死亡率
主要死亡原因为急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS)引发的呼吸衰竭。[1035]Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080116
http://www.ncbi.nlm.nih.gov/pubmed/32125452?tool=bestpractice.com
COVID-19 患者 ARDS 导致的总体死亡率为 39%;但是,各个国家之间有显著差异(例如中国为 69%,伊朗为 28%,法国为 19%,德国为 13%)。[1036]Hasan SS, Capstick T, Ahmed R, et al. Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis. Expert Rev Respir Med. 2020 Nov;14(11):1149-63.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544968
http://www.ncbi.nlm.nih.gov/pubmed/32734777?tool=bestpractice.com
无证据表明,与普通 ARDS 人群相比,COVID-19 相关性 ARDS 患者预后更差(即呼吸机脱机天数、重症监护病房住院时长或医院住院时长,以及死亡)。[1037]Dmytriw AA, Chibbar R, Chen PPY, et al. Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis. Expert Rev Respir Med. 2021 Apr 21 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/33882768?tool=bestpractice.com
呼吸衰竭危险因素包括年龄、性别为男性、心血管疾病,实验室指标(例如乳酸脱氢酶、淋巴细胞计数和 C-反应蛋白),以及入院时病毒载量过高。[1038]de la Calle C, Lalueza A, Mancheño-Losa M, et al. Impact of viral load at admission on the development of respiratory failure in hospitalized patients with SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis. 2021 Jun;40(6):1209-16.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787698
http://www.ncbi.nlm.nih.gov/pubmed/33409832?tool=bestpractice.com
其他常见的死亡原因包括脓毒症或脓毒性休克、脓毒症相关性多器官衰竭、细菌或病毒混合感染、静脉血栓栓塞和心力衰竭。[1039]Elezkurtaj S, Greuel S, Ihlow J, et al. Causes of death and comorbidities in hospitalized patients with COVID-19. Sci Rep. 2021 Feb 19;11(1):4263.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895917
http://www.ncbi.nlm.nih.gov/pubmed/33608563?tool=bestpractice.com
死亡率取决于年龄和存在的基础疾病。
对于 <65 岁的人群,即使在大流行震中,死亡风险也很小,而对于 <65 岁且无任何基础疾病的人群,死亡率极低。[1040]Ioannidis JPA, Axfors C, Contopoulos-Ioannidis DG. Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters. Environ Res. 2020 Sep;188:109890.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327471
http://www.ncbi.nlm.nih.gov/pubmed/32846654?tool=bestpractice.com
儿童和年轻人死亡较为少见。一项系统评价和荟萃分析发现,基于社区研究,3.3% 的儿童接受住院治疗,0.3% 的儿童被收入重症监护病房治疗,0.02% 的儿童死亡;而基于医院筛查研究,对应比例分别为 23.9%、2.9% 和 0.2%)。[1041]Sumner MW, Kanngiesser A, Lotfali-Khani K, et al. Severe outcomes associated with SARS-CoV-2 infection in children: a systematic review and meta-analysis. Front Pediatr. 2022 Jun 9;10:916655.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218576
http://www.ncbi.nlm.nih.gov/pubmed/35757137?tool=bestpractice.com
一项美国队列研究显示,约 99% COVID-19 死亡患者至少存在一种基础疾病。死亡的最强风险因素为肥胖、焦虑和恐惧相关疾病、糖尿病以及基础疾病种类总数。[154]Kompaniyets L, Pennington AF, Goodman AB, et al. Underlying medical conditions and severe illness among 540,667 adults hospitalized with COVID-19, March 2020 – March 2021. Prev Chronic Dis. 2021 Jul 1;18:E66.
https://www.cdc.gov/pcd/issues/2021/21_0123.htm
http://www.ncbi.nlm.nih.gov/pubmed/34197283?tool=bestpractice.com
已故患者中 3 种最常见的合并症为高血压、糖尿病和呼吸系统疾病。[1042]Justino DCP, Silva DFO, Costa KTDS, et al. Prevalence of comorbidities in deceased patients with COVID-19: a systematic review. Medicine (Baltimore). 2022 Sep 23;101(38):e30246.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508958
http://www.ncbi.nlm.nih.gov/pubmed/36197209?tool=bestpractice.com
危重患者死亡率很高。
2020 年,全球重症监护病房全因死亡率为 35%,危重患者住院死亡率为 32%。然而,死亡率因地区而异。例如,死亡率在东南亚高达 48%,在美国则低至 15%。[1043]Qian Z, Lu S, Luo X, et al. Mortality and clinical interventions in critically ill patient with coronavirus disease 2019: a systematic review and meta-analysis. Front Med (Lausanne). 2021 Jul 23;8:635560.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342953
http://www.ncbi.nlm.nih.gov/pubmed/34368175?tool=bestpractice.com
尽管患者特征稳定,但死亡率却随时间下降。
在一项对 80,000 多名患者进行的英国队列研究中,2020 年 3 月至 2020 年 8 月期间,住院死亡率从 32.3% 降至 16.4%。所有年龄组、所有种族、男性和女性以及伴或不伴合并症的患者,死亡率均呈现下降,其超出了疾病严重程度对死亡率下降的贡献。[1044]Docherty AB, Mulholland RH, Lone NI, et al. Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK. Lancet Respir Med. 2021 Jul;9(7):773-85.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121531
http://www.ncbi.nlm.nih.gov/pubmed/34000238?tool=bestpractice.com
英国第一波疫情早期,调整后的院内死亡率有所下降,第二波大流行期间,其基本保持不变。[1045]Gray WK, Navaratnam AV, Day J, et al. COVID-19 hospital activity and in-hospital mortality during the first and second waves of the pandemic in England: an observational study. Thorax. 2021 Nov 24 [Epub ahead of print].
