The Joy of Sharing Science No.2, Everything you need to know about COVID-19 Biology Supplement

No:2,COVID-19 BiologySupplement
JoSS
JoyofSharingScience
26June2020
AnindependentinitiativeofUskudarAmericanAcademyvolunteerstudents
Editor: FazılOnuralpArdıç
EologyandtheSourceofCOVID-19
Whatistherelaonbetweengender,raceandcoronavirus?
AdaÖzgirin
EcePaksoy,YaseminYüksel
TheStructureandgenecmakeupofSARS-CoV-2 WhataredifferenttestsbeingimplementedforCOVID-19
MehmetEfeKılıç
andhowdothesetestscompare?
HowdoestheepidemiologyofCOVID-19differenate EdaPaksoy,YaseminYüksel
from otherviruses,SARS-CoVandMERS-CoV? WhereareweonCOVID-19treatment?
ElifDemir,SelinEdaSağnak
Howdopre-exisngcondionsaffectCOVID-19?
İrem Yaşa
NairaAltunkeser
ClinicalTrialsforCOVID-19
CeylinGün

Joy of Sharing Science 2020
This newspaper is an independent initiative of Uskudar American Academy volunteer students.
The Joy of Sharing Science is a weekly newspaper that explores the physics/biology/chemistry
behind interesting real life phenomena in a concise and easily understandable way. Each week,
3 phenomena concerning physics, chemistry, and biology will be published. The aim of this
project is to explore the science hidden in plain sight, evoke curiosity, and elevate scientific
literacy.
Advisor: Yasemin Sarıhan, Head of Science Department UAA
Editor: Fazıl Onuralp Ardıç, Senior student
Issue Authors:
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Elif Demir,
Ceylin Gün,
Mehmet Efe Kılıç,
Ada Özgirin,
Ece Paksoy,
Eda Paksoy,
Selin Eda Sağnak,
İrem Yaşa,
Yasemin Yüksel,
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Junior student
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Contact: uaajoss@gmail.com
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Etiology and the Source of
COVID-19
Ada Özgirin
Coronaviruses are a family of RNA viruses; they inject their genetic
information via an RNA message. The common cold and severe acute
respiratory syndrome (SARS) are examples of such viruses. COVID-19
and SARS are unique among this family because they originate from
animal coronaviruses. COVID-19’s genome has been recently
published in GenBank and it is known that its genetic composition is
very similar to SARS and MERS. Even though there are many genome
sequencing techniques, the most efficient technology is Nextgeneration
sequencing methods.
Next-generation sequencing (hereafter referred to as NGS) has recently
revolutionized genomic research. It has enabled whole genomes to be sequenced in
a matter of hours while the human genome was first sequenced in 13 years. In NGS,
the most basic principle is that millions of individual nucleotide fragments are
sequenced simultaneously in parallel capillary tubes. In this technology, DNA
polymerase enzymes incorporate fluorescently dyed deoxyribonucleotide
triphosphates (dNTPs) into template DNA strands during DNA synthesis. The
small fragments of dyed DNA strands are separated through the capillary tubes, the
smallest fragments travel faster so at the end of these capillaries the strands are
separated according to their sizes. The dNTPs that are used have distinct colors for
each nucleotide so when a laser detects these distinct colors at the end of the

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capillaries, the sequence of the whole genome is obtained. Lastly, bioinformatics
tools are used to piece together the sequenced fragments or to compare the
sequence of these genomes to other sequences to obtain a phylogenetic tree for the
determination of origins.
(Image taken from Gauthier, “Simulation of polymer translocation through small channels:
A molecular dynamics study and a new Monte Carlo approach”)
The NGS results of COVID-19 are used to determine the epidemiology of the
virus or to discover the new mutations. Sequence comparisons suggest that
2019-nCoV and a Bat SARS-like coronavirus sequence (BatCoV RaTG13) has
a sequence similarity of 96.3%. While these results do not suggest that the bat
virus is the exact variant causing the outbreak, it is very likely that COVID-19
has originated from bats.
References:
“An Introduction to Next-Generation Sequencing Technology.”
Https://Emea.illumina.com/Content/Dam/Illumina-
Marketing/Documents/Products/illumina_sequencing_introduction.Pdf, Illumina, 2017,
emea.illumina.com/content/dam/illuminamarketing/documents/products/illumina_sequencing_introduction.pdf.
“Coronavirus Disease 2019 (COVID-19).” Coronavirus Disease 2019 (COVID-19) -
Etiology | BMJ Best Practice US, bestpractice.bmj.com/topics/enus/3000168/aetiology#referencePop33.
Paraskevis, D., et al., “Full-Genome Evolutionary Analysis of the Novel Corona Virus
(2019-NCoV) Rejects the Hypothesis of Emergence as a Result of a Recent
Recombination Event.” Infection, Genetics and Evolution : Journal of Molecular
Epidemiology and Evolutionary Genetics in Infectious Diseases, U.S. National Library of
Medicine, pubmed.ncbi.nlm.nih.gov/32004758/.

