全球SARS-CoV-2再次感染率的Meta分析

马一瑞; 邓洁; 梁万年; 刘民; 刘珏

doi:10.16462/j.cnki.zhjbkz.2023.02.002

全球SARS-CoV-2再次感染率的Meta分析

doi: 10.16462/j.cnki.zhjbkz.2023.02.002

马一瑞¹,
邓洁¹,
梁万年²,
刘民^1, ,,
刘珏^1, ,

1.
100191 北京，北京大学公共卫生学院流行病与卫生统计学系
2.
100084 北京，清华大学万科公共卫生与健康学院，清华大学健康中国研究院

马一瑞和邓洁为共同第一作者

基金项目:

国家自然科学基金 72122001

国家自然科学基金 72211540398

国家自然科学基金 71934002

北京市自然科学基金-海淀原始创新联合基金 L222027

详细信息

通讯作者:
刘民，E-mail: liumin@bjmu.edu.cn

刘珏，E-mail: jueliu@bjmu.edu.cn

中图分类号: R183
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- 被引次数: 0
出版历程
- 收稿日期: 2022-12-30
- 修回日期: 2023-01-13
- 网络出版日期: 2023-02-20
- 刊出日期: 2023-02-10

Meta-analysis of SARS-CoV-2 reinfection rate in the world

MA Yi-rui¹,
DENG Jie¹,
LIANG Wan-nian²,
LIU Min^{1
, ,},
LIU Jue^{1
, ,}

1.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
2.
Vanke School of Public Health, Tsinghua University, Institute for Health China, Tsinghua University, Beijing 100084, China

MA Yi-rui and DENG Jie contributed equally to this article

Funds:

National Natural Science Foundation of China 72122001

National Natural Science Foundation of China 72211540398

National Natural Science Foundation of China 71934002

Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund L222027

More Information

Corresponding author: LIU Min, E-mail: liumin@bjmu.edu.cn; LIU Jue, E-mail: jueliu@bjmu.edu.cn

摘要

摘要: 目的系统评估SARS-CoV-2再次感染率，为减少SARS-CoV-2再次感染的发生提供循证依据。方法检索PubMed、Embase、Web of Science、中国知网和万方等电子数据库自建库至2022年12月11日与SARS-CoV-2再次感染相关的队列研究或病例对照研究，按照严格的纳入排除标准筛选文献、提取数据并进行质量评价，采用Stata 16.0统计软件进行统计分析。结果共纳入24篇文献，包含初次感染患者6 616 869例、再次感染者78 635例。初次感染者的再次感染率为2.06%(95% CI: 1.73%~2.40%)。相比于其他年龄组，40岁以上中年人的再次感染率更高，40~＜50岁人群为2.97%(95% CI: -1.20%~7.14%)，50~＜60岁人群为2.32%(95% CI: -0.74%~5.38%)。相比于接种新型冠状病毒疫苗(简称新冠疫苗)人群，未完全接种组的再次感染率为1.85%(95% CI: 1.63%~2.08%)，完全接种组的再次感染率为1.11%(95% CI: 0.34%~1.89%)，未接种疫苗人群的再次感染率更高为5.47%(95% CI: 1.99%~8.95%)。医护人员的再次感染率为6.02%(95% CI: 5.67%~6.37%)。结论 SARS-CoV-2存在再次感染的风险，但本研究结果表明再次感染的比例不高。建议科学认识SARS-CoV-2的再次感染风险，加强公众健康宣教，保持健康习惯，减少再次感染风险。
- 新型冠状病毒 /
- 再次感染 /
- Meta分析
Abstract: Objective We aimed to review the data available to explore prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection in the real world. Methods We searched observational cohort studies and case-control studies that described the SARS-CoV-2 reinfections in PubMed, Embase, Web of Science, CNKI and WanFang Data from inception to 11 Dec 2022. Studies, data extracted and quality assessed were selected according to strict inclusion exclusion criteria. All analyses were using Stata version 16.0. Results A total of 24 studies were included, involving 78 635 cases of SARS-CoV-2 reinfection and 6 616 869 cases of SARS-CoV-2 primary infection. In cases after the primary SARS-CoV-2 infection, the pooled prevalence of reinfection was 2.06% (95% CI: 1.73%-2.40%). Compared with other age groups, the secondary infection rate was higher in those aged 40- < 50 years 2.97% (95% CI: -1.20%-7.14%) and 50- < 60 years 2.32% (95% CI: -0.74%-5.38%). In vaccination status group, the pooled prevalence was 5.47% (95% CI: 1.99%-8.95%) in unvaccinated cases, 1.85% (95% CI: 1.63%-2.08%) for those received partial COVID-19 vaccination, and 1.11%(95% CI: 0.34%-1.89%) for those received fully vaccination. In addition, the pooled prevalence of SARS-CoV-2 reinfection was 6.02%(95% CI: 5.67%-6.37%) in the health care workers. Conclusions There is a risk of SARS-CoV-2 reinfection, but the results of this global real-world meta-analysis showed that the rate of reinfection is not high. It is recommended to scientifically understand the risk of SARS-CoV-2 reinfection, strengthen public health education, maintain healthy habits, and reduce the risk of SARS-CoV-2 reinfection.
- SARS-CoV-2 /
- Reinfection /
- Meta-analysis

