CSU BMS291: Online Scenario 1 - Coronavirus Infection Case Study

This case study, part of the BMS291 Pathophysiology and Pharmacology 1 course at Charles Sturt University, focuses on a medical student named Lilly and her potential exposure to the novel coronavirus (SARS-CoV-2) during a clinical placement in Wuhan, China. The assignment requires students to apply the chain of infection to explain Lilly's potential infection, detailing the pathogen, reservoir, portal of exit, means of transmission, portal of entry, and new host. Furthermore, the case study delves into the biology of coronaviruses, prompting an exploration of viral evolution through antigenic shift and drift. Students are tasked with hypothesizing how the virus may have mutated to infect humans, referencing previous outbreaks like SARS-CoV and MERS-CoV, and analyzing the virus's structure and genetic material. The assignment emphasizes the importance of referencing scientific articles and drug databases.

Online Scenario 1 ─ New due date: 19/04/20
This case study will assess content discussed in Topics 1-5. You will work on 6 questions that
will be marked totalling to a mark out of 60. This mark out of 60 will be converted to a
mark out of 12 because this assessment task is worth 12% of your final marks for this
subject.
Whilst your lecturers aim to create realistic and relevant learning opportunities within in a
safe environment, you may find that when working through a case study or scenario it may
impact on you in unexpected ways. This could include raising cultural, spiritual, psychological
or personal issues for you that you were not expecting. If this occurs, it is important that you
discuss these issues with a trusted friend, family member, staff member, or counsellor.
Remember: CSU offers a free counselling service to internal and distance education students
in-person and via phone, Skype (webcam) and e-mail. To access the CSU Counselling Service,
please visit https://student.csu.edu.au/services-support/health-wellbeing/counselling
Notes on referencing
You will not be penalised for incorrect referencing in this Online Scenario but you should use
this assessment task as practice and learn from the feedback given ahead of undertaking
Scenario 2. In Online Scenario 2, 4% of your final marks will be allocated to referencing (see
marking rubric in subject outline).
It is NOT appropriate to cite lecture slides, lecture recordings, or general websites. Please
ONLY use textbook chapters, scientific articles and drug databases as reference materials.
Some handy links to APA 7th edition referencing guide and Australian drug databases are
provided below. You can also browse scientific articles using platforms such as Google
scholar and then download them from CSU library, but please contact CSU librarians for
help with literature search if you need to.
APA referencing
https://cdn.csu.edu.au/__data/assets/pdf_file/0011/294977/Charles-Sturt-University-APA-
Referencing-Summary.pdf
MIMS online
https://www-mimsonline-com-au.ezproxy.csu.edu.au/Search/Search.aspx
Australian Medicine Handbook (AMS)
https://amhonline-amh-net-au.ezproxy.csu.edu.au/
Google scholar
https://scholar.google.com.au/
CSU library
https://www.csu.edu.au/division/library