The Structure and genetic
makeup of SARS-CoV-2?
Mehmet Efe Kılıç
A virus is a structure that has a nucleic acid (DNA or RNA) and a
protein layer that protects and holds the nucleic acid present. The
differences in the type of nucleic acid they carry and the content (what
the nucleic acids code for) of the nucleic acid they carry are the main
factors that differentiate the “species” of viruses.
Viruses look for host cells to infect in which they can increase their
numbers and “reproduce”. In order to infect a cell, they need to release
the nucleic acid they have into the host cell, and to do so, they need
special protein structures that will enable them to bind to the target
cells’ receptors (Receptor-mediated endocytosis). These protein
structures vary among viruses a lot as well since viruses target many
different types of cells from different organisms, each with different
receptors.

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Figure 1: An annotated diagram of
SARS-CoV-2 structure
(Taken from: “2019 Novel
Coronavirus.” Cusabio Life Science –
Your Biology Science Partner,
www.cusabio.com/2019-novelcoronavirus.html.)
Coronaviruses have a lipid envelope that surrounds the protein coat that
shields the nucleic acid. They usually cause mild respiratory infections but can
cause pneumonia as well. They are characterized by the spikes on their surface
which give the coronaviruses a crown-like shape, thus the name “corona”
(“crown” in Latin). Also, they are RNA viruses, meaning that the nucleic acid
they carry is an RNA molecule. The new SARS-CoV-2 differs from the other
coronaviruses mainly because it has a different RNA sequence.
Figure 2: An illustration of
SARS-CoV-2 viruses
(Taken from: “Coronaviruses.”
National Foundation for
Infectious Diseases, 17 June 2020,
www.nfid.org/infectiousdiseases/coronaviruses/.)
Two other very known coronaviruses are Middle East Respiratory Syndrome
(MERS) and Severe Acute Respiratory Syndrome (SARS). MERS was
reported in Saudi Arabia in 2012 for the first time, and it originated from
camels. It was mainly seen in the Arabian Peninsula. 3-4 out of 10 of the
people infected died due to MERS. SARS was seen in 2002 in Southern
China. It affected the respiratory systems and had a mortality rate of 10%
approximately. Covid-19 also affects the respiratory systems, and it reaches a
mortality rate from 2-3% to 13% in some countries.
These three viruses are very similar in their RNA size. The RNA molecules
they carry are 29844b, 29751b, and 30119b in COVID-19, SARS-CoV; and
MERS-CoV, respectively. When a sequence analysis was conducted, it was

The Structure and genetic makeup of SARS-CoV-2?
seen that COVID-19 and SARS-CoV were approximately 79% similar and that
COVID-19 and MERS-CoV were approximately 50% similar. The phylogenetic
tree generated also shows that Covid-19 and SARS-CoV are much more
similar to each other than they are to MERS-CoV.
Figure 3: The phylogenetic tree of coronaviruses (Taken from: Mousavizade, Leila, and
Sorayya Ghasemibc. “Genotype and Phenotype of COVID-19: Their Roles in Pathogenesis.”
Science Direct, 31 Mar. 2020,
www.sciencedirect.com/science/article/pii/S1684118220300827.)
Similar to SARS-CoV, Covid-19 uses the same host cell receptor, ACE-2 to
enter and infect the host cell, however, the affinity of Covid-19 to ACE-2
receptors is higher than SARS-CoV’s. Additionally, they use the same
protease that is needed to complete this process, TMPRSS2.
Figure 4: The attachment of the spike
protein of SARS-CoV and the new
COVID-19 to the cellular attachment
factor
(Taken from: Mousavizade, Leila, and
Sorayya Ghasemibc. “Genotype and
Phenotype of COVID-19: Their Roles in
Pathogenesis.” Science Direct, 31 Mar.
2020, www.sciencedirect.com/science/article/pii/S1684118220300827.)
References:

