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Coronavirus disease 2019 (COVID-19): A literature review

Harapan harapan.

a Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

b Tropical Disease Centre, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

c Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

d Division of Infectious Diseases, AichiCancer Center Hospital, Chikusa-ku Nagoya, Japan

Amanda Yufika

e Department of Family Medicine, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

Wira Winardi

f Department of Pulmonology and Respiratory Medicine, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

g School of Medicine, The University of Western Australia, Perth, Australia

Haypheng Te

h Siem Reap Provincial Health Department, Ministry of Health, Siem Reap, Cambodia

Dewi Megawati

i Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Warmadewa University, Denpasar, Indonesia

j Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA

Zinatul Hayati

k Department of Clinical Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

Abram L. Wagner

l Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, MI 48109, USA

Mudatsir Mudatsir

In early December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan City, Hubei Province, China. On January 30, 2020 the World Health Organization declared the outbreak as a Public Health Emergency of International Concern. As of February 14, 2020, 49,053 laboratory-confirmed and 1,381 deaths have been reported globally. Perceived risk of acquiring disease has led many governments to institute a variety of control measures. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In this literature review, the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and preventions strategies are all reviewed.

On December 31, 2019, the China Health Authority alerted the World Health Organization (WHO) to several cases of pneumonia of unknown aetiology in Wuhan City in Hubei Province in central China. The cases had been reported since December 8, 2019, and many patients worked at or lived around the local Huanan Seafood Wholesale Market although other early cases had no exposure to this market [1] . On January 7, a novel coronavirus, originally abbreviated as 2019-nCoV by WHO, was identified from the throat swab sample of a patient [2] . This pathogen was later renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group [3] and the disease was named coronavirus disease 2019 (COVID-19) by the WHO. As of January 30, 7736 confirmed and 12,167 suspected cases had been reported in China and 82 confirmed cases had been detected in 18 other countries [4] . In the same day, WHO declared the SARS-CoV-2 outbreak as a Public Health Emergency of International Concern (PHEIC) [4] .

According to the National Health Commission of China, the mortality rate among confirmed cased in China was 2.1% as of February 4 [5] and the mortality rate was 0.2% among cases outside China [6] . Among patients admitted to hospitals, the mortality rate ranged between 11% and 15% [7] , [8] . COVID-19 is moderately infectious with a relatively high mortality rate, but the information available in public reports and published literature is rapidly increasing. The aim of this review is to summarize the current understanding of COVID-19 including causative agent, pathogenesis of the disease, diagnosis and treatment of the cases, as well as control and prevention strategies.

The virus: classification and origin

SARS-CoV-2 is a member of the family Coronaviridae and order Nidovirales. The family consists of two subfamilies, Coronavirinae and Torovirinae and members of the subfamily Coronavirinae are subdivided into four genera: (a) Alphacoronavirus contains the human coronavirus (HCoV)-229E and HCoV-NL63; (b) Betacoronavirus includes HCoV-OC43, Severe Acute Respiratory Syndrome human coronavirus (SARS-HCoV), HCoV-HKU1, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV); (c) Gammacoronavirus includes viruses of whales and birds and; (d) Deltacoronavirus includes viruses isolated from pigs and birds [9] . SARS-CoV-2 belongs to Betacoronavirus together with two highly pathogenic viruses, SARS-CoV and MERS-CoV. SARS-CoV-2 is an enveloped and positive-sense single-stranded RNA (+ssRNA) virus [16] .

SARS-CoV-2 is considered a novel human-infecting Betacoronavirus [10] . Phylogenetic analysis of the SARS-CoV-2 genome indicates that the virus is closely related (with 88% identity) to two bat-derived SARS-like coronaviruses collected in 2018 in eastern China (bat-SL-CoVZC45 and bat-SL-CoVZXC21) and genetically distinct from SARS-CoV (with about 79% similarity) and MERS-CoV [10] . Using the genome sequences of SARS-CoV-2, RaTG13, and SARS-CoV [11] , a further study found that the virus is more related to BatCoV RaTG13, a bat coronavirus that was previously detected in Rhinolophus affinis from Yunnan Province, with 96.2% overall genome sequence identity [11] . A study found that no evidence of recombination events detected in the genome of SARS-CoV-2 from other viruses originating from bats such as BatCoV RaTG13, SARS-CoV and SARSr-CoVs [11] . Altogether, these findings suggest that bats might be the original host of this virus [10] , [11] .

However, a study is needed to elucidate whether any intermediate hosts have facilitated the transmission of the virus to humans. Bats are unlikely to be the animal that is directly responsible for transmission of the virus to humans for several reasons [10] : (1) there were various non-aquatic animals (including mammals) available for purchase in Huanan Seafood Wholesale Market but no bats were sold or found; (2) SARS-CoV-2 and its close relatives, bat-SL-CoVZC45 and bat-SL-CoVZXC21, have a relatively long branch (sequence identity of less than 90%), suggesting those viruses are not direct ancestors of SARS-CoV-2; and (3) in other coronaviruses where bat is the natural reservoir such as SARS-CoV and MERS-CoV, other animals have acted as the intermediate host (civets and possibly camels, respectively). Nevertheless, bats do not always need an intermediary host to transmit viruses to humans. For example, Nipah virus in Bangladesh is transmitted through bats shedding into raw date palm sap [12] .

