J oSS
No: 2, COVI D19 Bi ol ogySuppl ement
26J une2020
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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: Naire Altunkeser
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Elif Demir,
Junior student
Ceylin Gün,
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Mehmet Efe Kılıç,
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Ada Özgirin,
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Ece Paksoy,
Junior student
Eda Paksoy,
Junior student
Selin Eda Sağnak,
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İrem Yaşa,
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Yasemin Yüksel,
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Etiology and the Source of COVID-19 Ada Ă&#x2013;zgirin 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-19â&#x20AC;&#x2122;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/IlluminaMarketing/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-signaling14047077/#:~: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 COVID19: 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 COVID19 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., â&#x20AC;&#x153;New Insights of Emerging SARS-CoV-2: Epidemiology, Etiology, Clinical Features, Clinical Treatment, and Preventionâ&#x20AC;?)
(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/sag20-50-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-1-4-2003260.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)301713/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 COVID19 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-19pandemic-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 YĂźksel 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 cityâ&#x20AC;&#x2122;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 YĂźksel Polymerase Chain Reaction Tests
The first step in a PCR test is called extraction, where genetic material is purified from a patientâ&#x20AC;&#x2122;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 itâ&#x20AC;&#x2122;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 didnâ&#x20AC;&#x2122;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 Detects active infections Looks for genetic material (RNA)
Uses mucus typically taken from nose or throat
Antibody test Detect whoâ&#x20AC;&#x2122;s been infected and who should theoretically be immune to the virus. Looks for antibodies to the virus
Uses blood samples
Antigen test 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)
Generally produces results in a few minutes
Provides results in just a few minutes
Helps detect the virus very early on because viral RNA will be present before antibodies form or symptoms of the disease are present
Helps track the spread of the virus and what proportion of the population are theoretically immune to the virus
Helps screening patients for infection
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
Not certain if Covid-19 generates an immune response that creates antibodies which last a long time. Therefore, patients can be infected again.
Not as accurate as the PCR diagnostic test
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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 cellâ&#x20AC;&#x2122;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 COVID19")
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 hasnâ&#x20AC;&#x2122;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.
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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 COVID19.” 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 GĂźn 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 donâ&#x20AC;&#x2122;t belong to specific subsets,
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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/.