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“2019 Novel Coronavirus.” Cusabio Life Science – Your Biology Science Partner,
www.cusabio.com/2019-novel-coronavirus.html.
“ACE-2: The Receptor for SARS-CoV-2.” Www.rndsystems.com,
www.rndsystems.com/resources/articles/ace-2-sars-receptor-identified.
“Cell Signaling.” Nature News, Nature Publishing Group,
www.nature.com/scitable/topicpage/cell-signaling-
14047077/#:~:text=Cells%20have%20proteins%20called%20receptors,are%20specifi
c%20for%20different%20molecules.&text=In%20fact%2C%20there%20are%20hundr
eds,have%20different%20populations%20of%20receptors.
Cohen, Fredric S. “How Viruses Invade Cells.” Biophysical journal vol. 110,5 (2016):
1028-32. doi:10.1016/j.bpj.2016.02.006.
“Coronaviruses.” National Foundation for Infectious Diseases, 17 June 2020,
www.nfid.org/infectious-diseases/coronaviruses/.
Fehr, Anthony R, and Stanley Perlman. “Coronaviruses: an overview of their
replication and pathogenesis.” Methods in molecular biology (Clifton, N.J.) vol. 1282
(2015): 1-23. doi:10.1007/978-1-4939-2438-7_1.
Mousavizade, Leila, and Sorayya Ghasemibc. “Genotype and Phenotype of COVID-
19: Their Roles in Pathogenesis.” Science Direct, 31 Mar. 2020,
www.sciencedirect.com/science/article/pii/S1684118220300827.
“Naming the Coronavirus Disease (COVID-19) and the Virus That Causes It.” World
Health Organization, World Health Organization,
www.who.int/emergencies/diseases/novel-coronavirus-2019/technicalguidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causesit.
Ritchie, Research and data: Hannah. “Mortality Risk of COVID-19 - Statistics and
Research.” Our World in Data, https://ourworldindata.org/mortality-risk-covid.
“Virus Structure.” Molecular Expressions Cell Biology: Virus Structure,
https://micro.magnet.fsu.edu/cells/virus.html.
Wang, Nianshuang et al. “Structure of MERS-CoV spike receptor-binding domain
complexed with human receptor DPP4.” Cell research vol. 23,8 (2013): 986-93.
doi:10.1038/cr.2013.92.

How does the
epidemiology of COVID-19
differentiate from other
viruses, SARS-CoV and
MERS-CoV?
Elif Demir, Selin Eda Sağnak
Rate of Spreading
Basic Reproductive Number (R0) shows the number of possible cases
created from one case. It also predicts the infection rate for the virus.
The number is less than 1 for MERS–CoV, ranges between 1.4–1.9 for
SARSCoV and 2.0-2.6 for COVID-19. This indicates that COVID-19 is
the most contagious among the three and has the highest possibility to
become a pandemic. (SARS and MERS were known as epidemics.) In
120 days, COVID-19 spread to 210 countries and turned into an
international health concern.
Rate of Mortality
Even though COVID-19 is the most contagious among the three, it is
the least lethal. The mortality rate for COVID-19 is 5.82% compared to
the 10% of SARS-CoV and 37.1% of MERS-CoV.

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Incubation Period
For the ongoing analysis of the cases, primarily, the scientists assumed that
the incubation period of COVID-19 follows a log-normal distribution as it is a
common denominator for most of the acute respiratory viral infections. In the
studies, the range of the incubation period differs from 1.3 - 11.5 days with a
confidence level of 95%. This record is dramatically higher than the other
viruses. While SARS’s mean incubation period is 8 days, it diverges for other
viruses with MERS’s being 12, Swine Flu’s being 8. Since the incubation period
represents the time from infection to appearance of symptoms, the scientists
may suggest that pre-symptomatic transmission might be a major driver of
the virus since that was the case for Spanish flu. However, the recordings
show that people shed COVID-19 around 24-48 hours prior to showing
symptoms, the incubation period doesn’t seem to make a major difference.
Transmissibility
The major transmission mode for all three viruses is human to human contact.
For COVID-19 droplet and contact transmission are the accepted ways of
contagion. There are suggested ways of transmission such as fecal
transmission which appeared to be infectious for SARS-CoV however not
proven either to be infectious or not for COVID-19. It has been seen that the
COVID-19 infected patients held the risk of transmission even before showing
the symptoms, therefore, increasing the chance of infection.
Population Immunity
While COVID-19 may result in hospitalization and other severe health issues,
primarily, it attacks different age groups differently due to underlying health
conditions. It is supported by recorded cases that COVID-19 causes more fatal
complications in the patient belonging to an age-group higher than 60 since they are
more likely to have a clinical background with severe chronic diseases like diabetes
and cardiovascular diseases. Due to aging, the immune system’s resilience is
lowered which causes other lethal complications. When it comes to children and
adults, it is seen that children may develop severe complications but more rarely
than adults. In most of the cases with children, they don’t show any evidence of

