Research Article - (2020) Volume 5, Issue 3
Received: 12-May-2020
Published:
30-Jun-2020
, DOI: 10.37421/2736-6189.2020.5.186
Citation: Thavrin Manickum. "A 3-Month Preliminary Epidemiological Assessment of Some Factors Affecting the Human-To-Human Transmission of Causal Agent SARS-Cov-2 Virus for Infection Rates of COVID-19". Int J Pub Health Safe 5 (2020) doi: 10.37421/ijphs.2020.5.186
Copyright: © 2020 Manickum T. This is an open-access article distributed under the terms of the creative commons attribution license which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Aims: A preliminary epidemiological study, based on three months of diagnosed cases and deaths for COVID-19, for the beginning of the pandemic, January to 31 March 2020, was undertaken. Factors that were considered to affect the human-to-human transmission of the SARS-CoV-2 virus were: spike protein structure, the effect of country average monthly temperature. The study also investigated the median age of the country for the subjects who died and the corresponding case fatality ratio (%CFR).
Findings: The presence of the furin cleavage site, the 10 to 20 fold binding affinity of the spike protein, compared to SARS-CoV, were proposed as possible reasons for the much higher cases noted for COVID-19 compared to the SARS disease. The optimum temperature for viral infection with SARS-CoV-2, for COVID-19, appears to be ± 0.07ºC; viral transmission appears to be maximum at -2ºC up to +12ºC (95.3% of cases); transmission appears to decrease at >12ºC (2.0% of cases). The corresponding optimal temperature for SARS-CoV infection, for SARS disease, appears to be ± 6.25ºC. The average, global % CFR for COVID-19, based on 202 countries, is ± 3.2%. Subjects confirmed with COVID-19, in median age range 40.8 (± 4.7) years, are at higher risk of death. The USA has the highest number of infections (140640) as at 31 March 2020; Italy (11.4%) and Spain (8.6%) have the highest percentages of deaths from COVID-19 per population.
Conclusion: The preliminary study outcomes can be used for further investigation, to confirm the actual ages of subjects who died form COVID-19, to confirm the risk age groups for death from COVID-19, to confirm these preliminary optimal temperature ranges that may potentially assist countries to predict risk of future infection based on monthly temperatures per country.
Corona virus • SARS-CoV-2 • COVID-19 • Furin • Temperature • Median age • Case fatality rate
A novel corona virus 2019-nCoV (SARS-CoV-2) associated with humanto- human transmission and severe human respiratory infection (COVID-19 – corona virus disease 2019) was recently reported from the city of Wuhan in Hubei province, China [1,2], with a 2-3% fatality rate. The virus is presumed to have been initially transmitted from an animal reservoir to human, possibly via an intermediate host. Most of the original cases had close contact with local fresh seafood and an animal market [3]. Human-to-human transmission was reported, leading to a sustained epidemic spread with 9776 confirmed human infections, including 213 deaths, globally, as at 30 January 2020. This prompted WHO to declare it as a Global Health Emergency. After the viral genome was sequenced [4,5], Couthard et al. reported on their finding of a peculiar furin-like cleavage site in the spike glycoprotein, which was not observed in the lineage b of beta coronaviruses [6]. The estimated effective reproductive number (R) value of 2.90 (95%: 2.32-3.63) at the beginning of the outbreak raised the possibility of a pandemic [7]. On 11 March, with over 118,000 cases of the coronavirus illness in over 110 countries and territories around the world and the sustained risk of further global spread, the WHO declared COVID-19 as a pandemic: the declaration refers to the global spread of a new disease, rather than the severity of the illness it causes (WHO).
A total of 750 890 confirmed cases, covering 202 countries around the globe, were reported as at 31 March 2020 [8]; of the confirmed cases, 36 405 had died, giving an estimated Case fatality rate of 4.9%. Of note was the fairly high CFR estimate for Italy, ± 11.4% as at 31 March 2020, compared to China (± 4.0%) which was presumably attributed to the relatively older median age of the Italian population, compared to some of the other countries. Current preliminary data do indicate that the older age group of a population are at higher risk of dying from COVI-19. An unpublished study on the analysis of cases diagnosed as at 11 February in China showed that for the age group 30 to >80 years, the case fatality rate was: 1.3% for 50-59 year, 3.6% for 60-69 year, 8.0% for 70-79 year, and 14.8% for >80-year-old [9].
