流行病学
自大流行开始以来,各大洲均有病例见诸报道。全球已报道超过 6 亿确诊病例,以及超过 650 万例死亡病例。[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
更新的病例数量可从世界卫生组织(World Health Organization, WHO)和美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)获取:
2020 年 2 月至 2021 年 9 月期间的 CDC 数据表明,美国的疾病结局估计比率如下:[23]Centers for Disease Control and Prevention. Estimated COVID-19 burden. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burden.html
感染率:44,650/100,000(44.6%)
疾病症状率:37,764/100,000(37.8%)
住院率:2286/100,000(2.3%)
死亡率:281/100,000(0.28%)。
≥70 岁老年人和男性感染和重症风险升高。[24]Pijls BG, Jolani S, Atherley A, et al. Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies. BMJ Open. 2021 Jan 11;11(1):e044640. https://bmjopen.bmj.com/content/11/1/e044640.long http://www.ncbi.nlm.nih.gov/pubmed/33431495?tool=bestpractice.com 青少年对感染的易感性似乎与成人相当,儿童则具有更低的易感性。然而,证据存在冲突,年龄与感染易感性之间的详细关联尚需进一步研究。[25]Viner RM, Mytton OT, Bonell C, et al. Susceptibility to SARS-CoV-2 infection among children and adolescents compared with adults: a systematic review and meta-analysis. JAMA Pediatr. 2021 Feb 1;175(2):143-56. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2771181 http://www.ncbi.nlm.nih.gov/pubmed/32975552?tool=bestpractice.com [26]World Health Organization. COVID-19 disease in children and adolescents: scientific brief, 29 September 2021. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Children_and_adolescents-2021.1 与成年人不同,基于年龄或性别,儿童似乎不具有更高的重症罹患风险。[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 与野生型病毒相比,病毒变体可在幼儿中更有效、更快速的传播,但住院率却呈现下降。[28]Somekh I, Stein M, Karakis I, et al. Characteristics of SARS-CoV-2 infections in Israeli children during the circulation of different SARS-CoV-2 variants. JAMA Netw Open. 2021 Sep 1;4(9):e2124343. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783851 http://www.ncbi.nlm.nih.gov/pubmed/34491353?tool=bestpractice.com [29]Chen F, Tian Y, Zhang L, et al. The role of children in household transmission of COVID-19: a systematic review and meta-analysis. Int J Infect Dis. 2022 May 11;122:266-75. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091150 http://www.ncbi.nlm.nih.gov/pubmed/35562045?tool=bestpractice.com
医务工作者感染发病率为 0% 至 49.6%,血清阳性率为 1.6% 至 31.6% 之间。基于中等确定性证据,年龄、性别或医务工作者角色(即护士 vs 医生)与感染风险之间并无关联。基于中等确定性证据,与白种人或非西班牙裔相比,黑种人或西班牙裔与感染风险升高具有相关性。基于中等确定性证据,使用个人防护装备与感染风险降低具有相关性。[30]Chou R, Dana T, Buckley DI, et al. Epidemiology of and risk factors for coronavirus infection in health care workers: a living rapid review. Ann Intern Med. 2020 Jul 21;173(2):120-36. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240841 http://www.ncbi.nlm.nih.gov/pubmed/32369541?tool=bestpractice.com [31]Chou R, Dana T, Buckley DI, et al. Update alert 10: epidemiology of and risk factors for coronavirus infection in health care workers. Ann Intern Med. 2021 Nov 16;M21-4294. https://www.acpjournals.org/doi/10.7326/M21-4294 http://www.ncbi.nlm.nih.gov/pubmed/34781714?tool=bestpractice.com
危险因素
与可能病例或确诊病例产生接触者,感染风险升高。
世界卫生组织将接触者定义为出现以下任何一种暴露者:与可能或确诊病例面对面相处于 1 米以内(3 英尺),至少 15 分钟;与可能或确诊病例直接发生躯体接触;在未使用推荐的个人防护装备时,直接照护可能或确诊 COVID-19 患者;或当地卫生机构基于当地风险评估确定的其他情况。暴露必须发生于病例传染期内。对于有症状病例,这意味着病例出现症状的前 2 天和出现症状的后 10 天,再加上至少 3 天无症状期,总共为出现症状后至少 13 天。对于无症状病例,这意味着在确诊样本采集之日之前的 2 天和之后的 10 天。[126]World Health Organization. Public health surveillance for COVID-19: interim guidance. 2022 [internet publication]. https://www.who.int/publications/i/item/who-2019-nCoV-surveillanceguidance-2020.7
美国疾病预防控制中心将密切接触定义为症状发作前 2 天(或无症状患者接受检测前 2 天内),24 小时内在距感染者 2 米(6 英尺)范围内停留时间总计达 15 分钟以上者。[127]Centers for Disease Control and Prevention. Coronavirus disease 2019 (COVID-19): contact tracing - appendices. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/php/contact-tracing/contact-tracing-plan/appendix.html
在高传播风险地区生活或工作者,感染风险升高。
在传播高风险地区(例如,封闭环境、人道主义环境)居住或工作的人,以及在卫生服务机构的工作人员(包括医疗机构和住所)存在更高的感染风险。[126]World Health Organization. Public health surveillance for COVID-19: interim guidance. 2022 [internet publication]. https://www.who.int/publications/i/item/who-2019-nCoV-surveillanceguidance-2020.7
老年人感染和重症风险升高。[24]Pijls BG, Jolani S, Atherley A, et al. Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies. BMJ Open. 2021 Jan 11;11(1):e044640. https://bmjopen.bmj.com/content/11/1/e044640.long http://www.ncbi.nlm.nih.gov/pubmed/33431495?tool=bestpractice.com
住院和死亡风险随年龄增长而升高。基于高质量证据,已观察到年龄相关性住院死亡率、病例死亡率和住院风险分别增加了 5.7%、7.4% 和 3.4%。未观察到按年龄划分的重症监护病房收治和插管风险升高。无证据表明风险陡然上升的特定年龄阈值。[128]Romero Starke K, Reissig D, Petereit-Haack G, et al. The isolated effect of age on the risk of COVID-19 severe outcomes: a systematic review with meta-analysis. BMJ Glob Health. 2021 Dec;6(12):e006434. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678541 http://www.ncbi.nlm.nih.gov/pubmed/34916273?tool=bestpractice.com
根据美国数据,与 18 至 29 岁人群相比,85 岁及以上人群的住院风险和死亡风险分别高出 15 倍和 340 倍。[129]Centers for Disease Control and Prevention. Risk for COVID-19 infection, hospitalization, and death by age group. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-age.html
在英国,一项横断面研究数据表明,年龄 40 岁至 64 岁人群感染风险最高,其次为 75 岁及以上患者,而后为 65 岁至 74 岁人群。[130]de Lusignan S, Dorward J, Correa A, et al. Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study. Lancet Infect Dis. 2020 Sep;20(9):1034-42. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228715 http://www.ncbi.nlm.nih.gov/pubmed/32422204?tool=bestpractice.com 80 岁以上患者中观察到最高死亡率。[131]Bonanad C, García-Blas S, Tarazona-Santabalbina F, et al. The effect of age on mortality in patients with COVID-19: a meta-analysis with 611,583 subjects. J Am Med Dir Assoc. 2020 Jul;21(7):915-8. https://www.jamda.com/article/S1525-8610(20)30441-2/pdf http://www.ncbi.nlm.nih.gov/pubmed/32674819?tool=bestpractice.com
在美国,≥65 岁患者占所有病例 31%,占住院治疗者 45%,占重症监护病房收治患者 53%,占大流行早期死亡例数 80%,年龄 ≥85 岁患者出现严重结局的发病率最高。[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
尽管年龄是一个独立风险因素,但老年人风险也部分与老年人更可能伴有合并症有关。老年患者营养不良患病率较高,亦可能导致不良结局。[133]Damayanthi HDWT, Prabani KIP. Nutritional determinants and COVID-19 outcomes of older patients with COVID-19: a systematic review. Arch Gerontol Geriatr. 2021 Mar 31;95:104411. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010373 http://www.ncbi.nlm.nih.gov/pubmed/33836322?tool=bestpractice.com
男性感染和重症风险升高。[24]Pijls BG, Jolani S, Atherley A, et al. Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies. BMJ Open. 2021 Jan 11;11(1):e044640. https://bmjopen.bmj.com/content/11/1/e044640.long http://www.ncbi.nlm.nih.gov/pubmed/33431495?tool=bestpractice.com
一项荟萃分析发现,男性的感染、收住院、疾病严重程度、重症监护病房收治和死亡风险更高。[134]Pijls BG, Jolani S, Atherley A, et al. Temporal trends of sex differences for COVID-19 infection, hospitalisation, severe disease, intensive care unit (ICU) admission and death: a meta-analysis of 229 studies covering over 10M patients. F1000Res. 2022 Jan 5;11:5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034173 http://www.ncbi.nlm.nih.gov/pubmed/35514606?tool=bestpractice.com
已提出多种假说来解释这种差异,包括雄性激素驱动的发病机制(证据薄弱)、女性雌激素的免疫保护作用(证据相冲突)、睾酮缺乏引起的炎症风暴(证据有限且相冲突)和细胞因子免疫出生错误(需要更多的研究)。其原因可能是多因素的,且存在多种假说的重合特征。[135]Twitchell DK, Christensen MB, Hackett G, et al. Examining male predominance of severe COVID-19 outcomes: a systematic review. Androg Clin Res Ther. 2022;3(1):41-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527649 http://www.ncbi.nlm.nih.gov/pubmed/36199281?tool=bestpractice.com
属于少数种族/族裔人群者出现感染、重症、住院和死亡的风险将升高。[136]Sze S, Pan D, Nevill CR, et al. Ethnicity and clinical outcomes in COVID-19: a systematic review and meta-analysis. EClinicalMedicine. 2020 Dec;29:100630. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30374-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/33200120?tool=bestpractice.com [137]Mackey K, Ayers CK, Kondo KK, et al. Racial and ethnic disparities in COVID-19-related infections, hospitalizations, and deaths: a systematic review. Ann Intern Med. 2021 Mar;174(3):362-73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772883 http://www.ncbi.nlm.nih.gov/pubmed/33253040?tool=bestpractice.com [138]Khanijahani A, Iezadi S, Gholipour K, et al. A systematic review of racial/ethnic and socioeconomic disparities in COVID-19. Int J Equity Health. 2021 Nov 24;20(1):248. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611382 http://www.ncbi.nlm.nih.gov/pubmed/34819081?tool=bestpractice.com 然而,研究结论却并不一致,尤其对于少数种族/族裔群体的定义和社会经济状态的认定。
英国数据表明,即使考虑了社会人口统计、临床和家庭特征差异之后,与白种人相比,南亚、黑种人和混合族裔人群呈现检测阳性和不良结局(即住院、重症监护病房收治、死亡)风险亦有所增加。[139]Mathur R, Rentsch CT, Morton CE, et al. Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform. Lancet. 2021 May 8;397(10286):1711-24. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00634-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/33939953?tool=bestpractice.com [140]Siddiq S, Ahmed S, Akram I. Clinical outcomes following COVID-19 infection in ethnic minority groups in the UK: a systematic review and meta-analysis. Public Health. 2022 Jun 9 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181265 http://www.ncbi.nlm.nih.gov/pubmed/35970621?tool=bestpractice.com 种族可能在儿童和成人不良结局中起到重要作用。[141]Saatci D, Ranger TA, Garriga C, et al. Association between race and COVID-19 outcomes among 2.6 million children in England. JAMA Pediatr. 2021 Sep 1;175(9):928-38. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2780966 http://www.ncbi.nlm.nih.gov/pubmed/34152371?tool=bestpractice.com
在美国,美洲印第安人或阿拉斯加原住民、拉丁裔、黑种人,以及亚裔或太平洋岛民在大流行第一年呈现阳性检测结果、住院、入住重症监护病房或死亡的可能性高于白种人。[142]Acosta AM, Garg S, Pham H, et al. Racial and ethnic disparities in rates of COVID-19–associated hospitalization, intensive care unit admission, and in-hospital death in the United States from March 2020 to February 2021. JAMA Netw Open. 2021 Oct 1;4(10):e2130479. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785325 http://www.ncbi.nlm.nih.gov/pubmed/34673962?tool=bestpractice.com [143]Magesh S, John D, Li WT, et al. Disparities in COVID-19 outcomes by race, ethnicity, and socioeconomic status: a systematic-review and meta-analysis. JAMA Netw Open. 2021 Nov 1;4(11):e2134147. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785980 http://www.ncbi.nlm.nih.gov/pubmed/34762110?tool=bestpractice.com
此类患者的危险因素包括贫困、低教育水平、居住条件恶劣、家庭收入过低、使用母语以外的语言,以及居所人数超限。[138]Khanijahani A, Iezadi S, Gholipour K, et al. A systematic review of racial/ethnic and socioeconomic disparities in COVID-19. Int J Equity Health. 2021 Nov 24;20(1):248. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611382 http://www.ncbi.nlm.nih.gov/pubmed/34819081?tool=bestpractice.com
虽然多数少数族裔的诊断风险较高,然而一旦收住院,结局就不存在明显的不均衡(巴西少数族裔的高死亡率除外)。这表明少数族裔地位是 COVID 相关性健康结局的重要社会决定因素,可能与其他社会决定因素(例如住房、社会经济地位、就业、一般健康状况)具有相关性。[144]Agyemang C, Richters A, Jolani S, et al. Ethnic minority status as social determinant for COVID-19 infection, hospitalisation, severity, ICU admission and deaths in the early phase of the pandemic: a meta-analysis. BMJ Glob Health. 2021 Nov;6(11):e007433. https://gh.bmj.com/content/6/11/e007433.long http://www.ncbi.nlm.nih.gov/pubmed/34740916?tool=bestpractice.com 结局的种族差异亦可能部分归因于某些族裔合并症发病率较高。[145]Raharja A, Tamara A, Kok LT. Association between ethnicity and severe COVID-19 disease: a systematic review and meta-analysis. J Racial Ethn Health Disparities. 2021 Sep 1;175(9):928-38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659894 http://www.ncbi.nlm.nih.gov/pubmed/33180278?tool=bestpractice.com
长期照护机构人员感染和重症风险升高。[146]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 [147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
在英国,疗养院居民约占第一波大流行中英格兰和威尔士死亡总数三分之一;其他国家亦报道了类似情况。可能由于个人防护装备短缺、人群脆弱以及缺乏检测。[148]Burki T. England and Wales see 20 000 excess deaths in care homes. Lancet. 2020 May 23;395(10237):1602. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31199-5/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32446403?tool=bestpractice.com 一项针对四个养老院的研究发现,26% 居住者在 2 月内死亡,全因死亡率与往年相比,增加了 203%。约 40% 居住者 SARS-CoV-2 检测呈阳性,其中 43% 无症状,18% 出现非典型症状。[149]Graham N, Junghans C, Downes R, et al. SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes. J Infect. 2020 Sep;81(3):411-9. https://www.journalofinfection.com/article/S0163-4453(20)30348-0/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32504743?tool=bestpractice.com
