Coronavirus infection (SARS): 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 form of coronavirus infection, characterized by a cyclical course, severe intoxication, predominant damage to the alveolar epithelium and the development of acute respiratory failure.

Severe acute respiratory syndrome (SARS) is caused by a coronavirus that spreads, possibly by airborne droplets, and has an incubation period of 2-10 days. Flu-like symptoms develop, sometimes leading to severe respiratory failure. Mortality is about 10%. The diagnosis is clinical. To prevent spread, patients are isolated.

ICD-10 code

U04.9. SARS.

Epidemiology

The source of the ARVI pathogen is a patient and a carrier of coronaviruses. The transmission route is airborne, susceptibility to the virus is high. Mostly children get sick, humoral immunity is formed after the illness, the seasonality is winter. 80% of adults have antibodies to coronaviruses.

The first case of atypical pneumonia was registered on February 11, 2003 in China (Guangdong Province), the last - on June 20, 2003. During this period, 8461 cases of the disease were registered in 31 countries, 804 (9.5%) patients died. The source of the SARS virus are patients, it is believed that the virus can be excreted already at the end of the incubation period and convalescent carriage is possible. The main route of transmission of the atypical pneumonia virus is also airborne, it is the driving force of the epidemic process. Contamination of objects in the patient's environment with the virus is acceptable. The possibility of spreading the virus from the source of infection is determined by many factors: the severity of catarrhal symptoms (coughing, sneezing, runny nose), temperature, humidity and air speed. The combination of these factors determines a specific epidemiological situation. Outbreaks have been described in apartment buildings where people did not directly contact each other and the spread of the virus most likely occurred through the ventilation system. The probability of infection depends on the infectious dose of the virus, its virulence and the susceptibility of the infected person. The infectious dose of the virus, in turn, is determined by the amount of virus released by the source of infection and the distance from it. Despite the high virulence, susceptibility to the SARS virus is low, which is 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, infection occurred through close contact with a sick person in a closed room. Adults are sick, there are no registered cases of the disease developing in children, which is probably due to a higher level of immune protection due to a recent infection.

At the end of 2019, the world was shocked by a little-studied viral infection – the so-called “Chinese virus”, or coronavirus COVID-19. We are talking about an acute viral pathology, which is characterized by predominant damage to the respiratory system and, to a lesser extent, the digestive tract.

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What causes SARS?

Atypical pneumonia is caused by coronaviruses. The virus was first isolated in 1965 from a patient with acute rhinitis, and in 1968 the Coronaviridae family was organized. In 1975, the coronavirus was discovered by E. Caul and S. Clarke in the 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 club-shaped processes of glycoprotein, which give it an appearance easily recognizable under electron microscopy, resembling the solar corona during a solar eclipse, hence the name of this family of viruses. The virion has a complex structure, in the center there is a spiral single-stranded RNA molecule, the nucleocapsid is surrounded by a protein-lipid membrane, which includes 3 structural proteins (membrane protein, transmembrane protein and hemagglutinin). Viral replication occurs in the cytoplasm of affected cells.

Coronaviruses have a complex antigenic structure; they are divided into antigenic groups that have different antigenic cross-overs.

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

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

Sequencing of the SARS virus has shown that its nucleotide sequences differ from previously known groups of coronaviruses by 50-60%. The results of 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 quickly mutate. Coronaviruses are unstable in the environment, they instantly die when heated to 56 ° C, under the influence of disinfectants. There is evidence of higher resistance of the SARS virus. Thus, on a plastic surface, the virus can survive for up to 2 days, in sewage water up to 4 days. However, during these periods, the number of viral particles is constantly falling. It is assumed that the atypical pneumonia virus is the result of mutations of previously known types of coronavirus.

Coronaviruses 229EI, OC43 have long been known to cause the common cold. In late 2002, an outbreak of a respiratory viral disease called SARS was registered. SARS was caused by a coronavirus that was genetically different from known human and animal viruses.

It is believed to be a human pathogen that was first reported in Guangdong Province, China, in November 2002. The virus has been found in palm civets, raccoon dogs, and ferret badgers. SARS has spread to more than 30 countries. As of mid-July 2003, more than 8,000 cases and more than 800 deaths (mortality rate about 10%) have been reported; since 2003, all cases have been reported in China.