HTML全文

图 1 文献筛选流程

Figure 1. Flowchart of the study selection

下载: 全尺寸图片幻灯片

图 2 不同年龄组合并再次感染率的森林图

Figure 2. Forest plot for the pooled prevalence of SARS-CoV-2 reinfection in difference age group

下载: 全尺寸图片幻灯片

图 3 不同新冠疫苗接种状态组合并再次感染率的森林图

Figure 3. Forest plot for the pooled prevalence of SARS-CoV-2 reinfection in difference vaccination status

下载: 全尺寸图片幻灯片

图 4 Egger’s检验漏斗图，评估发表偏倚

Figure 4. Egger's test funnel plot for the assessment of publication bias

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表 1 全球SARS-CoV-2再次感染率Meta分析结果

Table 1. Meta-analysis results of pool prevalence of SARS-CoV-2 reinfection in the world

分组	研究数量	再次感染人数/ 初次感染人数(n/N)	再次感染率(%)	95% CI值(%)	P值	I²(%)	P值(异质性)
再次感染率(%)	26	78 635/6 616 869	2.06	1.73~2.40	< 0.05	100.0	< 0.05
年龄(岁)
0~＜20	2	1 632/608 897	0.15	0.14~0.16	< 0.05
20~＜30	2	4 154/734 735	0.32	0.31~0.33	< 0.05
30~＜40	2	5 844/732 436	0.33	0.32~0.35	< 0.05
40~＜50	3	5 680/654 762	2.97	-1.20~7.14	>0.05	99.9	< 0.05
50~＜60	3	4 596/621 313	2.32	-0.74~5.38	>0.05	99.9	< 0.05
60~＜70	3	2 516/348 760	1.73	-0.32~3.77	>0.05	99.8	< 0.05
70~＜80	3	1 333/197 206	1.56	0.49~2.64	< 0.05	99.1	< 0.05
≥80	3	2 393/228 470	1.80	1.12~2.48	< 0.05	95.8	< 0.05
≥65	2	88/26 337	0.18	0.13~0.23	< 0.05		< 0.05
新冠疫苗接种情况
未接种	5	14 097/314 257	5.47	1.99~8.95	< 0.05	100.0	< 0.05
不完全接种	2	277/13 510	1.85	1.63~2.08	< 0.05
完全接种	5	603/123 452	1.11	0.34~1.89	< 0.05	98.7	< 0.05
职业
医护人员	2	1 628/16 825	6.02	5.67~6.37	< 0.05

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表 2 全球SARS-CoV-2再次感染率亚组分析

Table 2. Subgroup analysis of SARS-CoV-2 reinfection pool prevalence in the world

