Middle east respiratory syndrome is an acute, highly lethal infectious disease caused by an RNA–containing beta-coronavirus. The pathognomonic symptoms of infection are a predominant lesion of the respiratory tract with a high probability of developing respiratory distress syndrome in adults. Clinically, the disease is manifested by fever, shortness of breath, cough, hemoptysis. Diagnosis of pathology implies the detection of the virus and the pathway to it in the biomaterial of the patient. Etiotropic therapy of the condition includes antiviral drugs; symptomatic agents (antipyretics, mucolytics and others) are also used in the treatment.
ICD 10
B34.2 Coronavirus infection, unspecified
General information
Middle East Respiratory Syndrome (MERS) is an acute viral lesion of the respiratory tract. For the first time, this disease became known in 2012, when a patient with symptoms of this disease was identified in Saudi Arabia. By 2015, the MERS epidemic had spread to 25 countries in the Middle East, Africa, Asia, and Europe. The most massive outbreak of infection caused by beta-coronavirus occurred in South Korea, where more than 30 people died, and almost 3,000 contacts were quarantined. The incidence increases in the winter-spring season (especially in March and April), which is associated with human infection from young camels. Adults (more than 90%) aged 50 years and older are more often affected.
Causes
The causative agent of the disease is a coronavirus of the Middle East respiratory syndrome, belonging to the genus of beta–coronaviruses of line C. For the first time in humans, this virus was isolated in 2012, previously it was found only among single-humped camels. The study of the issue showed that the animals were infected at birth or in the first months of life, in the future about a third of them became asymptomatic carriers of the coronavirus. Consequently, the sources of infection can be both sick animals, people, and carriers of the virus.
Infection of people with the help of an aerogenic transmission mechanism from camels has been proven in a small number of cases of the disease, most often the cause of infection was the consumption of unboiled camel milk, insufficiently heat-treated meat, contact with urine, blood and faeces of a sick animal when caring for it. Infection of healthy persons from a sick person occurs mainly by airborne droplets, can be realized by contact with infected biological fluids and in everyday life through household items contaminated with coronavirus.
Nosocomial infections are described: the South Korean epidemic is a consequence of intrahospital infection from a zero patient with an imported case of the disease. The pathogen is poorly resistant in the environment: it is sensitive to the effects of standard doses of disinfectants, ultraviolet irradiation and heating.
The risk groups for the disease are persons over 65 years of age, with concomitant diseases (diabetes mellitus, obesity, kidney pathology, heart disease, lung disease, HIV infection, malignant neoplasms), residents of communal apartments, barracks, dormitories, military personnel, veterinarians, cattle breeders, employees of zoos, circuses, medical workers and service sector employees. In children, the disease is rare, the described cases have been observed among patients with congenital pathologies (Down syndrome, cystic fibrosis and others).
Pathogenesis
The pathogenesis of the disease has not been studied enough, pathomorphological studies due to religious beliefs could not be carried out in a number of countries. It was determined that beta-coronavirus has a tropicity to bronchial epithelial cells and type 2 alveolar pneumocytes, kidney cells and T-lymphocytes. Upon entering the respiratory tract, the pathogen actively multiplies in the tracheal epithelium, causing cilia dyskinesia, bronchial cells, subjecting them to mass destruction and violating mucociliary clearance. Inside alveolocytes, the virus is able to cause dysregulatory changes in genes.
Renal failure in this pathology is due to the direct damaging effect of the virus, and, to no lesser extent, hypoxic tissue damage. Pathohistologically, hemorrhagic manifestations, apoptosis, diffuse lesions of the alveoli, squamous metaplasia of alveolocytes, bronchiolitis phenomena, as well as the formation of eosinophilic hyaline membranes, violation of surfactant activity are detected in MERS. The phenomena of portal lobular hepatitis and myositis with atrophic muscle changes were described; gray and white matter of the brain, cardiomyocytes in this disease had no specific damage.
Immunity after the disease, its duration, intensity are being studied; there is evidence of the possibility of re-infection. It is believed that the virus is capable of causing functional paralysis of the interferon production system, can delay the physiological formation of proinflammatory cytokines.
Symptoms
The incubation period is on average 5 days (from 2 to 14 days). The acute onset of the disease is characterized by severe chills, a rise in body temperature to 38-39 ° C, dizziness, pain in joints, muscles and throat. In a third of cases, the phenomena of nausea, vomiting, liquid watery stools are observed; dehydration usually does not occur. Patients complain of an unproductive debilitating cough, which increases in the evening or at night.
After 2-4 days, a clinic of severe viral pneumonia develops. The appearance of a cough with abundant sputum, a feeling of compression, tightness in the chest, shortness of breath with a tendency to aggravate, sometimes hemoptysis appears. The increase in respiratory insufficiency forces patients to take a special pose that facilitates their condition (sitting, leaning on their hands). There is a sinking of the intercostal spaces, supraclavicular pits, a bluish tinge of the skin of the extremities, changes in consciousness (from excitement to apathy). There may be signs of damage to the urinary system in the form of a tendency to oliguria.
