Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in Wuhan

ABSTRACT The emergence of a new type of COVID-19 patients, who were retested positive after hospital discharge with long-term persistent SARS-CoV-2 infection but without COVID-19 clinical symptoms (hereinafter, LTPPs), poses novel challenges to COVID-19 treatment and prevention. Why was there such a...

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Main Authors: Cuidan Li, Liya Yue, Yingjiao Ju, Jie Wang, Mengfan Chen, Hao Lu, Sitong Liu, Tao Liu, Jing Wang, Xin Hu, Bahetibieke Tuohetaerbaike, Hao Wen, Wenbao Zhang, Sihong Xu, Chunlai Jiang, Fei Chen
Format: Article
Language:English
Published: American Society for Microbiology 2022-12-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.01270-22
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author Cuidan Li
Liya Yue
Yingjiao Ju
Jie Wang
Mengfan Chen
Hao Lu
Sitong Liu
Tao Liu
Jing Wang
Xin Hu
Bahetibieke Tuohetaerbaike
Hao Wen
Wenbao Zhang
Sihong Xu
Chunlai Jiang
Fei Chen
author_facet Cuidan Li
Liya Yue
Yingjiao Ju
Jie Wang
Mengfan Chen
Hao Lu
Sitong Liu
Tao Liu
Jing Wang
Xin Hu
Bahetibieke Tuohetaerbaike
Hao Wen
Wenbao Zhang
Sihong Xu
Chunlai Jiang
Fei Chen
author_sort Cuidan Li
collection DOAJ
description ABSTRACT The emergence of a new type of COVID-19 patients, who were retested positive after hospital discharge with long-term persistent SARS-CoV-2 infection but without COVID-19 clinical symptoms (hereinafter, LTPPs), poses novel challenges to COVID-19 treatment and prevention. Why was there such a contradictory phenomenon in LTPPs? To explore the mechanism underlying this phenomenon, we performed quantitative proteomic analyses using the sera of 12 LTPPs (Wuhan Pulmonary Hospital), with the longest carrying history of 132 days, and mainly focused on 7 LTPPs without hypertension (LTPPs-NH). The results showed differential serum protein profiles between LTPPs/LTPPs-NH and health controls. Further analysis identified 174 differentially-expressed-proteins (DEPs) for LTPPs, and 165 DEPs for LTPPs-NH, most of which were shared. GO and KEGG analyses for these DEPs revealed significant enrichment of “coagulation” and “immune response” in both LTPPs and LTPPs-NH. A unity of contradictory genotypes in the 2 aspects were then observed: some DEPs showed the same dysregulated expressed trend as that previously reported for patients in the acute phase of COVID-19, which might be caused by long-term stimulation of persistent SARS-CoV-2 infection in LTPPs, further preventing them from complete elimination; in contrast, some DEPs showed the opposite expression trend in expression, so as to retain control of COVID-19 clinical symptoms in LTPPs. Overall, the contrary effects of these DEPs worked together to maintain the balance of LTPPs, further endowing their contradictory steady-state with long-term persistent SARS-CoV-2 infection but without symptoms. Additionally, our study revealed some potential therapeutic targets of COVID-19. Further studies on these are warranted. IMPORTANCE This study reported a new type of COVID-19 patients and explored the underlying molecular mechanism by quantitative proteomic analyses. DEPs were significantly enriched in “coagulation” and “immune response”. Importantly, we identified 7 “coagulation system”- and 9 “immune response”-related DEPs, the expression levels of which were consistent with those previously reported for patients in the acute phase of COVID-19, which appeared to play a role in avoiding the complete elimination of SARS-CoV-2 in LTPPs. On the contrary, 6 “coagulation system”- and 5 “immune response”-related DEPs showed the opposite trend in expression. The 11 inconsistent serum proteins seem to play a key role in the fight against long-term persistent SARS-CoV-2 infection, further retaining control of COVID-19 clinical symptom of LTPPs. The 26 proteins can serve as potential therapeutic targets and are thus valuable for the treatment of LTPPs; further studies on them are warranted.