Transmission

The role of the Huanan Seafood Wholesale Market in propagating disease is unclear. Many initial COVID-19 cases were linked to this market suggesting that SARS-CoV-2 was transmitted from animals to humans [13] . However, a genomic study has provided evidence that the virus was introduced from another, yet unknown location, into the market where it spread more rapidly, although human-to-human transmission may have occurred earlier [14] . Clusters of infected family members and medical workers have confirmed the presence of person-to-person transmission [15] . After January 1, less than 10% of patients had market exposure and more than 70% patients had no exposure to the market [13] . Person-to-person transmission is thought to occur among close contacts mainly via respiratory droplets produced when an infected person coughs or sneezes. Fomites may be a large source of transmission, as SARS-CoV has been found to persist on surfaces up to 96 h [16] and other coronaviruses for up to 9 days [17] .

Whether or not there is asymptomatic transmission of disease is controversial. One initial study published on January 30 reported asymptomatic transmission [18] , but later it was found that the researchers had not directly interviewed the patient, who did in fact have symptoms prior to transmitting disease [19] . A more recent study published on February 21 also purported asymptomatic transmission [20] , but any such study could be limited by errors in self-reported symptoms or contact with other cases and fomites.

Findings about disease characteristics are rapidly changing and subject to selection bias. A study indicated the mean incubation period was 5.2 days (95% confidence interval [95%CI]: 4.1–7.0) [13] . The incubation period has been found to be as long as 19 or 24 days [21] , [22] , although case definitions typically rely on a 14 day window [23] .

The basic reproductive number ( R 0 ) has been estimated with varying results and interpretations. R 0 measures the average number of infections that could result from one infected individual in a fully susceptible population [24] . Studies from previous outbreaks found R 0 to be 2.7 for SARS [25] and 2.4 for 2009 pandemic H1N1 influenza [26] . One study estimated that that basic reproductive number ( R 0 ) was 2.2 (95% CI: 1.4–3.9) [13] . However, later in a further analysis of 12 available studies found that R 0 was 3.28 [27] . Because R 0 represents an average value it is also important to consider the role of super spreaders, who may be hugely responsible for outbreaks within large clusters but who would not largely influence the value of R 0 [28] . During the acute phase of an outbreak or prepandemic, R 0 may be unstable [24] .

In pregnancy, a study of nine pregnancy women who developed COVID-19 in late pregnancy suggested COVID-19 did not lead to substantially worse symptoms than in nonpregnant persons and there is no evidence for intrauterine infection caused by vertical transmission [29] .

In hospital setting, a study involving 138 COVID-19 suggested that hospital-associated transmission of SARS-CoV-2 occurred in 41% of patients [30] . Moreover, another study on 425 patients found that the proportion of cases in health care workers gradually increased by time [13] . These cases likely reflect exposure to a higher concentration of virus from sustained contact in close quarters.

Outside China, as of February 12, 2020, there were 441 confirmed COVID-19 cases reported in 24 countries [6] of which the first imported case was reported in Thailand on January 13, 2020 [6] , [31] . Among those countries, 11 countries have reported local transmission with the highest number of cases reported in Singapore with 47 confirmed cases [6] .

Risk factors

The incidence of SARS-CoV-2 infection is seen most often in adult male patients with the median age of the patients was between 34 and 59 years [20] , [30] , [7] , [32] . SARS-CoV-2 is also more likely to infect people with chronic comorbidities such as cardiovascular and cerebrovascular diseases and diabetes [8] . The highest proportion of severe cases occurs in adults ≥60 years of age, and in those with certain underlying conditions, such as cardiovascular and cerebrovascular diseases and diabetes [20] , [30] . Severe manifestations maybe also associated with coinfections of bacteria and fungi [8] .

Fewer COVID-19 cases have been reported in children less than 15 years [20] , [30] , [7] , [32] . In a study of 425 COVID-19 patients in Wuhan, published on January 29, there were no cases in children under 15 years of age [13] , [33] . Nevertheless, 28 paediatric patients have been reported by January 2020 [34] . The clinical features of infected paediatric patients vary, but most have had mild symptoms with no fever or pneumonia, and have a good prognosis [34] . Another study found that although a child had radiological ground-glass lung opacities, the patient was asymptomatic [35] . In summary, children might be less likely to be infected or, if infected, present milder manifestations than adults; therefore, it is possible that their parents will not seek out treatment leading to underestimates of COVID-19 incidence in this age group.

Pathogenesis and immune response

Like most other members of the coronavirus family, Betacoronavirus exhibit high species specificity, but subtle genetic changes can significantly alter their tissue tropism, host range, and pathogenicity. A striking example of the adaptability of these viruses is the emergence of deadly zoonotic diseases in human history caused by SARS-CoV [36] and MERS-CoV [37] . In both viruses, bats served as the natural reservoir and humans were the terminal host, with the palm civet and dromedary camel the intermediary host for SARS-CoV and MERS-CoV, respectively [38] , [39] . Intermediate hosts clearly play a critical role in cross species transmission as they can facilitate increased contact between a virus and a new host and enable further adaptation necessary for an effective replication in the new host [40] . Because of the pandemic potential of SARS-CoV-2, careful surveillance is immensely important to monitor its future host adaptation, viral evolution, infectivity, transmissibility, and pathogenicity.

