Coronaviruses form a large family of viruses that may cause respiratory infections ranging from a mild cold to severe pneumonia. According to the World Health Organization (WHO), a new type of coronavirus, which had never been detected in humans before, was identified in the Chinese city of Wuhan on January 7, 2020. The virus strain has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is the causative agent of coronavirus disease 2019 (COVID-19).
Presentation
SARS-CoV-2 has been described as the causative agent of respiratory infections of varying severity. To cover the entire spectrum of disease courses, the term coronavirus disease 19 (COVID-19) has been coined. More severe infections of the lungs are also referred to as Severe Specific Contagious Pneumonia (SSCP) [1].
Fever above 39 °C, fatigue, and dry cough have been named as the most common symptoms in COVID-19 patients and are displayed by 60-100% of affected individuals [2] [3] [4]. Minor shares of patients present with dyspnea, productive cough, hemoptysis, myalgia, headache, sore throat, and rhinorrhea. Chest pain, abdominal pain, nausea, vomiting, and diarrhea have occasionally been observed. Interestingly, confusion can be noted in about 1 in 10 patients [2]. Recently, loss of smell and taste were also described as symptoms. Whereas mild infections may be self-limiting with a few days [5], the illness may evolve over a week or longer and give rise to severe disease with acute respiratory distress syndrome and septic shock. These patients are worsening rapidly and at high risk of death from multiorgan failure.
Diagnostic imaging is likely to show inflammatory changes in the lower respiratory tract that allow for the diagnosis of pneumonia, with bilateral findings being very common [3] [4]. Ground-glass and consolidative opacities are frequently observed, while lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy are not characteristic of COVID-19 [6]. Of note, the absence of pathological findings on chest images does not rule out an infection with SARS-CoV-2. Neutrophilia and lymphopenia have been found in about a third of COVID-19 patients [2] [4].
Workup
Precise criteria on whom to test for COVID-19 have been published by the WHO and the US American Centers for Disease Control and Prevention (CDC). They differ slightly and are prone to change as new data on the presence of SARS-CoV-2 outside the Hubei province, China, and possible routes of transmission become available [7] [8]. Beyond that, the WHO has prepared interim guidance for the laboratory diagnosis of 2019-nCoV infections and provides a list of institutions that may be contacted to this end [9]. They developed a series of genetic amplification assays, specifically real-time RT-PCR protocols, to confirm the presence of 2019-nCoV in respiratory samples [10] [11]. Nasopharyngeal and oropharyngeal swabs may be used as well as sputum, endotracheal aspirate or bronchoalveolar lavage. No recommendations have yet been given as to the preference of upper or lower respiratory specimens for virus detection in mild cases, although the use of lower respiratory material is strongly encouraged in severe and progressive disease.
Additionally, paired serum samples may be obtained from patients suspicious for SARS-CoV-2 infection [9]. They should be collected during the first week of illness as well as 2-3 weeks later and may allow for a more reliable diagnosis of mild infections once serological assays become available.
Of note, testing for SARS-CoV-2 should be carried out regardless of whether a conventional respiratory pathogen is found. Little is known about the prevalence of coinfections among COVID-19 patients and the presence of other pathogens does not rule out an infection with SARS-CoV-2 [9].
Any suspected and confirmed cases must immediately be reported to the relevant public health authorities. The same applies if unexpected results are obtained. In this context, it shall be emphasized that validation is still in progress for all test protocols published so far.
Treatment
No specific treatment directed against the causative agent is currently available. COVID-19 patients have been administered antivirals like oseltamivir, ganciclovir, lopinavir, and ritonavir, both intravenously and orally [2], but data regarding the efficacy of such measures are not yet available. Experiences from prior outbreaks of coronavirus-induced respiratory diseases are rather discouraging: No antiviral agents have been found to provide benefit for treating the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) [4].
Notwithstanding, patients benefit from meticulous supportive care and the treatment of comorbidities [2] [4]:
- Oxygen therapy is most commonly applied to improve lung function; mechanical ventilation and extracorporeal membrane oxygenation may become necessary.
- Broad-spectrum antibiotics and possibly antimycotics are administered to prevent and manage coinfections.
