撰文 | 唐小糖
1. Zhu, N. et al. A Novel Coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382, 727–733 (2020).
首次確認了2019年末在武漢暴發的不明原因肺炎（後命名為COVID-19）病原體是一種新型冠狀病毒（後命名為SARS-CoV-2），樣本來自於患者呼吸道表皮細胞。
2. Chan, J. F. et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 395, 514–523 (2020).
首次發現了SARS-CoV-2人傳人的明確證據。
3. Li, Q. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N. Engl. J. Med. 382, 1199–1207 (2020).
首次確認了早在2019年12月中旬就出現了SARS-CoV-2人傳人的證據，並首次提出R0值為2.2。
4. Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020).
首批被武漢金銀潭醫院收治的41名確診COVID-19患者的臨床特徵（包括髮熱、咳嗽等）和治療經過（華南海鮮市場是病原集中地）。
5. Guan, W. J. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382, 1708–1720 (2020).
首次描述了中國30個省552個醫院共1099例經實驗室確診的COVID-19患者臨床特徵，提出很多患者沒有發熱特徵，放射學檢查結果也未見異常。
6. Lu, R.J. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-574.
首次基因組測序揭示了SARS-CoV-2與SARS-CoV的相似度為79%，和MERS-CoV的相似度約為50%，並提出SARS-CoV-2的來源可能是蝙蝠，進入受體可能是ACE2。
7. Rothe, C. et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020 Mar 5;382(10):970-971.
首次證明了SARS-CoV-2的無症狀感染者也具有傳染性。
8. Wu, F. et al. A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269 (2020).
經基因組測序鑑定了SARS-CoV-2，發現與SARS樣蝙蝠冠狀病毒ZC45相似度為89.1%。
9. Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020).
經基因組測序鑑定了SARS-CoV-2，發現與SARS樣蝙蝠冠狀病毒RaTG13相似度為96%，是目前未知與SARS-CoV-2全基因組相似度最高的冠狀病毒。重要的是，本研究提供了確鑿的試驗證據，證明SARS-CoV-2的進入受體是ACE2。
10. Wrapp, D. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260–1263 (2020).
首次解析了SARS-CoV-2的S蛋白結構，證明了 ACE2與SARS-CoV-2的親和力比SARS-CoV更高。
11. Anderson, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C. & Garry, R. F. The proximal origin of SARS-CoV-2. Nat. Med. 26, 450–452 (2020).
首次對SARS-CoV-2的可能的來源進行系統地分析和討論，有力地駁斥了人工合成論。
12. Zhou, H. et al. A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein. Curr. Biol. 30, 2196–2203 (2020).
首次發現了SARS樣蝙蝠冠狀病毒RmYN02，與SARS-CoV-2相似度為93.3%。重要的是在RmYN02的S1和S2之間也自然插入了多個氨基酸，表明這種插入事件在自然界會隨機發生，有力地駁斥了SARS-CoV-2中的Furin位點的人工合成論。
13. Lam, T. T. et al. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature 583, 282–285 (2020).
14. Xiao, K. et al. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature 583, 286–289 (2020).
15. Zhang, T., Wu, Q. & Zhang, Z. Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. Curr. Biol. 30, 1346–1351 (2020).
首次發現了SARS樣穿山甲冠狀病毒在S蛋白受體結合區（RBD）的關鍵氨基酸區域與SARS-CoV-2幾乎完全相同，表明穿山甲很有可能是SARS-CoV-2的中間宿主。
16. Shi, J. et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science 368, 1016–1020 (2020).
首次系統地利用動物直接研究SARS-CoV-2對多種動物的易感性，證明了SARS-CoV-2能夠有效感染雪貂、貓，並能在雪貂和貓之間通過空氣途徑傳染；不易感染狗、豬、雞和鴨。
17. Korber, B. et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182, 812–827 (2020).
首次系統闡述了D614G突變株逐漸在全球成為主導毒株，感染性增加但與臨床症狀嚴重程度無關。
18. Cao, S. Post-lockdown SARS-CoV-2 nucleic acid screening in nearly ten million residents of Wuhan, China. Nat Commun. 2020 Nov 20;11(1):5917.
