Middle East respiratory syndrome coronavirus infection medical therapy: Difference between revisions

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==Medical Therapy==
==Medical Therapy==
[[MERS]] represents a great challenge in terms of treatment because it is caused by a relatively novel [[virus]] to which there is no approved therapy yet. According to
[[MERS]] represents a great challenge in terms of treatment because it is caused by a relatively novel [[virus]] to which there is no approved therapy yet. According to
the ''International Severe Acute Respiratory & Emerging Infection Consortium'' (ISARIC), supportive medical care continues to be the approved treatment for [[MERS]]. The search for broad-spectrum inhibitors aiming to minimize the impact of [[coronavirus]] [[infection]] remains the major goal. Recent studies are showing the potential use of other [[drugs]] and therapies to treat the [[MERS-CoV]], which are based on the experience of treatment of other [[coronaviruses]] like the [[SARS virus]]. This repurposing of [[drugs]] has advantages such as: better availability, lower cost and known safety and tolerability profiles. However, lack of evidence makes these new therapies uncertain.<ref name="pmid24841273">{{cite journal| author=Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J et al.| title=Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection. | journal=Antimicrob Agents Chemother | year= 2014 | volume=  | issue=  | pages=  | pmid=24841273 | doi=10.1128/AAC.03036-14 | pmc= | url=http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139281416  }} </ref>
the ''International Severe Acute Respiratory & Emerging Infection Consortium'' (ISARIC), supportive medical care continues to be the approved treatment for [[MERS]]. The search for broad-spectrum inhibitors aiming to minimize the impact of [[coronavirus]] [[infection]] remains the major goal. Recent studies are showing the potential use of other [[drugs]] and therapies to treat the [[MERS-CoV]], which are based on the experience of treatment of other [[coronaviruses]] like the [[SARS virus]]. This repurposing of [[drugs]] has advantages such as: better availability, lower cost and known safety and tolerability profiles. However, lack of evidence makes these new therapies uncertain.<ref name="pmid24841273">{{cite journal| author=Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J et al.| title=Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection. | journal=Antimicrob Agents Chemother | year= 2014 | volume=  | issue=  | pages=  | pmid=24841273 | doi=10.1128/AAC.03036-14 | pmc= | url=http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139281416  }} </ref>
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==Supportive Care==
==Supportive Care==
The supportive medical care aims to minimize as much as possible the damages caused by [[MERS]]. It is divided into 4 categories, according to the clinical status of the patient. These categories include:<ref name=WHO>{{cite web | title = Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do | url = http://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf }}</ref>
The supportive medical care aims to minimize as much as possible the damages caused by [[MERS]]. It is divided into 4 categories, according to the clinical status of the patient. These categories include:<ref name=WHO>{{cite web | title = Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do | url = http://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf }}</ref>


===Early recognition===
===Early recognition===
This section focuses on the early recognition of [[symptoms]] and management of patients with severe acute [[respiratory infections]]. This includes:<ref name=WHO>{{cite web | title = Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do | url = http://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf }}</ref>
This section focuses on the early recognition of [[symptoms]] and management of patients with severe acute [[respiratory infections]]. This includes:<ref name=WHO>{{cite web | title = Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do | url = http://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf }}</ref>
*Recognition of severe manifestations of acute [[respiratory infections]], such as [[pneumonia]] or [[sepsis]]
*Recognition of severe manifestations of acute [[respiratory infections]], such as [[pneumonia]] or [[sepsis]]
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*Reduce [[weakness]] by immobilization
*Reduce [[weakness]] by immobilization