The host range of a virus is governed by multiple molecular interactions, including receptor interaction. The envelope spike (S) protein receptor binding domain of SARS-CoV-2 was shown structurally similar to that of SARS-CoV, despite amino acid variation at some key residues [10] . Further extensive structural analysis strongly suggests that SARS-CoV-2 may use host receptor angiotensin-converting enzyme 2 (ACE2) to enter the cells [41] , the same receptor facilitating SARS-CoV to infect the airway epithelium and alveolar type 2 (AT2) pneumocytes, pulmonary cells that synthesize pulmonary surfactant [42] . In general, the spike protein of coronavirus is divided into the S1 and S2 domain, in which S1 is responsible for receptor binding and S2 domain is responsible for cell membrane fusion [10] . The S1 domain of SARS-CoV and SARS-CoV-2 share around 50 conserved amino acids, whereas most of the bat-derived viruses showed more variation [10] . In addition, identification of several key residues (Gln493 and Asn501) that govern the binding of SARS-CoV-2 receptor binding domain with ACE2 further support that SARS-CoV-2 has acquired capacity for person-to-person transmission [41] . Although, the spike protein sequence of receptor binding SARS-CoV-2 is more similar to that of SARS-CoV, at the whole genome level SARS-CoV-2 is more closely related to bat-SL-CoVZC45 and bat-SL-CoVZXC21 [10] .

However, receptor recognition is not the only determinant of species specificity. Immediately after binding to their receptive receptor, SARS-CoV-2 enters host cells where they encounter the innate immune response. In order to productively infect the new host, SARS-CoV-2 must be able to inhibit or evade host innate immune signalling. However, it is largely unknown how SARS-CoV-2 manages to evade immune response and drive pathogenesis. Given that COVID-19 and SARS have similar clinical features [7] , SARS-CoV-2 may have a similar pathogenesis mechanism as SARS-CoV. In response to SARS-CoV infections, the type I interferon (IFN) system induces the expression of IFN-stimulated genes (ISGs) to inhibit viral replication. To overcome this antiviral activity, SARS-CoV encodes at least 8 viral antagonists that modulate induction of IFN and cytokines and evade ISG effector function [43] .

The host immune system response to viral infection by mediating inflammation and cellular antiviral activity is critical to inhibit viral replication and dissemination. However, excessive immune responses together with lytic effects of the virus on host cells will result in pathogenesis. Studies have shown patients suffering from severe pneumonia, with fever and dry cough as common symptoms at onset of illness [7] , [8] . Some patients progressed rapidly with Acute Respiratory Stress Syndrome (ARDS) and septic shock, which was eventually followed by multiple organ failure and about 10% of patients have died [8] . ARDS progression and extensive lung damage in COVID-19 are further indications that ACE2 might be a route of entry for the SARS-CoV-2 as ACE2 is known abundantly present on ciliated cells of the airway epithelium and alveolar type II (cells (pulmonary cells that synthesize pulmonary surfactant) in humans [44] .

Patients with SARS and COVID-19 have similar patterns of inflammatory damage. In serum from patients diagnosed with SARS, there is increased levels of proinflammatory cytokines (e.g. interleukin (IL)-1, IL6, IL12, interferon gamma (IFNγ), IFN-γ-induced protein 10 (IP10), macrophage inflammatory proteins 1A (MIP1A) and monocyte chemoattractant protein-1 (MCP1)), which are associated with pulmonary inflammation and severe lung damage [45] . Likewise, patients infected with SARS-CoV-2 are reported to have higher plasma levels of proinflammatory cytokines including IL1β, IL-2, IL7, TNF-α, GSCF, MCP1 than healthy adults [7] . Importantly, patients in the intensive care unit (ICU) have a significantly higher level of GSCF, IP10, MCP1, and TNF-α than those non-ICU patients, suggesting that a cytokine storm might be an underlying cause of disease severity [7] . Unexpectedly, anti-inflammatory cytokines such as IL10 and IL4 were also increased in those patients [7] , which was uncommon phenomenon for an acute phase viral infection. Another interesting finding, as explained before, was that SARS-CoV-2 has shown to preferentially infect older adult males with rare cases reported in children [7] , [8] . The same trend was observed in primate models of SARS-CoV where the virus was found more likely to infect aged Cynomolgus macaque than young adults [46] . Further studies are necessary to identify the virulence factors and the host genes of SARS-CoV-2 that allows the virus to cross the species-specific barrier and cause lethal disease in humans.

Clinical manifestations

Clinical manifestations of 2019-nCoV infection have similarities with SARS-CoV where the most common symptoms include fever, dry cough, dyspnoea, chest pain, fatigue and myalgia [7] , [30] , [47] . Less common symptoms include headache, dizziness, abdominal pain, diarrhoea, nausea, and vomiting [7] , [30] . Based on the report of the first 425 confirmed cases in Wuhan, the common symptoms include fever, dry cough, myalgia and fatigue with less common are sputum production, headache, haemoptysis, abdominal pain, and diarrhoea [13] . Approximately 75% patients had bilateral pneumonia [8] . Different from SARS-CoV and MERS-CoV infections, however, is that very few COVID-19 patients show prominent upper respiratory tract signs and symptoms such as rhinorrhoea, sneezing, or sore throat, suggesting that the virus might have greater preference for infecting the lower respiratory tract [7] . Pregnant and non-pregnant women have similar characteristics [48] . The common clinical presentation of 2019-nCoV infection are presented in Table 1 .

