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Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study

Identifieur interne : 000091 ( PascalFrancis/Curation ); précédent : 000090; suivant : 000092

Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study

Auteurs : Ali S. Omrani [Arabie saoudite] ; Mustafa M. Saad [Arabie saoudite] ; Kamran Baig [Arabie saoudite] ; Abdelkarim Bahloul [Arabie saoudite] ; Mohammed Abdul-Matin [Arabie saoudite] ; Amal Y. Alaidaroos [Arabie saoudite] ; Ghaleb A. Almakhlafi [Arabie saoudite] ; Mohammed M. Albarrak [Arabie saoudite] ; Ziad A. Memish [Arabie saoudite] ; Ali M. Albarrak [Arabie saoudite]

Source :

RBID : Pascal:14-0276185

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English descriptors

Abstract

Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used X2 and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5 • 88 × 109/L [SD 3 • 95] vs 9 • 88 × 109/L [6 • 63]; p=0.023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0 • 004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0 • 54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4 • 32 g/L [SD 2 • 47] vs 2 • 14 g/L [1 • 90]; p=0 • 002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.
pA  
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A03   1    @0 Lancet. Infect. dis. : (print)
A05       @2 14
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A08 01  1  ENG  @1 Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study
A11 01  1    @1 OMRANI (Ali S.)
A11 02  1    @1 SAAD (Mustafa M.)
A11 03  1    @1 BAIG (Kamran)
A11 04  1    @1 BAHLOUL (Abdelkarim)
A11 05  1    @1 ABDUL-MATIN (Mohammed)
A11 06  1    @1 ALAIDAROOS (Amal Y.)
A11 07  1    @1 ALMAKHLAFI (Ghaleb A.)
A11 08  1    @1 ALBARRAK (Mohammed M.)
A11 09  1    @1 MEMISH (Ziad A.)
A11 10  1    @1 ALBARRAK (Ali M.)
A14 01      @1 Division of Infectious Diseases, Prince Sultan Military Medical City @2 Riyadh @3 SAU @Z 1 aut. @Z 2 aut. @Z 4 aut. @Z 6 aut. @Z 10 aut.
A14 02      @1 Department of Infection Prevention and Control, Prince Sultan Military Medical City @2 Riyadh @3 SAU @Z 3 aut. @Z 6 aut.
A14 03      @1 Department of Medicine, Prince Sultan Military Medical City @2 Riyadh @3 SAU @Z 5 aut.
A14 04      @1 Department of Critical Care, Prince Sultan Military Medical City @2 Riyadh @3 SAU @Z 7 aut. @Z 8 aut.
A14 05      @1 Al-Faisal University and Ministry of Health @2 Riyadh @3 SAU @Z 9 aut.
A20       @1 1090-1095
A21       @1 2014
A23 01      @0 ENG
A43 01      @1 INIST @2 27478 @5 354000504575310230
A44       @0 0000 @1 © 2014 INIST-CNRS. All rights reserved.
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C01 01    ENG  @0 Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used X2 and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5 • 88 × 109/L [SD 3 • 95] vs 9 • 88 × 109/L [6 • 63]; p=0.023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0 • 004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0 • 54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4 • 32 g/L [SD 2 • 47] vs 2 • 14 g/L [1 • 90]; p=0 • 002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.
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C03 03  X  FRE  @0 Etude cohorte @5 07
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C03 05  X  FRE  @0 Antiviral @5 30
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C03 05  X  SPA  @0 Antiviral @5 30
C03 06  X  FRE  @0 Anticancéreux @5 31
C03 06  X  ENG  @0 Antineoplastic agent @5 31
C03 06  X  SPA  @0 Anticanceroso @5 31
C03 07  X  FRE  @0 Forme grave @4 INC @5 86
C03 08  X  FRE  @0 Syndrome respiratoire du Moyen-Orient @4 CD @5 96
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C07 04  X  FRE  @0 Analogue de nucléoside @5 37
C07 04  X  ENG  @0 Nucleoside analog @5 37
C07 04  X  SPA  @0 Análogo nucleósido @5 37
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C07 07  X  FRE  @0 Virose @5 40
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N21       @1 349
N44 01      @1 OTO
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Pascal:14-0276185

