Coronavirus infection (atypical pneumonia): causes, symptoms, diagnosis, treatment

Coronavirus infection - ARVI, which is characterized by a picture of rhinitis and a benign course of the disease.

SARS (atypical pneumonia) is a severe leaking form of coronavirus infection characterized by a cyclic course, pronounced intoxication, predominant alveolar epithelial involvement and development of acute respiratory failure.

Severe acute respiratory syndrome (SARS) is caused by a coronavirus, which spreads, perhaps, by airborne droplets, has an incubation period of 2-10 days. Influenza-like symptoms develop, which sometimes leads to the development of severe respiratory insufficiency. Mortality is about 10%. The diagnosis is clinical. To prevent spreading, patients are isolated.

ICD-10 code

U04.9. SARS.

Epidemiology

The source of the pathogen of ARVI is a patient and the carrier of coronaviruses. The transmission path is airborne, the susceptibility to the virus is high. Mostly children are ill, after the transferred illness humoral immunity forms, seasonality is winter. 80% of adults have antibodies to coronaviruses.

The first case of SARS was registered on February 11, 2003 in China (Guangdong Province), the latter on June 20, 2003. During this period, 8461 cases were registered in 31 countries, 804 (9.5%) patients died. The source of the SARS virus is sick, believe that the virus can be released at the end of the incubation period and possibly convalescence. The main way of transmission of the SARS virus is also airborne, it is the driving force behind the epidemic process. It is possible to contaminate the objects with the virus in the environment of the patient. The possibility of spreading the virus from the source of infection is determined by many factors: the severity of catarrhal phenomena (coughing, sneezing, runny nose), temperature, humidity and air speed. The combination of these factors determines the specific epidemiological situation. Outbreaks are described in apartment buildings where people did not directly contact each other and the spread of the virus was most likely through the ventilation system. The probability of infection depends on the infectious dose of the virus, its virulence and the susceptibility of the infected. The infectious dose of the virus, in turn, is due to the amount of virus released by the source of the infection and the distance from it. Despite the high virulence, susceptibility to the SARS virus is low, due to the presence of antibodies to coronaviruses in most people. This is evidenced by the small number of cases of the disease, as well as the fact that in most situations, the infection occurred with close contact with the patient indoors. The adults are ill, cases of the disease development in children are not registered, which is probably due to a higher level of immune protection due to the recently transferred infection.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]

What causes atypical pneumonia?

Atypical pneumonia is caused by coronaviruses. For the first time the virus was isolated in 1965 from a patient with acute rhinitis, and in 1968 the family Coronaviridae was organized . In 1975, coronavirus was detected by E. Caul and S. Clarke in feces of children suffering from gastroenteritis.

Coronaviruses are large RNA-containing viruses of spherical shape with a diameter of 80-160 nm. The surface of the virion is covered with clavate processes from the glycoprotein, which give it an easily recognizable shape in electron microscopy, reminiscent of the solar corona during a solar eclipse, hence the name of this family of viruses. The virion has a complex structure, the spiral single-stranded RNA molecule is located in the center, the nucleocapsid is surrounded by a protein-lipid shell, which consists of 3 structural proteins (membrane protein, transmembrane protein and hemagglutinin). Virus replication occurs in the cytoplasm of affected cells.

Coronaviruses have a complex antigenic structure, they are divided into antigenic groups that have different antigenic crossings.

• The first group is human coronavirus 229 E and viruses that infect g pigs, dogs, cats and rabbits. S
• The second group is the human OS-43 virus and viruses of mice, rats, pigs, cattle and turkeys.
• The third group is human intestinal coronaviruses and chicken and turkey viruses.

The causative agent of SARS is a previously unknown variant of coronavirus.

Sequencing of the SARS virus showed that it differs by nucleotide sequences from the previously known groups of coronaviruses by 50-60%. The results of the sequencing of virus isolates conducted by Chinese scientists differ significantly from the data obtained by Canadian and American researchers, which suggests the ability of the virus to rapidly mutate. Coronaviruses are unstable in the environment, instantly die when heated to 56 ° C, under the influence of disinfectants. There is evidence of a higher resistance of the SARS virus. So. On a plastic surface the virus can persist up to 2 days. In sewage waters up to 4 days. However, during these terms the number of virus particles is constantly falling. It is believed that the SARS virus was the result of mutations of previously known coronavirus species.

