The ongoing SARS-CoV-2 pandemic has lasted for 2 years, causing a severe global impact on social development. With widespread vaccinations, the number of new infections has dropped significantly, but with the emergence of diverse novel variants of concern (VOCs) and variants of interest (VOIs), there has been a second or third epidemic wave in many countries. Multiple variants have the potential to increase transmissibility, virulence, or evade immune responses. Among them, the Beta (B. 1.351) and Omicron (B. 1.1. 529) VOCs have significantly decreased neutralization even in fully vaccinated individuals, while the Delta VOC (B. 1.617. 2) has been reported to be more infectious and has indeed become globally dominant. 1, 2 All currently licensed vaccines are designed based on the firstreported strain and exhibit deficient cross-neutralization against variants, highlighting the risk for health care and other service workers. In addition, due to the imbalance of global development, many countries still cannot obtain ample vaccines. Furthermore, studies have shown that cats and dogs are also susceptible to SARS-CoV-2, and there is currently no vaccine for pets. 3 Given that current vaccine supplies are inadequate to meet the global demand and that it is challenging to reformulate existing vaccines to include diverse SARS-CoV-2 spike (S) antigens in a short time, so a safe, deployable, and broadly protective intervention against new evolving viruses has become particularly urgent.

Compared with vaccination, passive antibody administration can provide immediate immunity to protect susceptible persons. Convalescent plasma and monoclonal antibodies (mAbs) have been used to treat COVID-19, and multiple mAbs have been authorized for emergency use. However, antibody therapies are administered chiefly in hospitalized patients with severe pneumonia due to their high price. Furthermore, Omicron VOC caused more than 85% of mAbs to lose neutralizing activity, 2 suggesting that mAb therapies have limitations against emerging SARS-CoV-2 variants. In recent years, antibody therapy strategies based on egg yolk antibodies (Immunoglobulin Y, IgY) have gained attention, where promising results have been reported in treating SARS-CoV, influenza virus, hantavirus, norovirus, and Ebola virus infections. 4 Moreover, IgY antibodies have shown good thermal stability and can be stored stably in a liquid state at room temperature for 6 to 12 months. Strikingly, egg production has already been scaled up, making low-cost and large-scale IgY antibodies feasible. In the present study, we developed a broadly protective IgY antibody against SARS-CoV-2, and nasal delivery conferred significant protection against SARS-CoV-2 infection in the mice model.