https://thorax.bmj.com/content/early/2021/11/23/thoraxjnl-2021-218025
http://www.ncbi.nlm.nih.gov/pubmed/34819384?tool=bestpractice.com
大流行前 6 个月,美国死亡率急剧下降。[1046]Asch DA, Sheils NE, Islam MN, et al. Variation in US hospital mortality rates for patients admitted with COVID-19 during the first 6 months of the pandemic. JAMA Intern Med. 2021 Apr 1;181(4):471-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756246
http://www.ncbi.nlm.nih.gov/pubmed/33351068?tool=bestpractice.com
[1047]Nguyen NT, Chinn J, Nahmias J, et al. Outcomes and mortality among adults hospitalized with COVID-19 at US medical centers. JAMA Netw Open. 2021 Mar 1;4(3):e210417.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777028
http://www.ncbi.nlm.nih.gov/pubmed/33666657?tool=bestpractice.com
在一项对美国 209 家急诊医院 500,000 多名患者进行的队列研究中,自 2020 年 3 月至 2020 年 11 月,住院死亡率从 10.6% 降至 9.3%。[1048]Finelli L, Gupta V, Petigara T, et al. Mortality among US patients hospitalized with SARS-CoV-2 infection in 2020. JAMA Netw Open. 2021 Apr 1;4(4):e216556.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2778237
http://www.ncbi.nlm.nih.gov/pubmed/33830226?tool=bestpractice.com
美国某一教育研究型卫生系统收入重症监护病房危重患者中,研究期间死亡率从 43.5% 下降至 19.2%。[1049]Anesi GL, Jablonski J, Harhay MO, et al. Characteristics, outcomes, and trends of patients with COVID-19-related critical illness at a learning health system in the United States. Ann Intern Med. 2021 May;174(5):613-21.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901669
http://www.ncbi.nlm.nih.gov/pubmed/33460330?tool=bestpractice.com
这可能反映出医院策略和临床处理变化的影响,随着时间进展,危重患者对于诸如使用皮质类固醇、给予高流量鼻套管吸氧从而避免气管插管、俯卧位通气以及减少使用机械通气等循证标准诊疗具有更佳的依从性。需行进一步研究证实此类结果,并研究因果机制。
感染死亡率(infection fatality rate, IFR)
定义为所有感染个体(包括确诊病例、未诊断病例 [例如无症状或轻症病例])以及未报告病例中的死亡比例。与病死率相比,IFR 可以更准确的描述疾病致死性。
据估计,截至 2021 年 2 月,全球大约出现了 1.5 至 2 亿例感染,总体 IFR 为 0.15%。IFR 和感染分布在各大洲、国家和地区之间存在显著差异。[1050]Ioannidis JPA. Reconciling estimates of global spread and infection fatality rates of COVID-19: an overview of systematic evaluations. Eur J Clin Invest. 2021 Mar 26:e13554.
https://onlinelibrary.wiley.com/doi/10.1111/eci.13554
http://www.ncbi.nlm.nih.gov/pubmed/33768536?tool=bestpractice.com
预印本(未进行同行评议)数据表明,≥70 岁社区居民的中位 IFR 为 2.9%(≥70 岁人群为 4.9%),但更年轻人群则更低(在 0-19 岁、20-29 岁、30-39 岁、40-49 岁、50-59 岁和 60-69 岁时,中位数分别为 0.0013%、0.0088 %、0.021%、0.042%、0.14% 和 0.65%)。[1051]Axfors C, Ioannidis JPA. Infection fatality rate of COVID-19 in community-dwelling populations with emphasis on the elderly: an overview [preprint]. 2021 [internet publication].
https://www.medrxiv.org/content/10.1101/2021.07.08.21260210v2
美国疾病预防控制中心目前根据年龄对 IFR 的最佳估值为:[1052]Centers for Disease Control and Prevention. COVID-19 pandemic planning scenarios. 2021 [internet publication].
https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html
0 至 17 岁 – 0.002%
18 至 49 岁 – 0.05%
50 至 64 岁 – 0.6%
≥65 岁 – 9%.
根据这些数据,对于 <65 岁人群,整体 IFR 约为 0.2%。
钻石公主号游轮登船者中 IFR 为 0.85%,这是可对被隔离人群 IFR 进行准确评估的独特情况。但是,所有死亡都发生于 >70 岁患者,年轻、健康人群死亡率远远更低。[1053]Rajgor DD, Lee MH, Archuleta S, et al. The many estimates of the COVID-19 case fatality rate. Lancet Infect Dis. 2020 Jul;20(7):776-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270047
http://www.ncbi.nlm.nih.gov/pubmed/32224313?tool=bestpractice.com
此类评估具有局限性,并且随着大流行过程中出现更多数据(特别是在严重急性呼吸综合征冠状病毒 2 [severe acute respiratory syndrome coronavirus 2, SARS-CoV-2] 变体持续出现的背景下),数值可能发生变化。
病死率(case fatality rate, CFR)
定义为报告的总死亡数除以报告的检出病例总数。CFR 受选择偏倚的影响,因为更严重/住院病例更有可能接受检测。CFR 是随时间、人口、社会经济因素和疏缓措施而变化的动态估值。[1054]Ghayda RA, Lee KH, Han YJ, et al. Global case fatality rate of coronavirus disease 2019 (COVID-19) by continents and national income: a meta-analysis. J Med Virol. 2022 Jan 31 [Epub ahead of print].
https://onlinelibrary.wiley.com/doi/10.1002/jmv.27610
http://www.ncbi.nlm.nih.gov/pubmed/35099819?tool=bestpractice.com
世界卫生组织目前对全球 CFR 估值为 1%(截至 2022 年 10 月 2 日)。[22]World Health Organization. Coronavirus disease (COVID-19) weekly epidemiological updates. 2021 [internet publication].
