COVID-19 OUTBREAK; A Deadly Plague or a Panic Pandemic?

Acknowledgements Social Policy Officer & Policy Paper Author: Justin Cauchi President: James W. Caruana S-Cubed Administrative Board: Gianni Ciappara, Rachel Attard Chase, Rebekah Caruana and Francesca Camilleri S-Cubed Executive Board: Owen Cuschieri, Matteo Giorgino, Noelle Micallef, Stephanie Buttigieg and Martina Busuttil

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Table of Contents Acknowledgements ............................................................................................................................. 1 Introduction ........................................................................................................................................ 3 Origins of the Epidemic and Identification of the Novel Virus ............................................................ 4 Infectiousness of SARS-CoV-2 ........................................................................................................... 5 Symptoms and Lethality ..................................................................................................................... 6 Containing and Avoiding the Virus ..................................................................................................... 8 Conclusion ........................................................................................................................................ 10 References ........................................................................................................................................ 11

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Introduction The start of the new decade has been dominated by fear and worry over an epidemic of an influenzalike disease caused by a novel virus; named SARS-CoV-2. The epidemic originated in Wuhan, Hubei province within mainland China in December of 2019. By the date of writing of this paper, the virus had spread to 67 countries across all continents except Antarctica, infected a total of 87,470 people.

2,990 people died as a result of contracting this disease, called COVID-19, while 42,670 had recovered, leaving 44,800 still known to be infected (Dong et al, 2020).

The global media coverage of this outbreak has been extensive, increasing especially when the World Health Organisation (WHO) raised concern about the epidemic and the disease was exported outside of mainland China. The general public has so far been overwhelmed with a flood of information, most of which is quite often contradictory. Typically the two extremes of the type of information provided via the media are either that the disease is very deadly and dangerous, evoking fear and panic, encouraging stocking of food and public anxiety; or that the disease is no worse than the common flu and should not be of great national or global concern. This lack of concordant public information could have dire consequences in the event of an outbreak within the country as the public which chose to believe one extreme will not conform with the directives of the local authorities which may be in line with the other extreme of information type.

The aim of this paper, thus, is to analyse the scientific literature published so far on the outbreak and disease and therefore help the general public formulate a general understanding of the outbreak based on scientific knowledge.

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Origins of the Epidemic and Identification of the Novel Virus The outbreak originated in the city of Wuhan, located within the province of Hubei inside mainland China in December of 2019. A cluster of cases of pneumonia of unknown etiology raised the alarm.

By 7th of January, 2020, the virus was successfully isolated and its genome sequenced via deep sequencing analysis of samples from affected individuals’ respiratory tracts (Xu et al, 2020). This identified the virus as a previously unknown virus from the Coronaviridae family; a family which includes other known human-infecting viruses such as SARS-CoV and MERS-CoV; both coronaviruses which have caused outbreaks in 2002 and 2012 respectively. More specifically, SARSCoV-2 is a betacoronavirus like SARS-CoV and MERS-CoV; and the phylogenetically closestrelated, known betacoronavirus at 96% genetic similarity is BatCoV RaTG13, which is a SARS-like virus restricted to bats (WHO-China Joint Mission, 2020)

Figure 1 – Phylogenetic analysis of SARS-CoV-2 (indicated as 2019-nCoV), showing relation to BAT-SL-CoV, SARS-CoV and MERSCoV (Source – WHO-China Joint Mission, 2020).

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While the zoonotic origins of the SARS-CoV-2 virus has been confirmed through epidemiological linkage of initial cases to the exposure to Huanan seafood market in Wuhan, known to trade wild animals, as well as discovering that bats are reservoirs of the virus strain, the common hypothesis that the first non-human to human transmission of the virus occurred through consumption of bat meat is highly unlikely. This is so since at the time of first non-human to human transmission, bats species in Wuhan were hibernating, and investigations showed that no bat meat was present at the market (Lu et al, 2020). Moreover, the bats are known to be reservoirs of the virus not intermediate hosts; that is, bats are not part of the lifecycle of the virus else it would replicate and affect the bats, classifying them as intermediate hosts not reservoir. It is more likely that an, as of yet, unidentified, terrestrial intermediate host/s sold at Huanan market caused the first infection of humans. Nonetheless, it is important to also note the virus is an RNA-virus; which are notorious for very fast mutation rates.

