Though the relevance of co-secretion of BiP with β-coronavirus virions was not clarified (Fig. 2B), there might be two reasons why this can be a potential modulator of cell-non-autonomous UPR during infection as follows: (i) As secreted chaperones are known inducers of cell-non-autonomous UPR (49), BiP secreted during β-coronavirus infection might be a potential inducer of cell-non-autonomous UPR, perturbing organismal homeostasis and inducing systemic immune response to promote disease severity. The gene discussed is HSPA5; the disease is infection.