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
各个国家/地区之间 CFR 差异相当显著。 一项系统评价和荟萃分析中,普通人群总体 CFR 为 1%。[1055]Alimohamadi Y, Tola HH, Abbasi-Ghahramanloo A, et al. Case fatality rate of COVID-19: a systematic review and meta-analysis. J Prev Med Hyg. 2021 Jun;62(2):E311-20.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451339
http://www.ncbi.nlm.nih.gov/pubmed/34604571?tool=bestpractice.com
这远低于报告的严重急性呼吸综合征(severe acute respiratory syndrome, SARS) CFR(10%)以及中东呼吸综合征(Middle East respiratory syndrome, MERS) CFR(37%)。[35]Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/31986264?tool=bestpractice.com
CFR 随年龄增长而升高。
在美国,大多数死亡患者年龄 ≥65 岁。≥85 岁患者 CFR 最高(10% 至 27%),其次为 65 至 84 岁(3% 至 11%),然后是 55 至 64 岁(1% 至 3%),最后是 20 至 54 岁(<1%)。[132]CDC COVID-19 Response Team. Severe outcomes among patients with coronavirus disease 2019 (COVID-19): United States, February 12 - March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343-6.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm?s_cid=mm6912e2_w
http://www.ncbi.nlm.nih.gov/pubmed/32214079?tool=bestpractice.com
在中国,大多数死亡患者年龄 ≥60 岁。[1056]Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 17;41(2):145-51.
http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51
http://www.ncbi.nlm.nih.gov/pubmed/32064853?tool=bestpractice.com
≥80 岁患者 CFR 最高(13.4%),其次是 60 至 79 岁(6.4%),然后是 <60 岁(0.32%)。[1057]Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020 Jun;20(6):669-77.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158570
http://www.ncbi.nlm.nih.gov/pubmed/32240634?tool=bestpractice.com
在意大利,≥80 岁患者 CFR 最高(52.5%),其次是 70 至 79 岁(35.5%),然后是 60 至 69 岁(8.5%)。[1058]Sorbello M, El-Boghdadly K, Di Giacinto I, et al. The Italian COVID-19 outbreak: experiences and recommendations from clinical practice. Anaesthesia. 2020 Jun;75(6):724-32.
https://onlinelibrary.wiley.com/doi/full/10.1111/anae.15049
http://www.ncbi.nlm.nih.gov/pubmed/32221973?tool=bestpractice.com
儿童极少出现死亡。[27]Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 2020 Sep 1;174(9):882-9.
https://jamanetwork.com/journals/jamapediatrics/fullarticle/2765169
http://www.ncbi.nlm.nih.gov/pubmed/32320004?tool=bestpractice.com
[132]CDC COVID-19 Response Team. Severe outcomes among patients with coronavirus disease 2019 (COVID-19): United States, February 12 - March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343-6.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm?s_cid=mm6912e2_w
http://www.ncbi.nlm.nih.gov/pubmed/32214079?tool=bestpractice.com
在一项研究中,70% 的死亡病例处于 10-20 岁这一年龄段,20% 处于 1-9 岁年龄段,10% 处于 1 岁以下年龄段。[1059]Bixler D, Miller AD, Mattison CP, et al. SARS-CoV-2–associated deaths among persons aged <21 years: United States, February 12–July 31, 2020. MMWR Morb Mortal Wkly Rep. 2020 Sep 18;69(37):1324-9.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6937e4.htm
http://www.ncbi.nlm.nih.gov/pubmed/32941417?tool=bestpractice.com
CFR 随合并症存在而升高。
CFR 随病情严重程度增加而升高。
住院患者总体 CFR 为 13%。[1055]Alimohamadi Y, Tola HH, Abbasi-Ghahramanloo A, et al. Case fatality rate of COVID-19: a systematic review and meta-analysis. J Prev Med Hyg. 2021 Jun;62(2):E311-20.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451339
http://www.ncbi.nlm.nih.gov/pubmed/34604571?tool=bestpractice.com
危重症患者 CFR 最高,研究显示此类患者 CFR 为 26%-67%。[1056]Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 17;41(2):145-51.
http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51
http://www.ncbi.nlm.nih.gov/pubmed/32064853?tool=bestpractice.com
[1060]Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 6;323(16):1574-81.
https://jamanetwork.com/journals/jama/fullarticle/2764365
http://www.ncbi.nlm.nih.gov/pubmed/32250385?tool=bestpractice.com
[1061]Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020 Mar 19;323(16):1612-4.
https://jamanetwork.com/journals/jama/fullarticle/2763485
http://www.ncbi.nlm.nih.gov/pubmed/32191259?tool=bestpractice.com
IFR/CFR 局限性
在大流行早期阶段 IFR 和 CFR 估值存在很大的不确定性,并且随着更多数据出现,估值可能会发生变化。这些比率在大流行开始时往往很高,随着获得数据越来越多,呈下降趋势。[1062]Centre for Evidence-Based Medicine; Oke J, Heneghan C. Global COVID-19 case fatality rates. 2020 [internet publication].
https://www.cebm.net/global-covid-19-case-fatality-rates
确诊病例当前没有固定的病例定义,且病例定义各不相同。聚合酶链反应(polymerase chain reaction, PCR)阳性结果有时是识别病例的唯一标准;然而,PCR 检测结果阳性不一定等同于确诊患有 COVID-19,也不意味着某人受到了感染或具有传染性。[1063]Mahase E. Covid-19: the problems with case counting. BMJ. 2020 Sep 3;370:m3374.