在美国,一项超过 5000 名养老院居住者队列研究显示,其 30 天全因死亡率为 21%。高龄、性别为男性以及认知和机体功能受损,与死亡率呈独立相关。[150]Panagiotou OA, Kosar CM, White EM, et al. Risk factors associated with all-cause 30-day mortality in nursing home residents with COVID-19. JAMA Intern Med. 2021 Apr 1;181(4):439-48. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2774729 http://www.ncbi.nlm.nih.gov/pubmed/33394006?tool=bestpractice.com
存在合并症的患者罹患重症风险更高,合并症越多,风险越大。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html [151]Liu H, Chen S, Liu M, et al. Comorbid chronic diseases are strongly correlated with disease severity among COVID-19 patients: a systematic review and meta-analysis. Aging Dis. 2020 May 9;11(3):668-78. http://www.aginganddisease.org/article/2020/2152-5250/ad-11-3-668.shtml http://www.ncbi.nlm.nih.gov/pubmed/32489711?tool=bestpractice.com
在英国,一项对超过 20,000 例住院患者进行的队列研究报道称,最常见合并症为心脏病(31%)、单纯性糖尿病(21%)、非哮喘性慢性肺病(18%)和慢性肾病(16%)。[152]Docherty AB, Harrison EM, Green CA, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO clinical characterisation protocol: prospective observational cohort study. BMJ. 2020 May 22;369:m1985. https://www.bmj.com/content/369/bmj.m1985 http://www.ncbi.nlm.nih.gov/pubmed/32444460?tool=bestpractice.com 在英国住院的 65,000 名患者中,68% 在入院时报告了至少一种心脏代谢性疾病。基线心脏代谢状况与院内并发症风险升高具有相关性,并在伴有心脏代谢性多发合并症的情况下,该风险将升高。[153]Norris T, Razieh C, Zaccardi F, et al. Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19. Heart. 2021 Dec 15 [Epub ahead of print]. https://heart.bmj.com/content/early/2021/12/14/heartjnl-2021-320047.long http://www.ncbi.nlm.nih.gov/pubmed/34911741?tool=bestpractice.com
在美国,约 95% 住院成人至少有一种报告的基础疾病,最常见者为高血压、脂代谢障碍和肥胖。约 99% 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 据估计,大约 56% 成人和 32% 年轻成人由于伴有至少一种合并症,而存在罹患重症风险。[155]Adams ML, Katz DL, Grandpre J. Updated estimates of chronic conditions affecting risk for complications from coronavirus disease, United States. Emerg Infect Dis. 2020 Jul 3;26(9). https://wwwnc.cdc.gov/eid/article/26/9/20-2117_article http://www.ncbi.nlm.nih.gov/pubmed/32620181?tool=bestpractice.com [156]Adams SH, Park MJ, Schaub JP, et al. Medical vulnerability of young adults to severe COVID-19 illness: data from the National Health Interview Survey. J Adolesc Health. 2020 Jul 9;67(3):362-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355323 http://www.ncbi.nlm.nih.gov/pubmed/32674964?tool=bestpractice.com
全球范围内,高血压(21%)、肥胖(18%)和糖尿病(18%)是最普遍的合并症。癌症、慢性肾病、糖尿病和高血压与死亡率呈独立相关。从统计学角度进行分析,慢性肾病是导致死亡的最主要合并症。[157]Ng WH, Tipih T, Makoah NA, et al. Comorbidities in SARS-CoV-2 patients: a systematic review and meta-analysis. mBio. 2021 Feb 9;12(1):e03647-20. https://mbio.asm.org/content/12/1/e03647-20.long http://www.ncbi.nlm.nih.gov/pubmed/33563817?tool=bestpractice.com 代谢综合征亦与较高的死亡风险具有显著相关性。[158]Zuin M, Rigatelli G, Bilato C, et al. Prognostic role of metabolic syndrome in COVID-19 patients: a systematic review meta-analysis. Viruses. 2021 Sep 27;13(10):1938. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538673 http://www.ncbi.nlm.nih.gov/pubmed/34696368?tool=bestpractice.com
伴有肥胖、糖尿病、慢性肺病(不包括哮喘)、心脏病、癫痫,以及呈现免疫功能低下状态等合并症的儿童具有较高的重症患病率。[159]Choi JH, Choi SH, Yun KW. Risk factors for severe COVID-19 in children: a systematic review and meta-analysis. J Korean Med Sci. 2022 Feb 7;37(5):e35. https://jkms.org/DOIx.php?id=10.3346/jkms.2022.37.e35 http://www.ncbi.nlm.nih.gov/pubmed/35132841?tool=bestpractice.com
肥胖(≥30 kg/m²)及超重(25-30 kg/m²)者,罹患感染和呈现重症风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
截至 2021 年 2 月底,全球报道的 250 万死亡病例中,220 万人死于超重人口占一半以上的国家。不到半数成年人群被归类为超重的国家中,出现死亡的可能性约为超过半数成年人群被归类为超重的国家十分之一。[160]World Obesity Federation. COVID-19 and obesity: the 2021 atlas. 2021 [internet publication]. https://www.worldobesityday.org/assets/downloads/COVID-19-and-Obesity-The-2021-Atlas.pdf
荟萃分析证据发现,肥胖患者具有显著增加的感染、临床重症、住院、重症监护病房收治、需行机械通气和死亡风险。超重使得收住院风险升高,但死亡风险未见升高。[161]Cai Z, Yang Y, Zhang J. Obesity is associated with severe disease and mortality in patients with coronavirus disease 2019 (COVID-19): a meta-analysis. BMC Public Health. 2021 Aug 4;21(1):1505. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334342 http://www.ncbi.nlm.nih.gov/pubmed/34348687?tool=bestpractice.com [162]Sawadogo W, Tsegaye M, Gizaw A, et al. Overweight and obesity as risk factors for COVID-19-associated hospitalisations and death: systematic review and meta-analysis. BMJ Nutr Prev Health. 2022 Jan 19;5(1):10-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783972 http://www.ncbi.nlm.nih.gov/pubmed/35814718?tool=bestpractice.com 然而,随着时间推移,关联强度似乎已经削弱。[162]Sawadogo W, Tsegaye M, Gizaw A, et al. Overweight and obesity as risk factors for COVID-19-associated hospitalisations and death: systematic review and meta-analysis. BMJ Nutr Prev Health. 2022 Jan 19;5(1):10-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783972 http://www.ncbi.nlm.nih.gov/pubmed/35814718?tool=bestpractice.com
英国一项队列研究发现,体重指数 ≥23kg/m² 以上时,严重结局(例如住院、重症监护病房收治、死亡)风险逐渐升高,而与相关疾病(例如糖尿病)的其他风险不具相关性。40 岁以下者以及黑种人族裔相对风险尤为显著。体重指数每增加一个单位,则以下风险将呈现升高: 入院率增加 5%(体重指数 ≥23 kg/m²);重症监护病房收治率增加 10%(任何体重指数);和死亡增加 4%(体重指数 ≥28 kg/m²)。[163]Gao M, Piernas C, Astbury NM, et al. Associations between body-mass index and COVID-19 severity in 6.9 million people in England: a prospective, community-based, cohort study. Lancet Diabetes Endocrinol. 2021 Jun;9(6):350-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081400 http://www.ncbi.nlm.nih.gov/pubmed/33932335?tool=bestpractice.com
一项在美国进行的队列研究发现,体重指数与疾病严重程度之间存在非线性关系,体重指数接近健康体重和超重阈值时,风险最低,而后随体重指数增加而升高。[164]Kompaniyets L, Goodman AB, Belay B, et al. Body mass index and risk for COVID-19–related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death: United States, March – December 2020. MMWR Morb Mortal Wkly Rep. 2021 Mar 12;70(10):355-61. https://www.cdc.gov/mmwr/volumes/70/wr/mm7010e4.htm http://www.ncbi.nlm.nih.gov/pubmed/33705371?tool=bestpractice.com
心血管疾病患者罹患重症风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
在儿童和成人中,固有心血管疾病与不良结局具有相关性,包括疾病严重程度、疾病进展和死亡率。[165]Xu J, Xiao W, Liang X, et al. A meta-analysis on the risk factors adjusted association between cardiovascular disease and COVID-19 severity. BMC Public Health. 2021 Aug 11;21(1):1533. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355578 http://www.ncbi.nlm.nih.gov/pubmed/34380456?tool=bestpractice.com [166]Ehwerhemuepha L, Roth B, Patel AK, et al. Association of congenital and acquired cardiovascular conditions with COVID-19 severity among pediatric patients in the US. JAMA Netw Open. 2022 May 2;5(5):e2211967. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2792374 http://www.ncbi.nlm.nih.gov/pubmed/35579899?tool=bestpractice.com
心律失常、冠状动脉疾病和心血管疾病与重症监护病房收治呈显著相关。心力衰竭、心律失常、冠状动脉疾病和心血管疾病亦与死亡风险增加呈显著相关。[167]Hessami A, Shamshirian A, Heydari K, et al. Cardiovascular diseases burden in COVID-19: systematic review and meta-analysis. Am J Emerg Med. 2021 Aug;46:382-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561581 http://www.ncbi.nlm.nih.gov/pubmed/33268238?tool=bestpractice.com 固有心房颤动/心房扑动与更高的重症监护病房收治风险、住院死亡率和更劣的结局具有相关性。[168]Zuin M, Rigatelli G, Bilato C, et al. Pre-existing atrial fibrillation is associated with increased mortality in COVID-19 Patients. J Interv Card Electrophysiol. 2021 Nov;62(2):231-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046494 http://www.ncbi.nlm.nih.gov/pubmed/33855639?tool=bestpractice.com [169]Szarpak L, Filipiak KJ, Skwarek A, et al. Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19: a systematic review and meta-analysis. Cardiol J. 2022;29(1):33-43. http://www.ncbi.nlm.nih.gov/pubmed/34897631?tool=bestpractice.com 冠心病亦与疾病进展和病重/病危具有相关性。该关联受高血压影响;与不伴高血压患者相比,伴冠心病和高血压的患者预后不良风险升高。[170]Liang C, Zhang W, Li S, et al. Coronary heart disease and COVID-19: a meta-analysis. Med Clin (Engl Ed). 2021 Jun 11;156(11):547-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178966 http://www.ncbi.nlm.nih.gov/pubmed/34109276?tool=bestpractice.com 心肌损伤和周围动脉疾病亦与短期死亡率升高具有相关性。[171]Li Y, Pei H, Zhou C, et al. Myocardial injury predicts risk of short-term all-cause mortality in patients with COVID-19: a dose-response meta-analysis. Front Cardiovasc Med. 2022 May 2;9:850447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108210 http://www.ncbi.nlm.nih.gov/pubmed/35586652?tool=bestpractice.com [172]Zuin M, Rigatelli G, Bilato MJ, et al. Prevalence of pre-existing peripheral artery disease in COVID-19 patients and relative mortality risk: systematic review and meta-analysis. Vascular. 2022 May 20 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127456 http://www.ncbi.nlm.nih.gov/pubmed/35593210?tool=bestpractice.com
伴心血管疾病危险因素(例如高血压、糖尿病)者,重症和死亡风险亦升高(见下文)。[173]Bae S, Kim SR, Kim MN, et al. Impact of cardiovascular disease and risk factors on fatal outcomes in patients with COVID-19 according to age: a systematic review and meta-analysis. Heart. 2021 Mar;107(5):373-80. https://heart.bmj.com/content/early/2020/12/16/heartjnl-2020-317901.long http://www.ncbi.nlm.nih.gov/pubmed/33334865?tool=bestpractice.com [174]Pellicori P, Doolub G, Wong CM, et al. COVID-19 and its cardiovascular effects: a systematic review of prevalence studies. Cochrane Database Syst Rev. 2021 Mar 11;(3):CD013879. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013879/full http://www.ncbi.nlm.nih.gov/pubmed/33704775?tool=bestpractice.com
1 型和 2 型糖尿患者罹患重症风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
糖尿病与重症风险升高 2 倍以上,以及死亡风险略低于 2 倍的升高具有相关性。糖尿病亦与重症监护病房收治风险升高具有相关性。血糖水平升高(短期和长期)与较劣的结局具有相关性。无证据表明新发糖尿病患者和已有糖尿病患者的风险存在差异。数据不足以确定糖尿病是否可使患者更易感染。无数据表明糖尿病可升高儿童和青少年重症罹患风险。[175]Hartmann-Boyce J, Rees K, Perring JC, et al. Risks of and from SARS-CoV-2 infection and COVID-19 in people with diabetes: a systematic review of reviews. Diabetes Care. 2021 Dec;44(12):2790-811. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669527 http://www.ncbi.nlm.nih.gov/pubmed/34711637?tool=bestpractice.com 世界不同地区差异较显著,可影响总体趋势。[176]Kastora S, Patel M, Carter B, et al. Impact of diabetes on COVID-19 mortality and hospital outcomes from a global perspective: an umbrella systematic review and meta-analysis. Endocrinol Diabetes Metab. 2022 Apr 20:e338. https://onlinelibrary.wiley.com/doi/10.1002/edm2.338 http://www.ncbi.nlm.nih.gov/pubmed/35441801?tool=bestpractice.com
糖尿病患者预后不良和高死亡率的危险因素与一般人群中存在的危险因素相似,包括高龄、性别为男性、非白种人族裔、社会经济贫困、急性肾损伤、卒中或心力衰竭病史, 以及体重指数过高。其他更具体的风险因素包括糖尿病前期、血糖控制不佳、糖化血红蛋白水平过高、糖尿病酮症酸中毒、高血糖高渗性状态、糖尿病视网膜病变和胰岛素使用。[177]Chen Y, Yang D, Cheng B, et al. Clinical characteristics and outcomes of patients with diabetes and COVID-19 in association with glucose-lowering medication. Diabetes Care. 2020 Jul;43(7):1399-407. https://care.diabetesjournals.org/content/diacare/early/2020/05/13/dc20-0660.full.pdf http://www.ncbi.nlm.nih.gov/pubmed/32409498?tool=bestpractice.com [178]Holman N, Knighton P, Kar P, et al. Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study. Lancet Diabetes Endocrinol. 2020 Oct;8(10):823-33. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30271-0/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32798471?tool=bestpractice.com [179]Pal R, Banerjee M, Yadav U, et al. Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: a systematic review of literature. Diabetes Metab Syndr. 2020 Aug 18;14(6):1563-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434433 http://www.ncbi.nlm.nih.gov/pubmed/32853901?tool=bestpractice.com [180]Papadopoulos VP, Koutroulos MV, Zikoudi DG, et al. Diabetes-related acute metabolic emergencies in COVID-19 patients: a systematic review and meta-analysis. Diabetol Int. 2021 Mar 23;1-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985576 http://www.ncbi.nlm.nih.gov/pubmed/33777611?tool=bestpractice.com [181]Prattichizzo F, de Candia P, Nicolucci A, et al. Impact of pre-infection HbA1c levels on COVID-19 prognosis: systematic review and meta-analysis. Diabetes Metab Res Rev. 2021 May 20:e3476. https://onlinelibrary.wiley.com/doi/10.1002/dmrr.3476 http://www.ncbi.nlm.nih.gov/pubmed/34018307?tool=bestpractice.com [182]Heidarpour M, Abhari AP, Sadeghpour N, et al. Prediabetes and COVID-19 severity, an underestimated risk factor: a systematic review and meta-analysis. Diabetes Metab Syndr. 2021 Oct 9;15(6):102307. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501186 http://www.ncbi.nlm.nih.gov/pubmed/34731820?tool=bestpractice.com [183]Boden I, Bernabeu MO, Dhillon B, et al. Pre-existing diabetic retinopathy as a prognostic factor for COVID-19 outcomes amongst people with diabetes: a systematic review. Diabetes Res Clin Pract. 2022 Apr 5;187:109869. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982479 http://www.ncbi.nlm.nih.gov/pubmed/35395248?tool=bestpractice.com 对年龄、性别、种族、贫困和地理位置进行调整后的研究仍然发现糖尿病患者的死亡风险升高。几乎无证据表明合并症对于升高不良结局风险有所作用。[175]Hartmann-Boyce J, Rees K, Perring JC, et al. Risks of and from SARS-CoV-2 infection and COVID-19 in people with diabetes: a systematic review of reviews. Diabetes Care. 2021 Dec;44(12):2790-811. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669527 http://www.ncbi.nlm.nih.gov/pubmed/34711637?tool=bestpractice.com
