[12/22, 4:10 AM] ......
: respiratory syncytial virus, rhinovirus, human metapneumovirus and SARS
coronavirus. It is advisable to distinguish COVID-19 from other pneumonias such as mycoplasma
pneumonia, chlamydia pneumonia and bacterial pneumonia.33 Several published pieces of literature
based on the novel coronavirus reported in China declared that stool and blood samples can also
collected from the suspected persons in order to detect the virus. However, respiratory samples show
better viability in identifying the virus, in comparison with the other specimens. 34-36
6.2 Nucleic acid amplification tests (NAAT) for COVID-19 virus
The gold standard method of confirming the suspected cases of COVID-19 is carried out by detecting the
unique sequences of virus RNA through reverse transcription polymerase chain reaction (RT-PCR) along
with nucleic acid sequencing if needed. The various genes of virus identified so far include N, E, S (N:
nucleocapsid protein, E: envelope protein gene, S: spike protein gene) and RdRP genes (RNA- dependent
RNA polymerase gene).32
[12/22, 4:10 AM] ......: severe illness, to minimise the risk of exposure to COVID-19 during outbreaks.53
9 VACCINES
The strange coronavirus outbreak in the Chinese city of Wuhan, now termed COVID-19, and its rapid
transmission, threatens people around the world. Because of its pandemic nature, the National
Institutes of Health (NIH) and pharmaceutical companies are involved in the development of COVID-19
vaccines. Xu Nanping, China's vice-minister of science and technology, announced that the first vaccine
is expected to be ready for clinical trials in China at the end of April 2020.54 There is no approved
vaccine and treatment for COVID-19 infections.
Vaccine development is sponsored and supported by the Biomedical Advanced Research and
Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness
and Response (ASPR). Sanofi will use its egg-free, recombinant DNA technology to produce an exact
genetic match to proteins of the virus.55
[12/22, 4:11 AM] ......: of plasma cytokines, which suggests an immunopatho- logical process caused by a
cytokine storm60,86,87. In this cohort of patient, around 2.3% people died within a median time of 16
days from disease onset986. Men older than 68 years had a higher risk of respiratory fail- ure, acute
cardiac injury and heart failure that led to death, regardless of a history of cardiovascular disease86 (FIG.
4). Most patients recovered enough to be released from hospital in 2 weeks 9,80 (FIG. 4).
Early transmission of SARS-CoV-2 in Wuhan in December 2019 was initially linked to the Huanan Seafood
Wholesale Market, and it was suggested as the source of the outbreak9,22,60. However, community
transmission might have happened before that. Later, ongoing human-to-human transmission
propagated the outbreak. It is generally accepted that SARS-CoV-2 is more transmissible than SARS-CoV
and MERS-CoV; however, determination of an accurate reproduction number (RO) for COVID-19 is not
possible yet, as many asymptomatic infections cannot be accurately accounted for at this stage. An
estimated RO of 2.5 (ranging from 1.8 to 3.6) has been proposed for SARS-CoV-2 recently, compared
with 2.0-3.0 for SARS-CoV90. Notably, most of the SARS-CoV-2 human-to-human transmission early in
China occurred in family clusters, and in other countries large outbreaks also happened in other set-
tings, such as migrant worker communities, slaughter- houses and meat packing plants, indicating the
necessity of isolating infected people,12,91-93. Nosocomial transmis- sion was not the main source of
transmission in China because of the implementation of infection control measures in clinical settings.
By contrast, a high risk of nosocomial transmission was reported in some other
[12/22, 4:11 AM] ......: and other SARSr-CoVs (FIG. 2). Using sequences of five conserved replicative
domains in pplab (3C-like protease (3CLpro), nidovirus RNA-dependent RNA polymerase (RdRp)-
associated nucleotidyltransferase (NIRAN), RdRp, zinc-binding domain (ZBD) and HEL1), the
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses estimated the
pairwise patristic distances between SARS-CoV-2 and known coronaviruses, and assigned SARS-CoV-2 to
the existing species SARSr-CoV¹. Although phyloge- netically related, SARS-CoV-2 is distinct from all other
coronaviruses from bats and pangolins in this species.
The SARS-CoV-2 S protein has a full size of 1,273 amino acids, longer than that of SARS-CoV (1,255 amino
acids) and known bat SARSr-CoVs (1,245-1,269 amino acids). It is distinct from the S pro- teins of most
members in the subgenus Sarbecovirus, sharing amino acid sequence similarities of 76.7- 77.0% with
SARS-CoVs from civets and humans,
[12/22, 4:12 AM] ......: primary anti-genic epitopes mainly those recognised by neutralising antibodies.
The spike S-protein being in a spike form is subjected to a structural rearrangement process so that
fusing the outer membrane of the virus with the host- cell membrane becomes easier. 19, 20 Recent
SARS-CoV work has also shown that the membrane exopeptidase ACE enzyme (angiotensin-converting
enzyme) functions as a COVID-19 receptor to enter the human cell.21