Therefore, it is still possible that a mutation event rendered the virus capable of replicating in humans after it had already been transmitted to the first human host.

Infectiousness of SARS-CoV-2 Due to its zoonotic origins, it was initially feared that the mode of transmission of the virus was through consumption of some infected meat. However, despite closure of Huanan market, the disease continued to spread and it was quickly determined that the principal mode of propagation of the infection was through contact with infected individuals. Detailed studies of the viral infection showed that the virus targets human respiratory epithelial cells via interaction between viral S protein and angiotensin-converting enzyme 2 receptor (Xu et al ,2020), making it very infectious to humans.

Transmission mechanism has been found to be predominantly through droplets and fomites in recent, close, prolonged exposure to infected individuals (WHO-China Joint Mission, 2020). There is no evidence that the virus is capable of airborne transmission (WHO-China Joint Mission, 2020).

The situation, so far as of 1st March 2020, is a cumulative total of 87,470 laboratory-confirmed cases of infected individuals, of which 66,907 occurred in Hubei province. Currently, there are 41,810 existing cases worldwide, of which 34,946 (83.58%) are contained in mainland China. In mainland China; 32,610 or 93.31% of those existing cases are restricted to Hubei province. This has been achieved through successful quarantine measures employed by Chinese authorities which have contained the spread mostly to Hubei province and aggressively quarantined and limited the spread of the viruses in other provinces. The result is that in all provinces excluding Hubei, the number of currently existing, confirmed cases is below 330. Outside of mainland China the virus has been exported to a total of 66 countries, with 87.21% of active cases outside of mainland China being concentrated in Korea (50.68%), Italy (15.34%), Iran (10.91%) and the Diamond Princess cruise ship (10.27%) (Dong et al, 2020).

Compared to other betacoronavirus outbreaks such as SARS-CoV in 2002 which infected 8000 people and MERS-CoV in 2012 which infected 1000 people it is very clear that SARS-CoV-2 is highly infectious and more difficult to contain despite intensive containment efforts. However, in China successful containment is very close to being achieved, as the most recent epidemiological curve (Figure 2) shows that the number of daily new cases in mainland China has decreased significantly.

There is still the possibility that this may simply be the first incubation period or first wave of the epidemic, but should the number of new cases remain low for over two weeks (median incubation period of the virus is 10.5 days), it would mean that China has successfully contained the virus (WHO-China Joint Mission 2020; Shi et al, 2020). It should be commented that similar data is not yet

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available for situations outside of mainland China, and therefore it is unknown how effective containment efforts are in countries where the virus is spreading especially fast such as Korea and Italy.

Figure 2 – Epidemiological curve of new daily laboratory-confirmed cases in mainland China between 2/12/2019 and 20/2/2020.

(Source – WHO-China Joint Mission, 2020).

Symptoms and Lethality So far most of the symptoms observed in patients with the disease are non-diagnostic and influenzalike. This is expected as most betacoronavirus typically induce such symptoms, as was observed during past SARS-CoV and MERS-CoV outbreaks. Based on the data provided from 55,924 laboratory confirmed cases as of 20th February 2020 (WHO-China Joint Mission, 2020), Figure 3 below shows the known symptoms caused by the viral infection and the percentage probability of developing such symptoms.