二甲双胍、钠-葡萄糖协同转运蛋白 2 抑制剂、胰高血糖素样肽-1 受体激动剂的使用与 2 型糖尿病死亡率降低具有相关性。二肽基肽酶-4 抑制剂和胰岛素与死亡率升高具有相关性。磺脲类药物、噻唑烷二酮类药物和 α-葡萄糖苷酶抑制剂似乎并未增加或降低死亡风险。[184]Nguyen NN, Ho DS, Nguyen HS, et al. Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: a meta-analysis. Metabolism. 2022 Mar 31:155196. https://www.metabolismjournal.com/article/S0026-0495(22)00074-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35367460?tool=bestpractice.com [185]Zhu Z, Zeng Q, Liu Q, et al. Association of glucose-lowering drugs with outcomes in patients with diabetes before hospitalization for COVID-19: a systematic review and network meta-analysis. JAMA Netw Open. 2022 Dec 1;5(12):e2244652. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799219 http://www.ncbi.nlm.nih.gov/pubmed/36472874?tool=bestpractice.com 目前尚不清楚此类药物是否具有保护作用,需行进一步研究。
这些患者的不良结局原因可能在于糖尿病的综合征性质、合并症存在、免疫功能受损、介导病毒侵袭的生物酶可能上调,以及慢性炎症伴 SARS-CoV-2 引发的急性炎症反应所致炎症风暴倾向。[186]Apicella M, Campopiano MC, Mantuano M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020 Sep;8(9):782-92. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367664 http://www.ncbi.nlm.nih.gov/pubmed/32687793?tool=bestpractice.com [187]Yin Y, Rohli KE, Shen P, et al. The epidemiology, pathophysiological mechanisms, and management toward COVID-19 patients with type 2 diabetes: a systematic review. Prim Care Diabetes. 2021 Sep 6;15(6):899-909. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418914 http://www.ncbi.nlm.nih.gov/pubmed/34600859?tool=bestpractice.com
伴慢性肺疾病者(例如哮喘、慢性阻塞性肺疾病 [chronic obstructive pulmonary disease, COPD]、间质性肺疾病、肺栓塞、肺动脉高压、结核病、囊性纤维化和支气管扩张)罹患重症的风险升高。伴支气管肺发育不良或 α-1 抗胰蛋白酶缺乏症的患者发生重症的风险可能升高;然而,证据有限。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html 尚无明确证据表明哮喘或 COPD 患者具有更高的感染风险。[188]Halpin DMG, Faner R, Sibila O, et al. Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection? Lancet Respir Med. 2020 May;8(5):436-8. https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(20)30167-3.pdf http://www.ncbi.nlm.nih.gov/pubmed/32251625?tool=bestpractice.com [189]Centre for Evidence-Based Medicine; Hartmann-Boyce J, Otunla A, Drake J, et al. Asthma and COVID-19: risks and management considerations. 2020 [internet publication]. https://www.cebm.net/covid-19/asthma-and-covid-19-risks-and-management-considerations
COPD:与住院、重症监护病房收治和死亡等风险升高具有相关性。[190]Gerayeli FV, Milne S, Cheung C, et al. COPD and the risk of poor outcomes in COVID-19: A systematic review and meta-analysis. EClinicalMedicine. 2021 Mar;33:100789. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971471 http://www.ncbi.nlm.nih.gov/pubmed/33758801?tool=bestpractice.com 英国一项全国性、多中心前瞻性队列研究发现,COPD 患者比无潜在呼吸道疾病的患者接受危重症诊疗的可能性更低。[191]Bloom CI, Drake TM, Docherty AB, et al. Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK. Lancet Respir Med. 2021 Jul;9(7):699-711. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241313 http://www.ncbi.nlm.nih.gov/pubmed/33676593?tool=bestpractice.com
哮喘:与不伴哮喘患者相比,临床结局相似(如果未得到轻微改善)。一项大型系统评价汇总结果表明,总体而言,哮喘与严重结局(住院、重症监护病房收治、死亡)不具相关性。然而,证据确定性极低,并且由于哮喘严重程度的报告缺乏、无法解释的统计学异质性以及不精确性,结果具有局限性。伴过敏性哮喘者出现严重结局的风险似乎较低,而同时伴有哮喘和并发 COPD 者出现严重结局的风险似乎较高。既往的系统评价和荟萃分析产生的结论具有冲突。哮喘是否与感染风险升高具有相关性,或是否与严重结局的出现具有相关性,仍不清楚。[192]Otunla A, Rees K, Dennison P, et al. Risks of infection, hospital and ICU admission, and death from COVID-19 in people with asthma: systematic review and meta-analyses. BMJ Evid Based Med. 2021 Dec 21 [Epub ahead of print]. https://ebm.bmj.com/content/early/2021/12/21/bmjebm-2021-111788.long http://www.ncbi.nlm.nih.gov/pubmed/34933924?tool=bestpractice.com [193]World Health Organization. Asthma and COVID-19: scientific brief, 19 April 2021. 2021 [internet publication]. https://www.who.int/publications/i/item/who-2019-ncov-sci-brief-asthma-2021.1
阻塞性睡眠呼吸暂停:与罹患重症、重症监护病房收治、进行机械通气和死亡风险升高具有相关性;但是,证据较为有限。[194]Hariyanto TI, Kurniawan A. Obstructive sleep apnea (OSA) and outcomes from coronavirus disease 2019 (COVID-19) pneumonia: a systematic review and meta-analysis. Sleep Med. 2021 Apr 1;82:47-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012298 http://www.ncbi.nlm.nih.gov/pubmed/33892451?tool=bestpractice.com [195]Strausz S, Kiiskinen T, Broberg M, et al. Sleep apnoea is a risk factor for severe COVID-19. BMJ Open Respir Res. 2021 Jan;8(1):e000845. https://bmjopenrespres.bmj.com/content/8/1/e000845.long http://www.ncbi.nlm.nih.gov/pubmed/33436406?tool=bestpractice.com
囊性纤维化:似乎与感染风险升高不具相关性;但是,有证据表明某些患者可能经历更为严重的临床病程(例如移植后)。[196]Mathew HR, Choi MY, Parkins MD, et al. Systematic review: cystic fibrosis in the SARS-CoV-2/COVID-19 pandemic. BMC Pulm Med. 2021 May 20;21(1):173. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135381 http://www.ncbi.nlm.nih.gov/pubmed/34016096?tool=bestpractice.com 其他严重结局的危险因素包括 FEV1<70%、年龄 >40 岁、糖尿病、胰腺功能不全、体重不足,以及使用阿奇霉素。[197]Terlizzi V, Motisi MA, Pellegrino R, et al. Risk factors for severe COVID-19 in people with cystic fibrosis: a systematic review. Front Pediatr. 2022 Aug 8;10:958658. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393295 http://www.ncbi.nlm.nih.gov/pubmed/36003489?tool=bestpractice.com
活动性肺结核:似乎与重症和死亡风险升高具有相关性。[198]Wang Y, Feng R, Xu J, et al. An updated meta-analysis on the association between tuberculosis and COVID-19 severity and mortality. J Med Virol. 2021 Oct;93(10):5682-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242817 http://www.ncbi.nlm.nih.gov/pubmed/34061374?tool=bestpractice.com [199]Aggarwal AN, Agarwal R, Dhooria S, et al. Active pulmonary tuberculosis and coronavirus disease 2019: a systematic review and meta-analysis. PLoS One. 2021;16(10):e0259006. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530351 http://www.ncbi.nlm.nih.gov/pubmed/34673822?tool=bestpractice.com
肺间质 病:似乎与重症和死亡风险升高具有相关性。[200]Ouyang L, Gong J, Yu M. Pre-existing interstitial lung disease in patients with coronavirus disease 2019: a meta-analysis. Int Immunopharmacol. 2021 Sep 9;100:108145. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450148 http://www.ncbi.nlm.nih.gov/pubmed/34547678?tool=bestpractice.com [201]Wang Y, Hao Y, Hu M, et al. Interstitial lung disease independently associated with higher risk for COVID-19 severity and mortality: a meta-analysis of adjusted effect estimates. Int Immunopharmacol. 2022 Oct;111:109088. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325673 http://www.ncbi.nlm.nih.gov/pubmed/35921779?tool=bestpractice.com
暂无小儿呼吸系统疾病(包括儿童哮喘)是否为感染或严重程度危险因素的数据。[202]Castro-Rodriguez JA, Forno E. Asthma and COVID-19 in children: a systematic review and call for data. Pediatr Pulmonol. 2020 Sep;55(9):2412-8. https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.24909 http://www.ncbi.nlm.nih.gov/pubmed/32558360?tool=bestpractice.com
伴慢性肾病者罹患重症风险升高,且感染风险亦可能升高。[130]de Lusignan S, Dorward J, Correa A, et al. Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study. Lancet Infect Dis. 2020 Sep;20(9):1034-42. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228715 http://www.ncbi.nlm.nih.gov/pubmed/32422204?tool=bestpractice.com [147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
与不伴慢性肾病者相比,伴慢性肾病的患者住院和全因死亡风险显著升高。对纳入研究和多变量调整研究亚组分析的总体分析发现,慢性肾病患者亦呈现更高的危重症进展风险,但结果均未获得统计学意义。[203]Lin YC, Lai TS, Lin SL, et al. Outcomes of coronavirus 2019 infection in patients with chronic kidney disease: a systematic review and meta-analysis. Ther Adv Chronic Dis. 2021;12:2040622321998860. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985947 http://www.ncbi.nlm.nih.gov/pubmed/33796245?tool=bestpractice.com
与无需进行肾脏替代治疗患者相比,接受透析患者的发病率似乎更高。[204]Chung EY, Palmer SC, Natale P, et al. Incidence and outcomes of COVID-19 in people with CKD: a systematic review and meta-analysis. Am J Kidney Dis. 2021 Dec;78(6):804-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339603 http://www.ncbi.nlm.nih.gov/pubmed/34364906?tool=bestpractice.com 接受肾脏替代治疗的终末期肾病患者重症监护病房收治、需行机械通气和死亡等风险亦有所升高。[205]Nopsopon T, Kittrakulrat J, Takkavatakarn K, et al. Covid-19 in end-stage renal disease patients with renal replacement therapies: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2021 Jun 15;15(6):e0009156. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0009156 http://www.ncbi.nlm.nih.gov/pubmed/34129609?tool=bestpractice.com
在英国,一项横断面研究数据发现,慢性肾病患者比无肾病患者阳性检测的校正比值比更高(32.9% vs 14.4%)。[130]de Lusignan S, Dorward J, Correa A, et al. Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study. Lancet Infect Dis. 2020 Sep;20(9):1034-42. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228715 http://www.ncbi.nlm.nih.gov/pubmed/32422204?tool=bestpractice.com
固有慢性肾病是进展为急性肾损伤并发症的独立危险因素。[206]Kunutsor SK, Laukkanen JA. Renal complications in COVID-19: a systematic review and meta-analysis. Ann Med. 2020 Jul 10;:1-9. https://www.tandfonline.com/doi/full/10.1080/07853890.2020.1790643 http://www.ncbi.nlm.nih.gov/pubmed/32643418?tool=bestpractice.com
伴慢性肝病者(例如肝硬化、代谢紊乱相关性脂肪肝、酒精性肝病和自身免疫性肝炎)罹患重症的风险升高。乙型或丙型肝炎患者罹患重症风险可能升高;但是证据有限。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
慢性肝病与重症和死亡风险增加具有相关性,但与感染风险升高不具相关性。[207]Kovalic AJ, Satapathy SK, Thuluvath PJ. Prevalence of chronic liver disease in patients with COVID-19 and their clinical outcomes: a systematic review and meta-analysis. Hepatol Int. 2020 Sep;14(5):612-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386238 http://www.ncbi.nlm.nih.gov/pubmed/32725453?tool=bestpractice.com 更高的肝硬化评分与更劣的预后具有相关性。[208]Liu M, Mei K, Tan Z, et al. Liver fibrosis scores and hospitalization, mechanical ventilation, severity, and death in patients with COVID-19: a systematic review and dose-response meta-analysis. Can J Gastroenterol Hepatol. 2022 Mar 29;2022:7235860. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966744 http://www.ncbi.nlm.nih.gov/pubmed/35369116?tool=bestpractice.com
肝硬化患者死亡风险升高。与非肝硬化患者相比,肝硬化患者死亡率升高了 2.48 倍。晚期肝硬化患者死亡风险可能更高。[209]Middleton P, Hsu C, Lythgoe MP. Clinical outcomes in COVID-19 and cirrhosis: a systematic review and meta-analysis of observational studies. BMJ Open Gastroenterol. 2021 Oct;8(1):e000739. https://bmjopengastro.bmj.com/content/8/1/e000739.long http://www.ncbi.nlm.nih.gov/pubmed/34675033?tool=bestpractice.com