https://www.bmj.com/content/370/bmj.m3374
http://www.ncbi.nlm.nih.gov/pubmed/32883657?tool=bestpractice.com
[1064]Centre for Evidence-Based Medicine; Spencer E, Jefferson T, Brassey J, et al. When is Covid, Covid? 2020 [internet publication].
https://www.cebm.net/covid-19/when-is-covid-covid
由于存在与死亡报道相关的延误,在特定日期报道的死亡例数,可能无法准确反映前一天的死亡例数。因此很难知道死亡例数是否会在短期内随时间而下降。[1065]Centre for Evidence-Based Medicine; Oke J, Heneghan C. Reconciling COVID-19 death data in the UK. 2020 [internet publication].
https://www.cebm.net/covid-19/reconciling-covid-19-death-data-in-the-uk
在某些国家/地区,“患”COVID-19 而后死亡的患者和“死于”COVID-19 的患者可能均计入死亡人数。例如,在意大利,只有 12% 的死亡证明报告了与 COVID-19 的直接因果关系,而 88% 的死亡患者至少有一种合并症。[1062]Centre for Evidence-Based Medicine; Oke J, Heneghan C. Global COVID-19 case fatality rates. 2020 [internet publication].
https://www.cebm.net/global-covid-19-case-fatality-rates
[1066]Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020 May 12;323(18):1775-6.
https://jamanetwork.com/journals/jama/fullarticle/2763667
http://www.ncbi.nlm.nih.gov/pubmed/32203977?tool=bestpractice.com
预后因素
与重症、收住入院或重症监护病房收治、不良结局和死亡风险增加相关的预后因素包括:[1067]Izcovich A, Ragusa MA, Tortosa F, et al. Prognostic factors for severity and mortality in patients infected with COVID-19: a systematic review. PLoS One. 2020;15(11):e0241955.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671522
http://www.ncbi.nlm.nih.gov/pubmed/33201896?tool=bestpractice.com
[1068]Booth A, Reed AB, Ponzo S, et al. Population risk factors for severe disease and mortality in COVID-19: a global systematic review and meta-analysis. PLoS One. 2021 Mar 4;16(3):e0247461.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247461
http://www.ncbi.nlm.nih.gov/pubmed/33661992?tool=bestpractice.com
[1069]Zhang L, Hou J, Ma FZ, et al. The common risk factors for progression and mortality in COVID-19 patients: a meta-analysis. Arch Virol. 2021 Aug;166(8):2071-87.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017903
http://www.ncbi.nlm.nih.gov/pubmed/33797621?tool=bestpractice.com
[1070]Dumitrascu F, Branje KE, Hladkowicz ES, et al. Association of frailty with outcomes in individuals with COVID-19: a living review and meta-analysis. J Am Geriatr Soc. 2021 Sep;69(9):2419-29.
https://agsjournals.onlinelibrary.wiley.com/doi/epdf/10.1111/jgs.17299
http://www.ncbi.nlm.nih.gov/pubmed/34048599?tool=bestpractice.com
[1071]Bellou V, Tzoulaki I, van Smeden M, et al. Prognostic factors for adverse outcomes in patients with COVID-19: a field-wide systematic review and meta-analysis. Eur Respir J. 2021 Jun 25 [Epub ahead of print].
https://erj.ersjournals.com/content/early/2021/06/10/13993003.02964-2020
http://www.ncbi.nlm.nih.gov/pubmed/34172467?tool=bestpractice.com
[1072]Santus P, Radovanovic D, Saderi L, et al. Severity of respiratory failure at admission and in-hospital mortality in patients with COVID-19: a prospective observational multicentre study. BMJ Open. 2020 Oct 10;10(10):e043651.
https://bmjopen.bmj.com/content/10/10/e043651
http://www.ncbi.nlm.nih.gov/pubmed/33040020?tool=bestpractice.com
[1073]Shi C, Wang L, Ye J, et al. Predictors of mortality in patients with coronavirus disease 2019: a systematic review and meta-analysis. BMC Infect Dis. 2021 Jul 8;21(1):663.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264491
http://www.ncbi.nlm.nih.gov/pubmed/34238232?tool=bestpractice.com
患者因素
合并症的发生
症状/征象
肌痛
咽痛
痰液产生
畏寒
恶心
呼吸困难
胸闷
头晕
头痛
咯血
呼吸急促
低氧血症
呼吸衰竭
低血压
心动过速
并发症
休克
急性感染或脓毒症
急性肾、肝或心脏损伤
急性呼吸窘迫综合征
静脉血栓栓塞
心律失常
心衰
检查
死亡患者中最常见基础疾病为高血压、糖尿病和心血管疾病。[1074]Javanmardi F, Keshavarzi A, Akbari A, et al. Prevalence of underlying diseases in died cases of COVID-19: a systematic review and meta-analysis. PLoS One. 2020 Oct 23;15(10):e0241265.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584167
http://www.ncbi.nlm.nih.gov/pubmed/33095835?tool=bestpractice.com
在儿童和青少年中,先天性心脏病、慢性肺病、神经系统疾病、肥胖、多系统炎症综合征、呼吸短促、急性呼吸窘迫综合征、急性肾损伤、胃肠道症状以及 C 反应蛋白和 D-二聚体升高与不良预后具有相关性。[1075]Shi Q, Wang Z, Liu J, et al. Risk factors for poor prognosis in children and adolescents with COVID-19: a systematic review and meta-analysis. EClinicalMedicine. 2021 Nov;41:101155.