Case study: 2019 Novel Coronavirus
Part I — Oh no, could I have been infected with this new virus?
Lilly is a medical student at Wuhan University, located in the city of Wuhan, Hubei Province
in China. She was undertaking a clinical placement at the end of February 2020 and they
were receiving lots of patients with flu symptoms, some even progressing to pneumonia.
Although taking several precautions and following standard strict healthcare hygiene
The following are the specific steps underlying the ways in how Lilly may have acquired an illnessl, as per
the six steps of the chain of infection:
1. Pathogen: The first step responsible for facilitating the chain of infection is the pathogen, that is,
the primary microorganism responsible for causing a particular disease or illness. Pathogens in
chain of infection, refer to a virus or a bacterial strain (Pawar et al., 2016). In this case, the
pathogen is viral in nature and is responsible for inducing flu and pneumonia like symptoms in
patients treated by Lily in her clinical placement. In case of the emerging issue of novel coronavirus
incidences in Wuhan, the pathogen responsible is a novel viral strain named ‘severe acute
respiratory syndrome coronavirus 2’ (SARS-CoV-2) (Zhu et al., 2020).
2. Reservoir: This step of the chain of infection implies the natural environment in which the
pathogen has to reside for the purpose of survival. For SARS-CoV-2, the reservoir is a human host –
which in this case, includes the patients at Wuhan in Lily’s clinical placement who have presented
with symptoms of flu and pneumonia. Thus, it is likely that Lilly’s infection with the virus is via an
exposure to reservoirs carrying SARS-CoV-2, which include the patients at Wuhan in her clinical
placement.
3. Portal of Exit: This step of the chain of infection highlights the processes which are required for the
pathogen to leave its reservoir (Aiello et al., 2016). In this case, the portals of exit which are
required for SARS-CoV-2 to leave the human reservoirs, that is the patients at Wuhan, include
coughing and sneezing by these patients, which may have likely occurred in the vicinity of Lilly
(Huang et al., 2020).
4. Means of Transmission: This step highlights the ways in which the pathogen can come in contact
with other potential reservoirs for continued transmission. For SARS-CoV-2, the viral strain is
transmitted in the form of droplets in the air, via coughing and sneezing by the patients and
Wuhan, followed by individuals like Lilly coming in direct contact with these droplets, during
treating such patients.
5. Portal of Entry: This step in the chain of infection outlines the key strategies with which the
pathogen gains entry into the potential reservoirs for transmission. For SARS-CoV-2, the mode of
transmission which may transmit infection to potential human reservoirs like Lilly include: direct
inhalation of the droplets released via the patient’s sneezing or coughing at Wuhan or Lilly
contacting any item used by these patients during coughing and sneezing followed by toughing her
face, mouth or nose (Wang et al., 2020).
6. New Host: This step outlines the new reservoir upon which the pathogen exerts of characteristic
symptoms. In this case, the SARS-CoV-2 has entered the new reservoir Lilly and has begun to inflict
symptoms of fever and coughing (Wang et al., 2020).

procedures, Lilly had started to feel unwell on Saturday after having worked a couple of
shifts during the week. She started coughing frequently and had a temperature…
Question 1 – Apply the chain of infection to this case by providing an example of how Lilly
could have been infected from working at the hospital. In your example, make sure
to outline and define each step in the chain of infection (max 400 words). (10 marks)
Part II — what is coronavirus
Lilly starts her own investigations about the coronavirus in the scientific literature. She
learns that this is not the first time a member of the large Corona virus family has infected
humans. The most recent outbreaks with previous corona virus strains happened in 2003,
causing a human infection named Severe Acute Respiratory Syndrome (SARS-CoV) that
killed 774 people in China, and in 2012, the Middle East Respiratory Syndrome (MERS-CoV)
killed 912 people in Saudi Arabia. These viruses are zoonotic (transmitted to people from
animals in a process known as spillover), although human infections are relatively rare and
most known strains have never infected humans. SARS-CoV was transmitted from civet cats
and MERS-COV from dromedary camels, yet so far, the origin of the novel coronavirus
(COVID-19) remains uncertain.
The 2019 Novel corona virus (COVID-19) was previously unknown until its outbreak in China
in late 2019. It started to appear as cases of pneumonia in the population of Wuhan and was
supposedly firstly acquired in seafood markets, spreading first to family members and
healthcare providers. The morbidity rate has been quickly growing in China and the
mortality rate has not yet been precisely determined as it’s so new, although it has been the
cause of death of around 2-3% of the affected individuals.
The Corona are RNA viruses, consisting of the longest known viral RNA molecules wrapped
in an envelope, which is coated with protein “spikes”, making the virus look like a crown
when looked under an electronic microscope. In fact, this is the very reason this viral family
was named “corona”, which means “crown” in Latin. The really long RNA genetic material
codes for several proteins and enzymes that participate in the viruses’ structure and life
cycle.