Clinical symptoms of patients with 2019-nCoV infection.

Severe complications such as hypoxaemia, acute ARDS, arrythmia, shock, acute cardiac injury, and acute kidney injury have been reported among COVID-19 patients [7] , [8] . A study among 99 patients found that approximately 17% patients developed ARDS and, among them, 11% died of multiple organ failure [8] . The median duration from first symptoms to ARDS was 8 days [30] .

Efforts to control spread of COVID-19, institute quarantine and isolation measures, and appropriately clinically manage patients all require useful screening and diagnostic tools. While SARS-CoV-2 is spreading, other respiratory infections may be more common in a local community. The WHO has released a guideline on case surveillance of COVID-19 on January 31, 2020 [23] . For a person who meets certain criteria, WHO recommends to first screen for more common causes of respiratory illness given the season and location. If a negative result is found, the sample should be sent to referral laboratory for SARS-CoV-2 detection.

Case definitions can vary by country and will evolve over time as the epidemiological circumstances change in a given location. In China, a confirmed case from January 15, 2020 required an epidemiological linkage to Wuhan within 2 weeks and clinical features such as fever, pneumonia, and low white blood cell count. On January 18, 2020 the epidemiological criterion was expanded to include contact with anyone who had been in Wuhan in the past 2 weeks [50] . Later, the case definitions removed the epidemiological linkage.

The WHO has put forward case definitions [23] . Suspected cases of COVID-19 are persons (a) with severe acute respiratory infections (history of fever and cough requiring admission to hospital) and with no other aetiology that fully explains the clinical presentation and a history of travel to or residence in China during the 14 days prior to symptom onset; or (b) a patient with any acute respiratory illness and at least one of the following during the 14 days prior to symptom onset: contact with a confirmed or probable case of SARS-CoV-2 infection or worked in or attended a health care facility where patients with confirmed or probable SARS-CoV-2 acute respiratory disease patients were being treated. Probable cases are those for whom testing for SARS-CoV-2 is inconclusive or who test positive using a pan-coronavirus assay and without laboratory evidence of other respiratory pathogens. A confirmed case is one with a laboratory confirmation of SARS-CoV-2 infection, irrespective of clinical signs and symptoms.

For patients who meet diagnostic criteria for SARS-CoV-2 testing, the CDC recommends collection of specimens from the upper respiratory tract (nasopharyngeal and oropharyngeal swab) and, if possible, the lower respiratory tract (sputum, tracheal aspirate, or bronchoalveolar lavage) [51] . In each country, the tests are performed by laboratories designated by the government.

Laboratory findings

Among COVID-19 patients, common laboratory abnormalities include lymphopenia [8] , [20] , [30] , prolonged prothrombin time, and elevated lactate dehydrogenase [30] . ICU-admitted patients had more laboratory abnormalities compared with non-ICU patients [30] , [7] . Some patients had elevated aspartate aminotransferase, creatine kinase, creatinine, and C-reactive protein [20] , [7] , [35] . Most patients have shown normal serum procalcitonin levels [20] , [30] , [7] .

COVID-19 patients have high level of IL1β, IFN-γ, IP10, and MCP1 [7] . ICU-admitted patients tend to have higher concentration of granulocyte-colony stimulating factor (GCSF), IP10, MCP1A, MIP1A, and TNF-α [7] .

Radiology findings

Radiology finding may vary with patients age, disease progression, immunity status, comorbidity, and initial medical intervention [52] . In a study describing 41 of the initial cases of 2019-nCoV infection, all 41 patients had pneumonia with abnormal findings on chest computed tomography (CT-scan) [7] . Abnormalities on chest CT-scan were also seen in another study of 6 cases, in which all of them showed multifocal patchy ground-glass opacities notably nearby the peripheral sections of the lungs [35] . Data from studies indicate that the typical of chest CT-scan findings are bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities [7] , [8] , [20] , [30] , [32] , [53] . The consolidated lung lesions among patients five or more days from disease onset and those 50 years old or older compared to 4 or fewer days and those 50 years or younger, respectively [47] .

As the disease course continue, mild to moderate progression of disease were noted in some cases which manifested by extension and increasing density of lung opacities [49] . Bilateral multiple lobular and subsegmental areas of consolidation are typical findings on chest CT-scan of ICU-admitted patients [7] . A study among 99 patients, one patient had pneumothorax in an imaging examination [8] .

Similar to MERS-CoV and SARS-CoV, there is still no specific antiviral treatment for COVID-19 [54] . Isolation and supportive care including oxygen therapy, fluid management, and antibiotics treatment for secondary bacterial infections is recommended [55] . Some COVID-19 patients progressed rapidly to ARDS and septic shock, which was eventually followed by multiple organ failure [7] , [8] . Therefore, the effort on initial management of COVID-19 must be addressed to the early recognition of the suspect and contain the disease spread by immediate isolation and infection control measures [56] .

Currently, no vaccination is available, but even if one was available, uptake might be suboptimal. A study of intention to vaccinate during the H1N1 pandemic in the United States was around 50% at the start of the pandemic in May 2009 but had decreased to 16% by January 2010 [57] .