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00435-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34693233?tool=bestpractice.com
再次入院
基于极低质量证据,大约 10% 的康复患者在出院后第一年内需再次入院。多数再入院发生于出院后 30 天内。具有基础疾病的患者据报道再入院率较高,但当前证据存在冲突,并且来自于证据水平较低的研究。与发展中国家相比,发达国家报道的再入院率亦较高,原因可能在于发达国家提供的医疗服务更好,医疗福利更高。康复患者出院后 1 年内全因死亡率为 7.87%。[1076]Ramzi ZS. Hospital readmissions and post-discharge all-cause mortality in COVID-19 recovered patients: a systematic review and meta-analysis. Am J Emerg Med. 2022 Jan;51:267-79.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570797
http://www.ncbi.nlm.nih.gov/pubmed/34781153?tool=bestpractice.com
据报道,免疫功能低下者可出现持续性感染。[1077]Choi B, Choudhary MC, Regan J, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med. 2020 Dec 3;383(23):2291-3.
https://www.nejm.org/doi/full/10.1056/NEJMc2031364
http://www.ncbi.nlm.nih.gov/pubmed/33176080?tool=bestpractice.com
初次感染而未入院的患者,发生严重急性后并发症的风险似乎较低。然而,与 SARS-CoV-2 检测呈阴性者相比,他们发生静脉血栓栓塞、呼吸困难和起始支气管扩张剂或曲坦类药物治疗的风险可能略有升高。与检测结果呈阴性患者相比,此类患者在初次感染后更常至全科医生和门诊医疗诊所就诊,提示持续性症状不致给予特定药物治疗或收治入院。[1078]Lund LC, Hallas J, Nielsen H, et al. Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study. Lancet Infect Dis. 2021 May 10 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110209
http://www.ncbi.nlm.nih.gov/pubmed/33984263?tool=bestpractice.com
再感染
再感染是指既往确诊感染之后的新发感染(即严重急性呼吸系统综合征冠状病毒 2 [severe acute respiratory syndrome coronavirus 2, SARS-CoV-2]实时逆转录聚合酶链反应[reverse transcription polymerase chain reaction, RT-PCR]呈阳性),与持续感染和感染复发有所不同。目前尚无 SARS-CoV-2 再感染标准病例定义。[1079]Public Health England. COVID-19: investigation and management of suspected SARS-CoV-2 reinfections. 2021 [internet publication].
https://www.gov.uk/government/publications/covid-19-investigation-and-management-of-suspected-sars-cov-2-reinfections
关于再次感染的信息还很有限。
研究表明康复后 1-60 天的患者出现 RT-PCR 再次阳性的概率为 7%-23%,总再次阳性率估计为 12%。[1080]Mattiuzzi C, Henry BM, Sanchis-Gomar F, et al. SARS-CoV-2 recurrent RNA positivity after recovering from coronavirus disease 2019 (COVID-19): a meta-analysis. Acta Biomed. 2020 Sep 7;91(3):e2020014.
https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/10303
http://www.ncbi.nlm.nih.gov/pubmed/32921710?tool=bestpractice.com
病史较长、年龄较小的患者更有可能出现 RT-PCR 阳性复发,而重症、糖尿病和淋巴细胞计数较低的患者则较为少见。[1081]Azam M, Sulistiana R, Ratnawati M, et al. Recurrent SARS-CoV-2 RNA positivity after COVID-19: a systematic review and meta-analysis. Sci Rep. 2020 Nov 26;10(1):20692.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691365
http://www.ncbi.nlm.nih.gov/pubmed/33244060?tool=bestpractice.com
目前尚不清楚其是否由再感染引发;是否由诸如样本采集类型和拭子检测相关性技术误差、变异 SARS-CoV-2 感染或持续性病毒脱落等因素引发;或检测结果是否在出院时呈假阴性。[1082]SeyedAlinaghi S, Oliaei S, Kianzad S, et al. Reinfection risk of novel coronavirus (COVID-19): a systematic review of current evidence. World J Virol. 2020 Dec 15;9(5):79-90.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747024
http://www.ncbi.nlm.nih.gov/pubmed/33363000?tool=bestpractice.com
研究已反复报道了直至初次感染后 90 天为止都可出现 RT-PCR 检测阳性;因此,最有可能的原因是这类病例实际上并未康复、仍处于初次感染期。重要的是要意识到尽管有报道称持续病毒脱落可持续至感染发生后 90 天,在症状发作 10-20 天(取决于疾病严重程度)后就已经无法分离出具有复制能力的病毒了。[1083]Arafkas M, Khosrawipour T, Kocbach P, et al. Current meta-analysis does not support the possibility of COVID-19 reinfections. J Med Virol. 2021 Mar;93(3):1599-604.
https://onlinelibrary.wiley.com/doi/10.1002/jmv.26496
http://www.ncbi.nlm.nih.gov/pubmed/32897549?tool=bestpractice.com
一项对 200 名既往感染患者进行的队列研究发现,尽管咽部 RT-PCR 检测在康复后长达 90 天呈持续阳性,但未观察到密切接触者传播,表明此类患者在感染症状后阶段并无传染性。[1084]Vibholm LK, Nielsen SS, Pahus MH, et al. SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses. EBioMedicine. 2021 Jan 30;64:103230.
https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00023-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33530000?tool=bestpractice.com
再感染病例较为罕见。
再感染率相对较低。一项系统评价和荟萃分析发现总体再感染率为 0.65%。高危人群再感染率较高(1.6%),有症状再感染率较低(0.4%)。[1085]Mao YJ, Wang WW, Ma J, et al. Reinfection rates among patients previously infected by SARS-CoV-2: systematic review and meta-analysis. Chin Med J (Engl). 2021 Dec 13 [Epub ahead of print].