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

Coronavirus outbreak in 2013

The government of the Kingdom of Saudi Arabia, as well as WHO experts, are concerned about the outbreak of a new, as yet unstudied disease caused by the coronavirus nCoV. The first case of the unknown disease was recorded in 2012, but since May of this year, 13 patients have already been hospitalized in the country during the first week, seven people have died to date. According to updated information on the World Health Organization website, the virus can be transmitted from person to person, that is, by contact.

The nCoV coronavirus is a strain that has not previously been encountered in humans, it is genetically different from the virus that causes SARS - atypical pneumonia. The new strain of the virus is not selective in terms of age limits, the youngest patient was 24 years old, the oldest - 94 years old, mainly men are infected. Just 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 staying in the same ward with a patient with 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 contact transmission of the new dangerous coronavirus. Since Mr. Fukuda is responsible for health security and epidemic control, his words were taken very seriously.

The symptoms that the nCoV coronavirus can cause begin with acute respiratory complications. The clinical picture is very similar to the picture of SARS - SARS or SARI (severe acute respiratory syndrome or severe acute respiratory infection), the symptoms develop rapidly, accompanied by kidney failure. A vaccine against nCoV has not yet been developed, since the virus itself is still being studied.

Meanwhile, on May 9, 2013, the Saudi Arabian Minister of Health provided WHO with information on two more laboratory-confirmed cases. Both patients are alive, one has already been discharged. The condition of the second patient is assessed as stable but severe.

In view of the alarming current situation, WHO strongly recommends that all countries, especially those in the southwest Asian region, conduct thorough epidemiological surveillance, record and notify WHO of all atypical cases of infection. As of today, the identified strain is not highly transmissible, however, the sharp outbreak of diseases in Saudi Arabia in May of this year is a cause for well-founded concern.

Official statistics on the number of people infected with coronavirus nCoV are as follows:

• From September 2012 to May 2013, 33 laboratory-confirmed cases of coronavirus infection nCoV were recorded.
• One case of the disease in Jordan still raises doubts about whether the pathogen belongs to the coronavirus group.
• From September 2012 to May 9, 2013, 18 people died from the nCoV coronavirus.

WHO specialists continue to coordinate the actions of doctors in those countries where the majority of diseases are diagnosed. In addition, experts have developed guidelines for epidemiological surveillance, with the help of which clinicians can differentiate signs of infection; guidelines for infection control and algorithms for doctors' actions are already being distributed. Thanks to the joint efforts of microbiologists, doctors, analysts and experts, modern laboratory tests for determining the virus strain have been created; all major hospitals in Asian and European countries are supplied with reagents and other materials for conducting analyses that identify the new strain.

Pathogenesis

Coronaviruses affect the epithelium of the upper respiratory tract. The main target cells for the SARS virus are alveolar epithelial cells, in the cytoplasm of which the virus replicates. After the assembly of virions, they pass into cytoplasmic vesicles that migrate to the cell membrane and enter the extracellular space by exocytosis, and before this, there is no expression of viral antigens on the cell surface, so antibody formation and interferon synthesis are stimulated relatively late. By adsorbing on the cell surface, the virus promotes their fusion and the formation of syncytium. This ensures the rapid spread of the virus into the tissue. The action of the virus causes an increase in the permeability of cell membranes and increased transport of protein-rich fluid into the interstitial tissue of the lung and the lumen of the alveoli. At the same time, the surfactant is destroyed, which leads to the collapse of the alveoli, resulting in a sharp disruption of gas exchange. In severe cases, acute respiratory distress syndrome develops. accompanied by severe respiratory failure. Damage caused by the virus "opens the way" for bacterial and fungal flora, and viral-bacterial pneumonia develops. In some patients, soon after discharge, their condition worsens due to the rapid development of fibrous changes in the lung tissue, which suggests that the virus initiates apoptosis. It is possible that the coronavirus affects macrophages and lymphocytes, blocking all links in the immune response. However, lymphopenia observed in severe cases of SARS may also be due to the migration of lymphocytes from the bloodstream to the lesion. Thus, several links in the pathogenesis of SARS are currently distinguished.

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

Symptoms of atypical pneumonia

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

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

Atypical pneumonia has an acute onset, the first symptoms of atypical pneumonia are chills, headache, muscle pain, general weakness, dizziness, an increase in body temperature to 38 °C and above. This febrile phase lasts 3-7 days.