How does the epidemiology of COVID-19 differentiate from other viruses, SARS-CoV and MERS-CoV?
symptoms and acute respiratory infections. A misconception in the novel COVID-
19 is that children have a higher transmission rate than adults which is not yet
proven. Babies ranging between 0-24 months may experience respiratory infection
more severely since their immunity is not completely developed.
Figure 1: The distribution of patients across the world. (Taken from Guo, et al., “New Insights
of Emerging SARS-CoV-2: Epidemiology, Etiology, Clinical Features, Clinical Treatment, and
Prevention”)
(A) First reported date of case, by country, throughout the world, as of 28 April
2020. The date of the first reported COVID-19 patient in 213 countries and
regions around the world. The time sequence of reporting for each country is
labeled according to the earliest (red) and latest (green) date of onset. Blue

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indicates no reporting available. Data source: World Health Organization
(WHO);
(B) The distribution of laboratory-confirmed cases throughout the world, as
of 28 April 2020. Spatial distribution of the 2,954,222 cases of COVID-19
diagnosed around the world. The cumulative number of confirmed diagnoses
in each country is labeled in shades of red. Blue indicates no confirmed cases.
Data source: People's Daily, Chinese Center for Disease Control and
Prevention; World Health Organization (WHO);
(C) The distribution of laboratory-confirmed cases throughout China, as of 29
April 2020. Distribution of the 84,369 cases of COVID-19 were diagnosed in
China (including Hong Kong, Macao, and Taiwan) by city. The cumulative
number of confirmed diagnoses in each city is labeled in shades of red. Data
source: Chinese Center for Disease Control and Prevention.”
References:
Bulut, Cemal, and Yasuyuki Kato. “Epidemiology of COVID-19.” Turkish Journal of
Medical Sciences, 21 Apr. 2020, http://journals.tubitak.gov.tr/medical/issues/sag-
20-50-si-1/sag-50-si-1-12-2004-172.pdf.
C. Biscayart, P. Angeleri, et al. “The Indian Perspective of COVID-19 Outbreak.”
VirusDisease, Springer India, 1 Jan. 1970,
https://link.springer.com/article/10.1007/s13337-020-00587-x.
Guo, Gangqiang, et al. New Insights of Emerging SARS-CoV-2: Epidemiology, Etiology,
Clinical Features, Clinical Treatment, and Prevention. U.S. National Library of
Medicine, 22 May 2020, www.ncbi.nlm.nih.gov/pmc/articles/PMC7256189/.
Petersen, Eskild, and Deniz Gökengin. “SARS-CoV-2 Epidemiology and Control,
Different Scenarios for Turkey.” Turkish Journal of Medical Sciences, 21 Apr. 2020,
http://journals.tubitak.gov.tr/medical/issues/sag-20-50-si-1/sag-50-si-1-4-2003-
260.pdf.
Petrosillo, N., et al. “COVID-19, SARS and MERS: Are They Closely Related?”
Clinical Microbiology and Infection, 28 Mar. 2020,
www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30171-
3/fulltext.
Seladi-Schulman, Jill. “Coronavirus vs. SARS: How Do They Differ?” Healthline,
Healthline Media, 29 Apr. 2020, www.healthline.com/health/coronavirusvs-sars.
Swerdlow, David L., et al. “Epidemiology of Covid-19: NEJM.” The New England
Journal of Medicine, 27 Mar. 2020, www.nejm.org/doi/full/10.1056/NEJMc2005157.

How do pre-existing
conditions affect COVID-19?
İrem Yaşa
Cardiovascular diseases
COVID-19 is primarily a respiratory illness but cardiovascular
involvement can occur through several mechanisms. Acute cardiac injury
is the most reported cardiovascular abnormality in COVID-19, with
average incidence 8-12%.
Coronavirus disease 2019 (Covid-19) may disproportionately affect people
with cardiovascular disease. Concern has been aroused regarding a
potential harmful effect of angiotensin-converting–enzyme (ACE)
inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context.
High cholesterol level
Based on these findings and known loading of cholesterol into peripheral
tissue during aging and inflammation, we build a cholesterol dependent
model for COVID19 lethality in elderly and the chronically ill. As
cholesterol increases with age and inflammation (e.g. smoking and