伴代谢紊乱相关性脂肪性肝病(非酒精性脂肪性肝病)者罹患重症风险升高。[210]Tao Z, Li Y, Cheng B, et al. Risk of severe COVID-19 increased by metabolic dysfunction-associated fatty liver disease: a meta-analysis. J Clin Gastroenterol. 2021 Nov-Dec 01;55(10):830-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500209 http://www.ncbi.nlm.nih.gov/pubmed/34406175?tool=bestpractice.com 疾病严重程度与年龄 <60 岁以及纤维化-4(fibrosis-4, FIB-4)评分呈中等或较高水平,具有相关性。[211]Targher G, Mantovani A, Byrne CD, et al. Risk of severe illness from COVID-19 in patients with metabolic dysfunction-associated fatty liver disease and increased fibrosis scores. Gut. 2020 Aug;69(8):1545-7. https://gut.bmj.com/content/early/2020/05/15/gutjnl-2020-321611 http://www.ncbi.nlm.nih.gov/pubmed/32414813?tool=bestpractice.com [212]Zhou YJ, Zheng KI, Wang XB, et al. Younger patients with MAFLD are at increased risk of severe COVID-19 illness: a multicenter preliminary analysis. J Hepatol. 2020 Sep;73(3):719-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195041 http://www.ncbi.nlm.nih.gov/pubmed/32348790?tool=bestpractice.com
孕妇罹患重症的风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
据估计,无论出于何种原因就诊或入院的孕妇,以及近期受孕患者的总体比率均为 10%;但是,不同研究和不同国家得出的比率有所不同。[213]Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020 Sep 1;370:m3320. https://www.bmj.com/content/370/bmj.m3320 http://www.ncbi.nlm.nih.gov/pubmed/32873575?tool=bestpractice.com [214]Allotey J, Stallings E, Bonet M, et al. Update to living systematic review on covid-19 in pregnancy. BMJ. 2021 Mar 10;372:n615. https://www.bmj.com/content/372/bmj.n615 http://www.ncbi.nlm.nih.gov/pubmed/33692025?tool=bestpractice.com 一项对超过 2500 名确诊孕妇进行的荟萃分析发现,73.9% 患者处于妊娠晚期;50.8% 为黑种人、亚裔或少数族裔;38.2% 患者呈现肥胖;32.5% 伴慢性合并症。[215]Khalil A, Kalafat E, Benlioglu C, et al. SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis of clinical features and pregnancy outcomes. EClinicalMedicine. 2020 Aug;25:100446. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334039 http://www.ncbi.nlm.nih.gov/pubmed/32838230?tool=bestpractice.com
根据对约 400,000 名 15 至 44 岁有症状女性进行的分析,与非妊娠患者相比,孕妇更易被收住院、被转入重症监护病房、接受有创机械通气或给予体外膜肺氧合,并更易出现死亡。[216]Zambrano LD, Ellington S, Strid P, et al. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status: United States, January 22–October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020 Nov 6;69(44):1641-7. https://www.cdc.gov/mmwr/volumes/69/wr/mm6944e3.htm http://www.ncbi.nlm.nih.gov/pubmed/33151921?tool=bestpractice.com
严重感染孕妇更可能出现足月前分娩或足月前剖宫产,或者更可能出现胎儿死产或需要入住新生儿重症监护病房。[217]Vousden N, Ramakrishnan R, Bunch K, et al. Management and implications of severe COVID-19 in pregnancy in the UK: data from the UK Obstetric Surveillance System national cohort. Acta Obstet Gynecol Scand. 2022 Feb 25 [Epub ahead of print]. https://obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.14329 http://www.ncbi.nlm.nih.gov/pubmed/35213734?tool=bestpractice.com
孕妇出现重症、母体并发症和不良出生结局的危险因素包括年龄 ≥30 岁、混血、妊娠期糖尿病、糖尿病、高血压、心血管疾病、超重/肥胖、HIV 感染、孕前体重不足和贫血。[217]Vousden N, Ramakrishnan R, Bunch K, et al. Management and implications of severe COVID-19 in pregnancy in the UK: data from the UK Obstetric Surveillance System national cohort. Acta Obstet Gynecol Scand. 2022 Feb 25 [Epub ahead of print]. https://obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.14329 http://www.ncbi.nlm.nih.gov/pubmed/35213734?tool=bestpractice.com [218]Smith ER, Oakley E, Grandner GW, et al. Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis. Am J Obstet Gynecol. 2022 Aug 23 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9398561 http://www.ncbi.nlm.nih.gov/pubmed/36027953?tool=bestpractice.com
与高收入国家相比,中低收入国家孕妇和新生儿对不良结局更为脆弱。[219]Gajbhiye RK, Sawant MS, Kuppusamy P, et al. Differential impact of COVID-19 in pregnant women from high-income countries and low- to middle-income countries: a systematic review and meta-analysis. Int J Gynaecol Obstet. 2021 Oct;155(1):48-56. https://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.13793 http://www.ncbi.nlm.nih.gov/pubmed/34160059?tool=bestpractice.com
参阅 并发症章节,获取更多妊娠相关性并发症信息。
当前或既往曾吸烟者罹患重症风险有所增加。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
吸烟与严重或危重结局、重症监护病房收治和死亡风险增加具有相关性。该关联对于既往曾吸烟者似乎比当前吸烟者更为显著,对于年轻人群亦似乎更为显著。与不吸烟者相比,当前吸烟者罹患重症的风险更高。[220]Zhang H, Ma S, Han T, et al. Association of smoking history with severe and critical outcome in COVID-19 patients: a systemic review and meta-analysis. Eur J Integr Med. 2021 Feb 18:101313. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889467 http://www.ncbi.nlm.nih.gov/pubmed/33619437?tool=bestpractice.com [221]Patanavanich R, Glantz SA. Smoking is associated with worse outcomes of COVID-19 particularly among younger adults: a systematic review and meta-analysis. BMC Public Health. 2021 Aug 16;21(1):1554. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366155 http://www.ncbi.nlm.nih.gov/pubmed/34399729?tool=bestpractice.com 与非吸烟者相比,吸烟者呈加倍的死亡风险。[222]Salah HM, Sharma T, Mehta J. Smoking doubles the mortality risk in COVID-19: a meta-analysis of recent reports and potential mechanisms. Cureus. 2020 Oct 7;12(10):e10837. https://www.cureus.com/articles/39552-smoking-doubles-the-mortality-risk-in-covid-19-a-meta-analysis-of-recent-reports-and-potential-mechanisms http://www.ncbi.nlm.nih.gov/pubmed/33173643?tool=bestpractice.com 这可能是由于吸烟者中血管紧张素转换酶 2 受体的气道表达增加所致。[223]Cai G, Bossé Y, Xiao F, et al. Tobacco smoking increases the lung gene expression of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020 Jun 15;201(12):1557-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301735 http://www.ncbi.nlm.nih.gov/pubmed/32329629?tool=bestpractice.com 当前吸烟者的死亡风险似乎不因年龄而异;然而,既往曾吸烟者的风险则随着年龄增长呈现显著下降。[224]Patanavanich R, Siripoon T, Amponnavarat S, et al. Active smokers are at higher risk of COVID-19 death: a systematic review and meta-analysis. Nicotine Tob Res. 2022 Apr 1 [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/35363877?tool=bestpractice.com
世界卫生组织已对现有证据进行评估,得出结论认为,吸烟与住院患者疾病严重程度增加和死亡增加有关。[225]World Health Organization. Smoking and COVID-19: scientific brief. 2020 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Smoking-2020.2
肿瘤患者感染和重症风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html [226]Yu J Ouyang W, Chua ML, et al. SARS-CoV-2 transmission in patients with cancer at a tertiary care hospital in Wuhan, China. JAMA Oncol. 2020 Mar 25;6(7):1108-10. https://jamanetwork.com/journals/jamaoncology/fullarticle/2763673 http://www.ncbi.nlm.nih.gov/pubmed/32211820?tool=bestpractice.com
与普通人群相比,伴有肿瘤的患者罹患感染、重症、重症监护病房收治和遭遇死亡的风险升高。[227]Arayici ME, Kipcak N, Kayacik U, et al. Effects of SARS-CoV-2 infections in patients with cancer on mortality, ICU admission and incidence: a systematic review with meta-analysis involving 709,908 participants and 31,732 cancer patients. J Cancer Res Clin Oncol. 2022 Jul 13 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281353 http://www.ncbi.nlm.nih.gov/pubmed/35831763?tool=bestpractice.com 血液系统恶性肿瘤与最高的重症和死亡风险具有相关性(可能可以解释为对此类患者进行治疗时免疫抑制程度更高),其次为肺癌。治疗方法与死亡之间无明确关联。[228]Naimi A, Yashmi I, Jebeleh R, et al. Comorbidities and mortality rate in COVID-19 patients with hematological malignancies: a systematic review and meta-analysis. J Clin Lab Anal. 2022 Apr 6:e24387. https://onlinelibrary.wiley.com/doi/10.1002/jcla.24387 http://www.ncbi.nlm.nih.gov/pubmed/35385130?tool=bestpractice.com
癌症患者总体院内死亡风险为 14.1%。[229]Zarifkar P, Kamath A, Robinson C, et al. Clinical characteristics and outcomes in patients with COVID-19 and cancer: a systematic review and meta-analysis. Clin Oncol (R Coll Radiol). 2021 Mar;33(3):e180-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674130 http://www.ncbi.nlm.nih.gov/pubmed/33261978?tool=bestpractice.com 收入重症监护病房的肿瘤患者总体死亡率为 60.2%。[230]Nadkarni AR, Vijayakumaran SC, Gupta S, et al. Mortality in cancer patients with COVID-19 who are admitted to an ICU or who have severe COVID-19: a systematic review and meta-analysis. JCO Glob Oncol. 2021 Aug;7:1286-305. https://ascopubs.org/doi/10.1200/GO.21.00072 http://www.ncbi.nlm.nih.gov/pubmed/34406802?tool=bestpractice.com 肿瘤患者死亡率受固有非肿瘤合并症影响,高血压、心血管疾病、慢性阻塞性肺疾病和糖尿病患者死亡率明显升高。[231]Kaur H, Thakur JS, Paika R, et al. Impact of underlying comorbidities on mortality in SARS-COV-2 infected cancer patients: a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2021 May 1;22(5):1333-49. http://journal.waocp.org/article_89582_88818a41a7dc442aa8591bc9ae0c197a.pdf http://www.ncbi.nlm.nih.gov/pubmed/34048161?tool=bestpractice.com
与未罹患癌症的 COVID-19 患者相比,近期接受过癌症治疗的患者(COVID-19 诊断前 3 个月内)30 天死亡率、重症监护病房住院时间和住院风险呈现统计学显著增加。与未罹患癌症的患者相比,近期未接受癌症治疗的患者死亡率和重症监护病房收治风险相似,机械通气和住院风险较低。[232]Chavez-MacGregor M, Lei X, Zhao H, et al. Evaluation of COVID-19 mortality and adverse outcomes in US patients with or without cancer. JAMA Oncol. 2022 Jan 1;8(1):69-78. https://jamanetwork.com/journals/jamaoncology/fullarticle/2785677 http://www.ncbi.nlm.nih.gov/pubmed/34709356?tool=bestpractice.com
与不伴癌症的儿童相比,罹患癌症的儿童并未显得更为易感。有限数据显示,罹患癌症的儿科患者总体发病率较低,仅 5% 需收住院治疗以缓解症状。[233]Boulad F, Kamboj M, Bouvier N, et al. COVID-19 in children with cancer in New York City. JAMA Oncol. 2020 Sep 1;6(9):1459-60. https://jamanetwork.com/journals/jamaoncology/fullarticle/2766112 http://www.ncbi.nlm.nih.gov/pubmed/32401276?tool=bestpractice.com 在迄今为止规模最大的国际队列研究中,20% 罹患肿瘤儿童进展为重症或危重症,但多数患者在未得到高级支持的情况下得以恢复。约 35% 的儿童无症状。淋巴细胞减少和中性粒细胞减少与更为严重的疾病具有相关性。[234]Mukkada S, Bhakta N, Chantada GL, et al. Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study. Lancet Oncol. 2021 Oct;22(10):1416-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389979 http://www.ncbi.nlm.nih.gov/pubmed/34454651?tool=bestpractice.com 癌症儿童总体生存率极高(99.4%),儿童血液恶性肿瘤和实体肿瘤的住院或重症监护病房收治风险无显著差异。[235]Dorantes-Acosta E, Ávila-Montiel D, Klünder-Klünder M, et al. Survival and complications in pediatric patients with cancer and COVID-19: a meta-analysis. Front Oncol. 2020 Jan 21;10:608282. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861039 http://www.ncbi.nlm.nih.gov/pubmed/33552980?tool=bestpractice.com 有限证据表明,对 SARS-CoV-2 检测呈阳性的儿童继续给予化疗,未见相关性严重并发症。[236]Schlage S, Lehrnbecher T, Berner R, et al. SARS-CoV-2 in pediatric cancer: a systematic review. Eur J Pediatr. 2022 Jan 10;1-15. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8744033 http://www.ncbi.nlm.nih.gov/pubmed/35006377?tool=bestpractice.com
脑血管疾病患者罹患重症风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
与无脑血管疾病史患者相比,存在脑血管疾病史的患者,更易出现不良结局。[237]Xu J, Xiao W, Liang X, et al. The association of cerebrovascular disease with adverse outcomes in COVID-19 patients: a meta-analysis based on adjusted effect estimates. J Stroke Cerebrovasc Dis. 2020 Nov;29(11):105283. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455117 http://www.ncbi.nlm.nih.gov/pubmed/33066922?tool=bestpractice.com 固有脑血管疾病的患者,不良结局(包括收入重症监护病房、进行机械通气和死亡)出现几率高出 2.67 倍。[238]Patel U, Malik P, Shah D, et al. Pre-existing cerebrovascular disease and poor outcomes of COVID-19 hospitalized patients: a meta-analysis. J Neurol. 2021 Jan;268(1):240-7. https://link.springer.com/article/10.1007%2Fs00415-020-10141-w http://www.ncbi.nlm.nih.gov/pubmed/32770412?tool=bestpractice.com 既往卒中与重症、重症监护病房收治、机械通气和死亡具有显著相关性。[239]Huang H, Chen J, Fang S, et al. Association between previous stroke and severe COVID-19: a retrospective cohort study and an overall review of meta-analysis. Front Neurol. 2022 Jul 12;13:922936. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327441 http://www.ncbi.nlm.nih.gov/pubmed/35911884?tool=bestpractice.com
伴情感障碍(例如抑郁)和精神分裂症谱系障碍等心理健康障碍者罹患重症的风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
与无心理健康障碍的患者相比,伴心理健康障碍的患者住院和死亡风险更高。[240]Fond G, Nemani K, Etchecopar-Etchart D, et al. Association between mental health disorders and mortality among patients with COVID-19 in 7 countries: a systematic review and meta-analysis. JAMA Psychiatry. 2021 Nov 1;78(11):1208-17. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2782457 http://www.ncbi.nlm.nih.gov/pubmed/34313711?tool=bestpractice.com [241]Ceban F, Nogo D, Carvalho IP, et al. Association between mood disorders and risk of COVID-19 infection, hospitalization, and death: a systematic review and meta-analysis. JAMA Psychiatry. 2021 Oct 1;78(10):1079-91. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2782453 http://www.ncbi.nlm.nih.gov/pubmed/34319365?tool=bestpractice.com
