|
 
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| INVITED REVIEW ARTICLE |
|
| Year : 2020 | Volume
: 4
| Issue : 2 | Page : 52-57 |
|
Coronavirus disease 2019: The story so far
Ali S Omrani
Communicable Diseases Center, Hamad Medical Corporation; Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar
| Date of Submission | 24-Apr-2020 |
| Date of Acceptance | 25-Apr-2020 |
| Date of Web Publication | 22-May-2020 |
Correspondence Address:
Dr. Ali S Omrani
Communicable Diseases Center, Hamad Medical Corporation, PO Box 3050, Doha
Qatar
 Source of Support: None, Conflict of Interest: None  | 4 |
DOI: 10.4103/LJMS.LJMS_33_20
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) emerged in China in late 2019 and became a global pandemic by March 2020. SARS-CoV-2 is a highly transmissible virus that causes a clinical illness known as Coronavirus Disease 2019. The clinical spectrum ranges from mild respiratory and generalized symptoms to severe pneumonia with multiple organ failure. Overall mortality is high in older patients and those with comorbidities such as obesity and cardiovascular disease. Diagnosis is usually confirmed by polymerase chain reaction on upper or lower airway samples. Clinical management is largely supportive; no specific therapeutic options are currently available. Public health interventions have thus far been centered around social distancing, large-scale testing, and isolation. An unprecedent global effort has been mounted for the rapid development of effective SARS-CoV-2 vaccines. Until such time, further waves of SARS-CoV-2 are likely, if the restrictive control measures are removed.
Keywords: Coronavirus, coronavirus disease 2019, severe acute respiratory syndrome coronavirus-2, viral pneumonia
How to cite this article:
Omrani AS. Coronavirus disease 2019: The story so far. Libyan J Med Sci 2020;4:52-7 |
| Introduction | |  |
Public health officials in Hubei Province in China became aware of a cluster of undiagnosed pneumonia in Wuhan city in November and December 2019. In January 2020, the cause was identified as a novel betacoronavirus that had most probably emerged in a wet market in the city.[1],[2] The virus was subsequently named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and the disease it caused as Coronavirus Disease 2019 (COVID-19).[3] Herein is a summary of salient virologic, epidemiologic, and clinical features of COVID-19.
| Virology | | |
SARS-CoV-2 is genetically distinct from previously known human betacoronaviruses, including SARS-CoV and MERS-CoV.[4],[5],[6] Although not confirmed yet, it is likely that SARS-CoV-2 originated in bats before it was transmitted to humans directly or through an intermediate host.[4],[7] Like other human coronaviruses, SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus. Its genome encodes four major structural proteins: the spike (S) protein, nucleocapsid (N) protein, membrane (M) protein, and the envelope (E) protein, all of which are essential for its structure.[8] Viral attachment and entry into its host cells are mediated by a cellular Transmembrane Serine Protease (TMPRSS2) that primes the S1 unit of the viral S protein to facilitate binding to its cellular receptor, angiotensin-converting enzyme 2.[9]
| Transmission and Epidemiology | | |
The incubation period is typically 4–5 days but can be anywhere between 2 and 14 days.[2],[10],[11] SARS-CoV-2 is thought to be primarily transmissible via droplets and fomites.[12] Viable SARS-CoV-2 has been recovered from multiple surfaces around infected patients, including from furniture and a toilet seat.[13] Under certain conditions, SARS-CoV-2 may survive in the environment for extended periods. Viable virus was recovered after >20 h from copper and cardboard surfaces and nearly 80 h from stainless steel and plastic surfaces.[14] Although viable SARS-CoV-2 has also been recovered from aerosols, airborne transmissibility remains uncertain.[12],[14] Health-care workers, especially those with overwhelming workloads or in settings where personal protective equipment supply is limited, are at significant risk of SARS-CoV-2 infection. In some reports, health-care staff members constituted up to 10% of all COVID-19 patients.[15],[16],[17],[18],[19]
SARS-CoV-2 is highly transmissible among humans, including documented incidents of transmission from individuals with very mild or no symptoms.[15],[20],[21],[22],[23] The outbreak rapidly expanded across China and nearby countries.[15],[17],[21],[24] Travel facilitated the spread of SARS-CoV-2 to all continents, with numerous countries reporting self-sustained local transmission.[25],[26] On March 11, 2020, the World Health Organization (WHO) declared a SARS-CoV-2 pandemic.[27] By early March 2020, the rate of new SARS-CoV-2 infections declined substantially in China but continued to rise in Western Europe and North America.[28],[29] The exponential transmission potential of SARS-CoV-2 is self-evident. On January 21, 2020, the WHO reported a global total of 314 COVID-19 cases and 6 deaths.[30] Number of cases increased to nearly 78 thousands and more than 2 thousand deaths by February 22, 2020, and to more than 290 thousands and nearly 13 thousand deaths by March 22, 2020.[31],[32] By April 22, 2020, the total number of cases was a staggering 2.5 million, with approximately 170 thousand deaths.[33] The largest numbers of COVID-19 deaths have been reported from the United States of America, Italy, Spain, France, and the United Kingdom. However, the numbers are currently increasing at alarming rates in India, Latin America, and Africa as well.[32],[33]
