MERS-CoV

Brief overview

  • What is MERS? A (often) severe respiratory disease caused by the pathogen MERS-CoV.
  • Frequency: (Very) rare, a total of about 2,500 registered cases worldwide (as of 2019), after 2016 the number of diagnoses dropped sharply.
  • Symptoms: Fever, cough, shortness of breath, pneumonia, often neurological impairment and organ damage in severe cases; incubation period around 14 days.
  • Diagnosis: PCR test, antibody test, intensive medical monitoring.
  • Treatment: Mostly intensive care, no established drug therapy available; experimental use of protease inhibitors and immunomodulators; vaccine currently not available.
  • Prognosis: Often severe; one-third of patients die.

What is MERS?

Middle East Respiratory Syndrome (MERS) is a severe respiratory disease caused by an infection with the pathogen MERS-CoV (“Middle East Respiratory Syndrome Coronavirus”).

MERS is accompanied by typical symptoms such as fever, cough and shortness of breath. The mortality rate is high: around one third of infected people die.

Like SARS and Sars-CoV-2, MERS-CoV is a member of the beta-coronavirus genus. It is believed to have spread from dromedaries to humans. MERS-CoV is therefore a zoonotic virus.

Distribution

The pathogen was first discovered in Saudi Arabia in 2012. The World Health Organization (WHO) subsequently documented around 2,500 cases worldwide by 2019. Thus, the number of cases globally is low. Moreover, as of 2016, the spread of MERS-CoV abruptly ebbed.

Most known cases occurred on the Arabian Peninsula-apart from another major (isolated) outbreak in 2015 in South Korea.

Overall, cases have been confirmed in 27 countries, including states in North America, South Asia, and Europe. Here, however, they affected travelers who had been on the Arabian Peninsula at the peak of the spread. However, such isolated foci of infection did not result in a large-scale uncontrolled infection event.

Is it possible to be vaccinated against MERS?

No. There is currently no approved MERS vaccine. However, experts at the German Center for Infection Research (DZIF) are working on a first vaccine candidate against the MERS pathogen: MVA-MERS-S. This vaccine is based on vector technology such as that used for the MERS vaccine.

This is based on the same vector technology as, for example, the AstraZeneca vaccine against SARS-CoV-2. Researchers are using an attenuated cowpox virus (modified vaccinia ankara virus, MVA) as the vector (“gene shuttle”). In an initial pilot study, MVA-MERS-S proved to be well tolerated and was able to generate robust antibody responses.

Both vaccine candidates are at an early stage of development. However, based on these promising initial results, further studies on a larger scale are planned.

What are the symptoms of MERS?

As a typical respiratory disease, MERS presents with the following symptoms:

  • Cough
  • Sore throat
  • Fever
  • Respiratory distress
  • Shortness of breath
  • Severe pneumonia (lung infection)
  • Lung failure

In addition, MERS patients also showed:

  • Muscle and joint pain
  • Diarrhea
  • malaise and vomiting
  • Kidney failure

The period between infection and the onset of the first symptoms of the disease is two to 14 days (incubation period). The severity of symptoms ranges from asymptomatic to very severe.

Patients who develop a severe course of the disease usually require intensive care. Vulnerable groups are particularly affected by a severe course. These are elderly and immunocompromised patients as well as persons suffering from pre-existing diseases.

A final assessment of which neurological complications with which frequency could follow from a survived MERS-CoV infection is still open at the current state of knowledge. The documented cases are mostly based on individual case reports.

How is MERS-CoV diagnosed?

MERS can be reliably detected by a PCR test in specialized laboratories. This reacts to the characteristic genetic material of the virus.

Ideally, secretions from the deeper airways are used as sample material. Doctors obtain these by means of a so-called bronchoscopy. Mouth, nose and throat swabs, such as those taken for tests for Sars-CoV-2, are usually less suitable. This is because MERS-CoV particularly affects the deep airways. This is where the amount of detectable virus is highest.

Even more precise information can be obtained by complete genome sequencing of the pathogen.

Antibody tests, on the other hand, can be used to draw conclusions about a past MERS illness. They are unsuitable for acute diagnosis because it takes some time for the immune system of the infected person to react to the MERS pathogen with specific (detectable) antibodies.

