The infection with new coronavirus SARS-CoV-2

The new coronavirus, SARS-CoV-2, first identified in humans in Wuhan Province, China, in December 2019, has spread rapidly throughout the world, causing World Health Organization (WHO) to declare it a pandemic infection. This pathogenic agent belongs to the genus beta-coronavirus, alongside SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome). The large number of infected patients is mainly due to the modality of transmission, through respiratory droplets. The most common manifestation of the disease/infection COVID-19 is pneumonia, as there are not any specific clinical manifestations that differentiate this disease from other respiratory viral infections. The confirmation of COVID-19 is done by RT-PCR (Real-Time Polymerase Chain Reaction) of respiratory specimens. In most cases, the damage induced by this infection is not severe, and death occurs most frequently among older patients or with significant comorbidities. To control this pandemic infection, measures such as self-isolation at home or quarantine are recommended. Given both the large number of infected patients, as well as the large number of deaths, it is imperative to conduct studies that identify effective therapeutic measures.


INTRODUCTION
Coronaviruses are a large family of zoonotic viruses which, transmitted to humans, cause diseases with varying degrees of severity, from a common cold to severe diseases, such as SARS (Severe Acute Respiratory Syndrome) or MERS (Middle East Respiratory Syndrome) [1]. In December 2019, in Wuhan, a province of China, a new strain of coronavirus (SARS-CoV-2) was identified in a group of patients presenting with viral pneumo-nia. Epidemiological investigation pinpointed that the common element among those patients was a visit to a Huanan market [2]. The virus was isolated from biological samples and classified as a beta-coronavirus, alongside SARS and MERS [2]. Since the first confirmed case with SARS-CoV-2 infection, more than 150,000 cases and 5,000 deaths caused by this disease have been confirmed, with a mortality rate of about 3.4% [
SARS was first identified in southern China in 2002. It caused over 8,000 illnesses and 774 deaths, with a mortality rate of 7% [5]. Another beta-coronavirus who was a public health problem was MERS; it was first identified in 2012, in Saudi Arabia, and did not cause the first outbreak of infection until two years later, in 2014 [6,7]. The number of confirmed cases of MERS worldwide was 2,494 and the number of deaths was 858, with a mortality rate of 34.4% [8]. Figure 1 shows the relative impact of the three strains of coronavirus in terms of number of cases, number of deaths and mortality.  [5][6][7][8]

WAYS OF TRANSMISSION
Interpersonal transmission was confirmed by identifying the presence of infection in several members of a family or among medical staff who cared for patients with COVID-19. The main way of transmission is represented by respiratory droplets or saliva drops. The virus released in the respiratory/saliva secretion (in situations of coughing, sneezing or only interpersonal communication) will thus contaminate other people if these particles come directly into contact with the mucous membranes, especially at the face level [9]. The respiratory/saliva droplets can be spread over a distance of up to 6 m (2 m in average). The virus can be contacted directly from air, and indirectly from various contaminated surfaces, where it can survive several days [9]. The transmission can be done both from symptomatic and asymptomatic individuals, or patients being in the incubation period [10]. Although SARS-CoV-2was detected in samples of blood and stool, fecal-oral transmission does not seem to play a significant role in the spread of infection [11]. The incubation period is about 14 days, and in most cases, the symptoms appear within 4-5 days after primary infection [12]. A study that analyzed data from 181 patients infected with SARS-CoV-2, all reported in China, concluded that symptoms developed in 2.5% of those infected within 2.2 days and 97.5% of infected people in 11.5 days from the infection, the average incubation period being of 5.1 days [13]. A case with an incubation period of 19 days was reported [14]; also, Hubei Province local government declared a case with an incubation period of 27 days [15]. Under these circumstances and data, it can be concluded that the incubation period may vary between 2 and 27 days [15].

