病因学
病毒学
严重急性呼吸综合征冠状病毒 2(Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2)是一种过去未曾了解的 β 属冠状病毒,在中国湖北省武汉市 2019 年 12 月暴发不明原因肺炎患者群体的支气管肺泡灌洗液标本中得以发现。[42]Ren LL, Wang YM, Wu ZQ, et al. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J (Engl). 2020 May 5;133(9):1015-24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147275/ http://www.ncbi.nlm.nih.gov/pubmed/32004165?tool=bestpractice.com
冠状病毒是一大类有包膜 RNA 病毒,其中部分可导致人类患病(例如,普通感冒、严重急性呼吸综合征[SARS]、中东呼吸综合征[MERS]等),还有一些会在哺乳类和鸟类等动物中进行传播。动物冠状病毒很少会传播给人类,从而像 SARS 和 MERS 一样在人际间发生传播。
SARS-CoV-2 属于 冠状病毒科轮状病毒亚属,为已知的第七种可感染人类的冠状病毒。已发现该病毒与蝙蝠所携带的 SARS 样冠状病毒相似,但却不同于 SARS-CoV 和 MERS-CoV。[43]Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-33. https://www.nejm.org/doi/full/10.1056/NEJMoa2001017 http://www.ncbi.nlm.nih.gov/pubmed/31978945?tool=bestpractice.com [44]Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-74. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30251-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32007145?tool=bestpractice.com 已经测出该病毒的全基因组序列,并在 GenBank 数据库进行发布。 GenBank Opens in new window
初步研究表明,中国 SARS-CoV-2 病毒有两种主要类型(或毒株),分别命名为 L 型和 S 型。武汉暴发的早期,发现 L 型流行性更强,并可能更具侵略性(尽管这是一种推测),但其复制频率在 1 月初后有所下降。这一发现的相关性在现阶段尚未明确,需行进一步研究。[45]Tang X, Wu C, Li X, et al. On the origin and continuing evolution of SARS-CoV-2. Nat Sci Review. 2020 Mar 3 [Epub ahead of print]. https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa036/5775463 与野生型病毒感染患者相比,新加坡 SARS-CoV-2 病毒变异体(382 个核苷酸缺失)感染患者病程较轻。[46]Young BE, Fong SW, Chan YH, et al. Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study. Lancet. 2020 Aug 29;396(10251):603-11. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31757-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32822564?tool=bestpractice.com
病毒来源
疫情暴发最初阶段的多数患者称与华南海鲜市场(活禽或海鲜水产市场)有关,表明该病毒为人畜共患的起源。[4]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 [5]Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-13. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30211-7/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32007143?tool=bestpractice.com [47]Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-207. https://www.nejm.org/doi/full/10.1056/NEJMoa2001316 http://www.ncbi.nlm.nih.gov/pubmed/31995857?tool=bestpractice.com 对首批确诊的 425 例病例传播动力学的初步评估发现,2020 年 1 月 1 日之前,55% 病例与该市场相关联,而此后仅 8.6% 病例与该市场相关联。这表明自 2019 年 12 月中旬以来,在密切接触者之间已发生人际传播。[47]Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-207. https://www.nejm.org/doi/full/10.1056/NEJMoa2001316 http://www.ncbi.nlm.nih.gov/pubmed/31995857?tool=bestpractice.com
一些研究表明 SARS-CoV-2 可能是蝙蝠冠状病毒与来源未知的冠状病毒所形成的重组病毒。[43]Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-33. https://www.nejm.org/doi/full/10.1056/NEJMoa2001017 http://www.ncbi.nlm.nih.gov/pubmed/31978945?tool=bestpractice.com [44]Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-74. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30251-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32007145?tool=bestpractice.com [48]Paraskevis D, Kostaki EG, Magiorkinis G, et al. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol. 2020 Jan 29;79:104212. http://www.ncbi.nlm.nih.gov/pubmed/32004758?tool=bestpractice.com [49]Ji W, Wang W, Zhao X, et al. Cross-species transmission of the newly identified coronavirus 2019-nCoV. J Med Virol. 2020 Apr;92(4):433-40. https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25682 http://www.ncbi.nlm.nih.gov/pubmed/31967321?tool=bestpractice.com 有说法表示,穿山甲可能是中间宿主;但是,尚未在动物宿主中找到该病毒。[50]Zhang T, Wu Q, Zhang Z. Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. Curr Biol. 2020 Apr 6;30(7):1346-51. https://www.cell.com/current-biology/fulltext/S0960-9822(20)30360-2?_returnURL http://www.ncbi.nlm.nih.gov/pubmed/32197085?tool=bestpractice.com [51]Lam TT, Shum MH, Zhu HC, et al. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature. 2020 Jul;583(7815):282-5. https://www.nature.com/articles/s41586-020-2169-0_reference.pdf http://www.ncbi.nlm.nih.gov/pubmed/32218527?tool=bestpractice.com [52]Mallapaty S. Animal source of the coronavirus continues to elude scientists. Nature. 2020 May 18 [Epub ahead of print]. https://www.nature.com/articles/d41586-020-01449-8 http://www.ncbi.nlm.nih.gov/pubmed/32427902?tool=bestpractice.com 为了确定 SARS-CoV-2 起源,还需要进一步的研究。
传播动力学
呼吸道传播是主要传播方式,距离和通风是传播风险的关键决定因素。[53]Meyerowitz EA, Richterman A, Gandhi RT, et al. Transmission of SARS-CoV-2: a review of viral, host, and environmental factors. Ann Intern Med. 2020 Sep 17 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5008 http://www.ncbi.nlm.nih.gov/pubmed/32941052?tool=bestpractice.com 现有证据表明,人际传播主要是通过被感染者咳嗽、打喷嚏、言谈或歌唱时产生的唾液和呼吸道分泌物,以及呼吸道飞沫等感染分泌物与被感染者形成直接、间接或密切接触实现。[54]World Health Organization. Transmission of SARS-CoV-2: implications for infection prevention precautions – scientific brief. 2020 [internet publication]. https://www.who.int/publications/i/item/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations
在气溶胶生成性操作中,医疗机构内可产生空气传播。也有部分疫情暴发报告表明,在某些条件下,可能存在社区内气溶胶传播;但是,这些报告与通风不良的室内封闭拥挤空间(例如饭店、合唱团训练、健身操课)有关,在这些空间中,感染者可能曾大口呼吸。对此类聚集性病例的详细调查表明,飞沫和传染媒介传播亦可解释此类报告中的传播。[54]World Health Organization. Transmission of SARS-CoV-2: implications for infection prevention precautions – scientific brief. 2020 [internet publication]. https://www.who.int/publications/i/item/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations [55]Centers for Disease Control and Prevention. How COVID-19 spreads. 2020 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html
可能存在传染媒介传播(直接与传染媒介接触),但是目前尚无确凿证据表明存在这种传播方式。在少数被推定为传染媒介传播的病例中,呼吸道传播尚未完全排除。[53]Meyerowitz EA, Richterman A, Gandhi RT, et al. Transmission of SARS-CoV-2: a review of viral, host, and environmental factors. Ann Intern Med. 2020 Sep 17 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5008 http://www.ncbi.nlm.nih.gov/pubmed/32941052?tool=bestpractice.com 在实验条件下,与铜(最多 4 小时)和硬纸板(最多 24 小时)相比,该病毒在塑料和不锈钢表面更为稳定(最多 72 小时),但这不能反映实际情况。[56]van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020 Apr 16;382(16):1564-7. https://www.nejm.org/doi/full/10.1056/NEJMc2004973 http://www.ncbi.nlm.nih.gov/pubmed/32182409?tool=bestpractice.com 在医疗环境中,病毒在普通病房和重症监护病房中广泛分布于空气和物体表面。[57]Guo ZD, Wang ZY, Zhang SF, et al. Aerosol and surface distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards, Wuhan, China, 2020. Emerg Infect Dis. 2020 Apr 10;26(7). https://wwwnc.cdc.gov/eid/article/26/7/20-0885_article http://www.ncbi.nlm.nih.gov/pubmed/32275497?tool=bestpractice.com 但尚未从这些样本中培养出病毒,表明沉积物可能为无活性病毒 RNA。