Increasing evidence suggests that dysregulated immune responses are associated with the clinical outcome of coronavirus disease 2019 (COVID-19). Nucleocapsid protein (NP)-, spike (S)-, receptor binding domain (RBD)- specific immunoglobulin (Ig) isotypes, IgG subclasses and neutralizing antibody (NAb) were analyzed in 123 serum from 63 hospitalized patients with severe, moderate, mild or asymptomatic COVID-19. Mild to modest correlations were found between disease severity and antigen specific IgG subclasses in serum, of which IgG1 and IgG3 were negatively associated with viral load in nasopharyngeal swab. Multiple cytokines were significantly related with antigen-specific Ig isotypes and IgG subclasses, and IL-1β was positively correlated with most antibodies. Furthermore, the old patients (≥ 60 years old) had higher levels of chemokines, increased NAb activities and SARS-CoV-2 specific IgG1, and IgG3 responses and compromised T cell responses compared to the young patients (≤ 18 years old), which are related with more severe cases. Higher IgG1 and IgG3 were found in COVID-19 patients with comorbidities while biological sex had no effect on IgG subclasses. Overall, we have identified diseases severity was related to higher antibodies, of which IgG subclasses had weakly negative correlation with viral load, and cytokines were significantly associated with antibody response. Further, advancing age and comorbidities had obvious effect on IgG1 and IgG3.

Wild aquatic birds are the primary natural reservoir of influenza A viruses (IAVs), although a small number of viruses can spill over to mammals and circulate. The focus of IAV infection in mammals was largely limited to humans and swine variants, until the emergence of H3N2 canine influenza viruses (CIVs), which provides new perspective for interspecies transmission of the virus. In this study, we captured 54 canine-adaptive signatures in H3N2 CIVs through entropy computation, which were largely concentrated in the interaction region of polymerase proteins on ribonucleoprotein complex. The receiver operating characteristic curves of these sites showed >95% accuracy in distinguishing between the hosts. Nine of the 54 canine-adaptive signatures were shared in avian–human/equine or equine–canine (PB2-82; PB1-361; PA-277; HA-81, 111, 172, 196, 222, 489), suggesting their involvement in canine adaptation. Furthermore, we found that IAVs can establish persistent transmission in lower mammals with greater ease compared to higher mammals, and 25 common adaptation signatures of H3 IAVs were observed in diverse avian–mammals comparison. There were few human-like residues in H3N2 CIVs, which suggested a low risk of human infection. Our study highlights the necessity of identifying and monitoring the emerging adaptive mutations in companion animals by enhanced surveillance and provides a basis for mammal adaptation of avian influenza viruses.

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