精神分裂症者死亡的风险可能增加。危险因素包括高龄和吸烟史。[242]Pardamean E, Roan W, Iskandar KTA, et al. Mortality from coronavirus disease 2019 (Covid-19) in patients with schizophrenia: a systematic review, meta-analysis and meta-regression. Gen Hosp Psychiatry. 2022 Feb 4;75:61-7. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8813760 http://www.ncbi.nlm.nih.gov/pubmed/35182908?tool=bestpractice.com
实体器官或血液干细胞移植后免疫功能低下者罹患重症风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
实体器官移植受者住院、重症监护病房收治和死亡风险升高。但是,住院率的增加可能反映出一种更优的管理策略,(即对此类患者给予更为密切的住院监测),而非提示疾病严重程度。对人口统计学、临床特征以及疾病严重程度进行调整校正后,与一般人群相比,死亡风险未见升高。[243]Gatti M, Rinaldi M, Bussini L, et al. Clinical outcome in solid organ transplant recipients affected by COVID-19 compared to general population: a systematic review and meta-analysis. Clin Microbiol Infect. 2022 Mar 11 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916831 http://www.ncbi.nlm.nih.gov/pubmed/35289294?tool=bestpractice.com
造血干细胞移植(haematopoietic stem cell transplant, HSCT)受者的死亡风险呈现升高。与自体 HSCT 受者相比,allo-HSCT 受者的死亡率略高,但该差异无统计学意义。高死亡率的危险因素包括高龄、免疫抑制治疗、移植物抗宿主病和伴淋巴细胞减少的炎症标志物升高。[244]Shahzad M, Chaudhary SG, Zafar MU, et al. Impact of COVID-19 in hematopoietic stem cell transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis. 2022 Jan 14:e13792. https://onlinelibrary.wiley.com/doi/10.1111/tid.13792 http://www.ncbi.nlm.nih.gov/pubmed/35030267?tool=bestpractice.com
有失能性疾病者发生重症的风险增加,这些失能性疾病包括唐氏综合征、脑性瘫痪、先天畸形、学习障碍、注意缺陷多动障碍、智力和发育障碍,以及脊髓损伤。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
在英国,一项队列研究发现,唐氏综合征患者住院风险增加了 4 倍,死亡风险增加了 10 倍。[245]Clift AK, Coupland CAC, Keogh RH, et al. COVID-19 mortality risk in Down syndrome: results from a cohort study of 8 million adults. Ann Intern Med. 2021 Apr;174(4):572-6. https://www.acpjournals.org/doi/10.7326/M20-4986 http://www.ncbi.nlm.nih.gov/pubmed/33085509?tool=bestpractice.com 这可能由于存在免疫功能障碍、先天性心脏病和肺部疾病所致。
英国另一项研究发现,伴学习障碍的成人以及伴唐氏综合征或脑性瘫痪的成人住院和死亡风险显著高于观察到的非 COVID-19 死因风险。[246]Williamson EJ, McDonald HI, Bhaskaran K, et al. Risks of covid-19 hospital admission and death for people with learning disability: population based cohort study using the OpenSAFELY platform. BMJ. 2021 Jul 14;374:n1592. https://www.bmj.com/content/374/bmj.n1592 http://www.ncbi.nlm.nih.gov/pubmed/34261639?tool=bestpractice.com
在前两波大流行期间,与非残障者相比,残障者(包括伴学习障碍、神经系统疾病和脆弱者)的死亡风险更高。年轻残障者、残障女性和活动受限程度较高者相对风险较高。不良社会经济、人口和健康相关风险因素是导致风险升高的部分原因。[247]Bosworth ML, Ayoubkhani D, Nafilyan V, et al. Deaths involving COVID-19 by self-reported disability status during the first two waves of the COVID-19 pandemic in England: a retrospective, population-based cohort study. Lancet Public Health. 2021 Nov;6(11):e817-25. https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(21)00206-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/34626547?tool=bestpractice.com
痴呆患者发生感染和重症的风险可能升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html [248]Hariyanto TI, Putri C, Arisa J, et al. Dementia and outcomes from coronavirus disease 2019 (COVID-19) pneumonia: a systematic review and meta-analysis. Arch Gerontol Geriatr. 2020 Nov 19;93:104299. https://www.sciencedirect.com/science/article/pii/S016749432030296X?via%3Dihub http://www.ncbi.nlm.nih.gov/pubmed/33285424?tool=bestpractice.com
伴有痴呆的老年成人短期内具备较高的死亡风险。痴呆患者更易罹患高血压、糖尿病和肺炎等疾患,并且免疫功能低下。痴呆患者总体死亡率为 39%,而不伴痴呆的老年成人则为 20%。[249]Saragih ID, Saragih IS, Batubara SO, et al. Dementia as a mortality predictor among older adults with COVID-19: a systematic review and meta-analysis of observational study. Geriatr Nurs. 2021 Sep-Oct;42(5):1230-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955923 http://www.ncbi.nlm.nih.gov/pubmed/33824009?tool=bestpractice.com
在英国,从 2020 年 3 月至 2020 年 6 月,死于 COVID-19 者中,四分之一以上伴有痴呆。痴呆和阿尔茨海默病是 2020 年 3 月至 2020 年 6 月期间涉及 COVID-19 死亡中最常见的主要固有疾病。[250]Office for National Statistics. Deaths involving COVID-19, England and Wales: deaths occurring in June 2020. 2020 [internet publication]. https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsinvolvingcovid19englandandwales/deathsoccurringinjune2020
一项美国电子病历回顾性病例对照研究发现,与不伴痴呆患者相比,伴痴呆患者感染风险更高。与不伴 COVID-19 感染的痴呆患者,和不伴痴呆的 COVID-19 感染患者相比,其结局(6 个月住院风险和死亡风险)亦显著更劣。血管性痴呆患者风险最高。[251]Wang Q, Davis PB, Gurney ME, et al. COVID-19 and dementia: analyses of risk, disparity, and outcomes from electronic health records in the US. Alzheimers Dement. 2021 Aug;17(8):1297-306. https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12296 http://www.ncbi.nlm.nih.gov/pubmed/33559975?tool=bestpractice.com
免疫功能低下患者发生重症的风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
包括原发性免疫缺陷或长期使用皮质类固醇或其他免疫抑制剂者。
一旦入院,无论疫苗接种情况如何,与非免疫功能低下患者相比,免疫功能低下者的重症监护病房收治和死亡风险均有所升高(对临床和人口特征差异进行调整后)。[252]Singson JRC, Kirley PD, Pham H, et al. Factors associated with severe outcomes among immunocompromised adults hospitalized for COVID-19: COVID-NET, 10 States, March 2020 - February 2022. MMWR Morb Mortal Wkly Rep. 2022 Jul 8;71(27):878-84. https://www.cdc.gov/mmwr/volumes/71/wr/mm7127a3.htm http://www.ncbi.nlm.nih.gov/pubmed/35797216?tool=bestpractice.com
当前数据并未强烈表明与免疫介导性炎性疾病相关的药物治疗可增加感染或重症风险,皮质类固醇和利妥昔单抗除外。[253]Fagni F, Simon D, Tascilar K, et al. COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses. Lancet Rheumatol. 2021 Oct;3(10):e724-36. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397302 http://www.ncbi.nlm.nih.gov/pubmed/34485930?tool=bestpractice.com 风湿免疫性疾病患者糖皮质激素暴露 ≥10 mg/d(泼尼松龙)与更高的住院几率有相关性。[254]Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020 Jul;79(7):859-66. https://ard.bmj.com/content/early/2020/05/29/annrheumdis-2020-217871 http://www.ncbi.nlm.nih.gov/pubmed/32471903?tool=bestpractice.com 使用环孢素/他克莫司治疗的患者住院风险亦同时增加;但是,尚不清楚增加的风险是否与药物本身、患者接受治疗的潜在疾病,或其他因素具有相关性。[255]Nørgård BM, Nielsen J, Knudsen T, et al. Hospitalization for COVID-19 in patients treated with selected immunosuppressant and immunomodulating agents, compared to the general population: a Danish cohort study. Br J Clin Pharmacol. 2021 Apr;87(4):2111-20. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14622 http://www.ncbi.nlm.nih.gov/pubmed/33098713?tool=bestpractice.com
与普通人群相比,免疫抑制患者感染风险未呈现显著增加。[256]Tassone D, Thompson A, Connell W, et al. Immunosuppression as a risk factor for COVID-19: a meta-analysis. Intern Med J. 2021 Feb;51(2):199-205. https://onlinelibrary.wiley.com/doi/10.1111/imj.15142 http://www.ncbi.nlm.nih.gov/pubmed/33631862?tool=bestpractice.com
另请参见 HIV 感染 和 自身免疫性疾病 如下。
HIV 携带者罹患重症的风险可能升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
回顾性研究发现,虽然 HIV 感染者感染风险似乎并未升高,但与未感染 HIV 者相比,他们出现不良结局(即重症、住院、死亡)的风险升高。随着 HIV 疾病阶段进展,重症和住院风险有所升高。[257]Bhaskaran K, Rentsch CT, MacKenna B, et al. HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform. Lancet HIV. 2021 Jan;8(1):e24-32. https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(20)30305-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/33316211?tool=bestpractice.com [258]Tesoriero JM, Swain CE, Pierce JL, et al. COVID-19 outcomes among persons living with or without diagnosed HIV infection in New York State. JAMA Netw Open. 2021 Feb 1;4(2):e2037069. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775827 http://www.ncbi.nlm.nih.gov/pubmed/33533933?tool=bestpractice.com [259]Chanda D, Minchella PA, Kampamba D, et al. COVID-19 severity and COVID-19-associated deaths among hospitalized patients with HIV infection: Zambia, March-December 2020. MMWR Morb Mortal Wkly Rep. 2021 Jun 4;70(22):807-10. https://www.cdc.gov/mmwr/volumes/70/wr/mm7022a2.htm http://www.ncbi.nlm.nih.gov/pubmed/34081684?tool=bestpractice.com [260]Yang X, Sun J, Patel RC, et al. Associations between HIV infection and clinical spectrum of COVID-19: a population level analysis based on US National COVID Cohort Collaborative (N3C) data. Lancet HIV. 2021 Nov;8(11):e690-700. https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(21)00239-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/34655550?tool=bestpractice.com 然而,部分证据表明晚期(3 期或 4 期)HIV 患者可表现出更轻的症状,死亡率亦更低。其原因可能在于 HIV 阳性个体免疫系统不易引发通常会导致 COVID-19 患者较劣临床结果结局的细胞因子风暴。[261]SeyedAlinaghi S, Karimi A, MohsseniPour M, et al. The clinical outcomes of COVID-19 in HIV-positive patients: a systematic review of current evidence. Immun Inflamm Dis. 2021 Dec;9(4):1160-85. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426924 http://www.ncbi.nlm.nih.gov/pubmed/34324280?tool=bestpractice.com
荟萃得出的证据存在冲突。部分荟萃分析发现,HIV 感染与综合不良结局或死亡不具相关性。[262]Lee KW, Yap SF, Ngeow YF, et al. COVID-19 in people living with HIV: a systematic review and meta-analysis. Int J Environ Res Public Health. 2021 Mar 30;18(7):3554. https://www.mdpi.com/1660-4601/18/7/3554/htm http://www.ncbi.nlm.nih.gov/pubmed/33808066?tool=bestpractice.com [263]Favara G, Barchitta M, Maugeri A, et al. HIV infection does not affect the risk of death of COVID-19 patients: a systematic review and meta-analysis of epidemiological studies. J Glob Health. 2022 Aug 17;12:05036. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380965 http://www.ncbi.nlm.nih.gov/pubmed/35972980?tool=bestpractice.com 但是,其他荟萃分析发现,与不伴 HIV 感染者相比,HIV 感染者的感染和死亡风险有所上升。基于替诺福韦二吡呋酯用药方案者的感染和不良结局风险可能较低;然而,证据尚未得出定论。[264]Mellor MM, Bast AC, Jones NR, et al. Risk of adverse coronavirus disease 2019 outcomes for people living with HIV. AIDS. 2021 Mar 15;35(4):F1-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924978 http://www.ncbi.nlm.nih.gov/pubmed/33587448?tool=bestpractice.com [265]Hariyanto TI, Rosalind J, Christian K, et al. Human immunodeficiency virus and mortality from coronavirus disease 2019: a systematic review and meta-analysis. South Afr J HIV Med. 2021 Apr 15;22(1):1220. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063497 http://www.ncbi.nlm.nih.gov/pubmed/33936793?tool=bestpractice.com [266]Danwang C, Noubiap JJ, Robert A, et al. Outcomes of patients with HIV and COVID-19 co-infection: a systematic review and meta-analysis. AIDS Res Ther. 2022 Jan 14;19(1):3. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8759058 http://www.ncbi.nlm.nih.gov/pubmed/35031068?tool=bestpractice.com [267]Oyelade T, Alqahtani JS, Hjazi AM, et al. Global and regional prevalence and outcomes of COVID-19 in people living with HIV: a systematic review and meta-analysis. Trop Med Infect Dis. 2022 Feb 3;7(2):22. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8880028 http://www.ncbi.nlm.nih.gov/pubmed/35202217?tool=bestpractice.com
世界卫生组织指出,HIV 感染似乎是住院时重症或危重疾病和住院死亡的重要独立危险因素。调整年龄、性别、疾病严重程度和基础疾病后,与 HIV 阴性人群相比,HIV 感染与更高的死亡风险呈独立相关。年龄 >65 岁、性别为男性、糖尿病或高血压是入院时重症或危重疾病以及院内死亡的危险因素。数据主要来自南非,从而可能会限制结果的普适性。[268]World Health Organization. Clinical features and prognostic factors of COVID-19 in people living with HIV hospitalized with suspected or confirmed SARS-CoV-2 infection. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-Clinical-HIV-2021.1 [269]Bertagnolio S, Thwin SS, Silva R, et al. Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19. Lancet HIV. 2022 Jul;9(7):e486-95. https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00097-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35561704?tool=bestpractice.com 严重疾病的其他风险因素包括共存的心血管疾病、呼吸系统疾病和慢性肾病。[270]Wang H, Jonas KJ. The likelihood of severe COVID-19 outcomes among PLHIV with various comorbidities: a comparative frequentist and Bayesian meta-analysis approach. J Int AIDS Soc. 2021 Nov;24(11):e25841. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604378 http://www.ncbi.nlm.nih.gov/pubmed/34797952?tool=bestpractice.com
不进行体育锻炼者,罹患重症的风险升高。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