Neither is a treatment available. Therefore, the management of the disease has been mostly supportive referring to the disease severity which has been introduced by WHO. If sepsis is identified, empiric antibiotic should be administered based on clinical diagnosis and local epidemiology and susceptibility information. Routine glucocorticoids administration are not recommended to use unless there are another indication [58] . Clinical evidence also does not support corticosteroid treatment [59] . Use of intravenous immunoglobulin might help for severely ill patients [8] .

Drugs are being evaluated in line with past investigations into therapeutic treatments for SARS and MERS [60] . Overall, there is not robust evidence that these antivirals can significantly improve clinical outcomes A. Antiviral drugs such as oseltamivir combined with empirical antibiotic treatment have also been used to treat COVID-19 patients [7] . Remdesivir which was developed for Ebola virus, has been used to treat imported COVID-19 cases in US [61] . A brief report of treatment combination of Lopinavir/Ritonavir, Arbidol, and Shufeng Jiedu Capsule (SFJDC), a traditional Chinese medicine, showed a clinical benefit to three of four COVID-19 patients [62] . There is an ongoing clinical trial evaluating the safety and efficacy of lopinavir-ritonavir and interferon-α 2b in patients with COVID-19 [55] . Ramsedivir, a broad spectrum antivirus has demonstrated in vitro and in vivo efficacy against SARS-CoV-2 and has also initiated its clinical trial [63] , [64] . In addition, other potential drugs from existing antiviral agent have also been proposed [65] , [66] .

Control and prevention strategies

COVID-19 is clearly a serious disease of international concern. By some estimates it has a higher reproductive number than SARS [27] , and more people have been reported to have been infected or died from it than SARS [67] . Similar to SARS-CoV and MERS-CoV, disrupting the chain of transmission is considered key to stopping the spread of disease [68] . Different strategies should be implemented in health care settings and at the local and global levels.

Health care settings can unfortunately be an important source of viral transmission. As shown in the model for SARS, applying triage, following correct infection control measures, isolating the cases and contact tracing are key to limit the further spreading of the virus in clinics and hospitals [68] . Suspected cases presenting at healthcare facilities with symptoms of respiratory infections (e.g. runny nose, fever and cough) must wear a face mask to contain the virus and strictly adhere triage procedure. They should not be permitted to wait with other patients seeking medical care at the facilities. They should be placed in a separated, fully ventilated room and approximately 2 m away from other patients with convenient access to respiratory hygiene supplies [69] . In addition, if a confirmed COVID-19 case require hospitalization, they must be placed in a single patient room with negative air pressure – a minimum of six air changes per hour. Exhausted air has to be filtered through high efficiency particulate air (HEPA) and medical personnel entering the room should wear personal protective equipment (PPE) such as gloves, gown, disposable N95, and eye protection. Once the cases are recovered and discharged, the room should be decontaminated or disinfected and personnel entering the room need to wear PPE particularly facemask, gown, eye protection [69] .

In a community setting, isolating infected people are the primary measure to interrupt the transmission. For example, immediate actions taken by Chinese health authorities included isolating the infected people and quarantining of suspected people and their close contacts [70] . Also, as there are still conflicting assumptions regarding the animal origins of the virus (i.e. some studies linked the virus to bat [71] , [72] while others associated the virus with snake [73] ), contacts with these animal fluids or tissues or consumption of wild caught animal meet should be avoided. Moreover, educating the public to recognize unusual symptoms such as chronic cough or shortness of breath is essential therefore that they could seek medical care for early detection of the virus. If large-scale community transmission occurs, mitigating social gatherings, temporary school closure, home isolation, close monitoring of symptomatic individual, provision of life supports (e.g. oxygen supply, mechanical ventilator), personal hand hygiene, and wearing personal protective equipment such as facemask should also be enforced [74] .

In global setting, locking down Wuhan city was one of the immediate measure taken by Chinese authorities and hence had slowed the global spread of COVID-19 [74] . Air travel should be limited for the cases unless severe medical attentions are required. Setting up temperature check or scanning is mandatory at airport and border to identify the suspected cases. Continued research into the virus is critical to trace the source of the outbreak and provide evidence for future outbreak [74] .

Conclusions

The current COVID-19 pandemic is clearly an international public health problem. There have been rapid advances in what we know about the pathogen, how it infects cells and causes disease, and clinical characteristics of disease. Due to rapid transmission, countries around the world should increase attention into disease surveillance systems and scale up country readiness and response operations including establishing rapid response teams and improving the capacity of the national laboratory system.

Competing interests

The authors declare that they have no competing interests.

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Dissertation Databases

Content: National University & NCU student dissertations and literature reviews.

Purpose: Use for foundational research, to locate test instruments and data, and more. 

Special Features: Search by advisor (chair), degree, degree level, or department. Includes a read-aloud feature.

Content: Global student dissertations and literature reviews.

Special Features: Search by advisor (chair), degree, degree level, or department. Includes a read-aloud feature

The ProQuest Dissertations & Theses database (PQDT) is the world's most comprehensive collection of dissertations and theses. It is the database of record for graduate research, with over 2.3 million dissertations and theses included from around the world.