[58]Zhou J, Otter JA, Price JR, et al. Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London. Clin Infect Dis. 2020 Jul 8 [Epub ahead of print]. https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa905/5868534 http://www.ncbi.nlm.nih.gov/pubmed/32634826?tool=bestpractice.com [59]Colaneri M, Seminari E, Novati S, et al. Severe acute respiratory syndrome coronavirus 2 RNA contamination of inanimate surfaces and virus viability in a health care emergency unit. Clin Microbiol Infect. 2020 Aug;26(8):1094.e1-5. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30286-X/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32450255?tool=bestpractice.com [60]Colaneri M, Seminari E, Piralla A, et al. Lack of SARS-CoV-2 RNA environmental contamination in a tertiary referral hospital for infectious diseases in Northern Italy. J Hosp Infect. 2020 Mar 19;105(3):474-6. https://www.journalofhospitalinfection.com/article/S0195-6701(20)30117-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32201338?tool=bestpractice.com
尽管可能存在粪-口传播(或通过粪便气溶胶发生呼吸道传播),但仅有少量间接证据支持这种传播方式。[53]Meyerowitz EA, Richterman A, Gandhi RT, et al. Transmission of SARS-CoV-2: a review of viral, host, and environmental factors. Ann Intern Med. 2020 Sep 17 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5008 http://www.ncbi.nlm.nih.gov/pubmed/32941052?tool=bestpractice.com COVID-19 患者粪便 SARS-CoV-2 RNA 总体检测阳性率约为 51%,其中 64% 的样本在呼吸道样本转为阴性后,持续平均 12.5 天(最高长达 33 天)呈阳性。[61]van Doorn AS, Meijer B, Frampton CMA, et al. Systematic review with meta-analysis: SARS-CoV-2 stool testing and the potential for faecal-oral transmission. Aliment Pharmacol Ther. 2020 Aug 27 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/full/10.1111/apt.16036 http://www.ncbi.nlm.nih.gov/pubmed/32852082?tool=bestpractice.com
尚未报告通过其他体液的传播(包括性传播或血源性传播)。[53]Meyerowitz EA, Richterman A, Gandhi RT, et al. Transmission of SARS-CoV-2: a review of viral, host, and environmental factors. Ann Intern Med. 2020 Sep 17 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5008 http://www.ncbi.nlm.nih.gov/pubmed/32941052?tool=bestpractice.com 虽然已在血液、脑脊液、心包液、胸腔积液、尿液、精液、唾液、眼组织、眼泪和结膜分泌物中以及中耳和乳突中检测到该病毒,但病毒或病毒成分的存在并不等同具有传染性。[62]Zhang W, Du RH, Li B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect. 2020 Dec;9(1):386-9. https://www.tandfonline.com/doi/full/10.1080/22221751.2020.1729071 http://www.ncbi.nlm.nih.gov/pubmed/32065057?tool=bestpractice.com [63]To KK, Tsang OT, Chik-Yan Yip C, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 2020 Jul 28;71(15):841-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108139/ http://www.ncbi.nlm.nih.gov/pubmed/32047895?tool=bestpractice.com [64]Centre for Evidence-Based Medicine; Ferner RE, Murray PI, Aronson JK. Spreading SARS-CoV-2 through ocular fluids. 2020 [internet publication]. https://www.cebm.net/spreading-sars-cov-2-through-ocular-fluids/ [65]Sun T, Guan J. Novel coronavirus and central nervous system. Eur J Neurol. 2020 Mar 26 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.14227 http://www.ncbi.nlm.nih.gov/pubmed/32216009?tool=bestpractice.com [66]Seah IYJ, Anderson DE, Kang AEZ, et al. Assessing viral shedding and infectivity of tears in coronavirus disease 2019 (COVID-19) patients. Ophthalmology. 2020 Jul;127(7):977-9. https://www.aaojournal.org/article/S0161-6420(20)30311-0/pdf http://www.ncbi.nlm.nih.gov/pubmed/32291098?tool=bestpractice.com [67]Farina A, Uccello G, Spreafico M, et al. SARS-CoV-2 detection in the pericardial fluid of a patient with cardiac tamponade. Eur J Intern Med. 2020 Jun;76:100-1. https://www.ejinme.com/article/S0953-6205(20)30166-7/pdf http://www.ncbi.nlm.nih.gov/pubmed/32359887?tool=bestpractice.com [68]Algarroba GN, Rekawek P, Vahanian SA, et al. Visualization of severe acute respiratory syndrome coronavirus 2 invading the human placenta using electron microscopy. Am J Obstet Gynecol. 2020 Aug;223(2):275-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219376/ http://www.ncbi.nlm.nih.gov/pubmed/32405074?tool=bestpractice.com [69]Li D, Jin M, Bao P, et al. Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Netw Open. 2020 May 1;3(5):e208292. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765654 http://www.ncbi.nlm.nih.gov/pubmed/32379329?tool=bestpractice.com [70]Mei F, Bonifazi M, Menzo S, et al. First detection of SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay in pleural fluid. Chest. 2020 Oct;158(4):e143-6. https://journal.chestnet.org/article/S0012-3692(20)31660-3/pdf http://www.ncbi.nlm.nih.gov/pubmed/32534909?tool=bestpractice.com [71]Kashi AH, De la Rosette J, Amini E, et al. Urinary viral shedding of COVID-19 and its clinical associations: a systematic review and meta-analysis of observational studies. Urol J. 2020 Sep 5 [Epub ahead of print]. https://journals.sbmu.ac.ir/urolj/index.php/uj/article/view/6248/3994 http://www.ncbi.nlm.nih.gov/pubmed/32888186?tool=bestpractice.com [72]Frazier KM, Hooper JE, Mostafa HH, et al. SARS-CoV-2 virus isolated from the mastoid and middle ear: implications for COVID-19 precautions during ear surgery. JAMA Otolaryngol Head Neck Surg. 2020 Jul 23;146(10):964-6. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2768621 http://www.ncbi.nlm.nih.gov/pubmed/32701126?tool=bestpractice.com [73]Yan Y, Diao B, Liu Y, et al. Severe acute respiratory syndrome coronavirus 2 nucleocapsid protein in the ocular tissues of a patient previously infected with coronavirus disease 2019. JAMA Ophthalmol. 2020 Oct 8 [Epub ahead of print]. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2771320 http://www.ncbi.nlm.nih.gov/pubmed/33034620?tool=bestpractice.com