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diabetes), the cell surface is coated with viral entry points and optimally
assembled viral entry proteins.
Diabetes
If you have diabetes – regardless of what type you have – you are no more
likely to catch coronavirus than anyone else. The majority of people who do
get coronavirus will have mild symptoms and don’t need to go into hospital.
However everyone with diabetes, including those with type 1, type 2,
gestational and other types, is vulnerable to developing a severe illness if they
do get the coronavirus, but the way it affects them can vary from person to
person. Being ill can make your blood sugar go all over the place. Your body
tries to fight the illness by releasing stored glucose (sugar) into your
bloodstream to give you energy. But your body can’t produce enough or any
insulin to cope with this, so your blood sugar rises.
Asthma
There have been several reports that steroids are contraindicated in COVID-
19 disease, so many are wondering what people with asthma should do if their
controller medication is a steroid (inhaled or oral). The short answer is
continue taking your controller medications and do not stop them. The data
suggesting that steroids might increase the shedding of SARS-CoV-2 comes
from treating hospitalized patients with systemic steroids just for the viral
illness. The use of steroids for treating other diseases (like asthma) was not
studied.
Taking medications which repress the immune system
The American College of Allergy, Asthma & Immunology (ACAAI) is
providing guidance on the continued use of corticosteroids for patients with
allergies and asthma during the COVID-19 pandemic. There is no data that
continuing these allergy and asthma medications will have any effect on
increasing your risk of getting the COVID-19 infection or if you get the
infection, lead to a worse outcome. It is important to control your allergy and
asthma symptoms as they may lead to misdiagnosis of COVID-19 as there are
some overlap of symptoms.
References:
“During COVID-19 Pandemic, Normal Allergy and Asthma Medications Should Be
Continued.” ACAAI Public Website, 23 June 2020, acaai.org/news/during-covid-19-
pandemic-normal-allergy-and-asthma-medications-should-be-continued.

How do pre-existing conditions affect COVID-19?
Mehra, Mandeep R., et al. “Cardiovascular Disease, Drug Therapy, and Mortality in
Covid-19: NEJM.” New England Journal of Medicine, 18 June 2020,
www.nejm.org/doi/full/10.1056/NEJMoa2007621.
Wang, Hao. “The Role of High Cholesterol in Age-Related COVID19 Lethality.”
BioRxiv, Cold Spring Harbor Laboratory, 1 Jan. 2020,
www.biorxiv.org/content/10.1101/2020.05.09.086249v2.
“We're Calling for Applications for Research into Coronavirus (Covid-19) and
Diabetes.” Diabetes UK, www.diabetes.org.uk/about_us/news/urgent-funding-call.

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What is the relation
between gender, race and
coronavirus?
Ece Paksoy, Yasemin Yüksel
Does COVID-19 affect different races more severely?
The coronavirus is, after all, a virus that is not capable of active
discrimination. And yet the virus is having clearly different effects on
different groups of people.
Differences between Ethnic Groups
Early data of the Covid-19 crisis, the rates seem to vary between ethnic
groups. In the US, in Chicago, as of early April 2020, 72% of people
who died of coronavirus were black, although only one-third of the
city’s population is. The latest overall COVID-19 mortality rate for
Black Americans is 2.3 times as high as the rate for Whites and Asians,
and 2.2 times as high as the rate for Latinos.
But why? Racism itself.
Income inequality: In many majority-white countries like the US (as
well as some minority-white countries like South Africa), people from
other ethnic and racial groups have less access to economic resources.
Black US households in 2018 were twice as likely to be food insecure as
the national average, with one in five families lacking consistent

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access to enough food. Lacking access to consistent nutrition makes the black community
more prone to have diabetes, heart disease, and hypertension – which weaken lungs and
immune systems. As the researches have shown, people with pre-existing health
conditions are more likely to develop severe Covid-19 symptoms.
In addition to the health problems caused by racism, racial biases prevent safety measures.
Because black people are more likely to be seen as criminals or dangerous, rather than as
simply protecting their own health; black men in the US have reported being
uncomfortable wearing masks in public.
(Image taken from APM Research Lab, “COVID-19 Deaths Analyzed by Race and Ethnicity”)
Differences between Genders
Although the data for COVID-19 show equal numbers of cases between men and women so
far, there seem to be sex differences in mortality and vulnerability to the disease. Emerging
evidence suggests that more men than women are dying. In the US, for example, twice as
many men have died from the virus as women. Similarly, 69% of all coronavirus deaths across
Western Europe have been male. Similar patterns have been seen in China and other
countries.
Medical experts have long known men can be more susceptible to viruses than women. Philip
Goulder, professor of immunology at the University of Oxford explained the biological theory: “In
particular, the protein by which viruses such as coronavirus are sensed is encoded on the X
chromosome. As a result, this protein is expressed at twice the dose on many immune cells in
females compared to males, and the immune response to coronavirus is therefore amplified in
females.” This boost supports both the general reaction to infection (the innate response) and also to
the more specific response to microbes including antibody

