Nasal Mucosa Exploited by SARS-CoV-2 for Replicating and Shedding during Reinfection

Abstract

Reinfection risk is a great concern with regard to the COVID-19 pandemic because a large proportion of the population has recovered from an initial infection, and previous reports found that primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques without viral presence and pathological injury; however, a high possibility for reinfection at the current stage of the pandemic has been proven. We found the reinfection of SARS-CoV-2 in Syrian hamsters with continuous viral shedding in the upper respiratory tracts and few injuries in the lung, and nasal mucosa was exploited by SARS-CoV-2 for replication and shedding during reinfection; meanwhile, no viral replication or enhanced damage was observed in the lower respiratory tracts. Consistent with the mild phenotype in the reinfection, increases in mRNA levels in cytokines and chemokines in the nasal mucosa but only slight increases in the lung were found. Notably, the high levels of neutralizing antibodies in serum could not prevent reinfection in hamsters but may play roles in benefitting the lung recovery and symptom relief of COVID-19. In summary, Syrian hamsters could be reinfected by SARS-CoV-2 with mild symptoms but with obvious viral shedding and replication, and both convalescent and vaccinated patients should be wary of the transmission and reinfection of SARS-CoV-2.

The Abundant Distribution and Duplication of SARS-CoV-2 in the Cerebrum and Lungs Promote a High Mortality Rate in Transgenic hACE2-C57 Mice

“…In patients infected with SARS-CoV-2, increased levels of proinflammatory cytokines, including IL-1β, were found, and these increased cytokines and chemokines mediated infection immunopathogenesis and played important roles in the progression of COVID-19 [37,38]. An increase in IL-1β expression during SARS-CoV-2 infection was demonstrated in the serum of hACE2-aged mice [20] and in the nasal mucosa of hamsters [25]. Interestingly, increased IL-1β expression during SARS-CoV-2 infection was found in both the lungs and brain of newly weaned hamsters, and neuroinvasion of SARS-CoV-2 was demonstrated [39].…”

“…In previous reports, hamsters were infected with 8 × 10 4 CCID 50 [24], 1 × 10 5 CCID 50 [25] or 1 × 10 6 PFU [31]; ferrets were infected with 1 × 10 5.5 CCID 50 [32]; K18-hACE2 mice [18] were infected with 1 × 10 4 , 2 × 10 4 or 2 × 10 3 PFU; HFH4-hACE2 mice were intranasally infected with 3.3 × 10 4 CCID 50 [19]; knock-in mice were infected with 4 × 10 5 CCID 50 [20]; C57BL/6Smoc-Ace2 em3(hACE2-flag-Wpre-pA)Smoc hACE2 mice were infected with 1 × 10 4 CCID 50 [30] or 1 × 10 3 PFU [29]; and rhesus monkeys were infected with 1 × 10 6 CCID 50 [33]. According to these data, we infected the hACE2 mice intranasally by high and low infection dosages of 1 × 10 2 CCID 50 and 1 × 10 3 CCID 50 , while hamsters were infected by high and low infection dosages of 1 × 10 3 CCID 50 and 1 × 10 5 CCID 50 , and susceptibility to SARS-CoV-2 infection was evaluated in both animal models.…”

“…Interestingly, most cerebral cortex neurons in hamsters exhibited positive staining for ACE2 [23]; this finding might facilitate further investigations of possible neural tissue damage in hamsters, although to date, there have been no reports on the pathophysiology of this disease in the brain. Moreover, the presence of high viral loads in the respiratory tract of hamsters, combined with an acute course of infection followed by rapid viral clearance and rapid recovery in the pathological injuries by 10-14 dpi [24,25], closely mirrors SARS-CoV-2 infection in humans. The pathological injuries in the lungs of hamsters are consistent with human infections, including interstitial to broncho-interstitial pneumonia, alveolar hemorrhage, and granulocyte infiltration.…”