Selected Northcentral University Dissertations

• Advertising, Chaos Theory, and a Global Pandemic: A Qualitative Case Study of Micro and Small Businesses (MSBs) Strategic business tactics and conducting business are complicated by crisis for the micro and small business, especially a crisis like the coronavirus pandemic. The problem to be addressed by this study is the lack of advertising being conducted by owner/managers of micro and small businesses when faced with a global crisis. Author: Thain Yates Hagan, Northcentral University.
• How Healthcare Administrators in South Carolina Conceive of and Plan to Maintain Productive Operations during a Pandemic This qualitative study explored how healthcare administrators and professionals conceive of productive operations and how their management styles and decisions affected the organization during a pandemic. Author: Constance Renee Lorick-Walker, Northcentral University.
• Perceptions of High School Students Adaptability Challenges to Online Learning Due to Unforeseeable Circumstances Considering online learning is at its nascent stages especially in rural schools, it is not clear the various adaptability challenges that high school students face while transitioning from face-to-face learning to online learning due to the unforeseen emergence of the Covid-19 pandemic. The purpose of this narrative study was to explore through stories the adaptability challenges that 12th grade students face while transitioning from face-to-face learning to online learning in rural Mississippi. Author: Justin Watkins, Northcentral University.
• A Qualitative Case Study of the Evolution of Community College Faculty during a Rapid Transition from Direct to eLearning Instruction during a Pandemic The purpose of this qualitative, descriptive single-case study was to explore community college faculty experiences with transition from direct to eLearning instruction and uses of a learning management system in the context of the rapid change process before and during the COVID-19 pandemic. Author: Charlotte M. Applewhite, Northcentral University.
• Strategies to Translate Curriculum from Face-to-Face Instruction to Online Learning: A Multiple-Case Study This study provided rich, detailed information regarding the perceptions of elementary teachers’ in a northern urban school district in Illinois converting the F2F curriculum to the online format during the COVID-19 pandemic. Author: Dolores Merriweather, Northcentral University.
• Stress Levels and Work Performance among Employees during the COVID-19 Pandemic The purpose of the study was to explore the stress levels and work performance (motivation) from the Coronavirus (COVID-19) pandemic among employees. A qualitative single case study research design was selected for this study. There were two phases for examining employees in this study, including an open-ended survey and a focus group interview. Author: Crystal Annette McGlover, Northcentral University.
• Teachers’ Thriving, Job Satisfaction, and Burnout: A Polynomial Regression with Response Surface Analysis The purpose of this quantitative correlational research study was to determine how various combinations of the two components of thriving at work related to job satisfaction and burnout in teachers during the COVID–19 pandemic. Author: Joni Skiles Keith, Northcentral University.
• The Technological, Pedagogical and Content Knowledge of Saudi English as a Foreign Language University Instructors and Their Perceptions of Online Teaching during COVID-19 The present mixed-method triangulation design study examined instructor perceptions of the effectiveness of the implementation of English as a foreign language online teaching in a higher education institution in the Kingdom of Saudi Arabia during COVID-19. Author: Fatima Mahmoud Basaffar, Northcentral University.
• Technology Influences and Impact of the COVID-19 Pandemic on Religious Practices: An Exploratory Case Study The problem addressed by the study was the ambiguity of understanding how intergenerational congregation members of a Baptist church with predominantly African American members perceived the influence of technology and the COVID-19 pandemic on religious practices. Author: Frances Charmaine English, Northcentral University.
• Telehealth Services: The Effect that Pandemic Events Have on the Quality and Efficiency throughout the Healthcare Industry This study implied that the extended duration of the COVID-19 pandemic created an increased comfort level using telehealth that causes an increased use of telehealth after the COVID-19 pandemic ends. Author: Keith Joseph Pelletier, Northcentral University.
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• Last Updated: Oct 31, 2023 7:56 PM
• URL: https://resources.nu.edu/covid19

Coronavirus disease 2019 (COVID-19): A literature review

Affiliations.

• 1 Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Tropical Disease Centre, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia. Electronic address: [email protected].
• 2 Division of Infectious Diseases, AichiCancer Center Hospital, Chikusa-ku Nagoya, Japan. Electronic address: [email protected].
• 3 Department of Family Medicine, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia. Electronic address: [email protected].
• 4 Department of Pulmonology and Respiratory Medicine, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia. Electronic address: [email protected].
• 5 School of Medicine, The University of Western Australia, Perth, Australia. Electronic address: [email protected].
• 6 Siem Reap Provincial Health Department, Ministry of Health, Siem Reap, Cambodia. Electronic address: [email protected].
• 7 Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Warmadewa University, Denpasar, Indonesia; Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA. Electronic address: [email protected].
• 8 Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Tropical Disease Centre, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Department of Clinical Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia. Electronic address: [email protected].
• 9 Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, MI 48109, USA. Electronic address: [email protected].
• 10 Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Tropical Disease Centre, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia. Electronic address: [email protected].
• PMID: 32340833
• PMCID: PMC7142680
• DOI: 10.1016/j.jiph.2020.03.019

In early December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan City, Hubei Province, China. On January 30, 2020 the World Health Organization declared the outbreak as a Public Health Emergency of International Concern. As of February 14, 2020, 49,053 laboratory-confirmed and 1,381 deaths have been reported globally. Perceived risk of acquiring disease has led many governments to institute a variety of control measures. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In this literature review, the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and preventions strategies are all reviewed.

