Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-10-17

AUTHORS

Fabrizio Cantini, Delia Goletti, Linda Petrone, Saied Najafi Fard, Laura Niccoli, Rosario Foti

ABSTRACT

BackgroundBased on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring high-flow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated.ObjectivesThe purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported.MethodsThe efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020.ResultsAfter the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive.ConclusionsBeyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs. More... »

PAGES

1929-1946

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s40265-020-01421-w

DOI

http://dx.doi.org/10.1007/s40265-020-01421-w

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33068263


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31 schema:description BackgroundBased on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring high-flow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated.ObjectivesThe purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported.MethodsThe efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020.ResultsAfter the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive.ConclusionsBeyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs.
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39 COVID-19 patients
40 ConclusionsBeyond
41 English language
42 Google Scholar
43 Institute
44 MEDLINE
45 Meta-Analysis
46 National Institute
47 ObjectivesThe purpose
48 Preferred Reporting Items
49 RCTs
50 Reporting Items
51 SARS-CoV-2
52 SARS-CoV-2 infection
53 USA
54 accordance
55 admission
56 admission rates
57 agents
58 anakinra
59 antiviral therapy
60 antivirals
61 approach
62 article
63 assessment
64 available English-language
65 baricitinib
66 baricitinib 4
67 best therapeutic approach
68 care unit admission
69 cases
70 characteristics
71 chloroquine
72 clinical features
73 clinical impact
74 clinical series
75 colchicine
76 combination therapy
77 control group
78 criteria
79 cumulative number
80 current evidence
81 cytokine release syndrome
82 data
83 database
84 days
85 death
86 dexamethasone
87 dexamethasone 6
88 different therapeutic approaches
89 different therapies
90 different treatments
91 discharge number
92 disease
93 duplicate articles
94 dysregulation
95 efficacy
96 efficacy assessment
97 efficacy of baricitinib
98 eligibility criteria
99 end point
100 evidence
101 exclusion
102 exclusion of studies
103 favipiravir
104 features
105 first stage
106 group
107 guidelines
108 health
109 high-flow oxygen
110 hydroxychloroquine
111 immune dysregulation
112 immune response
113 immune therapy
114 impact
115 improvement
116 inclusion
117 infection
118 intensive care unit admission
119 intensive care unit admission rate
120 items
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122 language
123 large trials
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126 management
127 mavrilimumab
128 mechanism
129 medRxiv databases
130 mild-moderate disease
131 mortality
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134 ongoing RCTs
135 open-label trial
136 optimal management
137 oxygen
138 pathogenesis
139 pathogenic mechanisms
140 patients
141 paucity
142 paucity of studies
143 pediatric studies
144 point
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146 promising results
147 purpose
148 rate
149 rationale
150 recent guidelines
151 recovery
152 reduction
153 release syndrome
154 remdesivir
155 removal
156 response
157 results
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159 review
160 ritonavir
161 ruxolitinib
162 sarilumab
163 scholars
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167 siltuximab
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