数据显示,躯体活动不足与收住院和死亡风险升高具有相关性,躯体活动不足与人工通气风险升高可能具有相关性。有限数据表明,躯体活动不足与重症监护病房收治和气管插管具有相关性。[271]Rahmati M, Shamsi MM, Khoramipour K, et al. Baseline physical activity is associated with reduced mortality and disease outcomes in COVID-19: a systematic review and meta-analysis. Rev Med Virol. 2022 Apr 13:e2349. https://onlinelibrary.wiley.com/doi/10.1002/rmv.2349 http://www.ncbi.nlm.nih.gov/pubmed/35416354?tool=bestpractice.com [272]Centers for Disease Control and Prevention. Brief summary of findings on the association between physical inactivity and severe COVID-19 outcomes. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/downloads/clinical-care/E-Physical-Inactivity-Review.pdf [273]Ezzatvar Y, Ramírez-Vélez R, Izquierdo M, et al. Physical activity and risk of infection, severity and mortality of COVID-19: a systematic review and non-linear dose-response meta-analysis of data from 1 853 610 adults. Br J Sports Med. 2022 Aug 22 [Epub ahead of print]. https://bjsm.bmj.com/content/56/20/1188 http://www.ncbi.nlm.nih.gov/pubmed/35995587?tool=bestpractice.com
伴镰状细胞病或地中海贫血者重症风险可升高;然而,证据较为有限。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
与普通人群相比,血红蛋白病患者出现重症和死亡的风险并未升高。血红蛋白病患者死亡率为 6.9%。呼吸系统合并症和心血管合并症是死亡的重要预测指标。[274]Lee JX, Chieng WK, Lau SCD, et al. COVID-19 and hemoglobinopathies: a systematic review of clinical presentations, investigations, and outcomes. Front Med (Lausanne). 2021 Oct 13;8:757510. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549676 http://www.ncbi.nlm.nih.gov/pubmed/34722593?tool=bestpractice.com
在英国,镰状细胞病患者被发现住院风险升高 4 倍,死亡风险升高 2.6 倍。镰状细胞特性亦与此两种结局风险升高具有相关性,但相关程度较小。[275]Clift AK, Saatci D, Coupland CAC, et al. Sickle cell disorders and severe COVID-19 outcomes: a cohort study. Ann Intern Med. 2021 Oct;174(10):1483-7. https://www.acpjournals.org/doi/10.7326/M21-1375 http://www.ncbi.nlm.nih.gov/pubmed/34338553?tool=bestpractice.com
美国 178 例镰状细胞病患者中(平均患者年龄 <40 岁),69% 入院治疗,11% 接受重症诊疗,7% 死亡。[276]Panepinto JA, Brandow A, Mucalo L, et al. Coronavirus disease among persons with sickle cell disease, United States, March 20 – May 21, 2020. Emerg Infect Dis. 2020 Jul 8;26(10). https://wwwnc.cdc.gov/eid/article/26/10/20-2792_article http://www.ncbi.nlm.nih.gov/pubmed/32639228?tool=bestpractice.com 感染可在镰状细胞病患者中导致急性胸部综合征。[277]Hussain FA, Njoku FU, Saraf SL, et al. COVID-19 infection in patients with sickle cell disease. Br J Haematol. 2020 Jun;189(5):851-2. https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16734 http://www.ncbi.nlm.nih.gov/pubmed/32314798?tool=bestpractice.com [278]Nur E, Gaartman AE, van Tuijn CFJ, et al. Vaso-occlusive crisis and acute chest syndrome in sickle cell disease due to 2019 novel coronavirus disease (COVID-19). Am J Hematol. 2020 Jun;95(6):725-6. https://onlinelibrary.wiley.com/doi/10.1002/ajh.25821 http://www.ncbi.nlm.nih.gov/pubmed/32267016?tool=bestpractice.com
高血压患者罹患重症风险可能升高;但是证据有限。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
几乎所有现有证据均提示,高血压可增加重症或死亡风险,但有时不清楚该关联是否独立于其他危险因素。暂无系统评价或荟萃分析,对高血压患者是否具有更高感染风险进行研究。[279]World Health Organization. Hypertension and COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Hypertension-2021.1 [280]Qian Z, Li Z, Peng J, et al. Association between hypertension and prognosis of patients with COVID-19: a systematic review and meta-analysis. Clin Exp Hypertens. 2022 May 8:1-8. http://www.ncbi.nlm.nih.gov/pubmed/35531646?tool=bestpractice.com
高血压与不良复合结局增加有关,包括死亡、重症、急性呼吸窘迫综合征、危重症诊疗需求以及疾病进展。[281]Pranata R, Lim MA, Huang I, et al. Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: a systematic review, meta-analysis and meta-regression. J Renin Angiotensin Aldosterone Syst. 2020 Apr-Jun;21(2):1470320320926899. https://journals.sagepub.com/doi/10.1177/1470320320926899 http://www.ncbi.nlm.nih.gov/pubmed/32408793?tool=bestpractice.com [282]Kabia AU, Li P, Jin Z, et al. The effects of hypertension on the prognosis of coronavirus disease 2019: a systematic review and meta-analysis on the interactions with age and antihypertensive treatment. J Hypertens. 2022 Aug 9 [Epub ahead of print]. https://journals.lww.com/jhypertension/Fulltext/9900/The_effects_of_hypertension_on_the_prognosis_of.80.aspx http://www.ncbi.nlm.nih.gov/pubmed/35950998?tool=bestpractice.com 与不伴高血压患者相比,伴高血压患者罹患重症风险升高 2.98 倍,危重症风险升高 1.82 倍,死亡风险则升高 2.17 至 2.88 倍。[283]de Almeida-Pititto B, Dualib PM, Zajdenverg L, et al. Severity and mortality of COVID 19 in patients with diabetes, hypertension and cardiovascular disease: a meta-analysis. Diabetol Metab Syndr. 2020 Aug 31;12:75. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456786 http://www.ncbi.nlm.nih.gov/pubmed/32874207?tool=bestpractice.com [284]Du Y, Zhou N, Zha W, et al. Hypertension is a clinically important risk factor for critical illness and mortality in COVID-19: a meta-analysis. Nutr Metab Cardiovasc Dis. 2021 Mar 10;31(3):745-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831720 http://www.ncbi.nlm.nih.gov/pubmed/33549450?tool=bestpractice.com
最初,人们担心使用 ACE 抑制剂或血管紧张素 Ⅱ 受体拮抗剂者,可能由于 ACE2 受体表达上调,而使感染或重症风险升高。[285]Goldstein MR, Poland GA, Graeber CW. Are certain drugs associated with enhanced mortality in COVID-19? QJM. 2020 Jul 1;113(7):509-10. https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcaa103/5812790 http://www.ncbi.nlm.nih.gov/pubmed/32219440?tool=bestpractice.com 但是,高确定性证据表明,使用此类药物与重症无关,对有症状患者使用此类药物,与 SARS-CoV-2 阳性检测结果之间不具备关联。[286]Mackey K, King VJ, Gurley S, et al. Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults: a living systematic review. Ann Intern Med. 2020 Aug 4;173(3):195-203. https://www.acpjournals.org/doi/10.7326/M20-1515 http://www.ncbi.nlm.nih.gov/pubmed/32422062?tool=bestpractice.com [287]Mackey K, Kansagara D, Vela K. Update alert 7: risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults. Ann Intern Med. 2021 Feb;174(2):W25-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791405 http://www.ncbi.nlm.nih.gov/pubmed/33395346?tool=bestpractice.com
物质使用障碍患者罹患重症的风险可有所增加;但是证据有限。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html 其包括酒精、阿片类物质或可卡因使用障碍。
伴物质使用障碍者,尤其是使用可影响呼吸系统和心血管系统药物者,可能更易表现 COVID-19 不良呼吸道效应。队列研究已发现,物质使用障碍与住院率上升、重症监护病房收治增多、呼吸机使用率上升和死亡率增加等具有相关性。[288]Baillargeon J, Polychronopoulou E, Kuo YF, et al. The impact of substance use disorder on COVID-19 outcomes. Psychiatr Serv. 2021 May 1;72(5):578-81. https://ps.psychiatryonline.org/doi/10.1176/appi.ps.202000534 http://www.ncbi.nlm.nih.gov/pubmed/33138712?tool=bestpractice.com [289]Allen B, El Shahawy O, Rogers ES, et al. Association of substance use disorders and drug overdose with adverse COVID-19 outcomes in New York City: January-October 2020. J Public Health (Oxf). 2021 Sep 22;43(3):462-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799011 http://www.ncbi.nlm.nih.gov/pubmed/33367823?tool=bestpractice.com 一项系统评价和荟萃分析发现,阿片类物质使用障碍者住院、被收入重症监护病房和死亡的风险增加。[290]Behnoush AH, Bazmi E, Forouzesh M, et al. Risk of COVID-19 infection and the associated hospitalization, ICU admission and mortality in opioid use disorder: a systematic review and meta-analysis. Addict Sci Clin Pract. 2022 Nov 30;17(1):68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709364 http://www.ncbi.nlm.nih.gov/pubmed/36451181?tool=bestpractice.com
伴某些基础疾病儿童,罹患重症风险可能升高;但是证据有限。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
此类疾病包括肥胖、糖尿病、哮喘和慢性肺病、免疫抑制和镰状细胞病。若临床情况复杂,患有严重遗传、神经或代谢疾病,或患有先天性心脏病,则儿童亦可能存在风险。[147]Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. 2022 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
一项对美国 43,000 余名儿童进行的横断面研究发现,最常记录的基础疾病为肥胖、哮喘、神经发育障碍性疾病、焦虑和恐惧相关性疾病以及抑郁。伴 1 型糖尿病、心脏和循环先天异常、肥胖、高血压、癫痫、神经精神疾病和哮喘的儿童,以及伴慢性疾患的儿童,收住入院和呈现重症风险升高。有限数据表明,伴先天性心脏病儿童罹患重症风险可能升高。[291]Kompaniyets L, Agathis NT, Nelson JM, et al. Underlying medical conditions associated with severe COVID-19 illness among children. JAMA Netw Open. 2021 Jun 1;4(6):e2111182. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780706 http://www.ncbi.nlm.nih.gov/pubmed/34097050?tool=bestpractice.com
维生素 D 缺乏患者感染和重症风险可能升高;但是证据有限。
荟萃分析发现,血清维生素 D 水平偏低与感染风险升高呈显著相关,且重症、住院以及死亡等风险均上升。[292]Akbar MR, Wibowo A, Pranata R, et al. Low serum 25-hydroxyvitamin d (vitamin d) level is associated with susceptibility to COVID-19, severity, and mortality: a systematic review and meta-analysis. Front Nutr. 2021 Mar 29;8:660420. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039288 http://www.ncbi.nlm.nih.gov/pubmed/33855042?tool=bestpractice.com [293]Crafa A, Cannarella R, Condorelli RA, et al. Influence of 25-hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: a systematic review and meta-analysis. EClinicalMedicine. 2021 Jul;37:100967. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215557 http://www.ncbi.nlm.nih.gov/pubmed/34179737?tool=bestpractice.com [294]Szarpak L, Rafique Z, Gasecka A, et al. A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19. Cardiol J. 2021;28(5):647-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428943 http://www.ncbi.nlm.nih.gov/pubmed/34308537?tool=bestpractice.com [295]Shah K, V P V, Pandya A, et al. Low vitamin D levels and prognosis in a COVID-19 pediatric population: a systematic review. QJM. 2021 Nov 5;114(7):447-53. https://academic.oup.com/qjmed/article/114/7/447/6325519 http://www.ncbi.nlm.nih.gov/pubmed/34293161?tool=bestpractice.com [296]Borsche L, Glauner B, von Mendel J. COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/mL 25(OH)D3: results of a systematic review and meta-analysis. Nutrients. 2021 Oct 14;13(10):3596. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541492 http://www.ncbi.nlm.nih.gov/pubmed/34684596?tool=bestpractice.com [297]Ebrahimzadeh A, Mohseni S, Narimani B, et al. Association between vitamin D status and risk of covid-19 in-hospital mortality: a systematic review and meta-analysis of observational studies. Crit Rev Food Sci Nutr. 2021 Dec 9:1-11. http://www.ncbi.nlm.nih.gov/pubmed/34882024?tool=bestpractice.com [298]Dissanayake HA, de Silva NL, Sumanatilleke M, et al. Prognostic and therapeutic role of vitamin D in COVID-19: systematic review and meta-analysis. J Clin Endocrinol Metab. 2021 Dec 11 [Epub ahead of print]. https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgab892/6459715 http://www.ncbi.nlm.nih.gov/pubmed/34894254?tool=bestpractice.com 但是,尚不清楚这些关联是否具有统计学意义,证据确定性极低。[299]Bassatne A, Basbous M, Chakhtoura M, et al. The link between COVID-19 and vitamin D (VIVID): a systematic review and meta-analysis. Metabolism. 2021 Mar 24:154753. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989070 http://www.ncbi.nlm.nih.gov/pubmed/33774074?tool=bestpractice.com [300]Grove A, Osokogu O, Al-Khudairy L, et al. Association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19 including clinical course, morbidity and mortality outcomes? A systematic review. BMJ Open. 2021 May 28;11(5):e043737. https://bmjopen.bmj.com/content/11/5/e043737.long http://www.ncbi.nlm.nih.gov/pubmed/34049903?tool=bestpractice.com
一项对队列研究和随机对照试验进行的荟萃分析和 GRADE 评估发现,目前证据表明,维生素 D 缺乏与感染或死亡易感性并无显著相关性,补充维生素 D 并未显著改善临床结局。然而,证据总体质量较低。[301]Chen J, Mei K, Xie L, et al. Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort studies and RCTs. Nutr J. 2021 Oct 31;20(1):89. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557713 http://www.ncbi.nlm.nih.gov/pubmed/34719404?tool=bestpractice.com
服用质子泵抑制剂(proton-pump inhibitor, PPI)患者感染和重症风险可能升高;但是证据有限。[302]Fatima K, Almas T, Lakhani S, et al. The use of proton pump inhibitors and COVID-19: a systematic review and meta-analysis. Trop Med Infect Dis. 2022 Feb 28;7(3):37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950138 http://www.ncbi.nlm.nih.gov/pubmed/35324584?tool=bestpractice.com
使用 PPI 是否增加感染风险的数据存在冲突。迄今为止最大的荟萃分析发现,PPI 的使用与感染风险升高,以及重度感染和死亡风险升高略具名义上的相关性(但具有统计学意义)。[302]Fatima K, Almas T, Lakhani S, et al. The use of proton pump inhibitors and COVID-19: a systematic review and meta-analysis. Trop Med Infect Dis. 2022 Feb 28;7(3):37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950138 http://www.ncbi.nlm.nih.gov/pubmed/35324584?tool=bestpractice.com
与未服用 PPI 者相比,当前或定期服用 PPI 者,更易出现重症结局。此外,与未服用 PPI 者相比,当前服用 PPI 者,更易出现更长的住院时间,但这一差异无统计学意义。既往服用 PPI ,与对感染易感性增加或严重不良结局有关。[303]Li GF, An XX, Yu Y, et al. Do proton pump inhibitors influence SARS-CoV-2 related outcomes? A meta-analysis. Gut. 2021 Sep;70(9):1806-8. https://gut.bmj.com/content/gutjnl/early/2020/11/10/gutjnl-2020-323366.full.pdf http://www.ncbi.nlm.nih.gov/pubmed/33172925?tool=bestpractice.com
