Middle East respiratory syndrome coronavirus infection medical therapy
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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
Middle East Respiratory Syndrome (MERS) is a viral respiratory illness. It is caused by an emerging coronavirus, specifically a betacoronavirus called MERS-CoV (Middle East Respiratory Syndrome Coronavirus), first discovered in 2012. Being a relatively novel virus, there is no virus-specific prevention or treatment options for MERS patients. Outbreaks of MERS-CoV represent a great social challenge due to the fact that there is very limited time to develop and test new pharmaceutical drugs. The common clinical presentations documented so far include Acute Respiratory Distress Syndrome (ARDS), renal failure, pericarditis and disseminated intravascular coagulation. Therefore the supportive care should focus mainly in the prevention and monitoring of these conditions. Until now, supportive medical care has been the only treatment option, however, repurpose of drugs for other viruses and illnesses is presenting as an attractive alternative for MERS-CoV.[1][2]
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[3]; 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[4]; however, when tried in 5 critically ill patients in Saudi Arabia, this combination was inefficient in all cases, leading to a fatal outcome.[5]
Despite the absence of a specific therapy, some approaches are considered to be more worth of experimentation than others. These include:[6][7][8][2][9]
- Convalescent plasma - this therapy, along with others that involve antibodies for the MERS-CoV has the strongest evidence for intervention. Plasma from patients who recovered from MERS-CoV infection contains neutralizing antibodies, which represents the best therapy to neutralize the extracellular virus.
- Interferon - there is supporting evidence from in vitro (SARS virus and MERS-CoV) and in vivo (SARS virus) studies that interferon inhibits viral replication, especially when administered in the early course of the disease. Additionally it is commonly more available than plasma.
- Corticosteroids - there is no evidence of the benefit in the mortality rate and their use is only recommended in a planned treatment regimen or when the benefits of the drug outweigh the potential harms. When used, constant monitoring is mandatory and the ideal timing is the early course of the disease, during the period of maximal inflammatory response.
- Ribavirin - the most commonly used drug in the treatment of SARS. Due to the controversial results of clinical trials relating to the use of ribavirin for MERS and its high level of toxicity in humans, some experts recommend the withhold of the drug.
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 management steps required for the current health status of the MERS patient. These categories include:[2]
- Section 1 - focuses on the early recognition and management of patients with severe acute respiratory infections and includes early initiation of supportive and infection prevention, control measures and therapeutics
- Section 2 - focuses on management of patients who deteriorate and develop severe respiratory distress and ARDS
- Section 3 - focuses on the management of patients who deteriorate and develop septic shock
- Section 4 - focuses on ongoing care of the critically ill patient and best practices to prevent complications
Section 1
This section aims for the early recognition and management of symptoms. This includes:[2]
- Recognition of severe manifestations of acute respiratory infections
- Initiation of infection prevention and control measures
- Providing supplemental oxygen therapy to patients with severe acute respiratory infections
- Collection of respiratory and other specimens for laboratory testing
- Administration of empiric antibiotics to treat suspected pathogens, including community-acquired pathogens
- Administration of conservative fluid management in patients with severe acute respiratory infections when there is no evidence of shock
- Close monitoring of patients with severe acute respiratory infections for signs of clinical deterioration, such as severe respiratory distress or tissue hypoperfusion/shock
- Avoidance of high-dose systemic corticosteroids or other adjunctive therapies for viral pneumonitis outside the context of clinical trials
Section 2
This section targets the management of severe respiratory distress, hypoxemia and ARDS. It includes:[2]
- Recognition of severe cases, when severe respiratory distress may not be sufficiently treated by oxygen alone, even after administration at high flow rates
- Early initiation of mechanical ventilation in patients with increased work of breathing or hypoxemia that persists despite high-flow oxygen therapy, wherever available and when staff members are properly trained
- Consider non-invasive ventilation when local expertise is available, immunosuppression is present, or in cases of mild ARDS without impaired consciousness or cardiovascular failure
- Endotracheal intubation, in order to deliver invasive mechanical ventilation, if equipment and trained staff are available
- In patients with ARDS, use of a lung-protective ventilation strategy
- Adjunctive therapeutics in patients with severe ARDS particularly if failing to reach lung-protective ventilation targets
- Use of conservative fluid management strategy for ARDS patients who are not in shock in order to shorten the duration of mechanical ventilation
Section 3
This section targets the adequate management of septic shock. It includes:[2]
- Recognition of sepsis-induced shock when patients develop hypotension (SBP < 90 mm Hg) that persists after initial fluid challenge or show signs of tissue hypoperfusion. At the same time protocoled resuscitation should be initiated
- Early and rapid infusion of crystalloid intravenous fluids for septic shock should be administrated
- In the persistence of shock, use of vasopressors is recommended, despite liberal fluid resuscitation
- Administration of intravenous hydrocortisone (up to 200 mg/day) or prednisolone (up to 75 mg/day) to patients with persistent shock, who require escalating doses of vasopressors, should be considered
Section 4
This section is mainly based on prevention of complications. It includes:[2]
- Weaning protocols that include daily assessment for readiness to breathe spontaneously
- Sedation protocols to titrate administration of sedation to a specific target, with or without daily interruption of continuous sedative infusions
- Oral intubation is preferable to nasal intubation
- Perform regular antiseptic oral care
- Keep patient in semi-recumbent position
- Use a closed suctioning system; periodically drain and discard condensate in tubing
- Use a new ventilator circuit for each patient; once patient is ventilated, change circuit if it is soiled or damaged but not routinely
- Change heat moisture exchanger when it malfunctions, when soiled or every 5–7 days
- Reduce days of IMV
- Use pharmacological prophylaxis (for example, heparin 5000 units subcutaneously twice daily) in patients without contraindications. For those with contraindications, use mechanical prophylactic device such as intermittent pneumatic compression devices.
- Use a simple checklist during insertion as reminder of each step needed for sterile insertion and daily reminder to remove catheter if no longer needed
- Turn patient every two hours
- Give early enteral nutrition (within 24–48 hours of admission), administer histamine-2 receptor blockers or proton-pump inhibitors
- Early mobility
References
- ↑ 1.0 1.1 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.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do" (PDF).
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ "Treatment of MERS-CoV: Decision Support Tool".
- ↑ 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.
- ↑ 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.
- ↑ 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.