垂直传播很少发生,胎盘传播已有记载。总体而言,罹患 COVID-19 母体所娩婴儿中,有6.3% 在出生时 SARS-CoV-2 检测呈阳性。早产儿和足月儿均有传播报道。SARS-CoV-2 检测呈阴性的 COVID-19 母体所娩婴儿中,亦发现 SARS-CoV-2 抗体证据。[74]Bwire GM, Njiro BJ, Mwakawanga DL, et al. Possible vertical transmission and antibodies against SARS-CoV-2 among infants born to mothers with COVID-19: a living systematic review. J Med Virol. 2020 Oct 22 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/10.1002/jmv.26622 http://www.ncbi.nlm.nih.gov/pubmed/33090535?tool=bestpractice.com 婴儿经阴道分娩、母乳喂养或与经允许与母体接触时,感染率似乎不会升高。[75]Walker KF, O'Donoghue K, Grace N, et al. Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: a systematic review and critical analysis. BJOG. 2020 Oct;127(11):1324-36. https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1111/1471-0528.16362 http://www.ncbi.nlm.nih.gov/pubmed/32531146?tool=bestpractice.com 已在母乳中检测到病毒片段;但是,尚未检测到具有复制能力的病毒,表明其不易通过母乳传播。[76]Groß R, Conzelmann C, Müller JA, et al. Detection of SARS-CoV-2 in human breastmilk. Lancet. 2020 Jun 6;395(10239):1757-8. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31181-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32446324?tool=bestpractice.com [77]Tam PCK, Ly KM, Kernich ML, et al. Detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human breast milk of a mildly symptomatic patient with coronavirus disease 2019 (COVID-19). Clin Infect Dis. 2020 May 30 [Epub ahead of print]. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa673/5848850 http://www.ncbi.nlm.nih.gov/pubmed/32472683?tool=bestpractice.com [78]Costa S, Posteraro B, Marchetti S, et al. Excretion of SARS-CoV-2 in human breast milk. Clin Microbiol Infect. 2020 Oct;26(10):1430-2. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30304-9/pdf http://www.ncbi.nlm.nih.gov/pubmed/32502644?tool=bestpractice.com 若采取恰当的卫生预防措施,则不易发生垂直传播。[79]Salvatore CM, Han JY, Acker KP, et al. Neonatal management and outcomes during the COVID-19 pandemic: an observation cohort study. Lancet Child Adolesc Health. 2020 Oct;4(10):721-7. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30235-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32711687?tool=bestpractice.com
一项系统评价称院内传播见于 44% 患者;然而,这一评价的局限性在于病例系列来自武汉暴发早期,那时机构尚未采取合适的感染防控措施。[80]Zhou Q, Gao Y, Wang X, et al. Nosocomial infections among patients with COVID-19, SARS and MERS: a rapid review and meta-analysis. Ann Transl Med. 2020 May;8(10):629. http://atm.amegroups.com/article/view/42877/html http://www.ncbi.nlm.nih.gov/pubmed/32566566?tool=bestpractice.com 截至 2020 年 10 月 26 日,在英国 NHS 中,医院获得性感染(定义为入院 7 天以上建立诊断的患者)约占感染总数的 17%,某些地区高达 25%。[81]Centre for Evidence-Based Medicine; Heneghan C, Howdon D, Oke J, et al. The ongoing problem of UK hospital acquired infections. 2020 [internet publication]. https://www.cebm.net/covid-19/the-ongoing-problem-of-hospital-acquired-infections-across-the-uk/ 对暴露于指示病例(非气溶胶生成性操作)的医务工作者进行的研究发现,采取接触和飞沫防护措施时,几乎未发现院内感染。[54]World Health Organization. Transmission of SARS-CoV-2: implications for infection prevention precautions – scientific brief. 2020 [internet publication]. https://www.who.int/publications/i/item/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations [82]Rhee C, Baker M, Vaidya V, et al. Incidence of nosocomial COVID-19 in patients hospitalized at a large US academic medical center. JAMA Netw Open. 2020 Sep 1;3(9):e2020498. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770287 http://www.ncbi.nlm.nih.gov/pubmed/32902653?tool=bestpractice.com
与症状有关的传播动力学
有症状传播
有症状患者(尤其是症状发作时)最具传播性。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [83]Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med. 2020 Mar 5;382(10):970-71. https://www.nejm.org/doi/full/10.1056/NEJMc2001468 http://www.ncbi.nlm.nih.gov/pubmed/32003551?tool=bestpractice.com [84]Kupferschmidt K. Study claiming new coronavirus can be transmitted by people without symptoms was flawed. 2020 [internet publication]. https://www.sciencemag.org/news/2020/02/paper-non-symptomatic-patient-transmitting-coronavirus-wrong [85]Tong ZD, Tang A, Li KF, et al. Potential presymptomatic transmission of SARS-CoV-2, Zhejiang province, China, 2020. Emerg Infect Dis. 2020 May 17;26(5). https://wwwnc.cdc.gov/eid/article/26/5/20-0198_article http://www.ncbi.nlm.nih.gov/pubmed/32091386?tool=bestpractice.com [86]Hu Z, Song C, Xu C, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci. 2020 May;63(5):706-11. https://link.springer.com/content/pdf/10.1007/s11427-020-1661-4.pdf http://www.ncbi.nlm.nih.gov/pubmed/32146694?tool=bestpractice.com [87]Luo SH, Liu W, Liu ZJ, et al. A confirmed asymptomatic carrier of 2019 novel coronavirus (SARS-CoV-2). Chin Med J (Engl). 2020 May 5;133(9):1123-5. https://journals.lww.com/cmj/Citation/publishahead/A_confirmed_asymptomatic_carrier_of_2019_novel.99353.aspx http://www.ncbi.nlm.nih.gov/pubmed/32149768?tool=bestpractice.com [88]Lu S, Lin J, Zhang Z, et al. Alert for non-respiratory symptoms of Coronavirus Disease 2019 (COVID-19) patients in epidemic period: a case report of familial cluster with three asymptomatic COVID-19 patients. J Med Virol. 2020 Mar 19 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25776 http://www.ncbi.nlm.nih.gov/pubmed/32190904?tool=bestpractice.com [89]Li C, Ji F, Wang L, et al. Asymptomatic and human-to-human transmission of SARS-CoV-2 in a 2-family cluster, Xuzhou, China. Emerg Infect Dis. 2020 Mar 31;26(7). https://wwwnc.cdc.gov/eid/article/26/7/20-0718_article http://www.ncbi.nlm.nih.gov/pubmed/32228809?tool=bestpractice.com
症状出现前传播
潜伏期可能发生传播,通常在症状发作前 1 至 3 天。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
据报道,症状出现前发生传播的病例在中国有 12.6%,在新加坡有 6.4%。[90]Du Z, Xu X, Wu Y, et al. Serial interval of COVID-19 among publicly reported confirmed cases. Emerg Infect Dis. 2020 Mar 19;26(6). https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.25776 http://www.ncbi.nlm.nih.gov/pubmed/32191173?tool=bestpractice.com [91]Wei WE, Li Z, Chiew CJ, et al. Presymptomatic transmission of SARS-CoV-2: Singapore, January 23 - March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):411-5. https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e1.htm?s_cid=mm6914e1_w http://www.ncbi.nlm.nih.gov/pubmed/32271722?tool=bestpractice.com
无症状患者可能是暂时无症状,也可能持续无症状。
无症状传播
已有来自无症状病例(未出现症状的实验室确诊病例)的传播记录。[92]Liu J, Huang J, Xiang D. Large SARS-CoV-2 outbreak caused by asymptomatic traveler, China. Emerg Infect Dis. 2020 Jun 30;29(9). https://wwwnc.cdc.gov/eid/article/26/9/20-1798_article http://www.ncbi.nlm.nih.gov/pubmed/32603652?tool=bestpractice.com [93]Jiang XL, Zhang XL, Zhao XN, et al. Transmission potential of asymptomatic and paucisymptomatic severe acute respiratory syndrome coronavirus 2 infections: a three-family cluster study in China. 2020 Jun 11;221(12):1948-52. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188140/ http://www.ncbi.nlm.nih.gov/pubmed/32319519?tool=bestpractice.com 然而,相关证据有限,且世界卫生组织指出,与有症状病例相比,无症状病例传播病毒的可能性要小得多,且无症状病例并不是总体流行动态的主要驱动因素。[94]Luo L, Liu D, Liao X, et al. Contact settings and risk for transmission in 3410 close contacts of patients with COVID-19 in Guangzhou, China: a prospective cohort study. Ann Intern Med. 2020 Aug 13 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-2671 http://www.ncbi.nlm.nih.gov/pubmed/32790510?tool=bestpractice.com [95]World Health Organization. Advice on the use of masks in the context of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/advice-on-the-use-of-masks-in-the-community-during-home-care-and-in-healthcare-settings-in-the-context-of-the-novel-coronavirus-(2019-ncov)-outbreak 据多项研究报告,未发现从 SARS-CoV-2 携带者发生无症状传播的证据。