Coronaviruses 229EI, OC43 are known for a long time as causing colds. At the end of 2002, an outbreak of respiratory viral disease, called SARS, was reported. SARS was caused by coronavirus, which was genetically different from known human and animal viruses.

It is assumed that it is a human pathogen that was first registered in Guangdong province (China) in November 2002. The virus was found in palm wyvers, raccoon dogs, ferret badger. SARS is spread in more than 30 countries. As of mid-July 2003, more than 8,000 cases of the disease and more than 800 deaths have been reported (mortality of about 10%); In the late 2003 period, all cases of the disease were identified in China.

Transmission of the infection is probably carried out by airborne droplets and requires close personal contact. Nevertheless, transmission can be carried out accidentally, by aerosol. People are affected from 15 to 70 years.

Outbreak of coronavirus infection in 2013

The government of the Kingdom of Saudi Arabia, like the WHO experts, is concerned about the outbreak of a new, yet unexplained disease that is provoked by the coronavirus of the nCov or nCoV. The first case of an unknown disease was recorded in 2012, but starting from the month of May this year, 13 patients were hospitalized in the country for the first week, seven people have now died. According to the updated information of the World Health Organization website, the virus can be transmitted from person to person, that is, by contact.

Coronavirus nCoV (nCoV) is a strain that was not previously found in humans, it is genetically different from the virus that causes SARS - atypical pneumonia. The new strain of the virus is indiscriminate in terms of age limits, the youngest patient was 24 years old, the oldest - 94 years old, mostly infected with men. Literally a month ago, WHO experts believed that the main difference between coronavirus and SARS is low transmissibility and rapid development of renal failure. However, in May, French doctors reported a case of human infection after being in the same room with a sick coronavirus infection, the same information was confirmed by UK experts. At a recent press conference in Riyadh, Assistant Director-General of the World Health Organization, K. Fukuda, officially announced the possibility of a contact route for the transfer of a new dangerous coronavirus. Since Mr. Fukuda is responsible for safety in the field of public health and epidemiological control, his words were taken very seriously.

Symptoms that can cause coronavirus nCov begin with acute respiratory complications. The clinical picture is very similar to the picture SARS - SARS or Tori (severe acute respiratory syndrome or severe acute respiratory infection), the symptomatology develops rapidly, accompanied by renal insufficiency. The vaccine against nCoV (nCoV) has not yet been developed, since the virus itself is still being studied.

Meanwhile, on May 9, 2013, the Minister of Health of Saudi Arabia provided WHO with information about two regular, laboratory-confirmed diseases. Both patients are alive, one is already discharged. The condition of the second patient is assessed as stably heavy.

In analyzing the alarming current situation, WHO strongly encourages all countries, especially those in the south-western sector of Asia, to conduct thorough epidemiological surveillance, to record and notify WHO of all atypical cases of infection. As of today, the detected strain does not have high transmissibility, however, a sharp outbreak of diseases in Saudi Arabia in May this year causes quite legitimate anxiety.

The official statistical data on the number of cases affected by coronavirus nCoV (nCoV) are as follows: 

• From September 2012 to May 2013, 33 cases of coronavirus infection with nCoV confirmed by laboratory tests were recorded.
• One case of the disease in Jordan still raises doubts in the sense of belonging of the pathogen to the coronavirus group. 
• From September 2012 to May 9, 2013 from the coronavirus nCoV (nCoV) killed 18 people.

WHO specialists continue to coordinate the actions of doctors of those countries, in which the majority of diseases are diagnosed. In addition, experts have developed a surveillance guide through which clinicians can differentiate the signs of infection, the infection control manual and the algorithms of the doctors' actions are already being distributed. Thanks to the joint efforts of microbiologists, physicians, analysts and experts, modern laboratory tests have been created to determine the strain of the virus, all major hospitals in Asia and Europe are equipped with reagents and other materials for testing that reveal a new strain.