What is the relation between gender, race and coronavirus?
formation (adaptive immunity).
This might mean women are able
to tackle the novel coronavirus
more effectively but this has not
yet been proven.
Of course, this difference can’t
be linked to a single reason. The
disparity may be due to factors
related to sex (biological) or
gender (unhealthy habits such as
drinking or smoking). Thus, for
now, the reason is still unclear.
References:
“Coronavirus: Why Some Racial Groups Are More Vulnerable.” BBC Future, BBC,
21 Apr. 2020, www.bbc.com/future/article/20200420-coronavirus-why-someracial-groups-are-more-vulnerable.
“COVID-19 Deaths Analyzed by Race and Ethnicity.” APM Research Lab,
www.apmresearchlab.org/covid/deaths-by-race.
“Gender Inequality in Response to the New Coronavirus - Blog.” ISGlobal, 27 Apr.
2020, www.isglobal.org/en/healthisglobal/-/custom-blog-portlet/la-inequidadde-genero-en-respuesta-al-nuevo-coronavirus/5573964/0.
Roper, Willem, and Felix Richter. “Infographic: More Men Dying of COVID-19
Than Women.” Statista Infographics, 3 Apr. 2020,
www.statista.com/chart/21345/coronavirus-deaths-by-gender/.
“Why Covid-19 Is Different for Men and Women.” BBC Future, BBC, 13 Apr. 2020,
www.bbc.com/future/article/20200409-why-covid-19-is-different-for-men-andwomen.

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What are different tests
being implemented for
COVID-19 and how do
these tests compare?
Eda Paksoy, Yasemin Yüksel
Polymerase Chain Reaction Tests
The first step in a PCR test is called extraction, where genetic material
is purified from a patient’s clinical sample, such as a nasal swab. Next,
a mixture of enzymes, nucleotides (i.e., the building blocks of DNA),
and primers/probes are combined with that extracted genetic material.
The primers and probes are short pieces of DNA, that are designed to
bind to a specific gene sequence. The mixture is then placed on an
instrument that rapidly fluctuates the temperature inside the test,
potentially yielding millions of copies of the targeted gene sequence.
The probes in the test bind to the amplified sequences and produce a
fluorescent signal, which lets scientists know that the virus is present
in the sample.

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PCR tests can be very labor-intensive, with several stages at which errors may
occur between sampling and analysis. False negatives can occur up to 30% of
the time with different PCR tests, meaning they’re more useful for confirming
the presence of infection than giving a patient the all-clear. (Forsanari,“Testing
Individuals for COVID-19”)
Two common types of PCR testing are Nested PCR and Real-Time PCR.
Nested PCR: The nested PCR is useful for amplifying genes present in low
abundance. Product from one round of PCR using “outer primers” to amplify
a large fragment of the rRNA gene is used as a template in the second round
of PCR that targets a smaller region of the amplicon using “inner primers.”
Real-Time (Quantitative) PCR: Real-time PCR or quantitative PCR or qPCR
is an in vitro technique to quantify the presence of DNA templates
(Dhanasekaran et al., 2014). It is used to amplify and simultaneously quantify
a targeted DNA molecule.
Antibody Tests
This is a blood test. It looks for
antibodies to the coronavirus. Your
body produces antibodies in response
to an infectious agent such as a virus.
These antibodies generally arise after
four days to more than a week after
infection, so they are not used to
diagnose current disease.
Interesting Note: An antibody test tells
us what proportion of the population
has been infected. It won’t tell you who
is infected, because the antibodies are
generated after a week or two, after
which time the virus should’ve been
cleared from the system. But it tells you
who’s been infected and who should be
immune to the virus.

