- Department of Neurosurgery, Bezmialem Vakif University Medical School, Istanbul, Turkey,
- Department of Oncology, North Middlesex University Hospital, London, United Kingdom,
- Department of Oncology, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, United Kingdom.
Department of Neurosurgery, Bezmialem Vakif University Medical School, Istanbul, Turkey,
DOI:10.25259/SNI_191_2020Copyright: © 2020 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Georges Sinclair1,2, Philippa Johnstone3, Mustafa Aziz Hatiboglu1. Considerations for future novel human-infecting coronavirus outbreaks. 29-Aug-2020;11:260
How to cite this URL: Georges Sinclair1,2, Philippa Johnstone3, Mustafa Aziz Hatiboglu1. Considerations for future novel human-infecting coronavirus outbreaks. 29-Aug-2020;11:260. Available from: https://surgicalneurologyint.com/surgicalint-articles/10234/
Up until, June 13, 2020, >7,500,000 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and >400,000 deaths, across 216 countries, have been confirmed by the World Health Organization (WHO). With reference to the two previous beta-CoV outbreaks (SARS-CoV and middle east respiratory syndrome [MERS]), this paper examines the pathophysiological and clinical similarities seen across all three CoVs, with a special interest in the neuroinvasive capability and subsequent consequences for patients with primary or metastatic brain tumors. More widely, we examine the lessons learned from the management of such large-scale crises in the past, specifically looking at the South Korean experience of MERS and the subsequent shift in disaster management response to SARS-CoV-2, based on prior knowledge gained. We assess the strategies with which infection prevention and control can, or perhaps should, be implemented to best contain the spread of such viruses in the event of a further likely outbreak in the future.
Keywords: Infection control and prevention, Middle East respiratory syndrome, Neuroinvasion, Severe acute respiratory syndrome coronavirus 2, Severe acute respiratory syndrome coronavirus
Up until, June 13, 2020, >7,500,000 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and >400,000 deaths, across 216 countries, have been confirmed by the World Health Organization (WHO).[
While SARS-CoV-2 associated disease (also known as coronavirus disease or COVID 19) continued to spreading in most continents, East-Asian countries were the first to bring hope, with reports of small numbers of confirmed cases and low fatality rate 3–4 months following the outbreak in China.[
The first human infecting CoV presenting with respiratory symptoms was reported in the Lancet as early as 1966 by Gosain et al.[
1. The SARS-CoV
Emanating from an animal market in Guangdong (China), the virus spread to 37 countries, infecting >8000 persons; 774 casualties were reported between 2002 and 2003, setting the mortality rate at around 10%.[
2. The MERS-CoV
Initially identified in Saudi Arabia in 2012, this beta-CoV managed to spread to 27 countries.[
3. The SARS-CoV-2
With its epicenter in the city of Wuhan (China), this novel form of human-infecting betaCoV was first reported in late December 2019.[
Although SARS-CoV-2 appears to affect male and female patients equally in numbers, the fatality rate is seemingly higher in men, possibly due to a difference in immunological responses surrogate to gender itself and gender-associated social behavior, such as smoking.[
With an incubation time stretching from 1 to 14 days (commonly 3–7 days), the clinical management of SARS- Cov-2 remains structured on symptomatic care, dynamically hinging on the severity, and complexity of the clinical evolution. Non-neurologic symptoms from SARS-CoV-2 are often diffuse; pyrexia, shivers, fatigue, loss appetite, nasal congestion, sneezing, sore throat, cough, shortness of breath, nausea, vomiting, diarrhea, coagulopathies, skin rashes, and myalgia have been reported.[
MAS, also known as secondary hemophagocytic lymphohistiocytosis, has been commonly linked to viral infections, autoimmune disorders, and malignancy; although the pathogenesis is still poorly understood, it is thought that the cytokine storm results in activation of macrophages, causing hemophagocytosis and contributing to disseminated intravascular coagulation, as well as contributing to multi- organ dysfunction.[
Finally, the differential diagnosis can include bacterial infections (e.g., L. pneumophila, and S. pneumoniae), other viral infections (rhinovirus, adenovirus, influenza, parainfluenza, human metapneumovirus, and respiratory syncytial virus) and other non-infectious etiology, such as malignancies, pulmonary embolism, vasculitis, and dermatomyositis.[
Ramifications of neurotropism
Of interest, neurological symptoms such as headaches, nausea, anosmia, loss of taste, acute cerebrovascular complications, diplopia, ataxia, seizures, drowsiness, consciousness deficit, depression, anxiety, delirium, posttraumatic stress, and cortisone-free subthreshold of mania have also been reported.[
Therefore, in view of the genomic/phylogenetic, pathophysiological, and clinical traits shared among the above- mentioned human-infecting beta-CoVs, we hypothesize that, until proven otherwise, SARS-CoV-2 may well utilize similar mechanisms as those employed by MERS and SARS-CoV to effectively invade host neural cells and safely replicate in the CNS, ultimately leading to peripheral and central neurologic injury as well as extracranial symptomatology, including severe respiratory failure. Furthermore, considering the increased risk of COVID-19 in cancer patients,[
Unfortunately, as pointed out above, there are no specific antiviral treatments or vaccines against SARS-CoV-2 at present; symptomatic care remains the foundation of hospital management. Oxygen therapy, continuous positive airways pressure (CPAP) support, and mechanical ventilation are effective at different stages of the infection, hinging on the degree of severity of respiratory problems; thorough guidelines and indications have been developed in the context of SARS-CoV-2-associated ARDS and can be found in more detail elsewhere.[
Several SARS-CoV-2 trials are in pipeline across the US, Europe, and Asia, covering the fields of epidemiology, detection, treatment, and vaccination.[
Infection prevention and control (IPC) measures remain the cornerstone of SARS-Cov-2 management in many countries;[
Trying to understand the reasons as to how we failed to avoid the current situation remains complex from a geopolitical and world economics perspective. However, in the face of this type of outbreak, medical professionals across different disciplines have recognized the need for early measures such as (i) the systematic distribution and time-effective use of respiratory masks (e.g., FFP3 and N95 masks) and other personal protective equipment (PPE) for the directly exposed health-care staff, (ii) the sustainability of the medical supply chain, and (iii) the supply of equipment allowing non- invasive and invasive ventilation (such as oxygen supply, CPAP machines, and mechanical ventilators).