https://journals.lww.com/cmj/Abstract/9000/Reinfection_rates_among_patients_previously.98270.aspx
http://www.ncbi.nlm.nih.gov/pubmed/34908003?tool=bestpractice.com
在 18 项研究中,再感染风险位于 0% 至 2.2% 之间,既往感染将再感染风险降低了 87%。保护力在 80% 的接种者中可维持至少 7 个月,但 Delta 或奥密克戎变异株出现后,没有对患者进行追访的研究。[1086]Helfand M, Fiordalisi C, Wiedrick J, et al. Risk for reinfection after SARS-CoV-2: a living, rapid review for American College of Physicians practice points on the role of the antibody response in conferring immunity following SARS-CoV-2 infection. Ann Intern Med. 2022 Jan 25 [Epub ahead of print].
https://www.acpjournals.org/doi/10.7326/M21-4245
http://www.ncbi.nlm.nih.gov/pubmed/35073157?tool=bestpractice.com
存在下列情况时考虑再感染:[1079]Public Health England. COVID-19: investigation and management of suspected SARS-CoV-2 reinfections. 2021 [internet publication].
https://www.gov.uk/government/publications/covid-19-investigation-and-management-of-suspected-sars-cov-2-reinfections
诊断
与疾病符合的临床表现以及诊断证据(例如低 RT-PCR 循环阈值)足以诊断再感染。但是,诊断应与传染病专科医生共同做出,在此之前,应完成对包括可用性数据、诊断性信息和流行病学信息进行回顾的再感染可能性风险评估。如若可行,应通过配对样本全基因组测序确认再感染。[1079]Public Health England. COVID-19: investigation and management of suspected SARS-CoV-2 reinfections. 2021 [internet publication].
https://www.gov.uk/government/publications/covid-19-investigation-and-management-of-suspected-sars-cov-2-reinfections
总体而言,68.8% 再感染患者的疾病严重程度与初次发作相似,18.8% 症状更重,12.5% 症状更轻。[1087]Wang J, Kaperak C, Sato T, et al. COVID-19 reinfection: a rapid systematic review of case reports and case series. J Investig Med. 2021 Aug;69(6):1253-5.
https://jim.bmj.com/content/early/2021/05/18/jim-2021-001853.long
http://www.ncbi.nlm.nih.gov/pubmed/34006572?tool=bestpractice.com
治疗
此处提供的数据来自奥密克戎变异株出现前(为获取更多奥密克戎信息,请参阅 “分类”)。
免疫力
对 SARS-CoV-2 免疫反应尚未完全了解,但涉及细胞介导免疫和抗体介导免疫。
研究认为,适应性免疫发生在感染 7 至 10 天内。在感染的早期检测到了强烈的记忆 B 细胞和浆母细胞反应,症状发作后第 5 至 7 天分泌免疫球蛋白 A(immunoglobulin A, IgA)和 IgM 抗体,第 7 至 10 天分泌 IgG。T 细胞在感染的第一周被同时激活,SARS-CoV-2 特异性记忆 CD4+ 和 CD8+ T 细胞在 2 周内达到峰值。个体之间的抗体和 T 细胞反应不同,取决于年龄和疾病严重程度。[1088]Stephens DS, McElrath MJ. COVID-19 and the path to immunity. JAMA. 2020 Oct 6;324(13):1279-81.
https://jamanetwork.com/journals/jama/fullarticle/2770758
http://www.ncbi.nlm.nih.gov/pubmed/32915201?tool=bestpractice.com
抗体介导免疫
约 85% 至 99% 的感染者在自然感染后 4 周内会产生可检测的中和抗体。然而,这取决于疾病严重程度、研究环境、感染后时长,以及用于检测抗体的方法。[1089]World Health Organization. COVID-19 natural immunity: scientific brief. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci-Brief-Immunity-passport-2021.1
[1090]Savage HR, Santos VS, Edwards T, et al. Prevalence of neutralising antibodies against SARS-CoV-2 in acute infection and convalescence: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2021 Jul 8;15(7):e0009551.
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0009551
http://www.ncbi.nlm.nih.gov/pubmed/34237072?tool=bestpractice.com
中等强度证据表明,多数成人感染后产生达到可检出水平的 IgM 和 IgG 抗体。IgM 水平在病程早期约 20 天达到峰值,而后下降。IgG 水平在症状发作后约 25 天达到峰值,且可维持可检出水平至少 120 天。多数成人将产生中和抗体,其可存在数月。部分成人感染后未产生抗体;原因尚不清楚。[1091]Arkhipova-Jenkins I, Helfand M, Armstrong C, et al. Antibody response after SARS-CoV-2 infection and implications for immunity: a rapid living review. Ann Intern Med. 2021 Jun;174(6):811-21.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025942
http://www.ncbi.nlm.nih.gov/pubmed/33721517?tool=bestpractice.com
母体 SARS-CoV-2 IgG 抗体被发现其在妊娠期感染后,可通过胎盘。[1092]Flannery DD, Gouma S, Dhudasia MB, et al. Assessment of maternal and neonatal cord blood SARS-CoV-2 antibodies and placental transfer ratios. JAMA Pediatr. 2021 Jun 1;175(6):594-600.
https://jamanetwork.com/journals/jamapediatrics/fullarticle/2775945
http://www.ncbi.nlm.nih.gov/pubmed/33512440?tool=bestpractice.com
长期照护机构中的极端年龄者(部分人年龄超过 100 岁)、脆弱者被发现可引发强大的免疫反应,从而中和 SARS-CoV-2 病毒。[1093]Foley MK, Searle SD, Toloue A, et al. Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study. EClinicalMedicine. 2021 Jun 27:100975.
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00255-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34222846?tool=bestpractice.com
早期部分研究表明,无症状者对感染抗体反应较弱;然而,其尚未得到证实。[1094]Long QX, Tang XJ, Shi QL, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020 Aug;26(8):1200-4.
https://www.nature.com/articles/s41591-020-0965-6
http://www.ncbi.nlm.nih.gov/pubmed/32555424?tool=bestpractice.com
当前证据表明,多数人免疫反应在感染后至少 10 个月内保持强劲,可防止再次感染。[1095]Alfego D, Sullivan A, Poirier B, et al. A population-based analysis of the longevity of SARS-CoV-2 antibody seropositivity in the United States. EClinicalMedicine. 2021 May 24:100902.