Pathogenesis

Coronaviruses affect the epithelium of the upper respiratory tract. The main target cells for the SARS virus are the cells of the alveolar epithelium, in the cytoplasm of which the virus replicates. After the assembly of the virions, they pass into the cytoplasmic vesicles, which migrate to the cell membrane and exocytose out into the extracellular space, and before that the virus antigens are not expressed on the cell surface, therefore, antibody formation and interferon synthesis are stimulated relatively late. Sorbing on the surface of cells, the virus contributes to their fusion and the formation of syncytium. In this way, the virus spreads rapidly into tissues. The effect of the virus causes an increase in the permeability of cell membranes and enhanced transport of a fluid rich in protein into the interstitial lung tissue and lumen of the alveoli. At the same time, the surfactant is destroyed, which leads to the collapse of the alveoli, as a result of which the gas exchange is severely disrupted. In severe cases, an acute respiratory distress syndrome develops. Accompanied by a heavy NAM. The damage caused by the virus "opens the way" to the bacterial and fungal flora, viral-bacterial pneumonia develops. In a number of patients, soon after discharge, a deterioration occurs due to the rapid development of fibrotic changes in the pulmonary tissue, which suggests the initiation of apoptosis by the virus. Perhaps coronavirus affects macrophages and lymphocytes, blocking all links of the immune response. However, the lymphopenia observed in severe cases of SARS can also be caused by the migration of lymphocytes from the bloodstream to the lesion site. Thus, at present, several links in the pathogenesis of SARS are isolated.

• Primary infection with the virus of the alveolar epithelium.
• Increase the permeability of cell membranes.
• Thickening of interalveolar septa and accumulation of fluid in the alveoli.
• Accession of secondary bacterial infection.
• Development of severe respiratory failure, which is the main cause of death in the acute phase of the disease.

Symptoms of SARS

Atypical pneumonia has an incubation period that is 2-5 days, according to some data, up to 10-14 days.

The main symptom of ARI is profuse serous rhinitis. Body temperature normal or subfebrile. Duration of the disease up to 7 days. In children of early age, pneumonia and bronchitis are possible.

Atypical pneumonia has an acute onset, the first symptoms of SARS are chills, headache, muscle pain, general weakness, dizziness, fever of 38 ° C or more. This febrile (febrile) phase lasts 3-7 days.

Respiratory symptoms of atypical pneumonia, perspiration in the throat are not characteristic. Most patients have a mild form of the disease, and they recover after 1-2 weeks. Depressing patients after 1 week develops acute respiratory distress, which includes dyspnea, hypoxemia and rarely ARDS. Death occurs as a result of the progression of respiratory failure.

In addition to the above symptoms, cough, runny nose, and sore throat are seen in some patients, while hyperemia of the mucous membrane of the palate and the posterior pharyngeal wall is noted. There may also be nausea, one- or two-time vomiting, abdominal pain, loose stools. In 3-7 days. And sometimes even earlier the disease passes into the respiratory phase, which is characterized by a repeated increase in body temperature, the appearance of a persistent unproductive cough, shortness of breath, and difficulty breathing. On examination, paleness of the skin, cyanosis of the lips and nail plates, tachycardia, muffling of heart sounds, a tendency to arterial hypotension are revealed. With percussion of the thorax, the areas of blunting of percussion sound are determined, and small-bubbling rales are heard. In 80-90% of cases that develop during the week, the condition improves, the symptoms of respiratory failure regress and recovery occurs. In 10-20% of patients, the condition progressively worsens and develop symptoms similar to respiratory distress syndrome.

Thus, atypical pneumonia is a cyclically developing viral infection, in the development of which three phases can be distinguished.

• Feverish phase. If the course of the disease is completed at this phase, the mild course of the disease is ascertained.
• Respiratory phase. If the respiratory insufficiency characteristic for this phase is quickly resolved, the moderate course of the disease is ascertained.
• The phase of progressive respiratory failure, which requires prolonged ventilation, often ends in a fatal outcome. This dynamic of the course of the disease is characteristic of the severe course of SARS.

