Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

被引：95

作者：

Buckland, Matthew S. ^{[1
,2
]}

Galloway, James B. ^{[3
]}

Fhogartaigh, Caoimhe Nic ^{[4
]}

Meredith, Luke ^{[5
]}

Provine, Nicholas M. ^{[6
,7
]}

Bloor, Stuart ^{[8
,9
]}

Ogbe, Ane ^{[6
,7
,19
]}

Zelek, Wioleta M. ^{[10
,11
]}

Smielewska, Anna ^{[12
,13
]}

Yakovleva, Anna ^{[5
]}

Mann, Tiffeney ^{[14
]}

Bergamaschi, Laura ^{[8
,9
]}

Turner, Lorinda ^{[8
,9
]}

Mescia, Frederica ^{[8
,9
]}

Toonen, Erik J. M. ^{[15
]}

Hackstein, Carl-Philipp ^{[6
,7
]}

Akther, Hossain Delowar ^{[6
,7
]}

Vieira, Vinicius Adriano ^{[6
,7
]}

Ceron-Gutierrez, Lourdes ^{[16
]}

Periselneris, Jimstan ^{[17
,18
]}

Kiani-Alikhan, Sorena ^{[1
]}

Grigoriadou, Sofia ^{[1
]}

Vaghela, Devan ^{[19
]}

Lear, Sara E. ^{[20
]}

Torok, M. Estee ^{[8
,21
]}

Hamilton, William L. ^{[8
,22
]}

Stockton, Joanne ^{[23
]}

Quick, Josh ^{[23
]}

Nelson, Peter ^{[24
]}

Hunter, Michael ^{[24
]}

Coulter, Tanya I. ^{[24
,25
]}

Devlin, Lisa ^{[24
,25
]}

Bradley, John R. ^{[26
]}

Smith, Kenneth G. C. ^{[8
,9
]}

Ouwehand, Willem H. ^{[27
,28
]}

Estcourt, Lise ^{[29
]}

Harvala, Heli ^{[30
]}

Roberts, David J. ^{[29
,31
]}

Wilkinson, Ian B. ^{[9
]}

Screaton, Nick ^{[32
]}

Loman, Nicholas ^{[23
]}

Doffinger, Rainer ^{[17
,18
]}

Lyons, Paul A. ^{[8
,9
]}

Morgan, B. Paul ^{[10
,11
]}

Goodfellow, Ian G. ^{[5
]}

Klenerman, Paul ^{[6
,7
]}

Lehner, Paul J. ^{[8
,9
,19
]}

Matheson, Nicholas J. ^{[8
,9
,19
,28
]}

Thaventhiran, James E. D. ^{[8
,9
,14
,33
]}

机构：

[1] Barts Hlth, Dept Clin Immunol, London, England

[2] UCL GOSH Inst Child Hlth, Div Infect & Immun, Sect Cellular & Mol Immunol, London, England

[3] Kings Coll London, Ctr Rheumat Dis, London, England

[4] Barts Hlth NHS Trust, Dept Infect, London, England

[5] Univ Cambridge, Dept Pathol, Addenbrookes Hosp, Cambridge, England

[6] Peter Medawar Bldg Pathogen Res, South Parks Rd, Oxford OX1 3SY, England

[7] Univ Oxford, Nuffield Dept Clin Med, Oxford, England

[8] Jeffrey Cheah Biomed Ctr, Cambridge Inst Therapeut Immunol & Infect Dis, Cambridge Biomed Campus, Cambridge, England

[9] Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge, England

[10] Cardiff Univ, Syst Immun Inst, Cardiff, Wales

[11] Cardiff Univ, Dementia Res Inst, Cardiff, Wales

[12] Univ Cambridge, Dept Pathol, Div Virol, Addenbrookes Hosp, Cambridge, England

[13] Cambridge Univ Hosp NHS Fdn Trust, PHE Publ Hlth England Lab, Box 236,Hills Rd, Cambridge, England

[14] Univ Cambridge, Med Res Council, Toxicol Unit, Gleeson Bldg,Tennis Court Rd, Cambridge CB2 1QW, England

[15] Hycult Biotechnol, R&D Dept, Frontstr 2A, NL-5405 PB Uden, Netherlands

[16] Addenbrookes Hosp, Dept Clin Biochem & Immunol, Cambridge, England

[17] Kings Coll Hosp NHS Fdn Trust, Resp Dept, London, England

[18] Addenbrookes, Dept Clin Virol, Cambridge, England

[19] Cambridge Univ Hosp NHS Trust, Dept Infect Dis, Cambridge, England

[20] Cambridge Univ Hosp NHS Trust, Dept Immunol, Cambridge, England

[21] Cambridge Univ Hosp NHS Trust, Dept Microbiol, Cambridge, England

[22] Cambridge Univ Hosp NHS Trust, Cambridge, England

[23] Univ Birmingham, Inst Microbiol & Infect, Birmingham, W Midlands, England

[24] Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland

[25] Belfast Hlth & Social Care Trust, Reg Immunol Serv, Belfast, Antrim, North Ireland

[26] NIHR BioResource & NIHR Cambridge Biomed Res Ctr, Cambridge Biomed Campus, Cambridge, England

[27] Univ Cambridge, Dept Haematol, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England

[28] NHS Blood & Transplant, Cambridge Biomed Campus, Cambridge, England

[29] NHS Blood & Transplant, Oxford, England

[30] NHS Blood & Transplant, London, England

[31] Univ Oxford, Radcliffe Dept Med & BRC Haematol Theme, John Radcliffe Hosp, Oxford, England

[32] Papworth Hosp, Radiol, Cambridge, England

[33] Canc Res UK Cambridge Inst, Cambridge Biomed Campus, Cambridge, England

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会; 欧盟地平线“2020”;

关键词：

SARS CORONAVIRUS; ENTEROVIRUSES; RESPONSES; ANTIBODY; VIRUS;

D O I：

10.1038/s41467-020-19761-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.

引用

页数：11

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