亚组	研究数量	再次感染人数/初次感染人数(n/N)	再次感染率(%)	95% CI值(%)	P值	I²(%)	P值(异质性)	比重(%)
初次感染和再次感染的时间间隔(d)
≥40	1	34/1 086	1.88	1.31~2.62	< 0.05			3.60
≥45	1	30/14 320	0.21	0.14~0.30	< 0.05			4.11
≥90	22	76 009/6 436 871	2.27	1.90~2.64	< 0.05			84.08
≥100	1	2 522/149 032	1.69	1.63~1.76	< 0.05			4.11
≥120	1	40/14 840	0.27	0.19~0.37	< 0.05			4.11
初次感染的SARS-CoV-2优势毒株
Wild type	4	5 100/107 288	5.74	3.92~7.56	< 0.05	100.0	< 0.05	13.85
Alpha and Beta	1	1 339/353 326	0.38	0.36~0.40	< 0.05			4.12
Alpha and Delta	2	16 303/4 548 472	0.36	0.35~0.36	< 0.05	100.0	< 0.05	8.23
Delta	2	2 997/427 841	0.60	0.58~0.62	< 0.05			8.22
再次感染的SARS-CoV-2优势毒株
Wild type, Alpha, and Delta	3	2 057/100 517	7.71	0.22~15.20	< 0.05			9.79
Alpha and Beta	1	1 339/353 326	0.38	0.36~0.40	< 0.05			4.12
Alpha and Delta	2	16 303/4 548 472	0.36	0.35~0.36	< 0.05			8.23
Delta	5	5 683/584 538	1.47	0.85~2.10	< 0.05	99.7	< 0.05	20.01
合计	26	78 635/6 616 869	2.06	1.73~2.40	< 0.05	100.0	< 0.05	100.00

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表 3 根据初次感染优势毒株对不同疫苗接种情况人群的全球SARS-CoV-2再次感染率的亚组分析结果

Table 3. Subgroup analysis of SARS-CoV-2 reinfection pool prevalence in cases with different vaccination status by the variant wave of reinfection

亚组	研究数量	再次感染人数/ 初次感染人数(n/N)	再次感染率(%)	95% CI值(%)	P值	I²(%)	P值(异质性)	比重(%)
未接种
Wild type, Alpha, and Delta	4	830/100 517	3.12	0.10~6.13	< 0.05	-	-	61.50
Delta	4	60/472	12.71	9.84~16.06	< 0.05	-	-	17.87
合计	5	14 097/314 257	5.47	1.99~8.95	< 0.05	100.0	< 0.05	100.00
完全接种
Wild type, Alpha, and Delta	4	261/100 517	0.85	0.05~1.65	< 0.05	-	-	61.30
Delta	4	17/1 089	1.56	0.91~2.50	< 0.05	-	-	17.75
合计	5	603/123 452	1.11	0.34~1.89	< 0.05	98.7	< 0.05	100.00

下载: 导出CSV

参考文献(42)

