Red blood cells may be critical for coronavirus to orchestrate a multiorgan conquer

AYELEN TORO; ANA PAULA AREVALO; GASTON PASCUAL; AGUSTINA SABATER; MARIANOEL PEREIRA; JORGE PORFIDO; SOFIA LAGE VICKERS; JUAN BIZZOTTO; PABLO SANCHIS; JAVIER COTIGNOLA; ELBA VAZQUEZ; GONZALO MORATORIO; MARTINA CRISPO; GERALDINE GUERON

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2022

Increasing evidence exhibits that long COVID is a multisystemic disease with a wide range of persistent symptoms whose manifestations vary broadly among patients and do not resolve over the course of time. Thus, it is imperative to delineate the cell types and anatomical sites in association with replication-competent forms of the virus to increase long COVID-19 treatment effectiveness. In this work, we analyzed single cell RNA-seq data from healthy donors, symptomatic and asymptomatic COVID-19 patients and evidenced multiorgan presence of viral receptors. Next, we assessed viral organotropism in association with clinical manifestations in a validated murine model of coronavirus infection. BALB/cJ mice were randomly distributed in 2 groups: non-infected (n=10) and infected (n=10). Mice were infected with the Mouse Hepatitis Virus (MHV, 6000 PFU), a single stranded RNA coronavirus. Five days post-infection, mice were euthanized and multiorgan dissection was performed for histological and viral load (VL) analyses. Peripheral blood samples were collected pre- and post-infection to determine biochemical and hematological parameters. Liver, lung and brain presented the higher VLs. Hepatic VL was positively associated with liver weight and macroscopic organ alterations. Moreover, hepatic transaminase levels were increased in infected mice while total protein and albumin levels were reduced. Further, infection was also associated with lower count of red blood cells (RBC) and hematocrit. Blood fractionation was performed and VL was evaluated in plasma and RBC. Results showed the presence of viral genome in both fractions, identifying the higher VL levels in RBCs. In conclusion, our results evidence the multiorgan extent of coronavirus infection and reveal a viral association with RBC.