自身免疫性疾病(包括风湿和肌肉骨骼疾病)患者感染和重症风险可能升高;但是证据有限。[304]Akiyama S, Hamdeh S, Micic D, et al. Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis. Ann Rheum Dis. 2020 Oct 13 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554412 http://www.ncbi.nlm.nih.gov/pubmed/33051220?tool=bestpractice.com [305]Conway R, Grimshaw AA, Konig MF, et al. SARS-CoV-2 infection and COVID-19 outcomes in rheumatic diseases: a systematic literature review and meta-analysis. Arthritis Rheumatol. 2021 Nov 22 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/10.1002/art.42030 http://www.ncbi.nlm.nih.gov/pubmed/34807517?tool=bestpractice.com
当前数据并未强烈表明免疫介导性炎性疾病的存在可增加感染或重症风险。部分研究报道的风险升高,可能原因在于免疫介导性炎性疾病相关的合并症或患者正在采用的药物治疗(皮质类固醇、利妥昔单抗)。此类患者住院率升高与死亡率升高不具相关性。[253]Fagni F, Simon D, Tascilar K, et al. COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses. Lancet Rheumatol. 2021 Oct;3(10):e724-36. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397302 http://www.ncbi.nlm.nih.gov/pubmed/34485930?tool=bestpractice.com 与其他治疗方案(例如甲氨蝶呤、硫唑嘌呤、Janus 激酶抑制剂)相比,肿瘤坏死因子(tumour necrosis factor, TNF)-α 抑制剂单药治疗与免疫介导炎症性疾病患者住院或死亡风险降低具有相关性。[306]Izadi Z, Brenner EJ, Mahil SK, et al. Association between tumor necrosis factor inhibitors and the risk of hospitalization or death among patients with immune-mediated inflammatory disease and COVID-19. JAMA Netw Open. 2021 Oct 1;4(10):e2129639. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785080 http://www.ncbi.nlm.nih.gov/pubmed/34661663?tool=bestpractice.com 在一项队列研究中,除利妥昔单抗外,其他风湿病、抗肿瘤或抗代谢治疗未使机械通气或住院死亡风险升高。[307]Andersen KM, Bates BA, Rashidi ES, et al. Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative. Lancet Rheumatol. 2022 Jan;4(1):e33-41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592562 http://www.ncbi.nlm.nih.gov/pubmed/34806036?tool=bestpractice.com
炎性关节炎:证据并未显示炎性关节炎(例如类风湿性关节炎、脊柱关节炎)与感染风险或不良结局(例如住院、重症监护病房收治、需行机械通气或死亡)之间存在密切关联。然而,证据存在冲突。部分研究确实报道了不良结局风险升高,但研究存在局限性。[253]Fagni F, Simon D, Tascilar K, et al. COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses. Lancet Rheumatol. 2021 Oct;3(10):e724-36. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397302 http://www.ncbi.nlm.nih.gov/pubmed/34485930?tool=bestpractice.com
炎症性肠病:炎症性肠病患者的患病率似乎较低。[308]Tripathi K, Godoy Brewer G, Thu Nguyen M, et al. COVID-19 and outcomes in patients with inflammatory bowel disease: systematic review and meta-analysis. Inflamm Bowel Dis. 2021 Oct 27 [Epub ahead of print]. https://academic.oup.com/ibdjournal/advance-article/doi/10.1093/ibd/izab236/6412576 http://www.ncbi.nlm.nih.gov/pubmed/34718595?tool=bestpractice.com 证据表明,如果患者疾病控制良好且未使用皮质类固醇,则感染风险和重症风险情况与一般人群相似。[253]Fagni F, Simon D, Tascilar K, et al. COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses. Lancet Rheumatol. 2021 Oct;3(10):e724-36. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397302 http://www.ncbi.nlm.nih.gov/pubmed/34485930?tool=bestpractice.com 皮质类固醇使用与重症和重症监护病房收治(但并非死亡)等风险升高具有相关性。[309]Alrashed F, Battat R, Abdullah I, et al. Impact of medical therapies for inflammatory bowel disease on the severity of COVID-19: a systematic review and meta-analysis. BMJ Open Gastroenterol. 2021 Oct;8(1):e000774. https://bmjopengastro.bmj.com/content/8/1/e000774.long http://www.ncbi.nlm.nih.gov/pubmed/34725056?tool=bestpractice.com 三分之一炎症性肠病患者需收住院治疗,不到 4% 患者需重症监护病房收治。[308]Tripathi K, Godoy Brewer G, Thu Nguyen M, et al. COVID-19 and outcomes in patients with inflammatory bowel disease: systematic review and meta-analysis. Inflamm Bowel Dis. 2021 Oct 27 [Epub ahead of print]. https://academic.oup.com/ibdjournal/advance-article/doi/10.1093/ibd/izab236/6412576 http://www.ncbi.nlm.nih.gov/pubmed/34718595?tool=bestpractice.com 较高的疾病活动度和急性发作可导致感染易感性增加和更劣的结局。[310]Bezzio C, Saibeni S, Variola A, et al. Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study. Gut. 2020 Jul;69(7):1213-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242872 http://www.ncbi.nlm.nih.gov/pubmed/32354990?tool=bestpractice.com 溃疡性结肠炎和使用皮质类固醇、硫嘌呤、氨基水杨酸或联合治疗的患者,其结局(住院、重症监护病房收治和死亡率)更劣。使用生物制剂的患者结局更佳。[308]Tripathi K, Godoy Brewer G, Thu Nguyen M, et al. COVID-19 and outcomes in patients with inflammatory bowel disease: systematic review and meta-analysis. Inflamm Bowel Dis. 2021 Oct 27 [Epub ahead of print]. https://academic.oup.com/ibdjournal/advance-article/doi/10.1093/ibd/izab236/6412576 http://www.ncbi.nlm.nih.gov/pubmed/34718595?tool=bestpractice.com [311]Singh S, Khan A, Chowdhry M, et al. Risk of severe coronavirus disease 2019 in patients with inflammatory bowel disease in the united states: a multicenter research network study. Gastroenterology. 2020 Oct;159(4):1575-8. https://www.gastrojournal.org/article/S0016-5085(20)34755-7/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32522507?tool=bestpractice.com [312]Ungaro RC, Brenner EJ, Gearry RB, et al. Effect of IBD medications on COVID-19 outcomes: results from an international registry. Gut. 2021 Apr;70(4):725-32. https://gut.bmj.com/content/early/2020/10/26/gutjnl-2020-322539.long http://www.ncbi.nlm.nih.gov/pubmed/33082265?tool=bestpractice.com [313]Singh AK, Jena A, Kumar-M P, et al. Risk and outcomes of coronavirus disease in patients with inflammatory bowel disease: a systematic review and meta-analysis. United European Gastroenterol J. 2021 Mar;9(2):159-76. https://journals.sagepub.com/doi/10.1177/2050640620972602 http://www.ncbi.nlm.nih.gov/pubmed/33210980?tool=bestpractice.com 已经开发出一种风险计算器,可以预测哪些炎症性肠病患者出现不良结局的风险更高。[314]Sperger J, Shah KS, Lu M, et al. Development and validation of multivariable prediction models for adverse COVID-19 outcomes in patients with IBD. BMJ Open. 2021 Nov 12;11(11):e049740. https://bmjopen.bmj.com/content/11/11/e049740 http://www.ncbi.nlm.nih.gov/pubmed/34772750?tool=bestpractice.com
结缔组织病:多项研究表明,与普通人群和其他免疫介导性炎性疾病患者相比,结缔组织病(例如系统性红斑狼疮、干燥综合征、系统性硬化症、多发性肌炎和皮肌炎)患者感染风险有所升高。这可能是由于皮质类固醇在此类患者中的广泛使用。与结局相关的数据较为缺乏,证据存在冲突。[253]Fagni F, Simon D, Tascilar K, et al. COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses. Lancet Rheumatol. 2021 Oct;3(10):e724-36. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397302 http://www.ncbi.nlm.nih.gov/pubmed/34485930?tool=bestpractice.com 狼疮性肾炎患者出现重症或危重症的风险升高。[315]Sakthiswary R, Chuah HY, Chiang KS, et al. COVID-19 in systemic lupus erythematosus: a pooled analysis and systematic review of case reports and series. Lupus. 2021 Oct;30(12):1946-54. https://journals.sagepub.com/doi/10.1177/09612033211045057 http://www.ncbi.nlm.nih.gov/pubmed/34565208?tool=bestpractice.com
银屑病:风险和结局数据令人信服的表明,其与一般人群所观察到的风险状况相当,在队列研究中,亦未见感染或重症易感性增加的报道。[253]Fagni F, Simon D, Tascilar K, et al. COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses. Lancet Rheumatol. 2021 Oct;3(10):e724-36. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397302 http://www.ncbi.nlm.nih.gov/pubmed/34485930?tool=bestpractice.com
血管炎:基于有限数据,皮质类固醇使用、高龄、性别为男性、中重度疾病活动度、合并症(例如呼吸系统疾病),以及利妥昔单抗或环磷酰胺的使用,与严重结局具有相关性。[316]Rutherford MA, Scott J, Karabayas M, et al. Risk factors for severe outcomes in patients with systemic vasculitis and COVID-19: a binational, registry-based cohort study. Arthritis Rheumatol. 2021 Sep;73(9):1713-9. https://onlinelibrary.wiley.com/doi/10.1002/art.41728 http://www.ncbi.nlm.nih.gov/pubmed/33750043?tool=bestpractice.com [317]Sattui SE, Conway R, Putman MS, et al. Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study. Lancet Rheumatol. 2021 Dec;3(12):e855-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570701 http://www.ncbi.nlm.nih.gov/pubmed/34778843?tool=bestpractice.com
多发性硬化:神经功能障碍、高龄、黑种人族裔、心血管合并症、近期皮质类固醇治疗和肥胖为重症危险因素。[318]Louapre C, Collongues N, Stankoff B, et al. Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis. JAMA Neurol. 2020 Sep 1;77(9):1079-88. https://jamanetwork.com/journals/jamaneurology/fullarticle/2767776 http://www.ncbi.nlm.nih.gov/pubmed/32589189?tool=bestpractice.com [319]Salter A, Fox RJ, Newsome SD, et al. Outcomes and risk factors associated with SARS-CoV-2 infection in a North American registry of patients with multiple sclerosis. JAMA Neurol. 2021 Jun 1;78(6):699-708. https://jamanetwork.com/journals/jamaneurology/fullarticle/2777735 http://www.ncbi.nlm.nih.gov/pubmed/33739362?tool=bestpractice.com 当前证据并未表明多发性硬化显著增加死亡率。最高住院率和死亡率见于未采用疾病修饰治疗的患者,其次是进行 B 细胞耗竭治疗的患者(例如利妥昔单抗、奥瑞珠单抗)。[320]Barzegar M, Mirmosayyeb O, Gajarzadeh M, et al. COVID-19 among patients with multiple sclerosis: a systematic review. Neurol Neuroimmunol Neuroinflamm. 2021 Jul;8(4):e1001. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142838 http://www.ncbi.nlm.nih.gov/pubmed/34016734?tool=bestpractice.com
甲状腺功能减退症患者重症风险可能升高;但是证据有限。[321]Giovanella L, Ruggeri RM, Ovčariček PP, et al. Prevalence of thyroid dysfunction in patients with COVID-19: a systematic review. Clin Transl Imaging. 2021 Mar 11:1-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950424 http://www.ncbi.nlm.nih.gov/pubmed/33728279?tool=bestpractice.com [322]Malik J, Zaidi SMJ, Waqar AU, et al. Association of hypothyroidism with acute COVID-19: a systematic review. Expert Rev Endocrinol Metab. 2021 Sep;16(5):251-7. http://www.ncbi.nlm.nih.gov/pubmed/34424110?tool=bestpractice.com
甲状腺疾病(甲状腺功能减退症和未明确的甲状腺异常,但并非甲状腺功能亢进症)与不良结局风险(包括重症、住院、重症监护病房收治和死亡)升高具有相关性。这种关联与年龄增长和高血压患病具有显著相关性。[323]Damara FA, Muchamad GR, Ikhsani R, et al. Thyroid disease and hypothyroidism are associated with poor COVID-19 outcomes: a systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2021 Oct 22;15(6):102312. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530797 http://www.ncbi.nlm.nih.gov/pubmed/34731819?tool=bestpractice.com [324]Permana H, Soeriadi EA, Damara FA, et al. The prognostic values of thyroid disorders in predicting COVID-19 composite poor outcomes: a systematic review and meta-analysis. Diabetes Metab Syndr. 2022 Mar 18;16(5):102464. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8930180 http://www.ncbi.nlm.nih.gov/pubmed/35508091?tool=bestpractice.com
帕金森病患者感染或重症风险可能升高;但是证据有限。[325]Putri C, Hariyanto TI, Hananto JE, et al. Parkinson's disease may worsen outcomes from coronavirus disease 2019 (COVID-19) pneumonia in hospitalized patients: a systematic review, meta-analysis, and meta-regression. Parkinsonism Relat Disord. 2021 Jun;87:155-61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065236 http://www.ncbi.nlm.nih.gov/pubmed/33931304?tool=bestpractice.com [326]Chambergo-Michilot D, Barros-Sevillano S, Rivera-Torrejón O, et al. Factors associated with COVID-19 in people with Parkinson's disease: a systematic review and meta-analysis. Eur J Neurol. 2021 Oct;28(10):3467-77. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239569 http://www.ncbi.nlm.nih.gov/pubmed/33983673?tool=bestpractice.com [327]Khoshnood RJ, Zali A, Tafreshinejad A, et al. Parkinson's disease and COVID-19: a systematic review and meta-analysis. Neurol Sci. 2022 Feb;43(2):775-83. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596358 http://www.ncbi.nlm.nih.gov/pubmed/34787753?tool=bestpractice.com
感染的危险因素可包括肥胖、肺部疾病和住院治疗。维生素 D 补充与感染风险降低具有相关性。[326]Chambergo-Michilot D, Barros-Sevillano S, Rivera-Torrejón O, et al. Factors associated with COVID-19 in people with Parkinson's disease: a systematic review and meta-analysis. Eur J Neurol. 2021 Oct;28(10):3467-77. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239569 http://www.ncbi.nlm.nih.gov/pubmed/33983673?tool=bestpractice.com
一项荟萃分析显示,帕金森病与重症、较劣的住院结局和死亡相关。但是,存在关联的证据仍不尚清楚。该关联受年龄影响,但不受性别或痴呆、高血压或糖尿病影响。[325]Putri C, Hariyanto TI, Hananto JE, et al. Parkinson's disease may worsen outcomes from coronavirus disease 2019 (COVID-19) pneumonia in hospitalized patients: a systematic review, meta-analysis, and meta-regression. Parkinsonism Relat Disord. 2021 Jun;87:155-61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065236 http://www.ncbi.nlm.nih.gov/pubmed/33931304?tool=bestpractice.com