DIAGNOSIS
COVID-19 can affect all age groups, although middle-aged and elderly adults are most commonly affected. In a report by the Chinese Center for Disease Control and Prevention, 87% of patients were aged between 30 and 79 years [16]. If in children symptomatic infection is uncommon and usually mild, in the elderly COVID-19 is associated with a higher death rate compared to middle age adults who have the same disease [16]. Table 1 shows the fatality rate of COVID-19 by age [17]. The comorbidities also contribute to the death rate. Thus, in patients with cardiovascular disease the death rate was 10.5%, in patients with diabetes 7.3%, in patients with chronic respiratory diseases 6.3%, in patients with arterial hypertension 6%, and in patients with cancer 5.6% [17]. The most common manifestation of infection with SARS-CoV-2 is pneumonia. There are not any specific clinical manifestations that differentiate this disease from other respiratory viral infections [18]. The most common symptoms induced by the infection with SARS-CoV-2are shown in Table 2 [19,20].  (27) According to World Health Organization (WHO), a suspected case of SARS-CoV-2 infection is defined as a patient presenting with severe acute respiratory infection without an obvious cause and at least one of the following: history of travel in an area at risk, up to 14 days before the onset of symptoms, or medical personnel in a medical unit that is treating patients with severe acute respiratory infections of unknown etiology [21,22]. A confirmed case is the patient in whom the infection was identified by a SARS-CoV-2 laboratory test, regardless of the signs or symptoms [21,22].
Regarding laboratory tests, SARS-CoV-2infected patients may present: leukopenia, leukocytosis, and lymphopenia, the most common being lymphopenia [23]. They also may have elevated aminotransferase levels. Procalcitonin levels are usually normal in patients with pneumonia but may be higher in patients who require intensive therapy [23]. In some studies, high levels of D-dimers and severe lymphopenia are associated with a higher mortality rate [24]. Chest CT examination most commonly reveals ground-glass opacification. Other changes that may occur are: pleural thickening, pleural effusion and lymphadenopathy. They are usually bilateral, have a peripheral distribution and involve the lower lobes [25,26].
In patients suspected of being infected with the new coronavirus, it is recommended to test for both the pathogen agent, as well as other respiratory infectious agents. Thus, it is recommended that samples must be taken from the upper respiratory tract (nasopharyngeal and oropharyngeal swab) or lower respiratory tract (sputum, tracheal aspirates, or bronchoalveolar lavage). Additional biological samples, such as stool or urine, may be taken. Induced sputum collection is not recommended, and for safety reasons these samples will not be used in viral cultures. Identification of SARS CoV-2 RNA is performed by RT-PCR (Real-Time Polymerase Chain Reaction). A positive test confirms the infection, while a negative test cannot rule it out [9]. According to a report by the Chinese Center for Disease Control and Prevention, there are three degrees of damage induced by infection with SARS-CoV-2, listed in Table 3 [16,27]. In most cases, the damage caused by this infection is not severe and death generally occurs among patients who have significant comorbidities (cardiovascular disease [28,29], diabetes [30,31], chronic respiratory disease, hypertension [32,33], cancer, etc).

MANAGEMENT
To control this pandemic, measures such as early diagnosis, treatment and the quarantining of infected people to limit human-to-human transmission are recommended. In patients with mild impairment, the recommendations are self-isolation at home. In this situation, the main objectives are the limitation of infection transmission and self-health monitoring. In case of clinical deterioration, the patient requires hospitalization [9,33,34].
For patients with severe symptoms, hospitalization is recommended, in order to implement measures of infection control and supportive care [9]. Glucocorticoids should not be used in case of pneumonia determined by SARS-CoV-2 without other indications, such as chronic obstructive pulmonary disease exacerbation. This medication was associated with increased mortality in patients with influenza and viral clearance delay in patients infected with MERS [9,35]. Studies until now have identified a number of potentially effective agents against SARS-CoV-2 (interferon-α, lopinavir/ ritonavir, chloroquine phosphate, ribavirin, remdesivir, arbidol, favipiravir, darunavir) [35][36][37][38][39]. Table 4 presents possible ways of administration of these drugs [38]. The recovery period is approximately 2 weeks for mild forms of infection and 3-6 weeks for severe forms of infection [9].

CONCLUSIONS
The pandemic caused by the new coronavirus is the most important public health problem facing humanity at this time. Rapid transmission requires important prevention measures, such as self-isolation or quarantine in one's home. Studies to date have identified a number of therapeutic agents effective against SARS-CoV-2 in vitro. Given the disastrous situation, mainly through its effects on health and number of deaths, but also on the economies worldwide, further studies to elucidate the diagnostic and therapeutic possibilities are urgently required.