==''In Vitro'' Studies==
==References==
The development of an [[antiviral drug]] is a long-winded process that may not be compatible with the need of a [[drug]] to treat [[coronaviruses]], specifically [[MERS-CoV]]. Therefore, some studies using existing therapies are being developed in order to find a [[drug]] that will likely inhibit the [[infection]] by [[MERS-CoV]].<ref name="de WildeJochmans2014">{{cite journal|last1=de Wilde|first1=A. H.|last2=Jochmans|first2=D.|last3=Posthuma|first3=C. C.|last4=Zevenhoven-Dobbe|first4=J. C.|last5=van Nieuwkoop|first5=S.|last6=Bestebroer|first6=T. M.|last7=van den Hoogen|first7=B. G.|last8=Neyts|first8=J.|last9=Snijder|first9=E. J.|title=Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture|journal=Antimicrobial Agents and Chemotherapy|year=2014|issn=0066-4804|doi=10.1128/AAC.03011-14}}</ref><ref name="pmid23620378">{{cite journal| author=de Wilde AH, Raj VS, Oudshoorn D, Bestebroer TM, van Nieuwkoop S, Limpens RW et al.| title=MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment. | journal=J Gen Virol | year= 2013 | volume= 94 | issue= Pt 8 | pages= 1749-60 | pmid=23620378 | doi=10.1099/vir.0.052910-0 | pmc=PMC3749523 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23620378  }} </ref>
One of these studies was performed on cell cultures, in the hope of finding a previously approved [[FDA]] compounds that would inhibit the replication of the [[virus]] ''in vitro''. It was able to find four molecule inhibitors of the replication of [[MERS-CoV]]:<ref name="de WildeJochmans2014">{{cite journal|last1=de Wilde|first1=A. H.|last2=Jochmans|first2=D.|last3=Posthuma|first3=C. C.|last4=Zevenhoven-Dobbe|first4=J. C.|last5=van Nieuwkoop|first5=S.|last6=Bestebroer|first6=T. M.|last7=van den Hoogen|first7=B. G.|last8=Neyts|first8=J.|last9=Snijder|first9=E. J.|title=Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture|journal=Antimicrobial Agents and Chemotherapy|year=2014|issn=0066-4804|doi=10.1128/AAC.03011-14}}</ref><ref name="pmid23620378">{{cite journal| author=de Wilde AH, Raj VS, Oudshoorn D, Bestebroer TM, van Nieuwkoop S, Limpens RW et al.| title=MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment. | journal=J Gen Virol | year= 2013 | volume= 94 | issue= Pt 8 | pages= 1749-60 | pmid=23620378 | doi=10.1099/vir.0.052910-0 | pmc=PMC3749523 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23620378  }} </ref>
*[[Chloroquine]]
 
*[[Chlorpromazine]]
 
*[[Loperamide]]


*[[Lopinavir]]
{{reflist|2}}
 
Although the selectivity index of some compounds was limited, the researchers were able to determine a [[concentration]] of [[drug]] that inhibited the replication of the [[virus]] by more than 80%, preserving the viability of the [[cell]]. These [[drugs]] were also found to be able to inhibit the replication of other [[coronaviruses]], namely the ''HCoV-229E'' and the ''[[SARS-CoV]]''. The [[off-label]] use of these [[drugs]], particularly when used in combination, might be able to reduce the [[viral load]] of the host, therefore halting the course of [[infection]] and allowing the building of a proper [[immune response]] by the host's [[immune system]].<ref name="de WildeJochmans2014">{{cite journal|last1=de Wilde|first1=A. H.|last2=Jochmans|first2=D.|last3=Posthuma|first3=C. C.|last4=Zevenhoven-Dobbe|first4=J. C.|last5=van Nieuwkoop|first5=S.|last6=Bestebroer|first6=T. M.|last7=van den Hoogen|first7=B. G.|last8=Neyts|first8=J.|last9=Snijder|first9=E. J.|title=Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture|journal=Antimicrobial Agents and Chemotherapy|year=2014|issn=0066-4804|doi=10.1128/AAC.03011-14}}</ref>
 
Further studies will evaluate the potential benefit of the combination of 2+ of these [[drugs]], along with [[interferon]] as well. Of the above mentioned, the two presenting as better options for more [[animal studies]] and/or [[off-label]] use, are the [[chloroquine]] and [[lopinavir]]. This potential use is due to the fact that these [[drugs]] were able to inhibit replication of the [[virus]], in the tested cell cultures, in [[concentrations]] that are possible to be achieved in the human [[plasma]].<ref name="de WildeJochmans2014">{{cite journal|last1=de Wilde|first1=A. H.|last2=Jochmans|first2=D.|last3=Posthuma|first3=C. C.|last4=Zevenhoven-Dobbe|first4=J. C.|last5=van Nieuwkoop|first5=S.|last6=Bestebroer|first6=T. M.|last7=van den Hoogen|first7=B. G.|last8=Neyts|first8=J.|last9=Snijder|first9=E. J.|title=Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture|journal=Antimicrobial Agents and Chemotherapy|year=2014|issn=0066-4804|doi=10.1128/AAC.03011-14}}</ref>
 
==References==
{{Reflist|2}}


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

According to the available data, no specific treatment for MERS-CoV infection is currently available. Clinical management includes supportive management of complications and implementation of recommended infection prevention and control measures.

