key: cord-307932-7t41wvw3 authors: Guo, Xiaoqin; Guo, Zhongmin; Duan, Chaohui; chen, Zeliang; Wang, Guoling; Lu, Yi; Li, Mengfeng; Lu, Jiahai title: Long-Term Persistence of IgG Antibodies in SARS-CoV Infected Healthcare Workers date: 2020-02-14 journal: nan DOI: 10.1101/2020.02.12.20021386 sha: doc_id: 307932 cord_uid: 7t41wvw3 BACKGROUND: The ongoing worldwide outbreak of the 2019-nCoV is markedly similar to the severe acute respiratory syndrome (SARS) outbreak 17 years ago. During the 2002-2003 SARS outbreak, healthcare workers formed a special population of patients. Although virus-specific IgG play important roles in virus neutralization and prevention against future infection, limited information is available regarding the long term persistence of IgG after infection with SARS-like coronavirus. METHODS: A long-term prospective cohort study followed 34 SARS-CoV-infected healthcare workers from a hospital with clustered infected cases during the 2002-2003 SARS outbreak in Guangzhou, China, with a 13-year follow-up. Serum samples were collected annually from 2003-2015. Twenty SARS-CoV-infected and 40 non-infected healthcare workers were enrolled in 2015, and their serum samples were collected. All sera were tested for IgG antibodies with ELISA using whole virus and a recombinant nucleocapsid protein of SARS-CoV, as a diagnostic antigen. RESULTS: Anti SARS-CoV IgG was found to persist for up to 12 years. IgG titers typically peaked in 2004, declining rapidly from 2004-2006, and then continued to decline at a slower rate. IgG titers in SARS-CoV-infected healthcare workers remained at a significantly high level until 2015. Patients treated with corticosteroids at the time of infection were found to have lower IgG titers than those without. CONCLUSIONS: IgG antibodies against SARS-CoV can persist for at least 12 years. The presence of SARS-CoV IgG might provide protection against SARS-CoV and other betacoronavirus. This study provides valuable information regarding humoral immune responses against SARS-CoV and the 2019-nCoV. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint concerns that SARS-CoV will re-emerge in the future; consequently, studies are underway to 69 determine the mechanisms through which SARS-CoV interacts with the host immune system, crosses 70 host barriers, and other related aspects. SARS-CoV was initially identified as having occurred through interspecies transmission from small 72 carnivores (e.g., palm civets and raccoon dogs) to humans in 2003. 10 In our current study, we conducted a 13-year follow-up study on a cohort of SARS-CoV-infected 87 healthcare workers for analyzing the presence and persistence of antibodies against SARS-CoV. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint The study site was a teaching hospital and the main center for treating clustered SARS cases in is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint were missing in the follow-up (Table S2) respectively, for failing to arrange a physical examination or due to resignation. In addition, serum 112 samples from another 20 subjects, from the 95 SARS cases, were collected in 2015 (Table S3) . Another 40 non-SARS infected healthcare workers from the same hospital were enrolled and serum 114 samples were collected, as the control group, to verify the end result data of the 34 115 SARS-CoV-infected healthcare cohort in 2015 (Table S4 ). . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint Boxplots and heatmaps were used to show the temporal trends and variations in the antibody levels. Non-linear exponential decay models were used to estimate the average decay rates of the antibody CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint To analyze the general IgG distributions, subjects were divided into 2 groups: group 1 (n=46), including SARS-CoV-infected healthcare workers enrolled in the original cohort (n=26) and 172 an additional group of SARS-CoV-infected healthcare workers who were enrolled in 2015 173 (n=20), and group 2 (n=40) of non-infected healthcare worker, selected as the control. The 174 IgG against whole virus was above the cutoff value, and the IgG titers were significantly 175 higher in group 1 than in group 2 (p < 0.001; Figure 3A) . A similar trend was observed for IgG against N199 titers, as group 1 had significantly higher IgG titers than group 2 (p=0.034; 177 Figure 3B ). Moreover, in group 1 the positive rate of IgG binding to whole virus and N199 178 was 58.70% and 28.26% with statiscical significance (p < 0.005), respectively. Kappa test was used to estimate the consistency between the methods for testing IgG. The (Table S5) . . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint During the outbreak, some SARS-CoV-infected healthcare workers received corticosteroid 190 treatment, while others did not. The cohort was divided into two groups to assess the effect of antigen was used to detect its specific antibody, which has been demonstrated to be specific in 226 clinical diagnosis and SARS-CoV reservoir screening. 21 We therefore adopted the testing of 227 IgG against N199, combined with the titer analysis of IgG against the whole virus, to 228 comprehensively evaluate the SARS antibody duration. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint We found that the SARS-CoV-infected healthcare workers who were treated with 230 corticosteroids, such as prednisone and methylprednisolone, exhibited lower IgG titers during 231 the early stages of the disease than those who were not treated with corticosteroids (although 232 not significantly for IgG against N199). However, no differences were found between the two 233 groups after 2003, suggesting that corticosteroids may suppress the early production of 234 SARS-CoV IgG antibodies. In our cohort, we found that two healthcare workers might have been misdiagnosed with 236 SARS, as the IgG antibodies against both the whole virus and N199 antigen was persistently 237 lower than the cutoff value, for these two patients. Notably, all the cases enrolled in this study is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint 2015. Collectively, based on our results, we can infer that the IgG against SARS-CoV can persist at CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint The severe acute respiratory syndrome Identification of a novel coronavirus in patients with 302 severe acute respiratory syndrome Spatial pattern of severe acute respiratory syndrome in-out flow 304 in 2003 in Mainland China Coronavirus respiratory illness in Saudi Arabia Prevalence of IgG antibody to SARS-associated coronavirus in 308 animal traders Heroes of SARS: professional roles and ethics of health care workers Anti-SARS-CoV immunoglobulin G in healthcare workers China's latest SARS outbreak has been contained Canadian officials watch SARS-like mystery bug Isolation and characterization of viruses related to the SARS 318 coronavirus from animals in southern China Isolation and characterization of a bat SARS-like coronavirus that 320 uses the ACE2 receptor Structure of SARS coronavirus spike receptor-binding 324 domain complexed with receptor Isolation of a novel 326 coronavirus from a man with pneumonia in Saudi Arabia Human infection with MERS coronavirus after exposure 328 to infected camels, Saudi Arabia Longitudinal profiles of immunoglobulin G antibodies against severe 330 acute respiratory syndrome coronavirus components and neutralizing activities in recovered patients Two-year prospective study of the humoral immune response 333 of patients with severe acute respiratory syndrome A three-year follow-up study on sera specific antibody in severe 335 acute respiratory syndrome cases after the onset of illness Disappearance of antibodies to 338 SARS-associated coronavirus after recovery . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The red line is the cutoff value (0.40). P value of < 0.05 (two-tai) is considered to be statistically 400 significant (*). . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.02.12.20021386 doi: medRxiv preprint