[1]	穆雪纯, 王凌航. 新型冠状病毒再感染的研究进展[J]. 中华医学杂志, 2022, 102(40): 3229-3232. DOI: 10.3760/cma.j.cn112137-20220709-01517. Mu XC, Wang LH. Research progress of novel coronavirus reinfection[J]. Chin Med J, 2022, 102(40): 3229-3232. DOI: 10.3760/cma.j.cn112137-20220709-01517.
[2]	To KKW, Hung IFN, Ip JD, et al. Coronavirus Disease 2019 (COVID-19) Re-infection by a Phylogenetically Distinct Severe Acute Respiratory Syndrome Coronavirus 2 Strain Confirmed by Whole Genome Sequencing[J]. Clin Infect Dis, 2021, 73(9): e2946-e2951. DOI: 10.1093/cid/ciaa1275.
[3]	Flacco ME, Acuti Martellucci C, Baccolini V, et al. Risk of reinfection and disease after SARS-CoV-2 primary infection: Meta-analysis[J]. Eur J Clin Invest, 2022, 52(10): e13845. DOI: 10.1111/eci.13845.
[4]	Mensah AA, Lacy J, Stowe J, et al. Disease severity during SARS-COV-2 reinfection: a nationwide study[J]. J Infect, 2022, 84(4): 542-550. DOI: 10.1016/j.jinf.2022.01.012.
[5]	Abu-Raddad LJ, Chemaitelly H, Malek JA, et al. Assessment of the Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection in an Intense Reexposure Setting[J]. Clin Infect Dis, 2021, 73(7): e1830-e1840. DOI: 10.1093/cid/ciaa1846.
[6]	Vitale J, Mumoli N, Clerici P, et al. Assessment of SARS-CoV-2 Reinfection 1 Year After Primary Infection in a Population in Lombardy, Italy[J]. JAMA Intern Med, 2021, 181(10): 1407-1408. DOI: 10.1001/jamainternmed.2021.2959.
[7]	Chen JH, Wang R, Gilby NB, et al. Omicron Variant (B. 1.1.529): Infectivity, Vaccine Breakthrough, and Antibody Resistance[J]. J Chem Inf Model, 2022, 62(2): 412-422. DOI: 10.1021/acs.jcim.1c01451.
[8]	Pulliam JRC, van Schalkwyk C, Govender N, et al. Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa[J]. Science, 2022, 376(6593): eabn4947. DOI: 10.1126/science.abn4947.
[9]	Eythorsson E, Runolfsdottir HL, Ingvarsson RF, et al. Rate of SARS-CoV-2 Reinfection During an Omicron Wave in Iceland[J]. JAMA Netw Open, 2022, 5(8): e2225320. DOI: 10.1001/jamanetworkopen.2022.25320.
[10]	Altarawneh HN, Chemaitelly H, Hasan MR, et al. Protection against the Omicron Variant from Previous SARS-CoV-2 Infection[J]. N Engl J Med, 2022, 386(13): 1288-1290. DOI: 10.1056/NEJMc2200133.
[11]	中国政府网. 国务院联防联控机制新闻发布会[EB/OL]. (2022-12-20)[2022-12-30]. http://www.gov.cn/xinwen/gwylflkjz223/index.htm. China Government website. Press conference of The State Council Joint Prevention and control Mechanism[EB/OL]. (2022-12-20)[2022-12-30]. http://www.gov.cn/xinwen/gwylflkjz223/index.htm.
[12]	国家卫生健康委员会. 关于印发对新型冠状病毒感染实施"乙类乙管"总体方案的通知[EB/OL]. (2022-12-26)[2022-12-30]. http://www.nhc.gov.cn/xcs/zhengcwj/202212/e97e4c449d7a475794624b8ea12123c6.shtml. National Health Commission. Notice on the issuance of the "Class B, Tube B" General Plan for the implementation of novel coronavirus infection[EB/OL]. (2022-12-26)[2022-12-30]. http://www.nhc.gov.cn/xcs/zhengcwj/202212/e97e4c449d7a475794624b8ea12123c6.shtml.
[13]	Bowe B, Xie Y, Al-Aly Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection[J]. Nat Med, 2022, 28(11): 2398-2405. DOI: 10.1038/s41591-022-02051-3.
[14]	Lewis N, Chambers LC, Chu HT, et al. Effectiveness associated with vaccination after COVID-19 recovery in preventing reinfection[J]. JAMA Netw Open, 2022, 5(7): e2223917. DOI: 10.1001/jamanetworkopen.2022.23917.