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00182-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34056568?tool=bestpractice.com
[1096]Egbert ER, Xiao S, Colantuoni E, et al. Durability of spike immunoglobin G antibodies to SARS-CoV-2 among health care workers with prior infection. JAMA Netw Open. 2021 Aug 2;4(8):e2123256.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783618
http://www.ncbi.nlm.nih.gov/pubmed/34459910?tool=bestpractice.com
一项针对未接种疫苗成人的横断面研究发现感染后长达 20 个月的自然免疫证据,但尚不清楚抗体水平与未来保护力的关联,特别是对于新兴变体。[1097]Alejo JL, Mitchell J, Chang A, et al. Prevalence and durability of SARS-CoV-2 antibodies among unvaccinated US adults by history of COVID-19. JAMA. 2022 Feb 3 [Epub ahead of print].
https://jamanetwork.com/journals/jama/fullarticle/2788894
http://www.ncbi.nlm.nih.gov/pubmed/35113143?tool=bestpractice.com
部分刺突蛋白发生关键变化的 SARS-CoV-2 变体,对抗体中和的易感性降低。然而,自然感染引起的细胞免疫亦以往往较刺突蛋白更为保守的其他病毒蛋白为靶向。[1089]World Health Organization. COVID-19 natural immunity: scientific brief. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci-Brief-Immunity-passport-2021.1
细胞免疫
多数人都会对 CD4+ 和 CD8+ T 细胞产生强烈而广泛的 T 细胞反应,有些人会产生记忆表型。[1098]Centre for Evidence-Based Medicine; Plüddemann A, Aronson JK. What is the role of T cells in COVID-19 infection? Why immunity is about more than antibodies. 2020 [internet publication].
https://www.cebm.net/covid-19/what-is-the-role-of-t-cells-in-covid-19-infection-why-immunity-is-about-more-than-antibodies
CD4+ 和 CD8+ 细胞在得到恢复的成人中,经过一个 3 至 5 月的半衰期后出现减少,初次感染后至少 6 至 8 月,仍可能存在于多数成人。[1099]Dan JM, Mateus J, Kato Y, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021 Jan 6 [Epub ahead of print].
https://science.sciencemag.org/content/early/2021/01/06/science.abf4063.long
http://www.ncbi.nlm.nih.gov/pubmed/33408181?tool=bestpractice.com
[1100]Shrotri M, van Schalkwyk MCI, Post N, et al. T cell response to SARS-CoV-2 infection in humans: a systematic review. PLoS One. 2021;16(1):e0245532.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833159
http://www.ncbi.nlm.nih.gov/pubmed/33493185?tool=bestpractice.com
新兴数据表明,T 细胞应答在很大程度上不受 SARS-CoV-2 变体影响。[1101]Tarke A, Sidney J, Methot N, et al. Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals. Cell Rep Med. 2021 Jul 20;2(7):100355.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249675
http://www.ncbi.nlm.nih.gov/pubmed/34230917?tool=bestpractice.com
[1102]Redd AD, Nardin A, Kared H, et al. CD8+ T-cell responses in COVID-19 convalescent individuals target conserved epitopes from multiple prominent SARS-CoV-2 circulating variants. Open Forum Infect Dis. 2021 Jul;8(7):ofab143.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083629
http://www.ncbi.nlm.nih.gov/pubmed/34322559?tool=bestpractice.com
证据表明,SARS-CoV-2 自然感染可能会带来某种抵御再感染的高保护性免疫力。
多数康复患者在中重度感染后 12 个月内,都存在 SARS-CoV-2 强效抗体和 T 细胞免疫。中和抗体在感染后 6 至 12 个月内出现减少(多数呈现于老年人和危重患者)。然而,记忆 T 细胞具有对失去中和抗体反应的患者介导细胞免疫的能力。记忆 T 细胞对原始 SARS-CoV-2 毒株的反应未遭新变体干扰。[1103]Guo L, Wang G, Wang Y, et al. SARS-CoV-2-specific antibody and T-cell responses 1 year after infection in people recovered from COVID-19: a longitudinal cohort study. Lancet Microbe. 2022 Mar 23 [Epub ahead of print].
https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(22)00036-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35345417?tool=bestpractice.com
得以恢复的危重患者在出院后一年余时间内,可持续对 SARS-CoV-2 产生显著的适应性免疫反应和体液免疫反应。[1104]Venet F, Gossez M, Bidar F, et al. T cell response against SARS-CoV-2 persists after one year in patients surviving severe COVID-19. EBioMedicine. 2022 Mar 26;78:103967.
https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00151-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35349827?tool=bestpractice.com
荟萃分析已发现,感染后的保护水平较高(84% 至 87%),并持续至少 1 年。[1105]Petráš M. Highly effective naturally acquired protection against COVID-19 persists for at least 1 year: a meta-analysis. J Am Med Dir Assoc. 2021 Sep 16 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443339
http://www.ncbi.nlm.nih.gov/pubmed/34582779?tool=bestpractice.com
[1106]Chen Q, Zhu K, Liu X, et al. The protection provided by naturally acquired antibodies against subsequent SARS-CoV-2 infection: a systematic review and meta-analysis. Emerg Microbes Infect. 2022 Feb 23:1-44.