- Corticosteroids have been applied. They may reduce pulmonary inflammation and prevent respiratory failure, but also affect many other physiological and pathological processes.
- Furthermore, any deterioration in organ function, such as acute kidney injury, requires urgent attention and targeted measures.
Prognosis
Clinical and epidemiological data gathered to date suggest a higher risk of severe disease in the elderly, particularly in those with comorbidities [4]. The mortality rate of SSCP is currently estimated at 2-5% [1], but the overall share of SSCP in COVID-19 remains to be determined.
With regard to any patient's individual prognosis, Chen et al. stated that the characteristics of those who experienced poor outcomes were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia [2]. This model considers the presence of multilobular infiltrates, low lymphocyte counts, bacterial coinfections, a personal history of smoking, hypertension, and advanced age as unfavorable prognostic factors [12].
Etiology
Lu and colleagues realized an in-depth characterization of SARS-CoV-2 and provided the full-length genome sequence of the pathogen [13]. According to their phylogenetic analyses, SARS-CoV-2 belongs to the genus of betacoronaviruses and the subgenus of sarbecoviruses. Another well-known sarbecovirus is SARS-CoV, which caused the pandemic of SARS between 2002 and 2004. Owing to their relatively close relationship, SARS-CoV-2 has been proposed by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses the appropriate designation for the pathogen causing COVID-19 [14].
Interestingly, SARS-CoV-2 has been found to be even more closely related to two bat-derived SARS-like coronaviruses than to the causative agent of SARS [13]. Are we thus talking about a zoonotic disease? COVID-19 has, in fact, been described as a potential zoonosis [1], but an Italian-Brazilian study on the virus' evolution suggests the existence of an intermediate carrier: Benvenuto et al. have proposed that the virus has initially been harbored by bats but been transmitted to another, as-of-yet unknown animal species before infecting men [15]. Presumably, an animal sold at the seafood market in Wuhan, China, served as an intermediate host facilitating the emergence of the virus in humans [13]. Parallels can be drawn to prior coronavirus outbreaks, namely the aforementioned pandemic of SARS and the outbreak of MERS that started in 2012. Bats have been identified as the natural reservoir for both SARS-CoV and MERS-CoV, while other animals, namely the masked palm civet and dromedary camels, acted as intermediate hosts [16] [17].
Epidemiology
While SARS-CoV-2 emerged in the Chinese metropole Wuhan, travelers rapidly carried the virus across the country and beyond its borders, triggering secondary chains of transmission in a wider geographical area. On January 13, 2020, Thai authorities confirmed the first case outside China.
The current number of infections globally according to the Situation Report published by the WHO on March 17, 2022 is 460 280 168 [18].
Affected patients must promptly be identified to prevent any further spread of the disease. A coordinated international response is required to address this situation and to diminish the public health risk posed by SARS-CoV-2, which is why the WHO declared the outbreak a pandemic on March 11, 2020.
Pathophysiology
Transmission occurs from person to person, through droplets or by physical contact between two individuals [1]. Fomites may play a role in COVID-19 spread, too [18]. The incubation period may be as short as two days or extend over two weeks, and the possibility that the virus may be transmitted to others before symptoms develop should seriously be considered. While the infection from an asymptomatic contact has been reported in Germany, the respective case study was updated when new information became available that invalidated the original conclusions [5]. Thus, to date, there is no evidence that patients are contagious before presenting any symptoms. It is also not known for how long the virus may be spread by someone who has recovered from their illness.
Prevention
In order to prevent COVID-19, the basic principles to reduce the risk of contracting and transmitting acute respiratory infections apply. These principles include regular handwashing with soap, especially after direct contact with ill people or their environment, and the avoidance of close contact with those showing symptoms of respiratory disease. On the other side, people suffering from respiratory symptoms are encouraged to maintain their distance, to cover coughs and sneezes, and to take their personal hygiene seriously. Medical assistance should be sought early in the case of fever, cough, and possible exposure to SARS-CoV-2. Unprotected contact with farm and wild animals should generally be minimized. In healthcare settings, infection prevention and control practices should be applied strictly and be enhanced where necessary.