Respiratory symptoms of atypical pneumonia, sore throat are not typical. Most patients have a mild form of the disease, and they recover in 1-2 weeks. Other patients after 1 week develop acute respiratory distress, which includes dyspnea, hypoxemia and, less commonly, ARDS. Death occurs as a result of progression of respiratory failure.

In addition to the above symptoms, some patients experience cough, runny nose, sore throat, and hyperemia of the mucous membrane of the palate and back of the throat. Nausea, single or double vomiting, abdominal pain, and loose stools are also possible. After 3-7 days, and sometimes earlier, the disease enters the respiratory phase, which is characterized by a repeated increase in body temperature, persistent unproductive cough, shortness of breath, and difficulty breathing. Examination reveals pale skin, cyanosis of the lips and nail plates, tachycardia, muffled heart sounds, and a tendency to arterial hypotension. Percussion of the chest reveals areas of dullness of percussion sound, and fine bubbling rales. In 80-90% of patients, the condition improves within a week, the symptoms of respiratory failure regress, and recovery occurs. In 10-20% of patients, the condition progressively worsens and symptoms similar to respiratory distress syndrome develop.

Thus, atypical pneumonia is a cyclical viral infection, the development of which can be divided into three phases.

• Feverish phase. If the course of the disease ends at this phase, the disease is considered mild.
• Respiratory phase. If the respiratory failure characteristic of this phase quickly resolves, the disease is considered moderately severe.
• The phase of progressive respiratory failure, which requires long-term mechanical ventilation, often ends in death. Such dynamics of the disease course are typical for severe SARS.

Diagnosis of atypical pneumonia

Since the initial symptoms of atypical pneumonia are non-specific, SARS may be suspected in the appropriate epidemiological situation and clinical symptoms. Suspected cases should be reported to the state health authorities and all measures should be taken as for severe community-acquired pneumonia. Chest X-ray data are normal at the beginning of the disease; as respiratory symptoms progress, interstitial infiltrates appear, which sometimes merge with the subsequent development of ARDS.

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

In this regard, the criteria developed by the CDC (USA) are used as a guideline, according to which respiratory diseases of unknown etiology occurring as suspected of SARS 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);
• in individuals who traveled within 10 days before the illness to regions of the world affected by SARS, or who had contact with patients suspected of having SARS during this period.

From a clinical standpoint, the absence of rash, polyadenopathy, hepatosplenic syndrome, acute tonsillitis, damage to the nervous system, the presence of lymphopenia and leukopenia are also important.

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Specific and non-specific laboratory diagnostics of atypical pneumonia

Laboratory findings are nonspecific, but the white blood cell count is normal or decreased, and the absolute lymphocyte count is sometimes decreased. Transaminase, creatine phosphokinase, and lactate dehydrogenase may be elevated, but renal function is normal. CT may reveal peripheral subpleural opacities. Known respiratory viruses may be present from nasopharyngeal and oropharyngeal swabs, and the laboratory should be alerted to SARS. Although serologic and genetic diagnostic tests are being developed for SARS, their clinical utility is limited. From an epidemiologic standpoint, paired sera (taken 3 weeks apart) should be tested. Serum samples should be submitted to government health facilities.

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

Immunological diagnostics of atypical pneumonia allows for the reliable detection of antibodies to the SARS virus after 21 days from the onset of the disease, and ELISA after 10 days from the onset of the disease, thus they are suitable for retrospective diagnostics or for population studies to identify IIP.

Virological diagnostics of atypical pneumonia allows to detect the virus in blood samples, feces, respiratory secretions on cell cultures, and then identify it using additional tests. This method is expensive, labor-intensive and is 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 secretions (nasopharyngeal and bronchial swabs, sputum) at the earliest stages of the disease. At least 7 primers have been identified - nucleotide fragments specific to the SARS virus.

Instrumental diagnostics of atypical pneumonia

In some cases, X-ray examination reveals unilateral interstitial infiltrates on the 3rd or 4th day of the disease, which later generalize. In some patients, a picture of bilateral confluent pneumonia is revealed in the respiratory phase. In a smaller number of patients, X-ray changes in the lungs are absent throughout the disease. If pneumonia is confirmed by X-ray or RDS is detected in adults who died at autopsy without an obvious etiologic factor, suspicious cases are transferred to the "probable" category.