[96]Gao M, Yang L, Chen X, et al. A study on infectivity of asymptomatic SARS-CoV-2 carriers. Respir Med. 2020 May 13;169:106026. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219423/ http://www.ncbi.nlm.nih.gov/pubmed/32405162?tool=bestpractice.com [97]Chen F, Fu D, Yang Q, et al. Low transmission risk of 9 asymptomatic carriers tested positive for both SARS-CoV-2 nucleic acid and serum IgG. J Infect. 2020 Sep;81(3):452-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299860/ http://www.ncbi.nlm.nih.gov/pubmed/32562791?tool=bestpractice.com [98]Danis K, Epaulard O, Bénet T, et al. Cluster of coronavirus disease 2019 (Covid-19) in the French Alps, 2020. Clin Infect Dis. 2020 Jul 28;71(15):825-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184384/ http://www.ncbi.nlm.nih.gov/pubmed/32277759?tool=bestpractice.com
人群中无症状病例的患病率难以估量。一项对超过 50,000 人进行的 meta 分析发现,15.6% 的确诊病例在检测时无症状,近半数病例在之后出现症状。[99]He J, Guo Y, Mao R, et al. Proportion of asymptomatic coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. J Med Virol. 2020 Jul 21 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.26326 http://www.ncbi.nlm.nih.gov/pubmed/32691881?tool=bestpractice.com 然而,根据研究人群的不同,对无症状病例比例的估值差异很大,从 1.2% 到 80% 不等。[100]Al-Sadeq DW, Nasrallah GK. The incidence of the novel coronavirus SARS-CoV-2 among asymptomatic patients: a systematic review. Int J Infect Dis. 2020 Jul 2;98:372-80. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330573/ http://www.ncbi.nlm.nih.gov/pubmed/32623083?tool=bestpractice.com [101]Mizumoto K, Kagaya K, Zarebski A, et al. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill. 2020 Mar;25(10). https://www.doi.org/10.2807/1560-7917.ES.2020.25.10.2000180 http://www.ncbi.nlm.nih.gov/pubmed/32183930?tool=bestpractice.com [102]Day M. Covid-19: identifying and isolating asymptomatic people helped eliminate virus in Italian village. BMJ. 2020 Mar 23;368:m1165. https://www.bmj.com/content/368/bmj.m1165 http://www.ncbi.nlm.nih.gov/pubmed/32205334?tool=bestpractice.com [103]Centre for Evidence-Based Medicine; Heneghan C, Brassey J, Jefferson T. COVID-19: What proportion are asymptomatic? 2020 [internet publication]. https://www.cebm.net/2020/04/covid-19-what-proportion-are-asymptomatic/ [104]Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection: a narrative review. Ann Intern Med. 2020 Sep 1;173(5):362-7. https://www.acpjournals.org/doi/10.7326/M20-3012 http://www.ncbi.nlm.nih.gov/pubmed/32491919?tool=bestpractice.com [105]Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility: King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 3;69(13):377-81. https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e1.htm?s_cid=mm6913e1_w http://www.ncbi.nlm.nih.gov/pubmed/32240128?tool=bestpractice.com [106]Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med. 2020 May 28;382(22):2081-90. https://www.nejm.org/doi/full/10.1056/NEJMoa2008457 http://www.ncbi.nlm.nih.gov/pubmed/32329971?tool=bestpractice.com 感染后在整个感染过程中持续无症状患者的比例总估值为 20%。[107]Buitrago-Garcia D, Egli-Gany D, Counotte MJ, et al. Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: a living systematic review and meta-analysis. PLoS Med. 2020 Sep;17(9):e1003346. https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003346 http://www.ncbi.nlm.nih.gov/pubmed/32960881?tool=bestpractice.com
在无症状传播中,医务工作者可能是因素之一。在接触感染患者的医院部门工作的医务工作者中,约 7.6% SARS-CoV-2 抗体检测呈阳性;然而,这些工作者中只有 58% 表示此前有症状。[108]Stubblefield WB, Talbot HK, Feldstein L, et al. Seroprevalence of SARS-CoV-2 among frontline healthcare personnel during the first month of caring for COVID-19 patients – Nashville, Tennessee. Clin Infect Dis. 2020 Jul 6 [Epub ahead of print]. https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa936/5868028 http://www.ncbi.nlm.nih.gov/pubmed/32628750?tool=bestpractice.com 一项针对近 2800 名医务工作者进行的横断面研究发现,5.4% 面对 COVID-19 的无症状医务工作者,检测结果呈阳性,而未面对 COVID-19 的无症状医务工作者,检测结果阳性率则为 0.6%。[109]Vahidy FS, Bernard DW, Boom ML, et al. Prevalence of SARS-CoV-2 infection among asymptomatic health care workers in the Greater Houston, Texas, area. JAMA Netw Open. 2020 Jul 1;3(7):e2016451. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2768707 http://www.ncbi.nlm.nih.gov/pubmed/32716512?tool=bestpractice.com
儿童更可能无症状。[99]He J, Guo Y, Mao R, et al. Proportion of asymptomatic coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. J Med Virol. 2020 Jul 21 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.26326 http://www.ncbi.nlm.nih.gov/pubmed/32691881?tool=bestpractice.com 儿童无症状病例的汇总比例被认为较高(约 40%)。[110]Qiu H, Wu J, Hong L, et al. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis. 2020 Jun;20(6):689-96. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158906/ http://www.ncbi.nlm.nih.gov/pubmed/32220650?tool=bestpractice.com [111]Zheng B, Wang H, Yu C. An increasing public health burden arising from children infected with SARS-CoV2: a systematic review and meta-analysis. Pediatr Pulmonol. 2020 Aug 5 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/10.1002/ppul.25008 http://www.ncbi.nlm.nih.gov/pubmed/32757374?tool=bestpractice.com 然而,最近一项研究发现,儿童的无症状感染率为 1%,而成人为 9%。[112]Milani GP, Bottino I, Rocchi A, et al. Frequency of children vs adults carrying severe acute respiratory syndrome coronavirus 2 asymptomatically. JAMA Pediatr. 2020 Sep 14 [Epub ahead of print]. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2770117 http://www.ncbi.nlm.nih.gov/pubmed/32926119?tool=bestpractice.com
超级传播事件
已有超级传播事件报道。这些事件与暴发初期的爆炸性增长,以及后期持续传播有关。[113]Frieden TR, Lee CT. Identifying and interrupting superspreading events: implications for control of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020 Jun;26(6):1059-66. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258476/ http://www.ncbi.nlm.nih.gov/pubmed/32187007?tool=bestpractice.com
