- Superkingdom Viruses
In September 2012 some cases of a novel coronavirus (nCoV) raised concerns that another emerging disease causing severe respiratory illness might be emerging. The outbreak of what was subsequently named Middle East respiratory syndrome coronavirus (MERS-CoV) does not seem to reflect better technical ability to identify novel viruses. There could be a significant threat to public health if a viral strain develops high rates of transmission either by respiratory aerosol or stool spread. While as of 2013 there have been no major outbreak or pandemic problems, however clusters controlled by high standard isolation precautions do prove that there is human to human transmission with high mortality. The earliest case occurred in retrospect in late March 2012. Further cases occurred in April 2013 in Saudi Arabia . Clusters occur amongst healthcare workers, as with SARS, with both asymptomatic cases and outbreaks only recognised in retrospect occurring. As of March 2014 the case fatality rate of those presenting with SARI is about 45%. As of February 2015 an epidemic curve reveals that a significant outbreak did occur in April/May 2014. As of May 2015 the serology positive fatality rate is 38% and over 1100 cases have been confirmed. An outbreak in South Korea was associated with delayed recognition and breaking of quarantine. The virus genome has similarities to a coronavirus found in bats and binds to CD26. Deep bronchial lavage specimens may be needed for diagnosis.
- Binds to dipeptidyl peptase 4-receptor
- Member of genus β
- Single positive-stranded RNA genome 30,119 nucleotides long and contains 11 open reading frames (ORFs)
- The 5' end has two overlapping ORFs, ORF1a and ORF1b
- Translated to two large polyproteins, polyprotein 1a (pp1a) and polyprotein 1ab (pp1ab)
- Cleaved into 16 functional nonstructural proteins (nsps) by papain-like protease (PLpro) and 3C-like protease (3CLpro) that self-cleave from pp1ab
- These are responsible for viral RNA-dependent RNA polymerase activity (nsp12), RNA helicase activity (nsp13), exoribonuclease activity (nsp14), endoribonuclease activity (nsp15) and methyltransferase activity (nsp16)
- nsp14 is essential, as it is involved in proofreading by monitoring the mutation rate, a unique feature for an RNA virus
- The other ORFs encode:
- Structural proteins:
- Spike (S)
- Envelope (E)
- Membrane (M)
- Nucleocapsid (N)
- Accessory proteins
- Encoded by ORF3, ORF4a, ORF4b, ORF5 and ORF8b are unique and may help evade host immune response
- Structural proteins:
- The 5' end has two overlapping ORFs, ORF1a and ORF1b
- No positive human serology before 2012 reported.
- Antibodies that cross react with MERS corononavirus have been found in dromedary camels. Some primary cases are associated with recent camel exposure.
- Dromedary camels from Nigeria through to the Middle East have been exposed to a similar virus since at least 2003 and possibly for decades.
- All cases of human to human contact can be explained by transmission from symptomatic patients
- Super-spreaders exist as with SARS
- Incubation time 2-14 days (not infectious)
- Seasonal incidence appears highest April to May
- Risk association includes diabetes
- Mortality rate as of July 2013 was 56% but later studies found asymptomatic and minimal symptomatic infection especially after secondary human human transmission very common.
- Patients can shed the virus after resolution of symptoms, but the duration of infectivity is unknown. No evidence as of April 2014 that asymptomatic cases are contagious.
- URTI (definite transmission mechanism)
- Diarrhoea (probable transmission mechanism)
- Probably sub strain dependent
- Highest mortality is associated with pre-existing renal failure and diabetes mellitus
Infection control precautions
- Droplet precautions when providing care to all patients with symptoms of acute respiratory infection.
- Contact precautions and eye protection should be added when caring for probable or confirmed cases of MERS-CoV infection.
- Airborne precautions should be applied when performing aerosol generating procedures.
Treatments are to date unproven and there is little commercial incentive to develop new agents due to market size
- Ribavirin especially if cotreated with IFNα2b
- Loperamide, chlorpromazine, lopinavir and chloroquine inhibit MERS-CoV replication. More toxic possibilities are: mycophenolic acid, cyclosporin A, IFNα and IFNβ
Severe acute respiratory syndrome or SARS is caused by one of the coronavirus group. The virus probably originated in bats, then crossed into humans via masked palm civets.
The virus spread beyond its original outbreak in China when a businessman became unwell on his flight out of China and died in Vietnam in 2003. Further outbreaks appeared rapidly, as far afield as Toronto. Eventually led to 8000 cases globally, but rapid surveillance and isolation measured brought the epidemic to an abrupt end within 4 months.
Super shedders exist, who have much higher infectivity (1 case on a plane infected 120 others, whereas another plane had 4 cases on board, but no secondary cases occurred!). On the other hand, there is no documented transmission by asymptomatic cases, or between children.
Incubation period is 5-7 but up to 14 days. Spread is by respiratory, fomites, and faecal-oral routes. Peak shedding occurs at peak of clinical disease hence outbreaks were often among health care workers.
Symptoms are non-specific. Fever is universal, otherwise there may be cough, dyspnoea, myalgia, headache, gastrointestinal upset.
Those who do badly have sudden deterioration on 10th day, with ARDS. Mortality is around 10%, but very age dependent, reaching over 50% in the over 65s.
Children have lower viral loads. There are no distinguishing clinical features of paediatric SARS: 'flu-like illness, perhaps more gastrointestinal symptoms than respiratory.
Children under 5 yrs are hardly affected at all - perhaps because recent coronavirus infection protective, perhaps because of reduced immune reactivity.
No long term morbidity seen in children.
The diagnosis is suggested by the paucity of clinical signs (mild crepitations only, if anything) with an abnormal chest radiograph (non-specific), and laboratory evidence of leucopenia, lymphopenia, and thrombocytopenia. Raised AST/ALT also seen.
Protective measures effective if used properly - so buddy system. Full respiratory protection kit works.
Other active human strains
The four endemic human coronaviruses mainly associated with mild, self-limiting respiratory illnesses are:
- Identified in the 1960s
- Circulating in the human population since before 1988
- In the human population since 1995 but diverged genetically well before then
Over 70% of the general public has seroconverted towards all four non-severe human coronaviruses with primary infection shown to occur in childhood
- ↑ WHO statement on the tenth meeting of the IHR Emergency Committee regarding MERS 3rd September 2015
- ↑ WHO update 2nd May 2013
- ↑ MERS-CoV Update WHO 5 February 2015
- ↑ a b Durai P, Batool M, Shah M, Choi S. Middle East respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control. Experimental & molecular medicine. 2015; 47:e181.(Epub) (Link to article – subscription may be required.)
- ↑ Reusken CBEM, Messadi L, Feyisa A, Ularamu H, Godeke G-J, Danmarwa A, et al. Geographic distribution of MERS coronavirus among dromedary camels, Africa. Emerg Infect Dis. 2014 Jul. http://dx.doi.org/10.3201/eid2007.140590
- ↑ Tai DY. Pharmacologic Treatment of SARS: Current Knowledge and Recommendations. Annals of the Academy of Medicine, Singapore 2007;36(6):438-6.
- ↑ Berry M, Gamieldien J, Fielding BC. Identification of new respiratory viruses in the new millennium. Viruses. 2015 Mar; 7(3):996-1019.(Epub) (Link to article – subscription may be required.)
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