[15]	Vitale J, Mumoli N, Clerici P, et al. Assessment of SARS-CoV-2 reinfection 1 year after primary infection in a population in lombardy, Italy[J]. JAMA Intern Med, 2021, 181(10): 1407-1408. DOI: 10.1001/jamainternmed.2021.2959.
[16]	Vnsal O, Yazici O, Özdemir N, et al. Clinical and laboratory outcomes of the solid cancer patients reinfected with SARS-CoV-2[J]. Future oncol, 2022, 18(5): 533-541. DOI: 10.2217/fon-2021-0621.
[17]	Brouqui P, Colson P, Melenotte C, et al. COVID-19 re-infection[J]. Eur J Clin Investigation, 2021, 51(5): e13537. DOI: 10.1111/eci.13537.
[18]	Kim P, Gordon SM, Sheehan MM, et al. Duration of Severe Acute Respiratory Syndrome Coronavirus 2 Natural Immunity and Protection Against the Delta Variant: A Retrospective Cohort Study[J]. Clin Infect Dis, 2022, 75(1): e185-e190. DOI: 10.1093/cid/ciab999.
[19]	Hammerman A, Sergienko R, Friger M, et al. Effectiveness of the BNT162b2 Vaccine after Recovery from Covid-19[J]. N Engl J Med, 2022, 386(13): 1221-1229. DOI: 10.1056/NEJMoa2119497.
[20]	Yuguero O, Companys M, Guzmán M, et al. Epidemiological and clinical characteristics of SARS-CoV-2 reinfections in a Spanish region[J]. SAGE Open Med, 2022, 10: 20503121221108556. DOI: 10.1177/20503121221108556.
[21]	Alhaddad F, Abdulkareem A, Alsharrah D, et al. Incidence of SARS-CoV-2 reinfection in a paediatric cohort in Kuwait[J]. BMJ Open, 2022, 12(6): e056371. DOI: 10.1136/bmjopen-2021-056371.
[22]	Gazit S, Shlezinger R, Perez G, et al. The incidence of SARS-CoV-2 reinfection in persons with naturally acquired immunity with and without subsequent receipt of a single dose of BNT162b2 vaccine : a retrospective cohort study[J]. Ann Intern Med, 2022, 175(5): 674-681. DOI: 10.7326/m21-4130.
[23]	Suljič A, Sočan M, Mrzel M, et al. Milder outcomes of SARS-CoV-2 genetically confirmed reinfections compared to primary infections with the delta variant: A retrospective case-control study[J]. Front Med(Lausanne), 2022, 9: 962653. DOI: 10.3389/fmed.2022.962653.
[24]	Cortellini A, Aguilar-Company J, Salazar R, et al. Natural immunity to SARS-CoV-2 and breakthrough infections in vaccinated and unvaccinated patients with cancer[J]. Br J Cancer, 2022, 127(10): 1787-1792. DOI: 10.1038/s41416-022-01952-x.
[25]	Spicer KB, Glick C, Cavanaugh AM, et al. Protective Immunity after Natural Infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) - Kentucky, USA, 2020[J]. Int J Infect Dis, 2022, 114: 21-28. DOI: 10.1016/j.ijid.2021.10.010.
[26]	Flacco ME, Acuti Martellucci C, Soldato G, et al. Rate of reinfections after SARS-CoV-2 primary infection in the population of an Italian province: a cohort study[J]. J Public Health (Oxf), 2022, 44(4): e475-e478. DOI: 10.1093/pubmed/fdab346.
[27]	Arslan Y, Akgul F, Sevim B, et al. Re-infection in COVID-19: Do we exaggerate our worries?[J]. Eur J Investigation, 2022, 52(6): e13767. DOI: 10.1111/eci.13767.
[28]	Sheehan MM, Reddy AJ, Rothberg MB. Reinfection rates among patients who previously tested positive for Coronavirus Disease 2019: A retrospective cohort study[J]. Clin Infect Dis, 2021, 73(10): 1882-1886. DOI: 10.1093/cid/ciab234.