There has been some comment and speculation that lower temperatures may help to promote the transmission, and conversely, relatively higher temperatures may help to curb the spread of the virus between humans. Little is known about the environmental pattern in COVID-19 incidence and studies to date on COVID-19 transmission and meteorological factors, like temperature and humidity are few. There has also been conflicting reports regarding the effect of temperature on the SARS_Co-V-2 viral transmission. At the time of preparation of this manuscript, Briz-Redon et al. reported a spatio-temporal study of daily temperature on the number of COVID-19 cases in Spain [10]. They found no evidence suggesting a reduction in COVID-19 cases at warmer mean, minimum and maximum temperatures.
A study by Qi et al. in China, noted that for every 1°C increase in the average temperature led to a decrease in the daily confirmed cases by 36% to 57% when relative humidity was in the range from 67% to 85.5% [11]. Every 1% increase in relative humidity led to a decrease in the daily confirmed cases by 11% to 22% when average temperature was in the range from 5.04°C to 8.2°C. However, the authors noted that these associations were not consistent throughout Mainland China.
Another COVID-19 temperature study by Wang et al. covered China and 26 other countries around the world, for the period 20 January to 04 February [12]. Their study found out that to a certain extent, temperature could significantly change the COVID-19 transmission. There may be an optimum temperature for viral transmission, which partly explains why it first broke out in Wuhan. They concluded that low temperature is beneficial for viral transmission; no temperature or range was proposed.
Thus the aim of this current study is to investigate:
The effect of the spike glycoprotein structure on the transmission,
Effect of temperature on transmission, and
Higher risk of fatality for the aged that are diagnosed with COVID-19.
The number of diagnosed COVID-19 cases and deaths were obtained from the WHO website from the “situation reports” [13]. Temperature data were obtained from the stat.world website [14]; whilst this site has data up to the year 2013, it was noted that there were negligible differences in the average annual temperatures. COVID-19 testing data was obtained from Wikipedia [15]. Median age per country was obtained from Wikipedia web site [16].
Structure of the spike protein of 2019-nCoV (SARSCoV- 2)
The corona viruses are a diverse family of enveloped positive sensed RNA viruses distribute widely distributed among animal species. The emergence of the human CoV, responsible for sever acute respiratory syndrome (SARS) highlights the public health risks associated with the evolution and zoonotic spread of new CoVs.
Based on its genome sequence, 2019-nCoV (SARS-CoV-2) belongs to lineage b of Beta coronavirus, which also includes t h e SARS-CoV and bat CoV ZXC21, the latter and CoV ZC45 being the closest to 2019-nCoV. 2019- nCoV share s ~ 76% amino acid sequence identity in the S p i k e (S)-protein sequence with SARS-CoV and 80% with CoV ZXC21 [4].
Currently, seven human CoVs (HCoVs) have been confirmed. Specifically, they are named as Human coronavirus NL63 (HCoV-NL63) and Human coronavirus 229E (HCoV-229E), which belong to the alpha-coronavirus genus; whereas Human coronavirus OC43 (HCoV-OC43), Human coronavirus (HCoV-HKU1), SARS-CoV, SARS-CoV-2 and Middle East respiratory syndrome coronavirus (MERS-CoV), belong to the betacoronavirus genus. HCoV 229E, HCoV-NL63, HCoV-HKU1 and HCoV- OC43 strains of coronavirus cause mild respiratory diseases in humans. The SARS-CoV-2 is a zoonotic virus that belongs to the Coronaviridae family that can infect human and several animal species [17]. The SARS-CoV-2 belongs to the subgenus Sarbecovirus and mostly resembles a bat coronavirus, with which it shares 96.2% sequence homology [4].
The corona virus S-protein is the structural protein responsible for the crown-like shape of the CoV viral particle, from which the original name corona virus was derived.