On a larger scale, distinct measures can be taken to reduce the likelihood of pathogen emergence. Live animal markets, such as the seafood market in Wuhan, provide a perfect breeding ground for new infectious diseases: There's close contact between animals and humans and an extensive interchange of genetic material between viruses harbored by either species. These conditions largely increase the probability of human infection and eventual human-to-human transmission, which are two of the prerequisites for pandemics. That is why such animal markets have been subjected to harsh but well-founded criticism for years. It does not at all help the issue that the illicit trade with wild, possibly endangered animals is flourishing in those markets.
Summary
COVID-19 is an emergent infectious disease caused by SARS-CoV-2. This pathogen was first identified in the Chinese Hubei province and has subsequently been shown to originate from a live-animal market in the city of Wuhan. The WHO has assessed the current outbreak as a pandemic.
As of today, vaccines against COVID-19 are not available. Intense efforts are made by scientists in distinct countries to change that situation, but vaccines are not expected to be available in at least one more year. This increases the importance of strong measures to detect COVID-19 early, isolate and treat cases, trace contacts, and promote social distancing measures commensurate with the risk.
Patient Information
Much commotion has arisen over the emergence of 2019-nCoV, a new coronavirus causing mild to severe respiratory infections in China and many other countries all over the world. Preventive measures, such as avoiding close contact with anyone showing symptoms of respiratory illness, to seek medical advice in case of flu-like symptoms, and to provide information to health care workers to the best of their knowledge are recommended.
The disease caused by SARS-CoV-2 is commonly named COVID-19, as in "coronavirus disease 19". Symptoms typically develop within 2-14 days after exposure and include fever, fatigue, and cough. Some patients may also experience muscle aches, headaches, a sore throat or runny nose. While mild infections usually improve within a few days, COVID-19 may follow a severe course and lead to pneumonia, shock, and eventually death.
Because COVID-19 cannot be distinguished clinically from other causes of pneumonia, it is of utmost importance that patients provide precise information on recent travels, hospital stays, and close contact with anyone who may have been exposed. The patient's cooperation is key to counter the COVID-19 outbreak, to shorten the time until diagnosis and measures that prevent the exposure of others. If someone is identified as suspicious for COVID-19, they can be isolated, tested accordingly, and receive supportive care as needed.
References
- Wu YC, Chen CS, Chan YJ. Overview of The 2019 Novel Coronavirus (2019-nCoV): The Pathogen of Severe Specific Contagious Pneumonia (SSCP). J Chin Med Assoc. 2020.
- Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020.
- Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020.
- Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Jama. 2020.
- Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020.
- Chung M, Bernheim A, Mei X, et al. CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV). Radiology. 2020:200230.
- Centers for Disease Control and Prevention. Evaluating and Reporting Persons Under Investigation (PUI). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-criteria.html. Accessed March 12, 2020.
- World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected. Accessed March 12, 2020.
- World Health Organization. Coronavirus disease (COVID-19) technical guidance: Laboratory testing for 2019-nCoV in humans. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/laboratory-guidance. Accessed March 12, 2020.
- Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020; 25(3).
- Centers for Disease Control and Prevention. CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel: Instructions for Use. 2020.
- Guo L, Wei D, Zhang X, et al. Clinical Features Predicting Mortality Risk in Patients With Viral Pneumonia: The MuLBSTA Score. Front Microbiol. 2019; 10:2752.
- Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020.
- Gorbalenya AE, Baker SC, Baric RS, et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. 2020:2020.2002.2007.937862.
- Benvenuto D, Giovannetti M, Ciccozzi A, Spoto S, Angeletti S, Ciccozzi M. The 2019-new coronavirus epidemic: evidence for virus evolution. bioRxiv. 2020:2020.2001.2024.915157.
- Mohd HA, Al-Tawfiq JA, Memish ZA. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir. Virol J. 2016; 13:87.
- Shi Z, Hu Z. A review of studies on animal reservoirs of the SARS coronavirus. Virus Res. 2008; 133(1):74-87.
- World Health Organization. Coronavirus Disease (COVID-19) Dashboard. https://covid19.who.int/. Accessed March 17, 2022.