The emergence of COVID-19 caused by SARS-CoV-2
In mid-December of 2019, a pneumonia outbreak erupted once again in China, in the city of Wuhan, the province of Hubei (1). The outbreak spread during the next two months throughout the country, with currently over 80 000 cases and more than 2400 fatal outcomes (CFR 2.5%), according to official reports. Exported cases have been reported in 30 countries throughout the world, with over 2400 registered cases, of which 276 are in Europe. On February 25, the first case of COVID-19 was confirmed in Zagreb, Croatia, and was linked to the current outbreak in the Lombardy and Veneto regions of northern Italy (15).
The case definition was first established on January 10 and modified over time, taking into account both the virus epidemiology and clinical presentation. The clinical criteria were expanded on February 4 to include any lower acute respiratory diseases, and the epidemiological criterion was extended to the whole of China, with the possibility of expansion to some surrounding countries (16,17).
At the early stage of the outbreak, patients’ full-length genome sequences were identified, showing that the virus shares 79.5% sequence identity with SARS-CoV. Furthermore, 96% of its whole genome is identical to bat coronavirus. It was also shown that this virus uses the same cell entry receptor, ACE2, as SARS-CoV (18).
The full clinical spectrum of COVID-19 ranges from asymptomatic cases, mild cases that do not require hospitalization, to severe cases that require hospitalization and ICU treatment, and those with fatal outcomes. Most cases were classified as mild (81%), 14% as severe, and 5% as critical (ie, respiratory failure, septic shock, and/or multiple organ dysfunction or failure). The overall CFR was 2.3%, while the rate in patients with comorbidities was considerably higher – 10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory diseases, 6.0% for hypertension, and 5.6% for cancer. The CFR in critical patients was as high as 49.0% (4).
It is still not clear which factors contribute to the risk of transmitting the infection, especially by persons who are in the incubation stage or asymptomatic, as well as which factors contribute to the severity of the disease and fatal outcome. Evidence from various types of additional studies is needed to control the epidemic (19).
However, it is certain that the binding of the virus to the ACE 2 receptor can induce certain immunoreactions, and the receptor diversity between humans and animal species designated as SARS-CoV-2 reservoirs further increases the complexity of COVID-19 immunopathogenicity (20). Recently, a diagnostic RT-PCR assay for the detection of SARS-CoV-19 has been developed using synthetic nucleic acid technology, despite the lack of virus isolates and clinical samples, owing to its close relation to SARS. Additional diagnostic tests are in the pipeline, some of which are likely to become commercially available soon (21).
Currently, randomized controlled trials have not shown any specific antiviral treatment to be effective for COVID-19. Therefore, treatment is based on symptomatic and supportive care, with intensive care measures for the most severe cases (22). However, many forms of specific treatment are being tried, with various results, such as with remdesivir, lopinavir/ritonavir, chloroquine phosphate, convalescent plasma from patients who have recovered from COVID-19, and others (23-26).
No vaccine is currently available, but researchers and vaccine manufacturers have been attempting to develop the best option for COVID-19 prevention. So far, the basic target molecule for the production of a vaccine, as well as therapeutic antibodies, is the CoV spike (S) glycoprotein (27,28).
The spread of the epidemic can be only contained, and SARS-CoV-2 transmission in hospitals reduced, by strict compliance with infection prevention and control measures (contact, droplet, and airborne precautions) (22,29). During the current epidemic, health care workers have been at an increased risk of contracting the disease and consequent fatal outcome owing to direct exposure to patients. Early reports from the beginning of the epidemic indicated that a large proportion of the patients had contracted the infection in a health care facility (as high as 41%), and that health care workers constituted a large proportion of these cases (as high as 29%). However, the largest study to date on more than 72 000 patients from China has shown that health care workers make up 3.8% of the patients. In this study, although the overall CFR was 2.3%, among health care workers it was only 0.3%. In China, the number of severe or critical cases among health care workers has declined overall, from 45.0% in early January to 8.7% in early February (4). This poses numerous psychological and ethical questions about health care workers’ role in the spread, eventual arrest, and possible consequences of epidemics. For example, during the 2014-2016 Ebola virus disease epidemic in Africa, health care workers risked their lives in order to perform life-saving invasive procedures (intravenous indwelling, hemodialysis, reanimation, mechanical ventilation), and suffered high stress and fatigue levels, which may have prevented them from practicing optimal safety measures, sometimes with dire consequences (30).