What are different tests being implemented for COVID-19 and how do these tests compare?
Historical studies have indicated that people who survived the sudden acute
respiratory syndrome (SARS) outbreak had antibodies in their blood for years
after recovery. Both SARS and Covid-19 are caused by coronaviruses, but it’s
too early to say if Covid-19 will generate a similar immune response. Reports
also indicate that some people have been infected with the virus twice over,
meaning these particular patients didn’t develop any immunity at all.
If public health officials can get a handle on what proportion of the population
are theoretically immune to the virus, the information could help lift the social
distancing restrictions on movement.
Antigen Tests
A rapid antigen test is a rapid diagnostic test suitable for point-of-care testing
that directly detects the presence or absence of an antigen. This distinguishes
it from other medical tests that detect antibodies or nucleic acid, of either
laboratory or point of care types.
PCR test Antibody test Antigen test
Detects active infections
Looks for genetic material (RNA)
Uses mucus typically taken from
nose or throat
Detect who’s been infected and who
should theoretically be immune to the
virus. Looks for antibodies to the virus
Uses blood samples
Detects active
infections
Looks for
proteins from
the virus
Uses nose and
throat secretions
Can take several days to get results
back (samples are sent to centralized
labs)
Helps detect the virus very early on
because viral RNA will be present
before antibodies form or symptoms
of the disease are present
A few days may pass before the
virus starts replicating in the throat
and nose, so the test won't identify
someone who has recently been
infected
Generally produces results in a few
minutes
Helps track the spread of the virus
and what proportion of the
population are theoretically immune
to the virus
Not certain if Covid-19 generates an
immune response that creates
antibodies which last a long time.
Therefore, patients can be infected
again.
Provides results
in just a few
minutes
Helps screening
patients for
infection
Not as accurate
as the PCR
diagnostic test

Joy of Sharing Science
References:
“Advice on the Use of Point-of-Care Immunodiagnostic Tests for COVID-19.” World
Health Organization, World Health Organization, www.who.int/newsroom/commentaries/detail/advice-on-the-use-of-point-of-care-immunodiagnostictests-for-covid-19.
Binnicker, Matthew. “A Diagnostics Expert Breaks Down Two Different Types Of
Coronavirus Tests And How They Work.” Forbes, Forbes Magazine, 15 Apr. 2020,
www.forbes.com/sites/coronavirusfrontlines/2020/04/16/a-diagnostics-expertbreaks-down-two-different-types-of-coronavirus-tests-and-how-they-work/.
Harris, Richard. “How Reliable Are COVID-19 Tests? Depends Which One You
Mean.” NPR, NPR, 1 May 2020, www.npr.org/sections/healthshots/2020/05/01/847368012/how-reliable-are-covid-19-tests-depends-which-oneyou-mean.
Kent, Chloe. “What Are the Different Types of Covid-19 Test and How Do They
Work?” Verdict Medical Devices, 3 Apr. 2020, www.medicaldevicenetwork.com/features/types-of-covid-19-test-antibody-pcr-antigen/.
“Nested Polymerase Chain Reaction.” Nested Polymerase Chain Reaction - an Overview
| ScienceDirect Topics, www.sciencedirect.com/topics/biochemistry-genetics-andmolecular-biology/nested-polymerase-chain-reaction.
“Real-Time Polymerase Chain Reaction.” Real-Time Polymerase Chain Reaction - an
Overview | ScienceDirect Topics, www.sciencedirect.com/topics/agricultural-andbiological-sciences/real-time-polymerase-chain-reaction.

Where are we on COVID-19
treatment?
Naira Altunkeser
Current outbreak of COVID-19 virus has stopped the world for the past
four months. Coronaviruses are a group of viruses, from the
Coronavirdae family, that was named after the prominent characteristic
of their shape that looks like a crown. They generally affect the
respiratory tract in mammals and have been identified to have four
genera: Alpha-coronavirus (alphaCoV), Beta-coronavirus (betaCoV),
Delta-coronavirus (deltaCoV) and Gamma-coronavirus (gammaCoV).
For Covid-19 that has symptoms varying from mild cold to serious
respiratory illnesses like SARS and MERS, there haven't been any newly
developed vaccines or registered therapeutic treatments that stops the
replication of the virus within the host organism. Currently, drugs for
HIV and malaria are used along with oxygen treatment for most
patients.
Latest studies, however, have been more focused on therapeutic vaccine
development for ultimate halt for the replication of Covid-19. Covid-19
enters the host cell as its Spike glycoproteins (S proteins) that surround
its membrane bind to the specific receptor (ACE2 protein) on the host
cell’s membrane to induce fusion with the host cell as shown below.

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(Image Taken from El-Aziz & Stockand, “Recent progress and challenges in drug development
against COVID-19 coronavirus (SARS-CoV-2) - an update on the status”)
S proteins have two subunits: S1 with a ACE2 receptor binding domain/site and S2
that regulates fusion between the host cell and the viral assembly. S proteins induce
neutralization of antibodies in the host and thus induce a specific immune response
with T-cells in the host organism. Therefore, we can say that S proteins are
prominent to protective immune response in the host. Some say that vaccines that
target the S proteins of Covid-19 could be a solution but considering the future
mutations of the virus the vaccine may result in no effect ,or worse, with another
distinct immune response.
(Image Taken from El-Aziz & Stockand, “Recent progress and challenges in drug development
against COVID-19 coronavirus (SARS-CoV-2) - an update on the status”)
For developing vaccines, to have a rather lasting effect, specific enzymes and
nucleic acids that are unique to the virus have to be analyzed. Scientists have been
evaluating those for Covid-19 with real-time reverse transcription using PCR