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<term>Coronavirus</term>
<term>Interferon alpha 2a</term>
<term>Middle East respiratory syndrome</term>
<term>Ribavirin</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Ribavirine</term>
<term>Interféron alpha 2a</term>
<term>Etude cohorte</term>
<term>Coronavirus</term>
<term>Antiviral</term>
<term>Anticancéreux</term>
<term>Forme grave</term>
<term>Syndrome respiratoire du Moyen-Orient</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used X
<sup>2</sup>
and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5 • 88 × 10
<sup>9</sup>
/L [SD 3 • 95] vs 9 • 88 × 10
<sup>9</sup>
/L [6 • 63]; p=0.023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0 • 004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0 • 54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4 • 32 g/L [SD 2 • 47] vs 2 • 14 g/L [1 • 90]; p=0 • 002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.</div>
</front>
</TEI>
<inist>
<standard h6="B">
<pA>
<fA01 i1="01" i2="1">
<s0>1473-3099</s0>
</fA01>
<fA03 i2="1">
<s0>Lancet. Infect. dis. : (print)</s0>
</fA03>
<fA05>
<s2>14</s2>
</fA05>
<fA06>
<s2>11</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG">
<s1>Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study</s1>
</fA08>
<fA11 i1="01" i2="1">
<s1>OMRANI (Ali S.)</s1>
</fA11>
<fA11 i1="02" i2="1">
<s1>SAAD (Mustafa M.)</s1>
</fA11>
<fA11 i1="03" i2="1">
<s1>BAIG (Kamran)</s1>
</fA11>
<fA11 i1="04" i2="1">
<s1>BAHLOUL (Abdelkarim)</s1>
</fA11>
<fA11 i1="05" i2="1">
<s1>ABDUL-MATIN (Mohammed)</s1>
</fA11>
<fA11 i1="06" i2="1">
<s1>ALAIDAROOS (Amal Y.)</s1>
</fA11>
<fA11 i1="07" i2="1">
<s1>ALMAKHLAFI (Ghaleb A.)</s1>
</fA11>
<fA11 i1="08" i2="1">
<s1>ALBARRAK (Mohammed M.)</s1>
</fA11>
<fA11 i1="09" i2="1">
<s1>MEMISH (Ziad A.)</s1>
</fA11>
<fA11 i1="10" i2="1">
<s1>ALBARRAK (Ali M.)</s1>
</fA11>
<fA14 i1="01">
<s1>Division of Infectious Diseases, Prince Sultan Military Medical City</s1>
<s2>Riyadh</s2>
<s3>SAU</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="02">
<s1>Department of Infection Prevention and Control, Prince Sultan Military Medical City</s1>
<s2>Riyadh</s2>
<s3>SAU</s3>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</fA14>
<fA14 i1="03">
<s1>Department of Medicine, Prince Sultan Military Medical City</s1>
<s2>Riyadh</s2>
<s3>SAU</s3>
<sZ>5 aut.</sZ>
</fA14>
<fA14 i1="04">
<s1>Department of Critical Care, Prince Sultan Military Medical City</s1>
<s2>Riyadh</s2>
<s3>SAU</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</fA14>
<fA14 i1="05">
<s1>Al-Faisal University and Ministry of Health</s1>
<s2>Riyadh</s2>
<s3>SAU</s3>
<sZ>9 aut.</sZ>
</fA14>
<fA20>
<s1>1090-1095</s1>
</fA20>
<fA21>
<s1>2014</s1>
</fA21>
<fA23 i1="01">
<s0>ENG</s0>
</fA23>
<fA43 i1="01">
<s1>INIST</s1>
<s2>27478</s2>
<s5>354000504575310230</s5>
</fA43>
<fA44>
<s0>0000</s0>
<s1>© 2014 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45>
<s0>26 ref.</s0>
</fA45>
<fA47 i1="01" i2="1">
<s0>14-0276185</s0>
</fA47>
<fA60>
<s1>P</s1>
</fA60>
<fA61>
<s0>A</s0>
</fA61>
<fA64 i1="01" i2="1">
<s0>Lancet. Infectious diseases : (print)</s0>
</fA64>
<fA66 i1="01">
<s0>GBR</s0>
</fA66>
<fC01 i1="01" l="ENG">
<s0>Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used X
<sup>2</sup>
and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5 • 88 × 10
<sup>9</sup>
/L [SD 3 • 95] vs 9 • 88 × 10
<sup>9</sup>
/L [6 • 63]; p=0.023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0 • 004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0 • 54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4 • 32 g/L [SD 2 • 47] vs 2 • 14 g/L [1 • 90]; p=0 • 002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.</s0>
</fC01>
<fC02 i1="01" i2="X">
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</fC02>
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<s0>002B02S05</s0>
</fC02>
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<s0>Ribavirine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
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<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
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<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
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<s5>05</s5>
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<s5>10</s5>
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<s5>86</s5>
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<s4>CD</s4>
<s5>96</s5>
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<s4>CD</s4>
<s5>96</s5>
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<s0>Coronaviridae</s0>
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<s5>37</s5>
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<s0>Nucleoside analog</s0>
<s5>37</s5>
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<s0>Análogo nucleósido</s0>
<s5>37</s5>
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<s5>38</s5>
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<s5>38</s5>
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<s5>40</s5>
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<s5>40</s5>
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<s0>Infección</s0>
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<s1>349</s1>
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<s1>OTO</s1>
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