| Clinical Features and Outcomes | | |
In the majority of patients, COVID-19 is a mild illness characterized by pharyngeal pain, dry cough, fatigue, and fever.[2],[34],[35],[36],[37],[38] A small proportion of patients may experience gastrointestinal symptoms, including nausea, vomiting, and diarrhea.[16],[34],[37],[38] Common laboratory abnormalities include lymphopenia, thrombocytopenia, and high CRP.[16],[34],[36],[37],[38] Plain X-rays are abnormal in approximately 60% of patients, while computed tomography scans show ground-glass opacities and patchy infiltrates in >85% of cases.[37],[39] Moderate-to-severe pneumonia occurs in 15%–20% of patients and is usually associated with shortness of breath and more extensive radiological infiltrates.[34],[37],[38] Around 5%–10% of COVID-19 patients may develop severe pneumonia with hypoxia, acute respiratory distress syndrome, and multi-organ failure. Such patients require admission to an intensive care unit for critical support and mechanical ventilation.[34],[37],[38],[40],[41],[42] Interestingly, severe COVID-19 is associated with excessive production of pro-inflammatory cytokines, akin to cytokine storm syndrome.[16],[38],[43] Moreover, autopsy examination of lungs from COVID-19 patients showed extensive alveolar edema, proteinaceous exudate, and patchy inflammatory cellular infiltration.[44],[45] It has, therefore, been suggested that the pulmonary pathology associated with severe COVID-19 is, in large part, secondary to a dysregulated host immune response.[46],[47]
Children constitute only a small proportion of all COVID-19 patients, and their illness is typically mild or asymptomatic.[48],[49] On the other hand, COVID-19 is more likely to be severe in those with multiple comorbidities.[25],[42] Older age, especially those >70 years, systemic hypertension, obesity, and diabetes mellitus, are particularly important risk factors for severe COVID-19 and mortality.[26],[34],[41],[42],[50],[51]
Pregnancy does not seem to be associated with a higher risk of severe COVID-19.[52],[53],[54] In fact, mild and even asymptomatic COVID-19 has been reported in pregnant women in their third trimester and among those routinely screened at delivery.[52],[54] While some studies did not find evidence of vertical transmission of SARS-CoV-2,[53],[54],[55] others reported high levels of SARS-CoV-2 IgM with elevated blood interleukin (IL)-6 levels in neonates born to mothers with COVID-19.[56],[57] One report described three symptomatic neonates with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection.[58]
The reported overall case fatality rates (CFR) associated with COVID-19 range from 0.9% in South Korea and 2.3% in China, to as high as 7.2% in Italy.[15],[34],[50] However, the age composition of COVID-19 patients reported from different countries and the prevalence of underlying comorbidities are probably important drivers of the wide variations in CFRs from one geographic setting to another.[42],[50]
| Laboratory Diagnosis | | |
The diagnosis of COVID-19 can be confirmed by the detection of SARS-CoV-2 using real-time PCR (RT-PCR) assays of upper or lower respiratory tract samples.[59] The highest RT-PCR sensitivity rates are obtained from bronchoalveolar lavage fluid specimens (93%), followed by sputum (72%), nasal swabs (63%), bronchial brush biopsies (46%), and pharyngeal swabs (32%).[60] SARS-CoV-2 has also be detected in saliva specimens (11 out of 12, 92%), stool (44 out of 153, 29%), and blood (3 out of 307, 1%).[60],[61] SARS-CoV-2 viral load in upper airway specimens is highest during the first week after onset of COVID-19 symptoms and declines over time.[62],[63],[64] High SARS-CoV-2 viral loads have been detected in nasal and pharyngeal samples from asymptomatic or mildly symptomatic individuals, supporting the view that such individuals play a an important role in sustaining SARS-CoV-2 transmission.[63],[65],[66] In the majority of patients, viral shedding in the upper airways ceases within 14 days of symptom onset. However, the virus may continue to detected for several weeks, especially in patients with severe COVID-19.[17],[62],[63],[67] It is important to emphasize that all reports thus far of late detection of SARS-CoV-2 in various sample types are based on RT-PCR assays, not viral cultures. It is, therefore, not clear to what extent, if any, does prolonged viral shedding contribute to COVID-19 epidemiology.[17],[68]