Where are we on COVID-19 treatment?
diagnostic assays. This way the aim is to target genes that are essential for viral
replication, like Spike genes. A common drug that has been used in this manner is
Remdesivir. Remdesivir suppresses reproduction of Covid-19 in vitro (in cell).
Recent analysis showed that the catalytic domains, reaction inducing parts, of
enzymes are highly conserved within the corona family that also includes SARS.
Hence, spike proteins and enzymes that are specific to the corona family can be a
promising target for vaccination. Scientists are now searching for ways to alter
current registered drugs for SARS for further usage in Covid-19 outbreak. RdRp
protein is an essential protein for replication/transcription protein complex of
Covid-19 since it primarily catalyses RNA synthesis of Covid-19. Transcription
complexes are protein machinery that transcribe nucleic acids which carry the
genetic material, in the case of Covid-19 RNA is being transcribed. The transcription
complex of Covid-19 RdRp has a newly introduced β-hairpin domain at one of its
terminals as shown below.
(Image Taken from Song & Huang, "Pharmacological Therapeutics Targeting RNA-Dependent RNA
Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-
19")
Remdesivir binds to RdRp to inhibit the RNA interaction of RdRp; therefore the
replication of the virus reduces. It has been said that Remdesivir holds a promise
for a solid design of a new therapeutic treatment.
To conclude, there hasn’t been any vaccines or registered treatments specifically for
Covid-19 to stop the outbreak. Though every scientist around the world has been
focused on this issue, in all probability, it may take up to or perhaps more than a
year to develop a legitimate treatment for Covid-19.

Joy of Sharing Science
References:
El-Aziz, Tarek Mohamed Abd, and James D. Stockand. “Recent Progress and Challenges in Drug
Development against COVID-19 Coronavirus (SARS-CoV-2) - an Update on the Status.” Infection,
Genetics and Evolution, vol. 83, 2020, p. 104327., doi:10.1016/j.meegid.2020.104327.
Huang, Jiansheng, et al. “Pharmacological Therapeutics Targeting RNA-Dependent RNA
Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-
19.” Journal of Clinical Medicine, vol. 9, no. 4, 2020, p. 1131., doi:10.3390/jcm9041131.
Vellingiri, Balachandar, et al. “COVID-19: A Promising Cure for the Global Panic.” Science of The
Total Environment, vol. 725, 2020, p. 138277., doi:10.1016/j.scitotenv.2020.138277.

Clinical Trials for COVID-19
Ceylin Gün
Developing a vaccine for coronavirus will, in all likelihood, take at
least 12 to 18 months. This time period is to guarantee its safety on
humans. The first step towards a safe vaccine is research and
discovery; this is the step which we are currently at. During this stage,
companies and researchers are testing potential treatment methods on
animals. This is a pre-step towards human clinical trials.
Once the vaccines are proven successful, they need to be approved by
the relevant authority (for instance, the FDA in the United States).
Then the protocol for human clinical trials is initiated. The first phase is
to inject less than 100 healthy people with the potential vaccine and
observe its side effects for months. In this phase, it will be decided
whether the harmful side effects will prevent the vaccine from being
used or not. The second phase is to vaccinate hundreds of people and
monitor them for a longer period of time. This usually takes around
two years. However, in the case of the coronavirus pandemic that
affects people from diverse backgrounds, it is easier to recruit
volunteers for testing who don’t belong to specific subsets,

Joy of Sharing Science
which fastens the timeframe.
After a successful second phase, the third phase is to vaccinate thousands of people from
varying subsets of the population. The effects of the vaccine are monitored for people of
different ages, health, sex, background, etc.
After these three phases are proven to be successful, the vaccine will be approved for mass
production; however, its side effects will still be monitored by the producer company. If
proven harmful, the vaccine may be taken out of the market at any time.
You can visit the website to track ongoing clinical trials:
https://coronavirus.tghn.org/covid-therapeutic-trials/covid-ongoing-trials/
(Image Taken from “Current Worldwide Clinical Trials on COVID-19”)
References:
Leng, Dawei. “Current Worldwide Clinical Trials on COVID-19.” Targeting Covid-19
Portal , 6 May 2020, ghddi-ailab.github.io/Targeting2019-nCoV/clinical/.
“The Clinical Trial Process for a COVID-19 Vaccine.” Deep 6 AI, 13 Mar. 2020,
deep6.ai/the-clinical-trial-process-for-a-covid-19-vaccine/.