key: cord-0779300-q4m2uj6r authors: Bao, Linlin; Deng, Wei; Gao, Hong; Xiao, Chong; Liu, Jiayi; Xue, Jing; Lv, Qi; Liu, Jiangning; Yu, Pin; Xu, Yanfeng; Qi, Feifei; Qu, Yajin; Li, Fengdi; Xiang, Zhiguang; Yu, Haisheng; Gong, Shuran; Liu, Mingya; Wang, Guanpeng; Wang, Shunyi; Song, Zhiqi; Liu, Ying; Zhao, Wenjie; Han, Yunlin; Zhao, Linna; Liu, Xing; Wei, Qiang; Qin, Chuan title: Lack of Reinfection in Rhesus Macaques Infected with SARS-CoV-2 date: 2020-05-01 journal: bioRxiv DOI: 10.1101/2020.03.13.990226 sha: 8259ef2d0a7bcba91453c0adf969ae5b3c11916a doc_id: 779300 cord_uid: q4m2uj6r A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence Summary Neutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days. . Moreover, no remarked 117 abnormality of X-ray changes in M4 monkey at 33 dpi (5 dpr, Figure 3A ). The only 118 notable elevation was the concentration of antibodies against SARS-CoV-2 at 42 dpi 119 (14 dpr), which is significantly higher than that at 28 dpi or 0 dpr ( Figure 2H , ## p<0.01). 120 Using necropsy specimens, there were no detectable viral RNA ( Figure 3B at 5 or 7 dpi were much higher than that at 5 or 7 dpr. Secondly, increased percentage 131 of CD4 + T cells and decreased percentage of monocytes were observed at 7 dpr 132 compared to that at 7 dpi. Thirdly, also of the most importance, the concentration of 133 specific antibodies was much higher at 14 dpr than that at 14 dpi. The average titers of 134 neutralizing antibodies exhibited linearly increased enhancement post primary infection 135 (Table 1) . Such gradually increased neutralizing antibodies against SARS-CoV-2 have 136 provided an endurable humeral immunity aroused by primary infection, which might 137 protect the same nonhuman primates from reinfection. observation and detection were within the relative short time window that neutralizing 140 antibodies remained plateau after the primary infection. Moreover, all infected monkeys 141 affected relative mild-to-moderate pneumonia, which is similar to mild or common 142 clinical types of COVID-19 in the majority of the infected persons. Therefore, the 143 immunity of primarily infected hosts which have been mildly impaired could be 144 robustly resumed. Thirdly, mucosal immunity which have been aroused by primary Comparisons between the two groups were determined using two-tailed unpaired 287 Student's or Welch's t-test. All data were analyzed with GraphPad Prism 8.0 software. The level of statistical significance is designated as *p<0.05, **p<0.01. Table 1 Neutralizing antibody titers to protect of SARS-CoV-2-infected Monkeys from 381 reinfection. Notes: a M0 was euthanized and necropsied at 5 dpi. n/a, not applicable. Animal ID Primary challenge Rechallenge 21 dpi 28 dpi 33 dpi (5 dpr) 42 dpi (14 dpr) M0 a n/a n/a n/a n/a M1 b n/a n/a n/a n/a M2 A Novel Coronavirus from Patients with Pneumonia in China