0.8 0.9 3.7 4.8 5.0

Hemoptysis Nasal Congestion Chills

11.4 13.6 13.9 14.8 18.6

Sore Throat Shortness of Breath

33.4 Fatigue

38.1 67.7

Fever

87.9 0

10

20

30

40

50

60

70

80

90

100

Probability of Developing Symptom (%) Figure 3 – Graph showing symptoms observed in 55,924 laboratory confirmed cases as of 20th February 2020 based on data provided in the WHO-China Joint Mission Report (WHO-China Joint Mission, 2020) and their respective percentage probability of being developed in an infected patient.

All known cases of laboratory-confirmed COVID-19 patients can be classified into three broad categories according to the symptoms they showed. The first category includes patients with mild to

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moderate symptoms. This cohort includes both non-pneumatic and pneumatic cases, and even in the latter the pneumonia observed is always mild. This category makes the largest proportion of observed cases (as of 20th February 2020 (WHO-China Joint Mission, 2020)) at 80%. The other cases are either classified as severe (13.8% of all laboratory-confirmed cases as of 20th February 2020) or critical (6.1% of all laboratory-confirmed cases as of 20th February 2020). In the case of the latter, cases are characterised by respiratory failure, septic shock and potentially single/multiple organ dysfunction/failure. A few cases of asymptomatic infections have been recorded, but the majority turned out to develop symptoms later on and actual cases of asymptomatic infection are very rare.

Thus, it is very unlikely that the virus is spreading in an undetected fashion; i.e. as an asymptomatic strain. This is further supported by the fact that the addition of tests for SARS-CoV-2 incorporated into influenza-like-illness (ILI) and severe acute respiratory infection (SARI) surveillance systems in China identified only a additional handful of cases of subclinical infections (WHO-China Joint Mission, 2020).

From the data collected so far, it seems individuals either above the age of 60 or with pre-existing, underlying conditions (namely hypertension, diabetes, cardiovascular disease, chronic respiratory disease and cancer) are most predisposed to a severe or critical infection. Children do not seem to be vulnerable to COVID-19. Of the 55,924 laboratory confirmed cases as of 20th February 2020, only 2.4% were patients under 19 years. Of these, yet again only 2.5% (2.4% x 2.5% = 0.06% of all known cases) contracted a severe infection and 0.2% (2.4% x 0.2% = 0.0048% of all known cases) were in critical condition (WHO-China Joint Mission, 2020).

With regards to fatalities, as of the date of writing of this paper, the number of deaths caused by the disease was at 2990. This equates to a crude fatality ratio (CFR) of 3.4%. Compared to the CRF calculated at the time of writing of the WHO-China Joint Mission Report in using data up to the 20th of February 2020, which was estimated at 3.8%, it appears that it is decreasing with time as the rate of recoveries is overtaking the rate of fatalities more and more. It is worth mentioning that using the CFR as a measure of the lethality of an epidemic during the epidemic itself is often misleading and inflated. This is so since such a ratio assumes that all infected individuals have identical chances of succumbing to the disease, when in fact some are more prone to fatal infections than others. For example the CFR calculating only for cases involving patients over 80 years of age is 21.9% while that for patients with pre-existing conditions is only at 1.4%. Moreover, there is great regional variation in the CFR values and there have been cases where the CFR values dropped from 17.3% to 0.7%. This is due to the fact that as more time progresses, health services in affected areas became more adept at treatment and care of patients as scientific knowledge of the disease increased.

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Figure 4 – Graph showing changes crude fatality ratio over the period from the 1 st January to the 20th of February in mainland China (Source – WHO-China Joint Mission, 2020).

What often happens in the media is that a lot of importance is given to the number of deaths while no attention is given to the number of full recoveries. As of the date of writing of this paper, compared to 2,990 deaths, there were 42,670 recoveries to date. That means that there were 14.27 times more recoveries than deaths as well as 48.78% of all recorded cases up to that point had recovered and were no longer ill. Even cases of severe infections have shown high recovery rates with only 13.4% being fatal (this last percentage is based on data collected up to 20th of February 2020).