报道的传播事件包括教堂/宗教集会、家庭聚会、婚礼、合唱团排练、露宿青年营或高中课外活动、健身操课、室内娱乐性运动、商务会议以及呼叫中心办公。[53]Meyerowitz EA, Richterman A, Gandhi RT, et al. Transmission of SARS-CoV-2: a review of viral, host, and environmental factors. Ann Intern Med. 2020 Sep 17 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5008 http://www.ncbi.nlm.nih.gov/pubmed/32941052?tool=bestpractice.com [114]Schwartz NG, Moorman AC, Makaretz A, et al. Adolescent with COVID-19 as the source of an outbreak at a 3-week family gathering: four states, June–July 2020. MMWR Morb Mortal Wkly Rep. 2020 Oct 5 [Epub ahead of print]. https://www.cdc.gov/mmwr/volumes/69/wr/mm6940e2.htm http://www.ncbi.nlm.nih.gov/pubmed/33031365?tool=bestpractice.com [115]Atrubin D, Wiese M, Bohinc B. An outbreak of COVID-19 associated with a recreational hockey game: Florida, June 2020. MMWR Morb Mortal Wkly Rep. 2020 Oct 16;69(41):1492-3. https://www.cdc.gov/mmwr/volumes/69/wr/mm6941a4.htm http://www.ncbi.nlm.nih.gov/pubmed/33056952?tool=bestpractice.com [116]Pray IW, Gibbons-Burgener SN, Rosenberg AZ, et al. COVID-19 outbreak at an overnight summer school retreat: Wisconsin, July-August 2020. MMWR Morb Mortal Wkly Rep. 2020 Oct 30;69(43):1600-4. https://www.cdc.gov/mmwr/volumes/69/wr/mm6943a4.htm http://www.ncbi.nlm.nih.gov/pubmed/33119558?tool=bestpractice.com 据报道,广泛传播也已发生在长期照护机构、收容所、监狱、非法移民拘留中心、肉类和家禽加工厂房以及大型邮轮之上。[117]McMichael TM, Clark S, Pogosjans S, et al. COVID-19 in a long-term care facility: King County, Washington, February 27 – March 9, 2020. MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):339-42. https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e1.htm?s_cid=mm6912e1_w http://www.ncbi.nlm.nih.gov/pubmed/32214083?tool=bestpractice.com [118]Moriarty LF, Plucinski MM, Marston BJ, et al. Public health responses to COVID-19 outbreaks on cruise ships: worldwide, February-March 2020. MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):347-52. https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e3.htm?s_cid=mm6912e3_w http://www.ncbi.nlm.nih.gov/pubmed/32214086?tool=bestpractice.com [119]Yang H, Thompson JR. Fighting covid-19 outbreaks in prisons. BMJ. 2020 Apr 2;369:m1362. https://www.bmj.com/content/369/bmj.m1362.long http://www.ncbi.nlm.nih.gov/pubmed/32241756?tool=bestpractice.com [120]Rogers JH, Link AC, McCulloch D, et al. Characteristics of COVID-19 in homeless shelters: a community-based surveillance study. Ann Intern Med. 2020 Sep 15 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-3799 http://www.ncbi.nlm.nih.gov/pubmed/32931328?tool=bestpractice.com [121]Centre for Evidence-Based Medicine; Durand-Moreau Q, Adisesh A, Mackenzie G, et al. What explains the high rate of SARS-CoV-2 transmission in meat and poultry facilities? 2020 [internet publication]. https://www.cebm.net/covid-19/what-explains-the-high-rate-of-sars-cov-2-transmission-in-meat-and-poultry-facilities/ [122]Donahue M, Sreenivasan N, Stover D, et al. Notes from the field: characteristics of meat processing facility workers with confirmed SARS-CoV-2 infection – Nebraska, April-May 2020. MMWR Morb Mortal Wkly Rep. 2020 Aug 7;69(31):1020-2. https://www.cdc.gov/mmwr/volumes/69/wr/mm6931a3.htm http://www.ncbi.nlm.nih.gov/pubmed/32759920?tool=bestpractice.com [123]Steinberg J, Kennedy ED, Basler C, et al. COVID-19 outbreak among employees at a meat processing facility: South Dakota, March-April 2020. MMWR Morb Mortal Wkly Rep. 2020 Aug 7;69(31):1015-9. https://www.cdc.gov/mmwr/volumes/69/wr/mm6931a2.htm http://www.ncbi.nlm.nih.gov/pubmed/32759914?tool=bestpractice.com [124]Erfani P, Uppal N, Lee CH, et al. COVID-19 testing and cases in immigration detention centers, April-August 2020. JAMA. 2020 Oct 29 [Epub ahead of print]. https://jamanetwork.com/journals/jama/fullarticle/2772627 http://www.ncbi.nlm.nih.gov/pubmed/33119038?tool=bestpractice.com
有限传播已在托儿所、学校和大学中有报道,且感染病例可能将感染传播给家庭成员。[125]Lopez AS, Hill M, Antezano J, et al. Transmission dynamics of COVID-19 outbreaks associated with child care facilities: Salt Lake City, Utah, April–July 2020. MMWR Morb Mortal Wkly Rep. 2020 Sep 18;69(37):1319-23. https://www.cdc.gov/mmwr/volumes/69/wr/mm6937e3.htm http://www.ncbi.nlm.nih.gov/pubmed/32941418?tool=bestpractice.com [126]Leeb RT, Price S, Sliwa S, et al. COVID-19 trends among school-aged children: United States, March 1–September 19, 2020. MMWR Morb Mortal Wkly Rep. 2020 Oct 2;69(39):1410-5. https://www.cdc.gov/mmwr/volumes/69/wr/mm6939e2.htm http://www.ncbi.nlm.nih.gov/pubmed/33001869?tool=bestpractice.com [127]Wilson E, Donovan CV, Campbell M, et al. Multiple COVID-19 clusters on a university campus: North Carolina, August 2020. MMWR Morb Mortal Wkly Rep. 2020 Oct 2;69(39):1416-8. https://www.cdc.gov/mmwr/volumes/69/wr/mm6939e3.htm http://www.ncbi.nlm.nih.gov/pubmed/33001871?tool=bestpractice.com
某些个体是病毒超级脱落者,但是超级传播者事件背后的原因,通常不仅仅是病毒脱落量过大,而更为复杂,可能包括多种行为、宿主和环境因素。[128]Stein RA. Super-spreaders in infectious diseases. Int J Infect Dis. 2011 Aug;15(8):e510-3. https://www.ijidonline.com/article/S1201-9712(11)00024-5/fulltext http://www.ncbi.nlm.nih.gov/pubmed/21737332?tool=bestpractice.com
病毒传播因素
潜伏期
潜伏期估计为 1 至 14 天,中位时间为 5 至 6 天。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [129]McAloon C, Collins Á, Hunt K, et al. Incubation period of COVID-19: a rapid systematic review and meta-analysis of observational research. BMJ Open. 2020 Aug 16;10(8):e039652. https://bmjopen.bmj.com/content/10/8/e039652 http://www.ncbi.nlm.nih.gov/pubmed/32801208?tool=bestpractice.com [130]Wassie GT, Azene AG, Bantie GM, et al. Incubation period of SARS-CoV-2: a systematic review and meta-analysis. Curr Ther Res Clin Exp. 2020 Oct 11:100607. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548076/ http://www.ncbi.nlm.nih.gov/pubmed/33071295?tool=bestpractice.com 传染性在症状发作前 1 天左右达到峰值,并在 7 天内下降。[53]Meyerowitz EA, Richterman A, Gandhi RT, et al. Transmission of SARS-CoV-2: a review of viral, host, and environmental factors. Ann Intern Med. 2020 Sep 17 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5008 http://www.ncbi.nlm.nih.gov/pubmed/32941052?tool=bestpractice.com
基本传染数(R₀)
初步报告提示,基本传染数(即从感染者处获得感染的人数)据估计为 2.2-3.3。[47]Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-207. https://www.nejm.org/doi/full/10.1056/NEJMoa2001316 http://www.ncbi.nlm.nih.gov/pubmed/31995857?tool=bestpractice.com [131]Liu Y, Gayle AA, Wilder-Smith A, et al. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med. 2020 Mar 13;27(2). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074654/ http://www.ncbi.nlm.nih.gov/pubmed/32052846?tool=bestpractice.com [132]Xie Y, Wang Z, Liao H, et al. Epidemiologic, clinical, and laboratory findings of the COVID-19 in the current pandemic: systematic review and meta-analysis. BMC Infect Dis. 2020 Aug 31;20(1):640. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457225/ http://www.ncbi.nlm.nih.gov/pubmed/32867706?tool=bestpractice.com 美国疾病预防控制中心目前给出的最佳估值为 2.5(截至 2020 年 9 月 10 日)。[133]Centers for Disease Control and Prevention. COVID-19 pandemic planning scenarios. 2020 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html