Keywords: 2019-nCoV; COVID-19; Novel coronavirus; Outbreak; SARS-CoV-2.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Publication types

• Betacoronavirus
• Clinical Trials as Topic
• Coronavirus Infections* / epidemiology
• Coronavirus Infections* / immunology
• Coronavirus Infections* / therapy
• Coronavirus Infections* / virology
• Disease Outbreaks* / prevention & control
• Pneumonia, Viral* / epidemiology
• Pneumonia, Viral* / immunology
• Pneumonia, Viral* / therapy
• Pneumonia, Viral* / virology

Writing a dissertation during the pandemic

Polish student weronika denes shares some tips for other students studying remotely on how she wrote her dissertation during the pandemic.

Weronika Denes

Being in lockdown has been a difficult situation for everyone, however I have found it additionally difficult because I have also had to complete a dissertation project. Like many other students, I found myself in a new place where I needed to handle both the Covid-19 pandemic and university stress.

This is why it is vital to talk about the well-being of students, especially those in their final year who are writing up their dissertation.

Join the THE Student community and unlock free benefits

Writing a dissertation is a challenging task, whether there is a pandemic or not. It requires a lot of time and precision.

Therefore, it is important to continue to ask for help from university staff any time you get stuck during the process. They will be able to help you talk through your ideas and provide guidance on writing your dissertation. Make use of office hours and book in regular meetings with your dissertation supervisor to ensure you stay connected. 

Create a study plan with your supervisors for how you will structure your working hours. Take some time each week to map out when you will write and when you will do research. Having a clear plan, with small steps and tasks to complete each day, will make your dissertation feel less daunting. Ensure that you schedule regular breaks too. 

If you are struggling with your physical or mental well-being, it is  important to remember that your university will have well-being advisors you can get in touch with. You do not have to feel alone through this and a call or email to a specialist will help you manage the process.

Producing a dissertation requires a lot of energy so it also important to include some healthy habits in your routine to help you stay positive and motivated. For me, journalling has been an excellent way of relaxing. You can write down your everyday small goals or things you are grateful for. Or you can write down your feelings and frustrations as a way to process them. 

Other ways to manage stress include talking to friends, going for walks and spending some time on hobbies you enjoy. Don’t forget that Rome wasn’t built in a day so take your time when writing your dissertation. 

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Methodologies for COVID-19 research and data analysis

This collection has closed and is no longer accepting new submissions. 

This  BMC Medical Research Methodology collection of articles has not been sponsored and articles undergo the journal’s standard peer-review process overseen by our Guest Editors, Prof. Dr. Livia Puljak (Catholic University of Croatia in Zagreb, Croatia) and Prof. Dr. Martin Wolkewitz (University of Freiburg, Germany).  

Delays in reporting and publishing trial results during pandemics: cross sectional analysis of 2009 H1N1, 2014 Ebola, and 2016 Zika clinical trials

Pandemic events often trigger a surge of clinical trial activity aimed at rapidly evaluating therapeutic or preventative interventions. Ensuring rapid public access to the complete and unbiased trial record is...

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Open science saves lives: lessons from the COVID-19 pandemic

In the last decade Open Science principles have been successfully advocated for and are being slowly adopted in different research communities. In response to the COVID-19 pandemic many publishers and research...

Clinical research activities during COVID-19: the point of view of a promoter of academic clinical trials

During the COVID-19 emergency, IRST IRCCS, an Italian cancer research institute and promoter of no profit clinical studies, adapted its activities and procedures as per European and national guidelines to main...

Instruments to measure fear of COVID-19: a diagnostic systematic review

The COVID-19 pandemic has become a source of fear across the world. Measuring the level or significance of fear in different populations may help identify populations and areas in need of public health and edu...

A risk assessment tool for resumption of research activities during the COVID-19 pandemic for field trials in low resource settings

The spread of severe acute respiratory syndrome coronavirus-2 has suspended many non-COVID-19 related research activities. Where restarting research activities is permitted, investigators need to evaluate the ...

Outbreaks of publications about emerging infectious diseases: the case of SARS-CoV-2 and Zika virus

Outbreaks of infectious diseases generate outbreaks of scientific evidence. In 2016 epidemics of Zika virus emerged, and in 2020, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a p...

Analysis of clinical and methodological characteristics of early COVID-19 treatment clinical trials: so much work, so many lost opportunities

The COVID-19 pandemic continues to rage on, and clinical research has been promoted worldwide. We aimed to assess the clinical and methodological characteristics of treatment clinical trials that have been set...

The unintended consequences of COVID-19 mitigation measures matter: practical guidance for investigating them

COVID-19 has led to the adoption of unprecedented mitigation measures which could trigger many unintended consequences. These unintended consequences can be far-reaching and just as important as the intended o...

Short-term real-time prediction of total number of reported COVID-19 cases and deaths in South Africa: a data driven approach

The rising burden of the ongoing COVID-19 epidemic in South Africa has motivated the application of modeling strategies to predict the COVID-19 cases and deaths. Reliable and accurate short and long-term forec...

Incorporating and addressing testing bias within estimates of epidemic dynamics for SARS-CoV-2

The disease burden of SARS-CoV-2 as measured by tests from various localities, and at different time points present varying estimates of infection and fatality rates. Models based on these acquired data may su...