The virus belongs to the largest family of RNA viruses. Its genome ranges from 27 to 32 kilobases in size (~125 nanometers or 0.125 microns). It is a single stranded enveloped RNA virus which possess a positive-sense RNA genome also known as (+ssRNA) with a 5’-cap structure and 3’-poly-A tail. The viruses belonging to this category have a few common characteristics that are applicable to SARS-CoV-2 as well. The virus has four important structural proteins which are (E) the envelope protein, (M) the membrane protein, (S) the spike protein and (N), the nucleocapsid protein, which are required to regulate the function and viral structure [18]. Most important ones are N and S, where the former one helps the virus to develop the capsid and the entire viral structure appropriately and the latter one helps in the attachment of virus to the host cells [19,20]. The S protein has three major sections which are the large ectodomain, a single-pass transmembrane anchor and a short intracellular tail. These play a major role in anchoring the host cells. Among these sections the ectodomain has two subunits which are the S1 receptor-binding subunit and S2 the membrane fusion subunit.
It has been reported that the SARS-CoV and SARS-CoV-2 have similar kind of receptors, especially the receptor binding domain (RBD) and the receptor binding motif (RBM) in the viral genome [21-23]. It has also been proposed that SARS-CoV-2 mechanism of action in infection of humans is similar to the SARS. It has been reported that the RBM of the SARS-CoV-2 has a major amino acid residue (Gln493) that favors the attachment and fusion of the viral S protein with virus into the ACE2 protein of the human cell especially the one present in the lungs which results in respiratory infections in humans [21,24].
The 1200 aa S-protein belongs to Class-I viral fusion proteins, and it contributes to the cell receptor binding, tissue tropism and pathogenesis [25,26]. The spike S-protein of corona viruses facilitates viral entry into target cells. Entry of the virus depends on binding of the surface unit S1, of the surface protein, to a cellular receptor, which facilitates viral attachment to the surface of the target (host) cells. In addition, entry requires S-protein priming by cellular proteases, which entails S- protein cleavage at the s1/S2 and S2’ site, to allow the fusion of the viral and cellular membranes. The latter process is driven by the S2 subunit. The SARS S-protein engages angiotensin-converting enzyme 2 (ACE2) as the entry receptor [27], and employs the cellular serine protease TMPRSS2 for S-protein priming [28-30]. It has been found that 2019-nCoV S- protein uses ACE2 for host cell entry and that the serine protease TMPRSS2 primes the 2019-nCov S-protein for cellular entry [31,32]. However, it has been further shown, by biophysical and structural evidence shown that 2019-nCoV-S protein binds ACE2 with higher affinity, about 10-20-fold higher, compared to the SARS-CoV-S binding to ACE2 [33].
The present preliminary study has indicated the following:
• The presence of the furin cleavage site, the 10 to 20- fold binding affinity of the spike protein of the SARS-CoV-2 virus, compared to SARS-CoV, are possible reasons for the much higher cases noted for COVID-19 compared to the SARS disease.
• The optimum temperature for viral infection with SARS-CoV-2, for COVID-19, appears to be ± 0.07ºC; viral transmission appears to be maximum at +2 to -2ºC (42.9% of cases) and at 12 to 2ºC (42.9% of cases); transmission appears to decrease at >12ºC (2.0% of cases).
• The average % CFR for COVID-19, based on 202 countries, is 3.2%, as at 31 March 2020.
• Subjects confirmed with COVID-19, in median age range 40.8 (± 4.7) years, are at higher risk of death; for South Africa and China, the risk age range appears to be ≥ 80 year.
The % CFR is also impacted by other factors, like co-morbidity, due to pre-existing respiratory diseases, diseases of lifestyle, like cardiovascular disease, diabetes, AIDS/HIV, Tuberculosis, history of smoking, etc., which are very prevalent in Sub- Saharan Africa.
The preliminary study outcomes can be used for further investigation, to confirm the actual ages of subjects who died form COVID-19, to confirm the risk age groups for death from COVID-19, and to predict risk of future infection based on monthly temperatures per country. As more data becomes available, future studies must continue in the area of temperature and other environmental vectors on rates of viral transmission and virus stability that can aid countries at risk toward appropriate public health measures.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