Most health-care authorities de-isolate COVID-19 patients if two consecutive upper airway specimens, taken ≥24 h apart, are negative for SARS-CoV-2, in addition to the resolution of signs and symptoms of infection in those who were symptomatic. In addition, the Italian Ministry of Health criteria for virus clearance is documented appearance of SARS-CoV-2 specific IgG.[68] SARS-CoV-2 serological assays could provide a better understanding of the extent of asymptomatic or mildly symptomatic infections that may have gone undetected with molecular diagnostic methods.[68],[69] In one study, sera from 23 patients with laboratory-confirmed COVID-19 were tested by enzyme immuno assay for SARS-CoV-2 nucleoprotein (NP) and spike protein receptor-binding domain (RBD) IgM and IgG. By 14 days from symptoms onset, the rate of detectable antibodies was anti-NP IgM 88%, anti-NP IgG 94%, anti-RBD IgM 94%, and anti-RBD IgG 100%.[62] It is nevertheless important to emphasize that it is unknown at present if the presence of SARS-CoV-2 antibodies can be considered as reliable evidence of immunity against re-infection. Moreover, there are currently no validated, commercially available serological assays for use in routine diagnostic laboratories.[70]
| Clinical Management | | |
The management of patients with COVID-19 is principally supportive.[71],[72],[73] Key elements are the meticulous implementation of infection prevention and control precautions and symptom relief using antipyretics and simple pain killers.[74] Those with severe disease usually require supplemental oxygen, judicious fluid balance, circulatory support, and antibiotics for secondary infections.[72],[74]
There are currently no approved therapeutic options for COVID-19, but a number of potentially useful antiviral agents are in clinical development.[75],[76] Among the promising options is remdesivir, a nucleotide analog inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase.[77] Early data from observational, noncomparative studies appear encouraging, but results from ongoing randomized trials will provide a more reliable assessment of its safety and efficacy in the treatment of patients with COVID-19.[78],[79],[80]
Lopinavir-ritonavir, an HIV protease inhibitor, is known to havein vitro activity against coronaviruses, including SARS, MERS-CoV, and SARS-CoV-2.[81] However, a recent randomized clinical trial did not show benefit with lopinavir-ritonavir in comparison with standard care in terms of viral clearance, time to clinical improvement, or all-cause mortality. Furthermore, adverse event-related discontinuation was seen in 14% of lopinavir-ritonavir patients.[82] Another potential therapeutic approach is the use of protease inhibitors such as nafamostat mesylate to inhibit TMPRSS2-mediated SARS-CoV-2 viral attachment and fusion.[83]
Chloroquine, and the chemically related hydroxychloroquine, possessin vitro activity against SARS-CoV-2.[77],[81] Results from small studies with considerable methodological flaws are conflicting.[72],[73],[76] Both agents are associated with potentially serious cardiotoxicity, especially QT prolongation.[76] Therefore, current guidelines encourage that these agents are used only within clinical trials and with very careful monitoring.[71-73,84]
The well-characterized cytokine-mediated severe manifestations of COVID-19 led to an interest in immune-modulating agents as potential adjunctive therapies.[46],[47] IL-6 inhibitors (e.g.; tocilizumab and sarilumab), Janus kinase inhibitors (e.g.; tofacitinib and ruxolitinib), tumor necrosis factor inhibitors (e.g.; adalimumab) and antiangiogenics (e.g.; bevacizumab) are all currently undergoing evaluation in clinical trials to assess their role in the management of patients with severe COVID-19.[80]
Finally, there has been immense interest in the potential use of convalescent plasma from recovered COVID-19 patients for the treatment of those with severe SARS-CoV-2 infection.[85] As mentioned above, it is not yet clear if and when those who recover from COVID-19 develop neutralizing SARS-CoV-2 antibodies, or whether such antibodies are produced in adequate concentrations to enable useful deployment of convalescent plasma as therapy.[86] The published literature is currently limited to small case series with some suggestions of clinical response.[87],[88] At present, convalescent plasma can only be considered investigational therapy for COVID-19.
| How Will it End? | | |
The public health efforts to control SARS-CoV-2 have included various combinations of travel restrictions, social distancing interventions, proactive testing, and isolation of all confirmed and suspected cases and comprehensive contact tracing and screening, with varying degrees of success from one country to another.[89],[90],[91] There is, however, constant concern that relaxation of the more strict control measures could result in further waves of SARS-CoV-2 infections, potentially more serious than the initial epidemic.[92] An unprecedented effort is currently underway to develop an effective SARS-CoV-2 vaccine, with some candidates already in phase I human studies.[93] It may well be that the pandemic will not be truly controlled until effective vaccines become available, and a majority of the global population has become immune.[94] Bleak, as this forecast might seem, this virus has proven itself to be a challenge of historic magnitude. It will take a historic effort to develop and disseminate effective vaccination in record times to counter.[95]
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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