key: cord-1035479-cv32u0ox authors: Chen, Xiaoping; Ling, Jiaxin; Mo, Pingzheng; Zhang, Yongxi; Jiang, Qunqun; Ma, Zhiyong; Cao, Qian; Hu, Wenjia; Zou, Shi; Chen, Liangjun; Yao, Lei; Luo, Mingqi; Chen, Tielong; Deng, Liping; Liang, Ke; Song, Shihui; Yang, Rongrong; Zheng, Ruiying; Gao, Shicheng; Gui, Xien; Ke, Hengning; Hou, Wei; Lundkvist, Åke; Xiong, Yong title: Restoration of leukomonocyte counts is associated with viral clearance in COVID-19 hospitalized patients date: 2020-03-06 journal: nan DOI: 10.1101/2020.03.03.20030437 sha: e560eb28bb3f35099d2632f80adaa14436516474 doc_id: 1035479 cord_uid: cv32u0ox Background: Viral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Suboptimal T and B cell responses can delay viral clearance in MERS and SARS patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined.Methods: From January 26 to February 28, 2020, an observational study was launched at Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. We comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. Findings: In 25 enrolled COVID-19 patients, lymphopeniawas a common feature. After the treatment, 14 patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cellsand B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. Conclusions: By comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidanceas a criterion for releasing and discharging patients. . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint [10]. In our study, we also found some cases that had underlying diseases 2 8 8 but without any association with the disease outcome. Age is a risk factor 2 8 9 for a more severe disease outcome, because of the generally inferior 2 9 0 function of the immune system among older people. Based on the 2 9 1 guideline, the patients who have normal body temperature for more than 2 9 2 three days, mitigation of respiratory symptoms, improvement of 2 9 3 radiological evidences for lesions, and had been tested negative for 2 9 4 specific SARS-CoV-2 RT-PCR at least twice, can be discharged from the 2 9 5 hospital. The average hospitalized time was 17 days (IQR 11.5 -21.5), and even as long as 23 days for the patients that were released from our 2 9 7 study [5], suggesting the time for SARS-CoV-2 clearance is also around 2 9 8 . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.03.20030437 doi: medRxiv preprint 1 6 17 days or longer. This was also been observed in an earlier study where 2 9 9 the shedding of SARS-CoV-2 in saliva continued up to 11 days [17] . Until now, there is no effective antivirals available against SARS-CoV-2. . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.03.20030437 doi: medRxiv preprint escape from the immune responses, and survive and replicate in the host 3 2 0 cells, leading a further delay of the viral clearance [15, 23] . In our study, 3 2 1 COVID-19 patients at older ages needed a longer time for the recovery, 3 2 2 likely due to the fact that aging is associated with a set of functional and A rapid and generalized lymphopenia has been observed as a prominent . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.03.20030437 doi: medRxiv preprint 1 8 In the present study, we followed the current guidelines and used a 3 4 0 specific SARS-CoV-2 realtime RT-PCR for viral detection. Surprisingly, 3 4 1 one lymphopenia patient (37y, male, chronic liver disease) was found 3 5 9 . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.03.20030437 doi: medRxiv preprint 1 9 In conclusion, we retrospectively analyzed 25 COVID-19 cases and . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint researchers who have been fighting against the SARS-CoV-2 epidemic. We also acknowledge the supports from both nationwide and 3 7 1 international resources. . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https: //doi.org/10.1101 //doi.org/10. /2020 3 1 . B a u t i s t a E M , F e r m a n G S , G o l d e W T . I n d u c t i o n o f l y m p h o p e n i a a n d i n h i b i t i o n 4 5 5 o f T c e l l f u n c t i o n d u r i n g a c u t e i n f e c t i o n o f s w i n e w i t h f o o t a n d m o u t h d i s e a s e 4 5 6 v i r u s ( F M D V ) . . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10. 1101 /2020 Total bilirubin Lactate dehydrogenase CD3+ T cell count (×10⁹ /L) CD8+ T cell count (×10⁹ /L)