首次大型核酸篩查，武漢封城後，19天篩查了近千萬人，發現了300例無症狀核酸陽性患者（萬分之零點三）以及107例復陽患者（0.310%），所有核酸陽性患者病毒培養均為陰性。
19. To, K.K. et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis. 2020 Aug 25:ciaa1275.
首次經基因組測序發現了COVID-19康復患者被再次感染的案例。
20. Grifoni, A. et al. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020 Jun 25;181(7):1489-1501.e15.
首次系統闡述了未暴露的健康人中也存在能夠與SARS-CoV-2反應的T細胞。
21. Sekine, T. et al. Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell. 2020 Oct 1;183(1):158-168.e14.
首次系統闡述了在抗體陰性的康復無症狀或輕症患者中仍能檢測到SARS-CoV-2特異性的T細胞。
22. Rodda, L.B. Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19. Cell. 2020 Nov 23:S0092-8674(20)31565-8.
首次系統闡述了康復患者的 IgG、中和血漿、T細胞和B細胞三個月後的功能性SARS-CoV-特異性的免疫記憶。
23. Starr, T.N. et al. Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell. 2020 Sep 3;182(5):1295-1310.e20.
首次通過實驗證明了SARS-CoV-2 S蛋白RBD的所有氨基酸突變對蛋白摺疊和表達及其對與ACE2的親和力的影響。
24. Lumley, S.F. et al. Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. N. Engl. J. Med. 2020 Dec 23. doi: 10.1056/NEJMoa2034545.
首次提供了最具有說服力的證據，證明了絕大部分COVID-19康復患者在6個月後仍具有基於抗體的保護作用，可以免受SARS-CoV-2再次感染。
25. WHO Solidarity Trial Consortium. et al. Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. N Engl J Med. 2020 Dec 2:NEJMoa2023184.
WHO最大的全球性隨機對照試驗表明瑞德西韋、羥氯喹、洛匹那韋（加利托那韋）和干擾素治療均不能改善COVID-19患者死亡率。
26. Stone, J.H. et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020 Dec 10;383(24):2333-2344.
27. Salama, C. et al. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2020 Dec 17. doi: 10.1056/NEJMoa2030340.
臨床試驗顯示，託珠單抗（Tocilizumab）不能有效減少住院COVID-19患者死亡率。
28. Chen, P. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med. 2020 Oct 28:NEJMoa2029849.
29. Weinreich, D.M. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2020 Dec 17. doi: 10.1056/NEJMoa2035002.
SARS-CoV-2單克隆抗體LY-CoV555和抗體雞尾酒REGN-COV2臨床試驗表明，在COVID-19病程早期可以降低病毒載量，改善症狀；但對重症患者無顯著臨床益處。
領先的疫苗臨床試驗
30. Zhu, F. C. et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet 395, 1845–1854 (2020).
31. Zhu, F. C. et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 396, 479–488 (2020).
康希諾Ad5腺病毒載體疫苗臨床I、II期試驗結果（官方暫未公佈確切保護率）
32. Zhang, Y. et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2020 Nov 17;S1473-3099(20)30843-4.
科興滅活病毒疫苗CoronaVac臨床I/II期試驗結果（官方暫未公佈確切保護率）
33. Xia, S. et al. Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. JAMA. 2020 Sep 8;324(10):951-960.
34. Xia, S. et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis. 2020 Oct 15;21(1):39-51.
國藥中生兩種滅活病毒疫苗臨床I/II期試驗結果（官方暫未公佈確切保護率）
35. Folegatti, P.M. et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020 Aug 15;396(10249):467-478.
36. Ramasamy, M.N. et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet. 2021 Dec 19;396(10267):1979-1993.
37. Voysey, M. et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2020 Dec 8;S0140-6736(20)32661-1.
阿斯利康黑猩猩腺病毒載體疫苗ChAdOx1 COVID-19臨床I/II、II/III、III期試驗結果（III期試驗顯示保護率至少62.1%）
38. Jackson, L.A. An mRNA Vaccine against SARS-CoV-2 – Preliminary Report. N Engl J Med. 2020 Nov 12;383(20):1920-1931.
39. Anderson, E.J. et al. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N Engl J Med. 2020 Dec 17;383(25):2427-2438.
Moderna mRNA疫苗mRNA-1273臨床I期試驗結果（III期試驗顯示保護率94.1%）
40. Walsh, E.E. et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020 Dec 17;383(25):2439-2450.
41. Mulligan, M.J. et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature. 2020 Oct;586(7830):589-593.
42. Polack, F.P. et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 10;NEJMoa2034577.
輝瑞/bioNTech mRNA疫苗BNT162b臨床I、I/II、III期試驗結果（III期試驗顯示保護率95%）
43. Logunov, D.Y. et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020 Sep 26;396(10255):887-897.
俄羅斯腺病毒載體疫苗Sputnik V臨床I/II期試驗結果（III期試驗顯示保護率91.4%）