Diagnosis of SARS

Since the initial symptoms of SARS are not specific, suspicion of SARS may occur with the appropriate epidemiological situation and clinical symptoms. Suspicious cases should be reported to public health authorities and all activities, as in severe community-acquired pneumonia. X-ray data of the lungs at the beginning of the disease are normal; with the progression of respiratory symptoms appear interstitial infiltrates, which sometimes merge with the subsequent development of ARDS.

Clinically, coronavirus infection does not differ from the rhinovirus infection. Diagnosis of atypical pneumonia also presents great difficulties, since there are no pathognomonic symptoms of atypical pneumonia; a certain value, but only in typical severe and moderate cases, has a characteristic disease dynamics.

In this connection, the criteria developed by the CDC (USA), according to which the respiratory diseases of an unknown etiology, which include:

• with an increase in body temperature above 38 ° C;
• with the presence of one or more signs of respiratory disease (cough, rapid or difficult breathing, hypoxemia);
• for persons who traveled to the regions of the world for 10 days before the disease, affected by SARS, or who communicated with patients who were suspicious of SARS.

From the clinical position is also important the absence of rash, polyadenopathy, hepatolienal syndrome, acute tonsillitis, damage to the nervous system, the presence of lymphopenia and leukopenia.

[14], [15], [16], [17], [18], [19], [20], [21], [22]

Specific and nonspecific laboratory diagnostics of atypical pneumonia

Laboratory data are non-specific, but the number of white blood cells is normal or decreased, sometimes the absolute number of lymphocytes is reduced. The activity of transaminases, creatine phosphokinase, lactate dehydrogenase can be increased, but the kidney function is normal. During CT, peripheral subpleural matte shadows can be identified. There may be known respiratory viruses from the swabs of the mouth and nasopharynx, and the laboratory should be warned about SARS. Although SARS is actively developing serological and genetic methods of diagnosis, their usefulness for the clinic is low. From an epidemiological point of view, it is necessary to examine paired sera (taken at intervals of 3 weeks). Samples of sera should be submitted to public medical institutions.

The picture of peripheral blood in SARS is characterized by moderate thrombocytopenia, leukemia and lymphopenia, anemia: hypoalbuminemia is often observed, and hypoglobulinemia is less frequent, which is associated with the release of protein into the extravascular space due to increased permeability. Possible increase in ALT activity. ACT and CK. Which indicates the likelihood of organ damage (liver, heart) or the development of generalized cytolytic syndrome.

Immunological diagnosis of SARS allows reliable detection of antibodies to the SARS virus after 21 days from the onset of the disease, ELISA at 10 days from the onset of the disease, so they are suitable for retrospective diagnosis or for population studies to identify STIs.

Virological diagnosis of atypical pneumonia allows to identify the virus in blood samples, feces, respiratory secretions on cell cultures, and then identify it with additional tests. This method is expensive, time-consuming and used for scientific purposes. The most effective diagnostic method is PCR, which allows to detect specific fragments of the virus RNA in biological fluids (blood, feces, urine) and secrets (washings from the nasopharynx, bronchi, in sputum) in the earliest stages of the disease. At least 7 primers, nucleotide fragments specific for the SARS virus, have been identified.

Instrumental diagnosis of atypical pneumonia

Radiologically, in some cases on the 3-4th day of the disease, one-sided interstitial infiltrates are revealed, which are subsequently generalized. Part of the patients in the respiratory phase reveal a pattern of bilateral drain pneumonia. In a minority of patients throughout the disease, there are no x-ray changes in the lungs. When radiographically confirming pneumonia or detecting adults who died on autopsy of RDS without an explicit etiologic factor, suspicious cases are transferred to the category of "probable".

Differential diagnosis of SARS

Differential diagnosis of atypical pneumonia at the first stage of the disease should be carried out with influenza, other respiratory infections and enterovirus infections of the Coxsackie-ECHO group. In the respiratory phase, first of all, it is necessary to exclude atypical pneumonia (ornithosis, mycoplasmosis, respiratory chlamydia and legionellosis).