公共卫生措施(例如保持社交距离)落实到位时,R₀ 降低。[134]Inglesby TV. Public health measures and the reproduction number of SARS-CoV-2. JAMA. 2020 May 1 [Epub ahead of print]. https://jamanetwork.com/journals/jama/fullarticle/2765665 http://www.ncbi.nlm.nih.gov/pubmed/32356869?tool=bestpractice.com
人际传播间隔时间
从原发患者出现症状开始,到通过传播链感染的患者症状发作之间的时间,估计约为 5 至 6 天。[135]Zhang P, Wang T, Xie SX. Meta-analysis of several epidemic characteristics of COVID-19. J Data Sci. 2020 Jul;18(3):536-49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575205/ http://www.ncbi.nlm.nih.gov/pubmed/33088292?tool=bestpractice.com
续发率
续发率为暴露于指示病例(或原发病例)而患病的患者比例。
家庭总体续发率为 18.1%;但是,各研究之间存在显著异质性,比率从 3.9% 至 54.9% 不等。有症状指示病例比无症状病例比率更高,成人比儿童感染易感性更高。与其他家庭成员相比,指示病例的配偶更易受到感染。据估计,医疗机构中续发率约为 0.7%。[136]Koh WC, Naing L, Chaw L, et al. What do we know about SARS-CoV-2 transmission? A systematic review and meta-analysis of the secondary attack rate and associated risk factors. PLoS One. 2020 Oct 8;15(10):e0240205. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240205 http://www.ncbi.nlm.nih.gov/pubmed/33031427?tool=bestpractice.com
指示病例所有密切接触者的续发率约为 0.45% 至 3.7%。[94]Luo L, Liu D, Liao X, et al. Contact settings and risk for transmission in 3410 close contacts of patients with COVID-19 in Guangzhou, China: a prospective cohort study. Ann Intern Med. 2020 Aug 13 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-2671 http://www.ncbi.nlm.nih.gov/pubmed/32790510?tool=bestpractice.com [137]Burke RM, Midgley CM, Dratch A, et al. Active monitoring of persons exposed to patients with confirmed COVID-19 - United States, January-February 2020. MMWR Morb Mortal Wkly Rep. 2020 Mar 6;69(9):245-6. https://www.cdc.gov/mmwr/volumes/69/wr/mm6909e1.htm http://www.ncbi.nlm.nih.gov/pubmed/32134909?tool=bestpractice.com [138]Cheng HY, Jian SW, Liu DP, et al. Contact tracing assessment of COVID-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset. JAMA Intern Med. 2020 May 1 [Epub ahead of print]. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2765641 http://www.ncbi.nlm.nih.gov/pubmed/32356867?tool=bestpractice.com
根据一项针对 391 例指示病例的 3410 名密切接触者的研究,续发率随指示病例严重程度而上升(即无症状病例为 0.3%,而重症/危重病例则为 6.2%)。[94]Luo L, Liu D, Liao X, et al. Contact settings and risk for transmission in 3410 close contacts of patients with COVID-19 in Guangzhou, China: a prospective cohort study. Ann Intern Med. 2020 Aug 13 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-2671 http://www.ncbi.nlm.nih.gov/pubmed/32790510?tool=bestpractice.com
与症状前患者密切接触引起的总续发率约为 3.3%,其中家庭接触占 16.1%,社交接触占 1.1%,工作接触占 0%。[139]Zhang W, Cheng W, Luo L, et al. Secondary transmission of coronavirus disease from presymptomatic persons, China. Emerg Infect Dis. 2020 May 26;26(8). https://wwwnc.cdc.gov/eid/article/26/8/20-1142_article http://www.ncbi.nlm.nih.gov/pubmed/32453686?tool=bestpractice.com
与年龄较大的儿童相比,<5 岁的儿童续发率较低,如果家庭指示病例为母体,则感染风险更高。[140]Yung CF, Kam KQ, Chong CY, et al. Household transmission of SARS-CoV-2 from adults to children. J Pediatr. 2020 Jul 4 [Epub ahead of print]. https://www.jpeds.com/article/S0022-3476(20)30852-0/pdf http://www.ncbi.nlm.nih.gov/pubmed/32634405?tool=bestpractice.com 托儿所或学校中的儿童续发率为 1.2%。[141]Macartney K, Quinn HE, Pillsbury AJ, et al. Transmission of SARS-CoV-2 in Australian educational settings: a prospective cohort study. Lancet Child Adolesc Health. 2020 Aug 3 [Epub ahead of print]. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30251-0/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32758454?tool=bestpractice.com
病毒载量
在感染早期,上呼吸道(鼻咽和口咽)中的病毒载量最高,然后在下呼吸道中(痰)增加。症状发作后病毒载量迅速下降。重症患者病毒载量高于轻症患者。[53]Meyerowitz EA, Richterman A, Gandhi RT, et al. Transmission of SARS-CoV-2: a review of viral, host, and environmental factors. Ann Intern Med. 2020 Sep 17 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5008 http://www.ncbi.nlm.nih.gov/pubmed/32941052?tool=bestpractice.com
无症状患者和轻症患者的上呼吸道病毒载量相当。[142]Ra SH, Lim JS, Kim GU, et al. Upper respiratory viral load in asymptomatic individuals and mildly symptomatic patients with SARS-CoV-2 infection. Thorax. 2020 Sep 22 [Epub ahead of print]. https://thorax.bmj.com/content/early/2020/08/28/thoraxjnl-2020-215042.long http://www.ncbi.nlm.nih.gov/pubmed/32963115?tool=bestpractice.com
病毒脱落
据估计,症状消退后,病毒脱落的中位持续时间为 8 至 20 天。然而,已在各种样本中检测到脱落最长达 60 天,甚至在 1 名孕妇中检测到脱落时间为 104 天。[143]Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62. https://www.thelancet.com/pb-assets/Lancet/pdfs/S014067362305663.pdf http://www.ncbi.nlm.nih.gov/pubmed/32171076?tool=bestpractice.com [144]Chang, Mo G, Yuan X, et al. Time kinetics of viral clearance and resolution of symptoms in novel coronavirus infection. Am J Respir Crit Care Med. 2020 May 1;201(9):1150-2. https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0524LE http://www.ncbi.nlm.nih.gov/pubmed/32200654?tool=bestpractice.com [145]Yang JR, Deng DT, Wu N, et al. Persistent viral RNA positivity during recovery period of a patient with SARS-CoV-2 infection. J Med Virol. 2020 Apr 24 [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/32330293?tool=bestpractice.com [146]Jiang X, Luo M, Zou Z, et al. Asymptomatic SARS-CoV-2 infected case with viral detection positive in stool but negative in nasopharyngeal samples lasts for 42 days. J Med Virol. 2020 Apr 24 [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/32330309?tool=bestpractice.com [147]Li J, Zhang L, Liu B, et al. Case report: viral shedding for 60 days in a woman with novel coronavirus disease (COVID-19). Am J Trop Med Hyg. 2020 Jun;102(6):1210-3. http://www.ajtmh.org/content/journals/10.4269/ajtmh.20-0275 http://www.ncbi.nlm.nih.gov/pubmed/32342849?tool=bestpractice.com [148]Sun J, Xiao J, Sun R, et al. Prolonged persistence of SARS-CoV-2 RNA in body fluids. Emerg Infect Dis. 2020 May 8;26(8). https://wwwnc.cdc.gov/eid/article/26/8/20-1097_article http://www.ncbi.nlm.nih.gov/pubmed/32383638?tool=bestpractice.com [149]Molina LP, Chow SK, Nickel A, et al. Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in an obstetric patient with antibody seroconversion. Obstet Gynecol. 2020 Jul 21 [Epub ahead of print]. https://journals.lww.com/greenjournal/Abstract/9000/Prolonged_Detection_of_Severe_Acute_Respiratory.97292.aspx http://www.ncbi.nlm.nih.gov/pubmed/32701763?tool=bestpractice.com