https://www.tandfonline.com/doi/full/10.1080/22221751.2022.2046446
http://www.ncbi.nlm.nih.gov/pubmed/35195494?tool=bestpractice.com
英国卫生安全局一项研究发现,与既往未感染过该疾患者相比,既往感染导致的自然获得性免疫力可对再感染提供 84% 的保护性,保护性似乎可持续至少 5 个月。[1107]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). Lancet. 2021 Apr 17;397(10283):1459-69.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040523
http://www.ncbi.nlm.nih.gov/pubmed/33844963?tool=bestpractice.com
类似的,一项对丹麦 400 万 PCR 检测的人群水平观察性研究发现,年龄小于 65 岁人群再感染保护性为 80% 或更高,年龄大于 65 岁者则为 47%。尚无证据证实保护性随时间减弱。[1108]Hansen CH, Michlmayr D, Gubbels SM, et al. Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study. Lancet. 2021 Mar 27;397(10280):1204-12.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00575-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33743221?tool=bestpractice.com
瑞典一项基于注册数据的研究发现,与无免疫力相比,天然免疫力可降低 95% 的再感染风险和 87% 的收治入院风险达 20 个月。疫苗接种似乎可以进一步降低这两种结局的风险达 9 个月,但绝对数值差异较小。[1109]Nordström P, Ballin M, Nordström A. Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden. Lancet Infect Dis. 2022 Mar 31 [Epub ahead of print].
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00143-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35366962?tool=bestpractice.com
一项跨越美国 6 个州的队列研究发现,与既往未罹患 COVID-19 的未接种疫苗者相比,既往曾罹患症状性 COVID-19 的未接种疫苗者感染 COVID-19 的风险降低了 85%,从而表明自然免疫与疫苗对中重度疾病具有相似的保护力。[1110]Ridgway JP, Tideman S, Wright B, et al. Rates of COVID-19 among unvaccinated adults with prior COVID-19. JAMA Netw Open. 2022 Apr 1;5(4):e227650.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791312
http://www.ncbi.nlm.nih.gov/pubmed/35442459?tool=bestpractice.com
意大利伦巴第大区一项观察性研究发现,自然免疫似乎可以提供至少一年的保护作用;然而,该研究在 SARS-CoV-2 变体开始传播之前即已结束,目前尚不清楚对野生型病毒形成的天然免疫力如何防护此类变体。[1111]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. JAMA Intern Med. 2021 May 28 [Epub ahead of print].
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2780557
http://www.ncbi.nlm.nih.gov/pubmed/34048531?tool=bestpractice.com
SARS-CoV-2 固有免疫力
在 COVID-19 大流行之前采集的血液样本检测结果已表明,一些人已经具有识别 SARS-CoV-2 的免疫细胞。研究报道称,在已知无病毒暴露史的人群中,20%-50% 存在 T 细胞对 SARS-CoV-2 的反应。[1112]Doshi P. Covid-19: do many people have pre-existing immunity? BMJ. 2020 Sep 17;370:m3563.
https://www.bmj.com/content/370/bmj.m3563
http://www.ncbi.nlm.nih.gov/pubmed/32943427?tool=bestpractice.com
在一项研究中,约 5% 未感染成人和 62% 未感染儿童(6 岁至 16 岁)拥有可识别 SARS-CoV-2 的抗体。[1113]Ng KW, Faulkner N, Cornish GH, et al. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science. 2020 Dec 11;370(6522):1339-43.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857411
http://www.ncbi.nlm.nih.gov/pubmed/33159009?tool=bestpractice.com
这可能是真正的免疫记忆所致,部分由既往感染普通感冒冠状病毒或其他未知动物冠状病毒引起。但是,需要对人类是否已有对 SARS-CoV-2 的免疫力开展进一步研究。
自然免疫与疫苗诱导性免疫
自然感染后的保护力似乎与疫苗估计效力相当。[1085]Mao YJ, Wang WW, Ma J, et al. Reinfection rates among patients previously infected by SARS-CoV-2: systematic review and meta-analysis. Chin Med J (Engl). 2021 Dec 13 [Epub ahead of print].
https://journals.lww.com/cmj/Abstract/9000/Reinfection_rates_among_patients_previously.98270.aspx
http://www.ncbi.nlm.nih.gov/pubmed/34908003?tool=bestpractice.com
新兴证据提示,与疫苗诱导免疫力相比,自然免疫力可对 Delta 变异株或其他需要关注的变异株引发的感染、症状性疾病和住院提供至少相仿,或更为持续和强大的保护。[1114]Vacharathit V, Aiewsakun P, Manopwisedjaroen S, et al. CoronaVac induces lower neutralising activity against variants of concern than natural infection. Lancet Infect Dis. 2021 Aug 26 [Epub ahead of print].
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00568-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34454652?tool=bestpractice.com
[1115]Shenai MB, Rahme R, Noorchashm H. Equivalency of protection from natural immunity in COVID-19 recovered versus fully vaccinated persons: a systematic review and pooled analysis. Cureus. 2021 Oct 28;13(10):e19102.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627252
http://www.ncbi.nlm.nih.gov/pubmed/34868754?tool=bestpractice.com
在美国的 δ 变体流行期间(2021 年 5 月至 11 月),既往感染者(不论之前是否接种过疫苗)对于抵御感染具有最大保护力。至 10 月初,既往感染的存活者发病率低于单纯接种疫苗者。[1116]León TM, Dorabawila V, Nelson L, et al. COVID-19 cases and hospitalizations by COVID-19 vaccination status and previous COVID-19 diagnosis: California and New York, May – November 2021. MMWR Morb Mortal Wkly Rep. 2022 Jan 28;71(4):125-31.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7104e1.htm
http://www.ncbi.nlm.nih.gov/pubmed/35085222?tool=bestpractice.com
此处提供的数据来自奥密克戎变异株出现前(为获取更多奥密克戎信息,请参阅 “分类”)。