Medical Therapy

MERS represents a great challenge in terms of treatment because it is caused by a relatively novel virus to which there is no approved therapy yet. According to the International Severe Acute Respiratory & Emerging Infection Consortium (ISARIC), supportive medical care continues to be the approved treatment for MERS. The search for broad-spectrum inhibitors aiming to minimize the impact of coronavirus infection remains the major goal. Recent studies are showing the potential use of other drugs and therapies to treat the MERS-CoV, which are based on the experience of treatment of other coronaviruses like the SARS virus. This repurposing of drugs has advantages such as: better availability, lower cost and known safety and tolerability profiles. However, lack of evidence makes these new therapies uncertain.[1]

Cell and animal studies have shown conflicting results: the combination of ribavirin with interferon α-2b in a cell study reduced viral replication[2]; another study in rhesus monkeys with combination of intramuscular ribavirin and interferon α-2b, the group that received the treatment did not develop breathing abnormalities nor radiographic evidence of pneumonia[3]; however, when tried in 5 critically ill patients in Saudi Arabia, this combination was inefficient in all cases, leading to a fatal outcome.[4]

Despite the absence of a specific therapy, some approaches are considered to be more worth of experimentation than others. These include:[5][6][7][8][9]

Supportive Care

The supportive medical care aims to minimize as much as possible the damages caused by MERS. It is divided into 4 categories, according to the clinical status of the patient. These categories include:[8]

Early recognition

This section focuses on the early recognition of symptoms and management of patients with severe acute respiratory infections. This includes:[8]

Acute Respiratory Distress Syndrome

This section focuses on management of patients who deteriorate and develop ARDS. It includes:[8]

Septic Shock

This section targets the adequate management of septic shock. It includes:[8]

Prevention of Complications

This section is mainly based on preventing possible complications. It includes:[8]

  • preferring oral intubation
  • performing frequent antiseptic oral care
  • adjusting the patient to a reclined position
  • preferring a closed suctioning system
  • changing the ventilator circuit for every patient
  • monitoring the status of heat moisture exchanger
  • reducing intermittent mandatory ventilation

References

  1. Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J; et al. (2014). "Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection". Antimicrob Agents Chemother. doi:10.1128/AAC.03036-14. PMID 24841273.
  2. Falzarano D, de Wit E, Martellaro C, Callison J, Munster VJ, Feldmann H (2013). "Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin". Sci Rep. 3: 1686. doi:10.1038/srep01686. PMC 3629412. PMID 23594967.
  3. Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP; et al. (2013). "Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques". Nat Med. 19 (10): 1313–7. doi:10.1038/nm.3362. PMID 24013700.
  4. Al-Tawfiq JA, Momattin H, Dib J, Memish ZA (2014). "Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study". Int J Infect Dis. 20: 42–6. doi:10.1016/j.ijid.2013.12.003. PMID 24406736.
  5. "Treatment of MERS-CoV: Decision Support Tool".
  6. Guery B, van der Werf S (2013). "Coronavirus: need for a therapeutic approach". Lancet Infect Dis. 13 (9): 726–7. doi:10.1016/S1473-3099(13)70153-1. PMID 23782860.
  7. Ren Z, Yan L, Zhang N, Guo Y, Yang C, Lou Z; et al. (2013). "The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effective inhibitor targeting a 3C-like protease". Protein Cell. 4 (4): 248–50. doi:10.1007/s13238-013-2841-3. PMID 23549610.
  8. 8.0 8.1 8.2 8.3 8.4 8.5 "WHO-ISARIC joint MERS-CoV Outbreak Readiness Workshop: Clinical management and potential use of convalescent plasma" (PDF).
  9. Momattin H, Mohammed K, Zumla A, Memish ZA, Al-Tawfiq JA (2013). "Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)--possible lessons from a systematic review of SARS-CoV therapy". Int J Infect Dis. 17 (10): e792–8. doi:10.1016/j.ijid.2013.07.002. PMID 23993766.
  10. "NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary" (PDF).
  11. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM; et al. (2013). "Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012". Crit Care Med. 41 (2): 580–637. doi:10.1097/CCM.0b013e31827e83af. PMID 23353941.
  12. Papazian, Laurent; Forel, Jean-Marie; Gacouin, Arnaud; Penot-Ragon, Christine; Perrin, Gilles; Loundou, Anderson; Jaber, Samir; Arnal, Jean-Michel; Perez, Didier; Seghboyan, Jean-Marie; Constantin, Jean-Michel; Courant, Pierre; Lefrant, Jean-Yves; Guérin, Claude; Prat, Gwenaël; Morange, Sophie; Roch, Antoine (2010). "Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome". New England Journal of Medicine. 363 (12): 1107–1116. doi:10.1056/NEJMoa1005372. ISSN 0028-4793.
  13. Messerole E, Peine P, Wittkopp S, Marini JJ, Albert RK (2002). "The pragmatics of prone positioning". Am J Respir Crit Care Med. 165 (10): 1359–63. doi:10.1164/rccm.2107005. PMID 12016096.
  14. Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S; et al. (2006). "An intervention to decrease catheter-related bloodstream infections in the ICU". N Engl J Med. 355 (26): 2725–32. doi:10.1056/NEJMoa061115. PMID 17192537.