Complications
The danger of MERS is the development of acute respiratory distress syndrome, accompanied by severe hypoxia and hypoxemia. Independent breathing becomes difficult, patients need ventilation aid. In addition to DN, acute cardiac, renal, and multiple organ failure should be attributed to the most frequent complications of the Middle East respiratory syndrome. In connection with the implementation of invasive medical manipulations and medical procedures (intravenous, intramuscular injections, artificial lung ventilation, vascular, urinary catheters, etc.), secondary bacterial infection may occur.
Diagnostics
If a beta-coronavirus infection is suspected, it is mandatory to consult an infectious disease specialist, a pulmonologist and a resuscitator, with severe gastroenteritis – a gastroenterologist. Etiological verification of the pathogen and auxiliary diagnostics are carried out by physical, laboratory and instrumental methods, including:
- Evaluation of objective data. When examining a patient with MERS, acrocyanosis, pallor, increased moisture of the skin, increased number of respiratory movements, forced position of the patient, persistent tachycardia, fever are usually detected. With percussion of the pulmonary fields, a dulling of the percussion sound over the affected area is detected. Auscultatively, rigid, sometimes amphoric breathing, bilateral moist, small-bubbly wheezing and crepitation are determined. Pulse oximetry determines a progressive decrease in arterial oxygen saturation (SaO2 less than 90%).
- Molecular genetic diagnostics. By PCR in the material (smear from the nose, nasopharynx, throat), the virus can be isolated on the first day of the disease. It is preferable to take the material from the lower respiratory tract due to the high concentration of the virus in this localization (sputum, bronchoalveolar lavage, tracheal aspirate). It is also possible to isolate the pathogen from blood, urine and feces. According to the WHO diagnostic protocol, the search for the virus should be carried out at intervals of 2-3 days in the material obtained from different parts of the respiratory tract.
- Serological diagnostics. WHO recommendations also imply a dynamic blood test (ELISA) for the presence of antibodies to the Middle East respiratory syndrome coronavirus. The most informative ELISA becomes more than 14-21 days after the first clinical symptoms. Less often, in order to exclude other pathologies, a coprogram and bacteriological examination of bowel movements are used.
- Laboratory tests of blood and urine. The picture of the disease is characterized by leukopenia, lymphocytopenia, thrombocytopenia, acceleration of ESR. Biochemical parameters of lactate dehydrogenase, AST, ALT, urea and creatinine usually exceed laboratory standards. Normal density and osmolarity are preserved in the general clinical analysis of urine.
- Radiation diagnostics. An overview radiography of the lungs is performed, less often a chest MSCT. The X-ray picture is usually characterized by a diffuse decrease in the transparency of the pulmonary fields (a symptom of “frosted glass”), bilateral progressive darkening up to the disappearance of the mediastinal shadow, clearances along the course of medium and large bronchi (a symptom of “air bronchography”). Lung damage is most pronounced in the middle and lower parts. Less often there is the appearance of pleural effusion.
Differential diagnosis is performed with atypical pneumonia (SARS) and COVID-19. It is necessary to exclude other respiratory diseases: influenza, legionellosis, ornithosis, aspergillosis, mycoplasmosis, pneumocystosis, tuberculous caseous decay of the lungs. Differentiation with typhoid fever, sepsis, bacterial pneumonia, bronchitis is required. Symptoms of gastroenteritis should be differentiated with viral diarrhea, enterovirus infection, food poisoning, salmonellosis and shigellosis.
Treatment
All patients with suspected infection are subject to hospitalization in an infectious hospital. Contact persons are separated from the team for the maximum duration of the MERS incubation period (14 days). Patients are recommended to drink copious amounts, frequent intake of light and nutritious meals in small portions.
No specific treatment for Middle East respiratory syndrome has been developed. Existing etiotropic broad–spectrum drugs should be introduced in the first days, ideally in the first hours of the disease. During outbreaks in the Middle East and Korea, the best treatment results were achieved with the use of ribavirin, often in combination with interferon α2β. The use of monoclonal antibodies to beta-coronavirus, blood serum preparations of convalescents turned out to be successful. The use of systemic glucocorticosteroids did not affect the reduction of mortality in MERS patients, in some cases their use was justified by a decrease in the severity of immunopathological reactions.
Symptomatic therapy involves the use of mucolytics, vasoprotectors, antibiotics (in the case of proven secondary bacterial damage), detoxification agents (rheopolyglucin, glucose-salt solutions) and others. The increase in respiratory insufficiency is an indication for the initiation of oxygen therapy and the transfer of patients to artificial lung ventilation.
Prognosis and prevention
The prognosis of the disease depends on age, the presence of concomitant pathology, the timeliness of seeking medical help, but always serious. The average number of days before admission to the hospital is 0-4 days from the onset of clinical manifestations; before the onset of a condition requiring urgent resuscitation measures ‒ 1-5 days from the onset of the disease. Death most often occurs after 5-11 days; the mortality rate for the disease is about 35%.
There are no means of specific prevention (vaccines) at this stage of the development of medicine, but active developments are underway in this area. Non-specific preventive measures include avoiding visits to countries with a high incidence of MERS (UAE, Saudi Arabia, South Korea, Bahrain, Qatar and a number of others), eating camel meat and unboiled milk, refusing mass events, contacts with sick people and animals. If you are forced to stay near a potential source of infection, it is recommended to use disposable masks or respirators, protective glasses or eye shields, gloves, dressing gowns (these rules also apply to medical workers), frequent hygienic hand washing with soap or an alcohol-based antiseptic.