Differential diagnosis of atypical pneumonia

Differential diagnostics 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, atypical pneumonia (ornithosis, mycoplasmosis, respiratory chlamydia and legionellosis) should be excluded first of all.

• Ornithosis is characterized by severe fever and the development of interstitial pneumonia, most often affecting individuals who have professional or domestic contact with birds. Unlike SARS, ornithosis often causes pleural pain, enlarged liver and spleen, meningism is possible, but severe respiratory failure is not observed. X-ray examination reveals predominant lesions of the lower parts of the lungs. Interstitial, small-focal, large-focal and lobar pneumonia are probable, characterized by expansion of the roots of the lungs and enlargement of the mediastinal lymph nodes, a sharp increase in ESR in the blood.
• Mycoplasma pneumonia is observed mainly in children over 5 years old and adults under 30 years old. The disease develops gradually, starting with catarrhal symptoms, subfebrile condition, less often acutely, characterized by a debilitating non-productive cough from the first days of the disease, which becomes productive after 10-12 days. The fever is moderate, intoxication is weakly expressed, there are no signs of respiratory failure. X-ray reveals segmental, focal or interstitial pneumonia, pleural effusion, interlobitis are possible. Regression of pneumonia is slow in periods from 3-4 weeks to 2-3 months, extrapulmonary lesions are common: arthritis, meningitis, hepatitis.
• Legionella pneumonia is characterized by severe intoxication, high fever (39-40 °C) lasting up to 2 weeks, and pleural pain. Cough with scanty sputum, often with blood streaks, and extrapulmonary lesions (diarrhea syndrome, hepatitis, renal failure, encephalopathy) are observed. Physical data (shortened percussion sound, fine bubbling rales) are quite clear, radiologically reveal pleuropneumonia, usually extensive unilateral, less often bilateral, blood tests reveal neutrophilic leukocytosis, a significant increase in ESR. Severe respiratory failure may develop, requiring mechanical ventilation.

As for adult respiratory distress syndrome, differential diagnostics are performed based on the identification of the above-mentioned etiologic factors of the syndrome. In all suspicious cases, it is advisable to use laboratory tests to exclude the above-mentioned infections.

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Treatment of atypical pneumonia

Regime and diet

Patients with coronavirus infection are treated with symptomatic means on an outpatient basis, patients with suspected SARS are subject to hospitalization and isolation in specially equipped hospitals. The regime in the acute period of the disease is bed rest, no specific diet is required.

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Drug treatment of atypical pneumonia

There is no specific treatment for atypical pneumonia, the effectiveness of which has been confirmed by evidence-based medicine methods.

Treatment of atypical pneumonia is symptomatic, with mechanical ventilation if necessary. Oseltamivir, ribavirin, and glucocorticoids may be used, but there are no data on 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 alpha and its inducers were also used. It is advisable to conduct oxygen therapy by inhalation of an oxygen-air mixture or artificial ventilation in the assisted breathing mode, detoxification according to general rules. It is necessary, taking into account the activation of autoflora, to use broad-spectrum antibiotics, such as levofloxacin, ceftriaxone, etc. Promising is the use of inhalations of drugs containing surfactant (curosurf, surfactant-BL), as well as nitric oxide.

Approximate periods of incapacity for work

Patients are discharged after complete regression of inflammatory changes in the lungs, restoration of their function and stable normalization of body temperature within 7 days.

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Prevention of atypical pneumonia

Prevention of atypical pneumonia involves isolating patients, implementing quarantine measures at borders, and disinfecting vehicles. Individual prevention involves wearing gauze masks and respirators. For chemoprophylaxis, it is recommended to prescribe ribavirin, as well as interferon preparations and their inducers.

What is the prognosis for SARS?

Fatal outcomes from coronavirus infection are extremely rare. Atypical pneumonia has a favorable prognosis in mild and moderate cases (80-90% of patients), in severe cases requiring mechanical ventilation, the mortality rate is high. According to the latest data, the mortality rate in hospitalized patients is 9.5%, fatal outcomes are possible in the late stages of the disease. Most of the deceased are people over 40 years old with concomitant diseases. In patients who have had the disease, adverse effects are possible due to cicatricial changes in the lungs.