumonia phase that generally lasts no longer than three weeks after the initial infection. Evidence is accumulating for the existence of an enlengthened recovery process, even for non-hospitalized patients [5,6,7] In this phase, chronic symptoms and possible recurrence of disease can be detected, known as long-COVID or post-acute COVID [7,8]. It is still unknown how long this recovery phase lasts
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