患者可能出现帕金森症状显著恶化。[328]Jaiswal V, Alquraish D, Sarfraz Z, et al. The influence of coronavirus disease-2019 (COVID-19) on Parkinson's disease: an updated systematic review. J Prim Care Community Health. 2021 Jan-Dec;12:21501327211039709. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377313 http://www.ncbi.nlm.nih.gov/pubmed/34404266?tool=bestpractice.com
痛风似乎与感染和死亡风险升高具有相关性;但是证据有限。[329]Topless RK, Gaffo A, Stamp LK, et al. Gout and the risk of COVID-19 diagnosis and death in the UK Biobank: a population-based study. Lancet Rheumatol. 2022 Jan 28 [Epub ahead of print]. https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00401-X/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35128470?tool=bestpractice.com
英国生物库对超过 15,000 名痛风患者进行的一项人群研究发现,痛风与 COVID-19 诊断风险升高和 COVID-19 相关性死亡风险升高具有相关性,该关联独立于痛风的代谢合并症。女性较男性死亡风险更高。秋水仙碱或降尿酸治疗的给予与否,COVID-19 相关性死亡风险并无显著差异。[329]Topless RK, Gaffo A, Stamp LK, et al. Gout and the risk of COVID-19 diagnosis and death in the UK Biobank: a population-based study. Lancet Rheumatol. 2022 Jan 28 [Epub ahead of print]. https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00401-X/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35128470?tool=bestpractice.com 证据有限,尚需行进一步研究。
血脂异常似乎与重症和死亡风险增加相关;但是证据有限。[330]Choi GJ, Kim HM, Kang H. The potential role of dyslipidemia in COVID-19 severity: an umbrella review of systematic reviews. J Lipid Atheroscler. 2020 Sep;9(3):435-48. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521969 http://www.ncbi.nlm.nih.gov/pubmed/33024735?tool=bestpractice.com [331]Zuin M, Rigatelli G, Bilato C, et al. Dyslipidaemia and mortality in COVID-19 patients: a meta-analysis. QJM. 2021 Oct 7;114(6):390-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083520 http://www.ncbi.nlm.nih.gov/pubmed/33822215?tool=bestpractice.com [332]Liu Y, Pan Y, Yin Y, et al. Association of dyslipidemia with the severity and mortality of coronavirus disease 2019 (COVID-19): a meta-analysis. Virol J. 2021 Jul 27;18(1):157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314261 http://www.ncbi.nlm.nih.gov/pubmed/34315474?tool=bestpractice.com
男性、老年人和高血压患者的这种相关性更强。[333]Atmosudigdo IS, Pranata R, Lim MA, et al. Dyslipidemia increases the risk of severe COVID-19: a systematic review, meta-analysis, and meta-regression. J Clin Exp Hepatol. 2021 Feb 8 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868769 http://www.ncbi.nlm.nih.gov/pubmed/33584063?tool=bestpractice.com
起初,令人担忧的是,服用他汀类药物者可能面临更高感染风险或更严重疾病,因为他汀类药物已被证实可增加实验动物 ACE2 表达,并可促进急性呼吸窘迫综合征炎症通路活化。[285]Goldstein MR, Poland GA, Graeber CW. Are certain drugs associated with enhanced mortality in COVID-19? QJM. 2020 Jul 1;113(7):509-10. https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcaa103/5812790 http://www.ncbi.nlm.nih.gov/pubmed/32219440?tool=bestpractice.com 但是,目前为止,研究并不支持这一假说,有研究甚至表明其具有保护作用(死亡或重症风险降低)。[334]Kow CS, Hasan SS. The association between the use of statins and clinical outcomes in patients with COVID-19: a systematic review and meta-analysis. Am J Cardiovasc Drugs. 2021 Aug 3;1-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328743 http://www.ncbi.nlm.nih.gov/pubmed/34341972?tool=bestpractice.com 美国心脏协会 COVID-19 心血管疾病登记数据调查结果报道称,住院前服用他汀类药物的患者(主要是存在心血管疾病史和/或高血压病史的患者)死亡几率大大降低。[335]Daniels LB, Ren J, Kumar K, et al. Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: findings from the American Heart Association's COVID-19 Cardiovascular Disease Registry. PLoS One. 2021 Jul 15;16(7):e0254635. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281996 http://www.ncbi.nlm.nih.gov/pubmed/34264974?tool=bestpractice.com 一项瑞典登记注册研究亦报道了类似发现。[336]Bergqvist R, Ahlqvist VH, Lundberg M, et al. HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm, Sweden: a registry-based cohort study. PLoS Med. 2021 Oct;18(10):e1003820. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516243 http://www.ncbi.nlm.nih.gov/pubmed/34648516?tool=bestpractice.com
与无 COVID-19 患者相比,罹患 COVID-19 的患者手术死亡率和并发症率可更高。[337]Doglietto F, Vezzoli M, Gheza F, et al. Factors associated with surgical mortality and complications among patients with and without coronavirus disease 2019 (COVID-19) in Italy. JAMA Surg. 2020 Jun 12;155(8):1-14. https://jamanetwork.com/journals/jamasurgery/fullarticle/2767370 http://www.ncbi.nlm.nih.gov/pubmed/32530453?tool=bestpractice.com
对中国 34 例在 COVID-19 潜伏期进行择期手术的患者进行回顾性研究发现,所有患者术后均出现肺炎。此类患者中约 44% 需收入重症监护病房,20% 遭遇死亡。[338]Lei S, Jiang F, Su W, et al. Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection. EClinicalMedicine. 2020 Apr 5:100331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128617 http://www.ncbi.nlm.nih.gov/pubmed/32292899?tool=bestpractice.com
术后肺部并发症出现于半数围手术期 SARS-CoV-2 感染患者,与死亡率升高相关,尤其是对于男性和 70 岁以上者。[339]COVIDSurg Collaborative. Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet. 2020 Jul 4;396(10243):27-38. https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31182-X.pdf http://www.ncbi.nlm.nih.gov/pubmed/32479829?tool=bestpractice.com
A 型血患者感染和死亡风险可能升高,B 型血和 AB 型血患者感染风险可能升高;但是证据有限。[340]Liu N, Zhang T, Ma L, et al. The impact of ABO blood group on COVID-19 infection risk and mortality: A systematic review and meta-analysis. Blood Rev. 2020 Dec 8:100785. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834371 http://www.ncbi.nlm.nih.gov/pubmed/33309392?tool=bestpractice.com [341]Gutiérrez-Valencia M, Leache L, Librero J, et al. ABO blood group and risk of COVID-19 infection and complications: a systematic review and meta-analysis. Transfusion. 2022 Feb;62(2):493-505. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661771 http://www.ncbi.nlm.nih.gov/pubmed/34773411?tool=bestpractice.com [342]Soo KM, Chung KM, Mohd Azlan MAA, et al. The association of ABO and Rhesus blood type with the risks of developing SARS-CoV-2 infection: a meta-analysis. Trop Biomed. 2022 Mar 1;39(1):126-34. https://secureservercdn.net/72.167.241.180/114.7f7.myftpupload.com/files/Vol39No1/tb-39-1-015-Soo-K-M.pdf http://www.ncbi.nlm.nih.gov/pubmed/35507935?tool=bestpractice.com [343]Balaouras G, Eusebi P, Kostoulas P. Systematic review and meta-analysis of the effect of ABO blood group on the risk of SARS-CoV-2 infection. PLoS One. 2022 Jul 28;17(7):e0271451. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333251 http://www.ncbi.nlm.nih.gov/pubmed/35901063?tool=bestpractice.com
O 型血型似乎对于感染具有预防性;然而,证据质量为低至极低。与 Rh 阴性者相比,Rh 阳性者更易受到感染。[340]Liu N, Zhang T, Ma L, et al. The impact of ABO blood group on COVID-19 infection risk and mortality: A systematic review and meta-analysis. Blood Rev. 2020 Dec 8:100785. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834371 http://www.ncbi.nlm.nih.gov/pubmed/33309392?tool=bestpractice.com [344]Franchini M, Cruciani M, Mengoli C, et al. ABO blood group and COVID-19: an updated systematic literature review and meta-analysis. Blood Transfus. 2021 May 12;19(4):317-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297670 http://www.ncbi.nlm.nih.gov/pubmed/34059188?tool=bestpractice.com
一项全基因组关联研究发现,与其他血型相比,A 型血患者呼吸衰竭风险增加 45%。它还发现 O 型血有保护作用。两个染色体基因位点与呼吸衰竭有关,其中一个与 ABO 血型位点重合。[345]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 SARS-CoV-2 受体-结合域直接结合呼吸道上皮细胞表达的 A 型血抗原,直接使 A 型血和 SARS-CoV-2 产生关联。[346]Wu SC, Arthur CM, Wang J, et al. The SARS-CoV-2 receptor-binding domain preferentially recognizes blood group A. Blood Adv. 2021 Mar 9;5(5):1305-1309. https://ashpublications.org/bloodadvances/article/5/5/1305/475250/The-SARS-CoV-2-receptor-binding-domain http://www.ncbi.nlm.nih.gov/pubmed/33656534?tool=bestpractice.com
有限证据表明肠道和肺部菌群功能异常可能与 COVID-19 发病机理有关。[347]Yamamoto S, Saito M, Tamura A, et al. The human microbiome and COVID-19: a systematic review. PLoS One. 2021 Jun 23;16(6):e0253293. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253293 http://www.ncbi.nlm.nih.gov/pubmed/34161373?tool=bestpractice.com
已发现患者在急性期和恢复期出现肠道菌群失调。[348]Cheng X, Zhang Y, Li Y, et al. Meta-analysis of 16S rRNA microbial data identified alterations of the gut microbiota in COVID-19 patients during the acute and recovery phases. BMC Microbiol. 2022 Nov 14;22(1):274. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662111 http://www.ncbi.nlm.nih.gov/pubmed/36376804?tool=bestpractice.com 患者住院期间,似乎有益共生菌(例如凸腹真杆菌、直肠真杆菌、普氏粪杆菌、罗斯拜瑞氏菌和毛螺菌等菌群)耗竭,而机会病原体(例如哈氏梭菌、粘性放线菌、诺氏拟杆菌)则过度生长。[349]Dhar D, Mohanty A. Gut microbiota and Covid-19- possible link and implications. Virus Res. 2020 May 13;285:198018. https://www.sciencedirect.com/science/article/pii/S0168170220304603?via%3Dihub http://www.ncbi.nlm.nih.gov/pubmed/32430279?tool=bestpractice.com [350]Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology. 2020 Sep;159(3):944-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237927 http://www.ncbi.nlm.nih.gov/pubmed/32442562?tool=bestpractice.com [351]Gu S, Chen Y, Wu Z, et al. Alterations of the gut microbiota in patients with coronavirus disease 2019 or H1N1 influenza. Clin Infect Dis. 2020 Dec 17;71(10):2669-78. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314193 http://www.ncbi.nlm.nih.gov/pubmed/32497191?tool=bestpractice.com COVID-19 患者胃肠道菌群组成、细胞因子水平和炎症标志物之间的关联表明,胃肠道微生物群与疾病严重程度有关,可能通过调节宿主免疫应答引起。疾病消退后,消化道菌群失调可能对症状持续有所贡献。[352]Yeoh YK, Zuo T, Lui GC, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021 Apr;70(4):698-706. https://gut.bmj.com/content/early/2021/01/04/gutjnl-2020-323020 http://www.ncbi.nlm.nih.gov/pubmed/33431578?tool=bestpractice.com
气候和纬度:基于低等确定性证据和有限研究,较高温度可能减缓疾病流行进展;然而,气候变量本身并不能解释疾病传播中的大部分变异。温度、湿度、风速、紫外线和纬度可能在疾病流行中发挥作用,但需行进一步研究。[353]Zheng HL, Guo ZL, Wang ML, et al. Effects of climate variables on the transmission of COVID-19: a systematic review of 62 ecological studies. Environ Sci Pollut Res Int. 2021 Oct;28(39):54299-316. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364942 http://www.ncbi.nlm.nih.gov/pubmed/34398375?tool=bestpractice.com
空气污染:有限证据表明,暴露于环境空气污染,与 COVID-19 之间存在关联;但是证据不足以证明因果关系。[354]Centre for Evidence-Based Medicine; Hoang U, Jones NR. Is there an association between exposure to air pollution and severity of COVID-19 infection? 2020 [internet publication]. https://www.cebm.net/covid-19/is-there-an-association-between-exposure-to-air-pollution-and-severity-of-covid-19-infection [355]Copat C, Cristaldi A, Fiore M, et al. The role of air pollution (PM and NO₂) in COVID-19 spread and lethality: a systematic review. Environ Res. 2020 Aug 24;191:110129. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444490 http://www.ncbi.nlm.nih.gov/pubmed/32853663?tool=bestpractice.com [356]Frontera A, Cianfanelli L, Vlachos K, et al. Severe air pollution links to higher mortality in COVID-19 patients: the “double-hit” hypothesis. J Infect. 2020 Aug;81(2):255-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240268 http://www.ncbi.nlm.nih.gov/pubmed/32447007?tool=bestpractice.com [357]Ogen Y. Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality. Sci Total Environ. 2020 Apr 11;726:138605. https://www.sciencedirect.com/science/article/pii/S0048969720321215 http://www.ncbi.nlm.nih.gov/pubmed/32302812?tool=bestpractice.com [358]Yu Z, Bellander T, Bergström A, et al. Association of short-term air pollution exposure with SARS-CoV-2 infection among young adults in Sweden. JAMA Netw Open. 2022 Apr 1;5(4):e228109. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791305 http://www.ncbi.nlm.nih.gov/pubmed/35442452?tool=bestpractice.com
居住于城市或贫困地区:有限证据提示,与郊区相比,居住于城市地区者患病率更高,与不甚贫困地区相比,居住于贫困地区者患病率更高。[130]de Lusignan S, Dorward J, Correa A, et al. Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study. Lancet Infect Dis. 2020 Sep;20(9):1034-42. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228715 http://www.ncbi.nlm.nih.gov/pubmed/32422204?tool=bestpractice.com [359]Bowyer RCE, Varsavsky T, Thompson EJ, et al. Geo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app. Thorax. 2021 Jul;76(7):723-5. https://thorax.bmj.com/content/76/7/723 http://www.ncbi.nlm.nih.gov/pubmed/33376145?tool=bestpractice.com
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