Commonalities of MERS-CoV, SARS and Sars-CoV-2?

SARS, MERS-CoV and Sars-CoV-2 are enveloped RNA viruses from the genus Betacoronavirus. They belong to the coronavirus family (Coronaviridae) and can cause disease in humans.

Their genetic material consists of a single-stranded ribonucleic acid (RNA). The genetic material of MERS-CoV and (SARS and) Sars-CoV-2 is largely identical. That is, MERS-CoV is (structurally) almost identical to Sars-CoV-2.

The viral genome stores all the information that the virus needs to replicate in the infected host cell. It thus contains all the blueprints for proteins needed to build new virus particles and to copy the viral genome itself.

The MERS-CoV genome consists of about 30,000 nucleobases that code for three types of viral proteins in particular:

RNA-dependent RNA polymerases: MERS-CoV possesses two distinct RNA replicases (ORF1ab, ORF1a). These enzymes are responsible for replicating the RNA genome in the host cell.

Structural proteins: These are the proteins that give the MERS-CoV virus particle its outer (and inner) shape:

  • Spike protein (S): external protein structure that allows MERS-CoV to infect human lung cells.
  • Nucleocapsid (N): A structural protein molecule that stabilizes the viral genome.
  • Envelope protein (E): part of the outer envelope of the virus particle.

Non-structural proteins: In addition, other so-called non-structural proteins – also called “accessory proteins” – are present in the genome of MERS-CoV (including ORF 3, ORF 4a, ORF 4b, ORF 5). Although not yet conclusively proven, experts discuss whether these proteins possibly inhibit important processes of human immune defense (acting as so-called “interferon antagonists”).

Why was there no MERS-CoV pandemic?

Why there was no MERS-CoV pandemic has not yet been conclusively explained. Experts suspect that it is related to the particular infection mechanism of MERS-CoV, which is different from the highly contagious pathogen Sars-CoV-2.

As is typical for most respiratory diseases, MERS-CoV spreads mainly by droplet infection or via aerosols. However, MERS-CoV does not appear to be able to infect the upper respiratory tract.

Sars-CoV-2 enters human cells via the ACE2 receptor, which is widely distributed in the body – and also present in the upper respiratory tract. MERS-CoV, on the other hand, appears to use exclusively the so-called “dipeptidyl peptidase 4 receptor” (DPP4 or CD26) as a “gateway”.

This uneven distribution of the DPP4 receptor within the respiratory tract and lungs, could explain the “moderate” infectivity of MERS-CoV. This also seems to be the reason why MERS-CoV did not spread uncontrollably during its maximum spread phase.

How is MERS treated?

A commonly established drug treatment that can cure MERS is not currently available.

Doctors therefore try to stabilize the health of affected patients as best they can in the event of an emergency. This can buy the immune system of those affected time to defeat the MERS virus.

Use of already known antiviral drugs?

In some cases, doctors also use drugs that have already been developed against other diseases. Here, “broad-spectrum antivirals” take on a special role. These drugs should at least slow down the replication of the MERS pathogen in infected patients. Combinations of active ingredients are being discussed:

Lopinavir and ritonavir: The combination drugs lopinavir and ritonavir are also discussed. They are both used to treat HIV infections. Both drugs belong to the group of protease inhibitors, which block an important viral enzyme for building new virus particles. Initial studies in the context of MERS-CoV show a slightly positive effect on disease progression. However, viral replication is unlikely to be completely suppressed with this combination treatment.

DPP4 inhibitors: The DPP4 receptor plays an important role in the entry of MERS-CoV into the human cell. If the DPP4 receptor is specifically blocked by drugs – so the hypothesis goes – the entry of the MERS-CoV pathogen could possibly be stopped.

However, DPP4 also fulfills important roles in controlling the human immune system. The concern is that inhibition of the DPP4 receptor could decrease the desired activity of certain T effector cells. Although not yet conclusively clarified, DPP4 inhibitors are therefore suspected of causing (systemic) side effects. Further studies in this context are therefore urgently needed.