[29]	Armstrong JN, Campbell L, Rabatsky-Her T, et al. Repeat positive SARS-CoV-2 RNA testing in nursing home residents during the initial 9 months of the COVID-19 pandemic: an observational retrospective analysis[J]. Lancet Reg Health Am, 2021, 3: 100054. DOI: 10.1016/j.lana.2021.100054.
[30]	Barzegar M, Manteghinejad A, Bagherieh S, et al. Risk and severity of SARS-CoV-2 reinfection among patients with multiple sclerosis vs. the general population: a population-based study[J]. BMC Neurol, 2022, 22(1): 379. DOI: 10.1186/s12883-022-02907-8.
[31]	Medić S, Anastassopoulou C, Lozanov-Crvenković Z, et al. Risk and severity of SARS-CoV-2 reinfections during 2020-2022 in Vojvodina, Serbia: A population-level observational study[J]. Lancet Reg Health Eur, 2022, 20: 100453. DOI: 10.1016/j.lanepe.2022.100453.
[32]	Mensah AA, Campbell H, Stowe J, et al. Risk of SARS-CoV-2 reinfections in children: a prospective national surveillance study between January, 2020, and July, 2021, in England[J]. Lancet Child Adolesc Health, 2022, 6(6): 384-392. DOI: 10.1016/s2352-4642(22)00059-1.
[33]	Pilz S, Chakeri A, Ioannidis JP, et al. SARS-CoV-2 re-infection risk in Austria[J]. Eur J Clin Invest, 2021, 51(4): e13520. DOI: 10.1111/eci.13520.
[34]	Malhotra S, Mani K, Lodha R, et al. SARS-CoV-2 Reinfection Rate and Estimated Effectiveness of the Inactivated Whole Virion Vaccine BBV152 Against Reinfection Among Health Care Workers in New Delhi, India[J]. JAMA Netw Open, 2022, 5(1): e2142210. DOI: 10.1001/jamanetworkopen.2021.42210.
[35]	Abu-Raddad LJ, Chemaitelly H, Bertollini R. Severity of SARS-CoV-2 Reinfections as Compared with Primary Infections[J]. N Engl J Med, 2021, 385(26): 2487-2489. DOI: 10.1056/NEJMc2108120.
[36]	Beyzarov E, Chen Y, Caubel P. Reporting of COVID-19 reinfection and potential role of immunosuppressant/immunomodulating agents: a cross-sectional observational analysis based on a spontaneous reporting database[J]. Clin Drug Investig, 2022, 42(10): 807-812. DOI: 10.1007/s40261-022-01200-3.
[37]	Rivelli A, Fitzpatrick V, Blair C, et al. Incidence of COVID-19 reinfection among Midwestern healthcare employees[J]. PLoS One, 2022, 17(1): e0262164. DOI: 10.1371/journal.pone.0262164.
[38]	Lacy J, Mensah A, Simmons R, et al. Protective effect of a first SARS-CoV-2 infection from reinfection: a matched retrospective cohort study using PCR testing data in England[J]. Epidemiol Infect, 2022, 150: e109. DOI: 10.1017/s0950268822000966.
[39]	Hall VJ, Foulkes S, Charlett A, et al. SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN)[J]. Lancet, 2021, 397(10283): 1459-1469. DOI: 10.1016/s0140-6736(21)00675-9.
[40]	Elene Flacco M, Soldato G, Acuti Martellucci C, et al. Risk of SARS-CoV-2 Reinfection 18 Months After Primary Infection: Population-Level Observational Study[J]. Front Public Health, 2022, 10: 884121. DOI: 10.3389/fpubh.2022.884121.
[41]	Nguyen NN, Houhamdi L, Hoang VT, et al. High rate of reinfection with the SARS-CoV-2 Omicron variant[J]. J Infect, 2022, 85(2): 174-211. DOI: 10.1016/j.jinf.2022.04.034.
[42]	Altarawneh HN, Chemaitelly H, Ayoub HH, et al. Protective Effect of Previous SARS-CoV-2 Infection against Omicron BA. 4 and BA. 5 Subvariants[J]. N Engl J Med, 2022, 387(17): 1620-1622. DOI: 10.1056/NEJMc2209306.