有症状患者病毒脱落持续时间比无症状患者更长(分别为 25.2 天和 22.6 天),重症患者也比轻症患者持续时间长(分别为 21 天和 14 天)。[150]Noh JY, Yoon JG, Seong H, et al. Asymptomatic infection and atypical manifestations of COVID-19: comparison of viral shedding duration. J Infect. 2020 May 20 [Epub ahead of print]. https://www.journalofinfection.com/article/S0163-4453(20)30310-8/pdf http://www.ncbi.nlm.nih.gov/pubmed/32445728?tool=bestpractice.com [151]Zheng S, Fan J, Yu F, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January – March 2020: retrospective cohort study. BMJ. 2020 Apr 21;369:m1443. https://www.bmj.com/content/369/bmj.m1443.long http://www.ncbi.nlm.nih.gov/pubmed/32317267?tool=bestpractice.com
感染期远短于可检测出病毒脱落的持续时间。轻中症患者出现症状 10 天后,或者重症或危重症患者出现症状 20 天后,尽管病毒持续脱落,但未分离出活病毒。关于持续性无症状感染者病毒脱落动力学的数据不一致。[53]Meyerowitz EA, Richterman A, Gandhi RT, et al. Transmission of SARS-CoV-2: a review of viral, host, and environmental factors. Ann Intern Med. 2020 Sep 17 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5008 http://www.ncbi.nlm.nih.gov/pubmed/32941052?tool=bestpractice.com 暂无具备说服力的证据表明病毒脱落持续时间与传染性持续时间相关。[152]Widders A, Broom A, Broom J. SARS-CoV-2: the viral shedding vs infectivity dilemma. Infect Dis Health. 2020 Aug;25(3):210-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237903/ http://www.ncbi.nlm.nih.gov/pubmed/32473952?tool=bestpractice.com
与长时间病毒脱落有关的因素包括男性、高龄、合并高血压、症状发作后入院延迟或入院时呈重症,以及使用有创机械通气或皮质类固醇。[153]Xu K, Chen Y, Yuan J, et al. Factors associated with prolonged viral RNA shedding in patients with COVID-19. Clin Infect Dis. 2020 Jul 28;71(15):799-806. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184421/ http://www.ncbi.nlm.nih.gov/pubmed/32271376?tool=bestpractice.com
病理生理学
病理生理学尚未完全了解;但是,更多信息正在获取。[154]Cevik M, Kuppalli K, Kindrachuk J, et al. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ. 2020 Oct 23;371:m3862. https://www.bmj.com/content/371/bmj.m3862 http://www.ncbi.nlm.nih.gov/pubmed/33097561?tool=bestpractice.com
血管紧张素转换酶-2(ACE2) 受体
严重急性呼吸综合征冠状病毒 2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)可与 ACE2 受体结合,表明其与 SARS 具有相似的发病机制。[44]Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-74. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30251-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32007145?tool=bestpractice.com [155]Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science. 2020 Mar 27;367(6485):1444-8. https://science.sciencemag.org/content/early/2020/03/03/science.abb2762 http://www.ncbi.nlm.nih.gov/pubmed/32132184?tool=bestpractice.com
与 SARS-CoV-1 相比而言,SARS-CoV-2 突触糖蛋白受体结合域的独特结构特征(促使病毒侵入宿主细胞),使其对宿主细胞 ACE2 具有更高的结合亲和力。[156]Chen Y, Guo Y, Pan Y, et al. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. 2020 Feb 17;525(1):135-40. https://www.sciencedirect.com/science/article/pii/S0006291X20303399?via%3Dihub http://www.ncbi.nlm.nih.gov/pubmed/32081428?tool=bestpractice.com 其他 SARS 样冠状病毒中不存在这种弗林蛋白酶样切割位点。[157]Coutard B, Valle C, de Lamballerie X, et al. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res. 2020 Feb 10;176:104742. http://www.ncbi.nlm.nih.gov/pubmed/32057769?tool=bestpractice.com 在所有被测病毒种类中,SARS-CoV-2 刺突蛋白和人类 ACE2 之间的结合能最高,表明只有 SARS-CoV-2 刺突蛋白发生了进化,可结合并感染表达 ACE2 的人类细胞。[158]Piplani S, Singh PK, Winkler DA, et al; arXiv. In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus. 2020 [internet publication]. https://arxiv.org/abs/2005.06199
来自其他冠状病毒机制证据表明,SARS-CoV-2 可能下调 ACE2,导致血浆血管紧张素-II 毒性过度蓄积,从而可能诱发急性呼吸窘迫综合征和暴发性心肌炎。[159]Hanff TC, Harhay MO, Brown TS, et al. Is there an association between COVID-19 mortality and the renin-angiotensin system: a call for epidemiologic investigations. Clin Infect Dis. 2020 Jul 28;71(15):870-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184340/ http://www.ncbi.nlm.nih.gov/pubmed/32215613?tool=bestpractice.com [160]Wu Z, Hu R, Zhang C, et al. Elevation of plasma angiotensin II level is a potential pathogenesis for the critically ill COVID-19 patients. Crit Care. 2020 Jun 5;24(1):290. https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03015-0 http://www.ncbi.nlm.nih.gov/pubmed/32503680?tool=bestpractice.com
根据对源自人类主要生理系统的单细胞 RNA 测序数据集进行分析,认为包括肺、心脏、食道、肾脏、膀胱和回肠在内的器官,由于其 ACE2 表达水平,而更容易受到 SARS-CoV-2 感染。[161]Zou X, Chen K, Zou J, et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020 Apr;14(2):185-92. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088738/ http://www.ncbi.nlm.nih.gov/pubmed/32170560?tool=bestpractice.com 这可以解释与感染相关的肺外表现。
与成人相比,年龄 <10 岁的儿童鼻上皮中 ACE2 表达水平较低,这可能解释了为什么 COVID-19 在儿童中的流行率较低;但是,对此需要进一步的研究。[162]Bunyavanich S, Do A, Vicencio A. Nasal gene expression of angiotensin-converting enzyme 2 in children and adults. JAMA. 2020 May 20;323(23):2427-9. https://jamanetwork.com/journals/jama/fullarticle/2766524 http://www.ncbi.nlm.nih.gov/pubmed/32432657?tool=bestpractice.com
跨膜丝氨酸蛋白酶 2(TMPRSS2)
SARS-CoV-2 使用宿主 TMPRSS2 进行 S 蛋白活化以及病毒和宿主细胞膜融合。[163]Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020 Apr 16;181(2):271-80. https://www.sciencedirect.com/science/article/pii/S0092867420302294 http://www.ncbi.nlm.nih.gov/pubmed/32142651?tool=bestpractice.com
相比亚洲人群、拉丁人群、白人和混合种族/民族的人群,黑人鼻粘膜上皮中 TMPRSS2 表达水平更高,这可能是一个导致黑人感染负担更重的因素。[164]Bunyavanich S, Grant C, Vicencio A. Racial/ethnic variation in nasal gene expression of transmembrane serine protease 2 (TMPRSS2). JAMA. 2020 Sep 10 [Epub ahead of print]. https://jamanetwork.com/journals/jama/fullarticle/2770682 http://www.ncbi.nlm.nih.gov/pubmed/32910146?tool=bestpractice.com
尸检研究
肺:尸检结果表明,因呼吸衰竭而死亡的患者有渗出性弥漫性肺泡损伤证据,伴大量毛细血管充血,且常伴微血栓形成。透明膜形成和肺细胞非典型增生十分常见。显微镜和大体两个水平均已发现肺动脉血栓物质阻塞。患者同时存在全身血栓性微血管病体征。与细胞内病毒存在和破裂细胞膜有关的严重内皮损伤已得到注意。其他发现包括支气管肺炎、肺栓塞、肺泡出血和血管炎。通过填充性血管新生产生的显著新血管生长使 COVID-19 肺部病变与重度流感感染不同。[165]Menter T, Haslbauer JD, Nienhold R, et al. Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction. Histopathology. 2020 May 4 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/abs/10.1111/his.14134 http://www.ncbi.nlm.nih.gov/pubmed/32364264?tool=bestpractice.com [166]Schaller T, Hirschbühl K, Burkhardt K, et al. Postmortem examination of patients with COVID-19. JAMA. 2020 May 21;323(24):2518-20. https://jamanetwork.com/journals/jama/fullarticle/2766557 http://www.ncbi.nlm.nih.gov/pubmed/32437497?tool=bestpractice.com [167]Lax SF, Skok K, Zechner P, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series. Ann Intern Med. 2020 May 14 [Epub ahead of print]. https://www.acpjournals.org/doi/full/10.7326/M20-2566 http://www.ncbi.nlm.nih.gov/pubmed/32422076?tool=bestpractice.com [168]Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020 Jul 9;383(2):120-8. https://www.nejm.org/doi/full/10.1056/NEJMoa2015432 http://www.ncbi.nlm.nih.gov/pubmed/32437596?tool=bestpractice.com [169]Fox SE, Akmatbekov A, Harbert JL, et al. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020 Jul;8(7):681-6. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30243-5/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32473124?tool=bestpractice.com [170]Carsana L, Sonzogni A, Nasr A, et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infect Dis. 2020 Jun 8 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279758/ http://www.ncbi.nlm.nih.gov/pubmed/32526193?tool=bestpractice.com
