key: cord-0730710-6ms4r8mr authors: YAMAGUCHI, Tomoyuki; SHINAGAWA, Toshie; KOBATA, Hisanobu; NAKAGAWA, Hidemitsu title: Immunity against seasonal human coronavirus OC43 mitigates fatal deterioration of COVID-19 date: 2021-07-14 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.07.015 sha: 721eeb489f9b06b05e3e2bbaa025ccfa1f1ac581 doc_id: 730710 cord_uid: 6ms4r8mr BACKGROUND: : The effects of high-intensity immunity on coronavirus disease 2019 (COVID-19) remain unclear. While it may be protective, antibodies against SARS-CoV-2 are more preferentially induced in inpatients with COVID-19 than in outpatients with milder disease, and immunosuppression is the standard therapy for severe cases. We studied the relationship between cross-reactive antibody production against seasonal human coronavirus and the clinical course of COVID-19. METHODS: : Among the SARS-CoV-2 immunogenic epitopes, conserved peptides in the human coronavirus OC43 were searched and synthesized. ELISA was designed to detect antibodies against synthesized peptides. Antibody titers against S2สน cleavage site epitopes near fusion peptides of SARS-CoV-2 and OC43 were determined in the sera of 126 COVID-19 inpatients. The correlation between antibody titers and clinical data was analyzed. RESULTS: : COVID-19 inpatients who produced antibodies against the OC43 peptide did not develop severe or fatal pneumonia. Antibody titers against the corresponding epitope of SARS-CoV-2 did not differ between inpatients with severe and mild COVID-19. The antibody titers against the OC43 epitope increased more than those against SARS-CoV-2 during the first 2 weeks of COVID-19. CONCLUSIONS: : Immunity to seasonal human coronavirus OC43 effectively enhanced recovery from COVID-19. Detecting cross-reactive antibodies to OC43 may help predict COVID-19 prognosis. In this study, we will assess the clinical effect of immunity against seasonal 97 HCoVs on COVID-19. We measured antibody titers against the most immunogenic 98 epitope near the fusion peptide in the S2 protein (Shrock et al., 2020) The peptides (S-SARS2, S-OC43, Hel, and NSP13 listed in Supplementary Table S1) 142 were synthesized and purified by HPLC at >50% purity by Eurofins Genomics K.K. (Tokyo, Japan). Dry peptides were dissolved in water at a concentration of 2 mM, 144 except for NSP13. NSP13 peptide was dissolved in water with a 10% volume of acetate. Table S1 ). In the S protein, an epitope candidate of 172 SARS-CoV-2, 816-SFIED-820, was found to share sequence with OC43 HCoV except 173 for 817-F. We synthesized two peptides, S-OC43 (906-919 of OC43 HCoV) and Table S1 ). This domain in the S2 in the U test) (Fig. 1E-F ). Fatality due to COVID-19 is known to be largely affected by age (Wiersinga et 254 al., 2020). Consistent with this, we observed that the ratio of severe COVID-19 cases 255 among hospitalized patients was high in older patients (Fig. 1C) . Plotting of the 256 antibody titers against ages revealed that antibody titers of anti-S-OC43 were not 257 increased in the elderly population, despite possible exposure to OC43 HCoV at more 258 time points during life (Fig. 1D ). This may be due to a reduction in antibody titers after were higher than 1 for anti-S-SARS2 (1.05 fold at the median) and anti-S-OC43 (1.12 293 fold at the median) (Fig. 2C ). More interestingly, the fold changes in antibody titers 294 were significantly higher in anti-S-OC43 than in anti-S-SARS2 among patients 295 hospitalized with COVID-19 (p<0.05, Wilcoxon signed-rank test, Fig. 2C-D) . We found 296 six cases with increased anti-S-OC43 but not anti-S-SARS2 (Fig. 2B, D) . These results Table 2 . B) 417 The change of antibody titers during 1-2 weeks after diagnosis of SARS-CoV-2. For 418 101 cases whose serum samples were available, antibody titers were compared in each 419 case between serum within 6 days after diagnosis (shown as circle) and serum 5-14 days Table 2 . Clinical data of severe cases with antibodies and cases who died from 535 other causes during the second epidemic period. As for SARS-CoV-2 infected hospitalized patients from July to October 2020, five pneumonia and were discharged on day 31, but was re-hospitalized due to respiratory 553 failure on day 82 and died on day 86 when SARS-CoV-2 was negative in qRT-PCR. The 554 case 18 was hospitalized due to hydrocephalus and arteriovenous malformation. SARS-CoV-2 infection was diagnosed by screening qRT-PCR test at hospitalization. Her respiratory condition recovered, but she died from brain damage. The cases 12 and 557 18 were classified into mild COVID-19. 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Minata for the analysis of clinical data, H. Nakamoto for critical 384