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spelling doaj.art-6ae88171a3334e3d98d11269f47834412022-12-23T15:19:27ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-12-0110610.1128/spectrum.01270-22Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in WuhanCuidan Li0Liya Yue1Yingjiao Ju2Jie Wang3Mengfan Chen4Hao Lu5Sitong Liu6Tao Liu7Jing Wang8Xin Hu9Bahetibieke Tuohetaerbaike10Hao Wen11Wenbao Zhang12Sihong Xu13Chunlai Jiang14Fei Chen15Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, ChinaBeijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, ChinaBeijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, ChinaBeijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, ChinaBeijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, ChinaBeijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, ChinaBeijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, ChinaBeijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, ChinaDivision II of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun, ChinaBeijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, ChinaABSTRACT The emergence of a new type of COVID-19 patients, who were retested positive after hospital discharge with long-term persistent SARS-CoV-2 infection but without COVID-19 clinical symptoms (hereinafter, LTPPs), poses novel challenges to COVID-19 treatment and prevention. Why was there such a contradictory phenomenon in LTPPs? To explore the mechanism underlying this phenomenon, we performed quantitative proteomic analyses using the sera of 12 LTPPs (Wuhan Pulmonary Hospital), with the longest carrying history of 132 days, and mainly focused on 7 LTPPs without hypertension (LTPPs-NH). The results showed differential serum protein profiles between LTPPs/LTPPs-NH and health controls. Further analysis identified 174 differentially-expressed-proteins (DEPs) for LTPPs, and 165 DEPs for LTPPs-NH, most of which were shared. GO and KEGG analyses for these DEPs revealed significant enrichment of “coagulation” and “immune response” in both LTPPs and LTPPs-NH. A unity of contradictory genotypes in the 2 aspects were then observed: some DEPs showed the same dysregulated expressed trend as that previously reported for patients in the acute phase of COVID-19, which might be caused by long-term stimulation of persistent SARS-CoV-2 infection in LTPPs, further preventing them from complete elimination; in contrast, some DEPs showed the opposite expression trend in expression, so as to retain control of COVID-19 clinical symptoms in LTPPs. Overall, the contrary effects of these DEPs worked together to maintain the balance of LTPPs, further endowing their contradictory steady-state with long-term persistent SARS-CoV-2 infection but without symptoms. Additionally, our study revealed some potential therapeutic targets of COVID-19. Further studies on these are warranted. IMPORTANCE This study reported a new type of COVID-19 patients and explored the underlying molecular mechanism by quantitative proteomic analyses. DEPs were significantly enriched in “coagulation” and “immune response”. Importantly, we identified 7 “coagulation system”- and 9 “immune response”-related DEPs, the expression levels of which were consistent with those previously reported for patients in the acute phase of COVID-19, which appeared to play a role in avoiding the complete elimination of SARS-CoV-2 in LTPPs. On the contrary, 6 “coagulation system”- and 5 “immune response”-related DEPs showed the opposite trend in expression. The 11 inconsistent serum proteins seem to play a key role in the fight against long-term persistent SARS-CoV-2 infection, further retaining control of COVID-19 clinical symptom of LTPPs. The 26 proteins can serve as potential therapeutic targets and are thus valuable for the treatment of LTPPs; further studies on them are warranted.https://journals.asm.org/doi/10.1128/spectrum.01270-22COVID-19SARS-CoV-2retest positivelong-term persistent COVID-19 patients (LTPPs)coagulation
spellingShingle Cuidan Li
Liya Yue
Yingjiao Ju
Jie Wang
Mengfan Chen
Hao Lu
Sitong Liu
Tao Liu
Jing Wang
Xin Hu
Bahetibieke Tuohetaerbaike
Hao Wen
Wenbao Zhang
Sihong Xu
Chunlai Jiang
Fei Chen
Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in Wuhan
Microbiology Spectrum
COVID-19
SARS-CoV-2
retest positive
long-term persistent COVID-19 patients (LTPPs)
coagulation
title Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in Wuhan
title_full Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in Wuhan
title_fullStr Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in Wuhan
title_full_unstemmed Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in Wuhan
title_short Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in Wuhan
title_sort serum proteomic analysis for new types of long term persistent covid 19 patients in wuhan
topic COVID-19
SARS-CoV-2
retest positive
long-term persistent COVID-19 patients (LTPPs)
coagulation
url https://journals.asm.org/doi/10.1128/spectrum.01270-22
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