COVID-19-related medical research: a meta-research and critical appraisal

Since the start of the COVID-19 outbreak, a large number of COVID-19-related papers have been published. However, concerns about the risk of expedited science have been raised. We aimed at reviewing and catego...

Use of out-of-hospital cardiac arrest registries to assess COVID-19 home mortality

In most countries, the official statistics for the coronavirus disease 2019 (COVID-19) take account of in-hospital deaths but not those that occur at home. The study’s objective was to introduce a methodology ...

Strengthening policy coding methodologies to improve COVID-19 disease modeling and policy responses: a proposed coding framework and recommendations

In recent months, multiple efforts have sought to characterize COVID-19 social distancing policy responses. These efforts have used various coding frameworks, but many have relied on coding methodologies that ...

Predictive accuracy of a hierarchical logistic model of cumulative SARS-CoV-2 case growth until May 2020

Infectious disease predictions models, including virtually all epidemiological models describing the spread of the SARS-CoV-2 pandemic, are rarely evaluated empirically. The aim of the present study was to inv...

Alternative graphical displays for the monitoring of epidemic outbreaks, with application to COVID-19 mortality

Classic epidemic curves – counts of daily events or cumulative events over time –emphasise temporal changes in the growth or size of epidemic outbreaks. Like any graph, these curves have limitations: they are ...

The Correction to this article has been published in BMC Medical Research Methodology 2020 20 :265

COVID19-world: a shiny application to perform comprehensive country-specific data visualization for SARS-CoV-2 epidemic

Data analysis and visualization is an essential tool for exploring and communicating findings in medical research, especially in epidemiological surveillance.

Social network analysis methods for exploring SARS-CoV-2 contact tracing data

Contact tracing data of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is used to estimate basic epidemiological parameters. Contact tracing data could also be potentially used for assessin...

Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children

COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clin...

Statistical design of Phase II/III clinical trials for testing therapeutic interventions in COVID-19 patients

Because of unknown features of the COVID-19 and the complexity of the population affected, standard clinical trial designs on treatments may not be optimal in such patients. We propose two independent clinical...

Rapid establishment of a COVID-19 perinatal biorepository: early lessons from the first 100 women enrolled

Collection of biospecimens is a critical first step to understanding the impact of COVID-19 on pregnant women and newborns - vulnerable populations that are challenging to enroll and at risk of exclusion from ...

Disease progression of cancer patients during COVID-19 pandemic: a comprehensive analytical strategy by time-dependent modelling

As the whole world is experiencing the cascading effect of a new pandemic, almost every aspect of modern life has been disrupted. Because of health emergencies during this period, widespread fear has resulted ...

A four-step strategy for handling missing outcome data in randomised trials affected by a pandemic

The coronavirus pandemic (Covid-19) presents a variety of challenges for ongoing clinical trials, including an inevitably higher rate of missing outcome data, with new and non-standard reasons for missingness....

Joint analysis of duration of ventilation, length of intensive care, and mortality of COVID-19 patients: a multistate approach

The clinical progress of patients hospitalized due to COVID-19 is often associated with severe pneumonia which may require intensive care, invasive ventilation, or extracorporeal membrane oxygenation (ECMO). T...

COVID-19 prevalence estimation by random sampling in population - optimal sample pooling under varying assumptions about true prevalence

The number of confirmed COVID-19 cases divided by population size is used as a coarse measurement for the burden of disease in a population. However, this fraction depends heavily on the sampling intensity and...

Coronavirus disease 2019 (COVID-19): an evidence map of medical literature

Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of June 2020, gaps and longitudinal trends in the COVID-19 medical litera...

Group testing performance evaluation for SARS-CoV-2 massive scale screening and testing

The capacity of the current molecular testing convention does not allow high-throughput and community level scans of COVID-19 infections. The diameter in the current paradigm of shallow tracing is unlikely to ...

Research methodology and characteristics of journal articles with original data, preprint articles and registered clinical trial protocols about COVID-19

The research community reacted rapidly to the emergence of COVID-19. We aimed to assess characteristics of journal articles, preprint articles, and registered trial protocols about COVID-19 and its causal agen...

Using online technologies to improve diversity and inclusion in cognitive interviews with young people

We aimed to assess the feasibility of using multiple technologies to recruit and conduct cognitive interviews among young people across the United States to test items measuring sexual and reproductive empower...

Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: case study of COVID-19 in Alberta, Canada and Philadelphia, USA

Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of...

The semi-automation of title and abstract screening: a retrospective exploration of ways to leverage Abstrackr’s relevance predictions in systematic and rapid reviews

We investigated the feasibility of using a machine learning tool’s relevance predictions to expedite title and abstract screening.

Social media as a recruitment platform for a nationwide online survey of COVID-19 knowledge, beliefs, and practices in the United States: methodology and feasibility analysis

The COVID-19 pandemic has evolved into one of the most impactful health crises in modern history, compelling researchers to explore innovative ways to efficiently collect public health data in a timely manner....

Current methods for development of rapid reviews about diagnostic tests: an international survey

Rapid reviews (RRs) have emerged as an efficient alternative to time-consuming systematic reviews—they can help meet the demand for accelerated evidence synthesis to inform decision-making in healthcare. The s...

Methodological challenges of analysing COVID-19 data during the pandemic