Furthermore, in view of the basic reproduction number of SARS-CoV-2 combined with factors such an aging population, restricted hospital resources (particularly in some Emergency departments and Intensive Care Units), and lack of specific anti-SARS-CoV-2 treatment (or vaccine), medical professionals stressed from the early stages of COVID-19, the need to bring the effective reproduction number <1 through unrestricted, “targeted” testing of all symptomatic cases. The benefits of upfront testing using the reverse transcriptase- polymerase chain reaction (RT-PCR) test on collected saliva and mucus samples have been widely documented;[
Following the outbreak of SARS-CoV in China, South Korea implemented a series of restrictive measures, which ultimately led to three confirmed cases of SARS-CoV with no fatalities. Already then, the WHO acknowledged South Korea as a model nation for its effective fight against SARS-CoV.[
From an early stage, experts identified a series of dysfunctions in terms of disaster management and communication capability; experts also recognized the importance of a short window between the identification of cases and the activation of control measures to restrain the spread of MERS or other agents with similar behavioral patterns.[
On January 20, 2020, the first individual with SARS- CoV-2 was identified in South Korea; the number of cases rapidly increased during the following few weeks, with its epicenter in Daegu.[
In terms of governmental action, after confirming their first case, the South Korean authorities escalated the crisis level from blue to yellow, establishing a Korean CDC COVID-19 rapid response team. A week later (January 27), the crisis level was further elevated to orange, and the Ministry of Health and Welfare Central Accident Management Headquarters for the COVID-19 was established.[
In addition to the above, the benefits of incorporating cutting edge technology to public control measures cannot be underestimated; for example, from an early stage, the South Korean Ministry of Interior and Safety developed a smartphone application (app) to allow those infected or in isolation to keep in contact with case workers with positive results, allowing local authorities to keep track of “superspreaders,” among others. Another app, the “Co100,” was also rapidly developed from governmental data to inform users when they come within 100 m of a site visited by someone infected. Alike the latter mentioned apps, a third app was produced to specifically inform citizens of possible shortage and supply of masks at specific sites such as pharmacies.
Finally, despite South Korea’s proximity to China and not launching a total “lockdown” as in the case of many European countries, the WHO and South Korean authorities have reported a sustained, stable number of infected cases with low fatality cases following the escalation and implementation of these measures (12,051 confirmed cases and 277 deaths up to June 13, despite a population >50,000,000 ); similar results in Taiwan, Japan, Singapore, and Germany further support an approach comparable to that seen in South Korea.[
This is the third outbreak by a novel human-infecting beta- CoVs in 18 years, with worldwide consequences; this should be taken as sign of warning, as it unlikely to be the last. SARS- CoV, MERS, and SARS-CoV-2 all share common and complex clinical, genomic, and pathophysiologic characteristics with potentially lethal outcomes. Of these three aforementioned CoVs, SARS-CoV-2 has the highest mortality rate due to an inherent high R0 value and an ability to master both animal- to-animal and animal-to-human transmission. Due to several factors, not least including a lack of current targeted treatment, infection control, and preventive measures remain the cornerstone of the management of these types of agents. As proven by the South Korean model, prompt, large-scale testing of suspected individuals, contact tracing and isolation are critical steps in early crisis management aiming to avoid irrational ‘full’ lockdown measures with ensuing detrimental outcomes in the short- and long term. As such, transparent international cooperation between governments and health- institutions based on strict guidelines and obligatory crisis- oriented health-care resources ought to be implemented to prevent further global crises related to novel infectious agents.[
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