• Ornithosis is characterized by severe fever and the development of interstitial pneumonia, most often people with professional or household contact with birds are ill. In contrast to SARS, ornithosis is not uncommon for pleural pains, enlargement of the liver and spleen, meningism is possible, but no significant respiratory failure is observed. Radiographic examination reveals the primary lesions of the lower parts of the lungs. Probable interstitial, small-focal, large-focal and lobar pneumonia, characterized by the expansion of the roots of the lungs and an increase in mediastinal lymph nodes, in the blood - a sharp increase in ESR.
• Mycoplasmal pneumonia is observed mainly in children older than 5 years and adults up to 30 years. The disease develops gradually, beginning with catarrhal phenomena, subfebrile condition, rarely acute, characterized by a grueling, unproductive cough from the first days of the disease, which in 10-12 days becomes productive. The fever is moderate, intoxication is poorly expressed, there are no signs of respiratory failure. X-ray reveals segmental, focal or interstitial pneumonia, pleural effusion, interlobit is possible. Regression of pneumonia slow in the period from 3-4 weeks to 2-3 months, extrapulmonary lesions are not uncommon: arthritis, meningitis, hepatitis.
• Legionellosis pneumonia is characterized by severe intoxication, high fever (39-40 ° C) for up to 2 weeks and pleural pain. Observe cough with scant sputum, often with blood veins and extrapulmonary lesions (diarrhea syndrome, hepatitis, renal failure, encephalopathy). The physical data (shortening of percussion sound, small bubbling rales) are fairly clear, radiologically detecting pleuropneumonia, usually a vast one-sided, rarely bilateral, in the study of blood, neutrophilic leukocytosis, a significant increase in ESR. Possible development of severe respiratory failure, requiring the use of ventilation.

With regard to adult respiratory distress syndrome, differential diagnosis is performed based on the identification of the above-listed etiological factors of the syndrome. In all suspicious cases, it is advisable to use laboratory tests to exclude the above infections.

[23], [24], [25], [26]

Treatment of SARS

Diet and diet

Patients with coronavirus infection are treated symptomatically in an outpatient setting, patients with suspected SARS are hospitalized and isolated in specially equipped hospitals. The regime in the acute period of the disease is bed, a specific diet is not required.

[27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38]

Medicamentous treatment of atypical pneumonia

Specific treatment of atypical pneumonia, the effectiveness of which is confirmed by the methods of evidence-based medicine, is absent.

Treatment of atypical pneumonia is symptomatic, if necessary - mechanical ventilation of the lungs. Oseltamivir, ribavirin and glucocorticoids can be used, but there is no evidence of their effectiveness.

During the epidemic, ribavirin was used at a dose of 8-12 mg / kg every 8 hours for 7-10 days. The drug was prescribed taking into account contraindications, interferon alpha-2b, interferon alfa and its inducers were also used. It is advisable to perform oxygen therapy by inhalation of an oxygen-air mixture or ventilation in the auxiliary respiration regime, carrying out detoxification according to general rules. It is necessary, taking into account the activation of autoflora, the use of broad-spectrum antibiotics such as levofloxacin, ceftriaxone, etc. Prospective use of inhalants with preparations containing surfactant (kurosurf, surfactant-BL), as well as nitric oxide.

Approximate terms of incapacity for work

The discharge of patients is carried out after complete regression of inflammatory changes in the lungs, restoration of their function and stable normalization of body temperature for 7 days.

[39], [40], [41]

Prevention of atypical pneumonia

Prevention of atypical pneumonia involves isolation of patients, carrying out quarantine measures at the borders, disinfection of vehicles. Individual prevention involves wearing gauze masks and respirators. For chemoprevention, ribavirin, as well as preparations of interferon and its inducers, are recommended.

What is the prognosis of atypical pneumonia?

The lethal outcome of coronavirus infection is extremely rare. Atypical pneumonia has a favorable prognosis for mild and moderate flow (80-90% of patients), in severe cases requiring the use of mechanical ventilation, the lethality is high. According to the latest data, mortality in stationary patients is 9.5%, deaths are possible in late terms of the disease. Most of the deceased are over 40 years old with concomitant diseases. Patients who have suffered the disease may have adverse effects due to cicatricial changes in the lungs.