Neutralizing and binding activities against SARS‐CoV‐1/2, MERS‐CoV, and human coronaviruses 229E and OC43 by normal human intravenous immunoglobulin derived from healthy donors in Japan

Background There are several types of coronaviruses that infect humans and cause disease. The latest is severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which is an emerging global threat with no current effective treatment. Normal intravenous immunoglobulin (N‐IVIG) has been administered to coronavirus disease 2019 (COVID‐19) patients to control severe inflammation and the cellular immune response. However, the neutralizing activity of N‐IVIG against SARS‐CoV‐2 has not yet been fully evaluated. The aim of this study was to determine whether N‐IVIG manufactured before the start of the COVID‐19 pandemic contained IgG antibodies against the circulating human coronaviruses (HCoVs) that cross‐react with the highly pathogenic coronaviruses SARS‐CoV‐1, Middle East respiratory syndrome coronavirus (MERS‐CoV), and SARS‐CoV‐2. No cases of SARS‐CoV‐1 or MERS‐CoV have been reported in Japan. Study Design and Methods The neutralizing and binding activities of N‐IVIG against SARS‐CoV‐1, MERS‐CoV, SARS‐CoV‐2, HCoV 229E, and HCoV OC43 were evaluated. Nine N‐IVIG lots manufactured between 2000 and 2018, derived from donors in Japan, were tested. Binding activity was evaluated by indirect immunofluorescence assay. Results None of the N‐IVIG lots tested displayed neutralizing or binding activity against SARS‐CoV‐1, MERS‐CoV, or SARS‐CoV‐2. However, they displayed substantial neutralizing and binding activity against HCoV OC43 and weak neutralizing and substantial binding activity against HCoV 229E. Conclusion N‐IVIG derived from healthy donors in Japan before the start of the COVID‐19 pandemic had no direct effect against SARS‐CoV‐2. Further studies are warranted to determine the effects of N‐IVIG manufactured after the start of the COVID‐19 pandemic against SARS‐CoV‐2.