Containing and Avoiding the Virus Whilst admittedly the virus infectiousness is very high and has allowed it to rapidly be exported from mainland China to numerous countries, containment efforts have been nonetheless relatively successful, especially in China. As previously discussed, spread of the disease in mainland China outside of Hubei province has been hindered significantly through effective surveillance and quarantine measures. So much so that in a large number of provinces which at some point exceeded the 1000 confirmed cases threshold are, as of the date of writing this paper, well on their way toward eradicating the disease, with active cases just over 100. All this shows that if countries adopt China’s quarantine methods and handling of the epidemic, they should be able to easily stop the further spread of the virus, both nationally and internationally. This goes especially to countries in which the number of infected patients is still rising rapidly such as South Korea, Italy and Iran. For as of yet uninfected countries, it is paramount that the necessary contingency plans based heavily on China’s experience are pre-emptively formulated so that, in the event of importation of the disease, rapid quarantine and containment of the virus could occur, hindering further propagation among the country’s populace.

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Figure 5 – Graph showing the number of new, confirmed cases daily and the proportion of new cases in and outside of China; clearly indicating that while spread in China has decreased, spread outside of China is increasing (Source – European Centre for Disease Prevention and Control, 2020).

In the report published by the WHO-China Joint Commission dated 24th February 2020, several guidelines are put forth for as of yet uninfected countries and the general public, among others. For uninfected countries such as Malta, the commission emphasises having what it describes as an “all-ofgovernment” and “all-of-society” contingency plan for virus importation. It is crucial that containment of the virus is of the uppermost priority for the entire government and not just leaving it as the responsibility of solely the Ministry for Health. Moreover, it is even more crucial that the general public understands the cruciality of following guidelines and complying with instructions from authorities to safeguard public health. More specifically on the guidelines for the authorities, the report also emphasises the need to include in the contingency plan extensive surveillance, rapid detection, response and isolation frameworks to immediately cordon off cluster to prevent community transmission. Of paramount importance is the part on surveillance. Not only is this crucial for detecting the first entry of the virus within the country but more importantly to cut human transmission chains once the virus has already been introduced. This has been the key to China’s successful containment efforts where large teams of epidemiologists tracked non-stop to trace close contacts of new cases and quarantine other infected individuals before any more community transmission could occur. Lastly, an aggressive information campaign and transparency in measures implemented is key to rooting out misinformation and ensuring the general public follows procedures to help curb the further spread of the virus within its communities.

With regards the general public; the commission advises that the general public ensures that they inform themselves from reliable sources on the virus and how to contain the disease. Moreover, it also encourages people to emphasize and adopt practices to improve personal hygiene and to collaborate extensively with authorities to limit the virus from spreading.

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Conclusion It is clear from the scientific literature so far that the virus is not as deadly as perhaps exaggerated by the media. Most cases are mild and there is no reason for panic and unnecessary anxiety. However, at the same time, it is important to keep in mind that while the majority of the general public is not at risk of dying from infection, there is still a minority for whom the virus could potentially be fatal. This minority includes the elderly and persons who are already suffering from other medical conditions, such as those who are immunodeficient, have some form of cancer or have serious respiratory or cardiovascular conditions. It is for the health of these minorities for which any worry is justified, and it is for the aim of shielding such individuals from the virus that it is crucial that the virus’s diffusion in both Malta and the rest of the world is hindered as much as possible. This will not only save lives, but prevent an economic shutdown and buy much needed time for the development and testing of both medication and vaccines both of which are at reasonably advanced stages from several companies (Cross, 2020).

Nonetheless, it cannot be emphasized enough how important it is that solidarity is shown by all of society and that full cooperation occurs between authorities and the public. Acts of irresponsibility such as; • •

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individuals travelling from affected countries disregarding quarantine guidelines, failing to inform authorities of potential infection out of fear of being “labelled” as infected with a disease which, more likely than not, will not involve worse symptoms than a simple fever, authorities failing to have the necessary contingency plans which not only need to be aggressive but also be readily available and well communicated to the public;

all severely hinder the nation’s capability of dealing with an outbreak.

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