神经:一项尸检研究中,脑样本组织病理学检查显示低氧改变,但无病毒所致脑炎或其他特定颅脑改变。脑组织中检测到低水平病毒。[171]Solomon IH, Normandin E, Bhattacharyya S, et al. Neuropathological features of Covid-19. N Engl J Med. 2020 Jun 12 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMc2019373 http://www.ncbi.nlm.nih.gov/pubmed/32530583?tool=bestpractice.com 另一项研究发现了轻度的神经病理改变,最常见的是脑干中明显的神经炎性改变。[172]Matschke J, Lütgehetmann M, Hagel C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol. 2020 Oct 5 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535629/ http://www.ncbi.nlm.nih.gov/pubmed/33031735?tool=bestpractice.com
心肌:尸检研究中,常于心肌组织检测出 SARS-CoV-2。[173]Lindner D, Fitzek A, Bräuninger H, et al. Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases. JAMA Cardiol. 2020 Jul 27 [Epub ahead of print]. https://jamanetwork.com/journals/jamacardiology/fullarticle/2768914 http://www.ncbi.nlm.nih.gov/pubmed/32730555?tool=bestpractice.com 小儿多系统炎性综合征儿童心肌组织中据报道已发现病毒和炎性改变。[174]Dolhnikoff M, Ferreira Ferranti J, de Almeida Monteiro RA, et al. SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome. Lancet Child Adolesc Health. 2020 Aug 20 [Epub ahead of print]. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30257-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32828177?tool=bestpractice.com
免疫学:免疫浸润评估显示,肺和其他若干器官中明显存在中性粒细胞聚集。中性粒细胞栓由中性粒细胞和中性粒细胞胞外诱捕网(neutrophil extracellular trap, NET)组成,或是 NET 和血小板的聚集体,存在于心脏、肾脏、肝脏和大脑中。因此,NET 可能在与 SARS-CoV-2 感染相关的凝血异常中起作用。与零星存在的病毒相比,聚集的中性粒细胞和 NET 不成比例,表明发生了自主的适应不良性免疫反应。[175]Schurink B, Roos E, Radonic T, et al. Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. Lancet Microbe. 2020 Sep 25 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518879/ http://www.ncbi.nlm.nih.gov/pubmed/33015653?tool=bestpractice.com
其他:尸检的其他新发现包括胰腺炎、心包炎、肾上腺微小梗死、继发性弥漫性毛霉菌病和脑小胶质细胞活化。[176]Hanley B, Naresh KN, Roufosse C, et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. Lancet Microbe. 2020 Aug 20 [Epub ahead of print]. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(20)30115-4/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32844161?tool=bestpractice.com
内皮功能障碍
有一个假说认为 COVID-19 是一种内皮性疾病。[177]Sardu C, Gambardella J, Morelli MB, et al. Hypertension, thrombosis, kidney failure, and diabetes: is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med. 2020 May 11;9(5): E1417. https://www.mdpi.com/2077-0383/9/5/1417/htm http://www.ncbi.nlm.nih.gov/pubmed/32403217?tool=bestpractice.com [178]Tibiriçá E, De Lorenzo A. Increased severity of COVID-19 in people with obesity: are we overlooking plausible biological mechanisms? Obesity (Silver Spring). 2020 May 13 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/10.1002/oby.22887 http://www.ncbi.nlm.nih.gov/pubmed/32403201?tool=bestpractice.com [179]Bermejo-Martin JF, Almansa R, Torres A, et al. COVID-19 as a cardiovascular disease: the potential role of chronic endothelial dysfunction. Cardiovasc Res. 2020 Aug 1;116(10):e132-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314234/ http://www.ncbi.nlm.nih.gov/pubmed/32420587?tool=bestpractice.com 内皮病和血小板活化似乎是住院患者 COVID-19 重要特征,并可能与凝血异常、重症和死亡相关。[180]Goshua G, Pine AB, Meizlish ML, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020 Aug;7(8):e575-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326446/ http://www.ncbi.nlm.nih.gov/pubmed/32619411?tool=bestpractice.com
高粘血症在患者中有所报道。已知其可损伤内皮,且为血栓形成的已知危险因素。高粘血症与血栓并发症之间的潜在关联值得进行进一步研究。[181]Maier CL, Truong AD, Auld SC, et al. COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia? Lancet. 2020 Jun 6;395(10239):1758-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247793/ http://www.ncbi.nlm.nih.gov/pubmed/32464112?tool=bestpractice.com
基因
遗传因素被认为发挥作用。在四例男性重症患者病例系列研究中,发现罕见的 TLR7 X 染色体功能缺失变体,这与干扰素应答受损有关。[182]van der Made CI, Simons A, Schuurs-Hoeijmakers J, et al. Presence of genetic variants among young men with severe COVID-19. JAMA. 2020 Jul 24;324(7):1-11. https://jamanetwork.com/journals/jama/fullarticle/2768926 http://www.ncbi.nlm.nih.gov/pubmed/32706371?tool=bestpractice.com
呼吸衰竭患者染色体 3p21.31 基因簇上发现了一个新易感基因位点,可能证实 ABO 血型系统的涉及。[183]Severe Covid-19 GWAS Group; Ellinghaus D, Degenhardt F, Bujanda L, et al. Genomewide association study of severe Covid-19 with respiratory failure. N Engl J Med. 2020 Oct 15;383(16):1522-34. https://www.nejm.org/doi/full/10.1056/NEJMoa2020283 http://www.ncbi.nlm.nih.gov/pubmed/32558485?tool=bestpractice.com
分类
世界卫生组织:COVID-19 病严重程度[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
轻症
有症状患者符合 COVID-19 病例定义,无缺氧或肺炎证据。
常见症状包括发热、咳嗽、乏力、厌食、呼吸困难和肌痛。其他非特异性症状包括咽痛、鼻塞、头痛、腹泻、恶心/呕吐和嗅觉/味觉丧失。
老年人和免疫抑制者可能会出现非典型症状(例如乏力、警觉性降低、活动能力下降、腹泻、纳差、谵妄、无发热)。
由于妊娠生理适应、不良妊娠事件(例如呼吸困难、发热、胃肠道症状、乏力)或其他疾病(例如疟疾)等所致症状,可能会与 COVID-19 症状产生交叠。
中度病变
青少年或成人:肺炎临床征象(即发热、咳嗽、呼吸困难、呼吸加快),但无重症肺炎征象,包括室内空气中,血氧饱和度(SpO₂)≥90%。
儿童:非重症肺炎临床征象(即咳嗽或呼吸困难加呼吸加快和/或胸部凹陷),无重症肺炎征象。呼吸加快定义为:
<2 月龄:呼吸 ≥60 次/min
2-11 月龄:呼吸 ≥50 次/min
1-5 岁:呼吸 ≥40 次/min。
尽管诊断可基于临床进行,但胸部影像学检查可辅助诊断,识别或排除肺部并发症。
严重疾病
青少年或成人:肺炎临床征象(即发热、咳嗽、呼吸困难、呼吸加快)加以下其中一项:
呼吸频率≥30 次/分
重症呼吸窘迫
室内空气环境中,SpO₂ ≤90%。
儿童:肺炎临床征象(即咳嗽或呼吸困难),加以下至少一项:
中央型紫绀或 SpO₂ <90%
严重呼吸窘迫(例如呼吸加快、痰鸣音、非常严重的胸部凹陷)
一般性危险征象:无法母乳喂养或饮水、昏睡或无意识,或出现惊厥
呼吸加快(<2 月龄:呼吸 ≥60 次/分;2-11 月龄:呼吸 ≥50 次/分;1-5 岁:呼吸 ≥40 次/分)。
尽管诊断可基于临床进行,但胸部影像学检查可辅助诊断,识别或排除肺部并发症。
危重疾病
出现急性呼吸窘迫综合征(ARDS)、脓毒症或脓毒性休克。
其他并发症包括急性肺栓塞、急性冠状动脉综合征、急性卒中和谵妄。
美国国立卫生研究院:COVID-19 临床分类[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
无症状或症状前感染
严重急性呼吸综合征冠状病毒 2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)呈阳性,但无症状者。
轻症
表现各种症状和征象(例如发热、咳嗽、咽痛、周身不适、头痛、肌肉疼痛),但无呼吸短促、呼吸困难或影像学检查异常者。
中度疾病
通过临床评估或影像学检查证实有下呼吸道疾病证据,且在海平面室内空气中,氧饱和度(SpO₂)>93%。
重度疾病
呼吸频率 >30次/分,在海平面室内空气中,氧饱和度(SpO₂)≤93%,氧动脉分压与吸入氧分数(PaO₂/FiO₂)比率 <300,或肺浸润 >50% 者。
重大疾病
伴呼吸衰竭、脓毒性休克和/或多器官功能障碍者。
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