Fig 1. Corona virus structure. Source: https://www.inquirer.com/business/drugs/coronavirus-johnson-and-
johnson-stoffels-wuhan-20200128.html
Lilly thinks — “Wow! How crazy is it that such a small, acellular, non-living organism can
cause so much damage to several species. How come some viruses can change so quickly
and become capable of infecting different hosts? Would it have to do with their structure
and the type of genetic material they carry? Oh no…I’m not feeling well but I have soooo
much reading to do!!”
Question 2 – Help Lilly understand by providing a hypothesis of how the corona virus may
have evolved. In your answer, make sure to explain the concepts of antigenic shift and
antigenic drift (up to 300 words). (8 marks)
The mechanisms by which the novel coronavirus strain may have mutated to transmit from
animals to humans can be hypothesized with the help of antigenic drift and shift mechanisms.
Antigenic shift is the mechanism of mutation which occurs when animal viruses and human
viruses cross to form a new viral strain which then is transmitted to humans (Marintcheva,
2016). It has been known that infections similar to the SARS-CoV-2 viral strain had occurred
previously in the form of Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute
Respiratory Syndrome (SARS-CoV) transmitted from the civet rats and camels. Recent
incidences of infections by the SARS-CoV-2 strain have been linked to seafood markets. Thus
as per the mechanism of antigenic shift, it can be hypothesized that previous strains of the
Corona virus family may have crossed between strains affecting rats, camels and seafood with
influenza or viral strains in humans thus resulting in the emergence in the novel SARS-CoV-2
viral strains affecting humans (Zhou et al., 2020).
Antigenic drift is a mechanism of mutation via which the RNA of influenza viruses acquire
minor mutations resulting in the development of accumulation of proteins like neuraminidase
(NA) and hemagglutinin (HA) on its surface. These surface proteins are capable of recognition
by the immune system which in turn, facilitates the production of antibodies and the resultant
immunological response. Antigenic drift can be examined across viral strains which are similar
or belonging to the same phylogenetic group (Naem et al., 2020). A number of such small
changes often accumulate to form a viral strain with novel antigenic properties unrecognizable
by the human immune system resulting in absence of antibody production and resultant
illness. Thus, as per the mechanisms of antigenic drift, it can be hypothesized that previous
Corona virus strains may have accumulated a number of RNA changes with respect to HA and
NA over time, resulting in the evolution of the new viral strain SARS-CoV-2 (Wu et al., 2020).

Diagnosis and treatment
Living up to her “nerdy” reputation, Lilly does further reading despite her headache to find
out that the diagnostic test of COVID-19 infection can be performed using a polymerase
chain reaction (PCR) that recognises the presence of the virus’ genetic footprint. This means
that RNA molecules are isolated from the patient’s saliva or sputum and matched with
known sequence fragments of the corona virus RNA. If there is a match, there is an
infection!
She then finds out that treatment and vaccination options are being quickly explored by
scientists all around the world. Some antiviral trials have been initiated but results are
predicted for April 2020. She reads this freshly published review from Nature Reviews Drug
Discovery to understand what options are on the table: "Therapeutic options for the 2019
novel coronavirus (2019-nCoV)” by Li and Clercq (2020).
Access link: https://www.nature.com/articles/d41573-020-00016-0.
Question 3 – Provide 3 examples of drugs that could be effective against COVID-2019 based
on the review by Li and Clercq (2020) cited above. What classes of antiviral pharmacology
(as presented in the lecture notes) would each one of these 3 investigated drugs belong to
(chose examples that fit into different antiviral classes)? Describe the general mechanism of
action of drugs in these antiviral classes and explain why they could be potentially effective
against COVID-2019 (400 words max). (12 marks)
As per the review by Li and Clercq (2020), the following three antiviral drugs and class can be
considered to be effective against COVID-2019:
1. Lopinavir: This drug belongs to the antiviral class known as antiretroviral protease
inhibitors. Drugs like lopinavir which belong to the antiretroviral protease inhibitors
exert their mechanism of action via inhibiting the functioning of a class of enzymes,
known as proteases, which play an essential function in viral life cycles. The lifecycle of
viral strains can be categorized into stages of assembly, formulation of viral compounds
and budding – which are largely regulated and controlled by structural proteins like the
Gap polyprotein. Protease enzymes are responsible for cleaving and activating this
polyprotein to thus facilitate the viral lifecycle (Gondrie et al., 2017). Protease
inhibitors like lopinavir can deregulate the same by inhibiting the functioning of these
essential enzymes. The SARS-CoV-2 virus contains papain-like and 3-chymotrypsin-like
proteases which is why antiretroviral protease inhibitors like lopinavir can be
considered to be a promising drug (Li & De Clercq, 2020).

2. Griffithsin: This drug belongs to the antiviral class known as lectins. Lectins have been
evidenced to exert their mechanism of action by binding to the high density glycans
present in the viral glycoproteins namely NA and HA. These proteins are responsible for
a range of functions essential for the life cycle of virus such as: encouraging assembly of
novel viral components, fusion of endosomal membranes with viral membranes and
binding with sialic acid cells receptors for cleavage and secretion of new viral particles
(Li et al., 2019). It has been evidenced that Griffithsin can treat SARS-CoV-2 infections
by binding with the spiked glycoproteins characteristic in Corona viruses and contribute
to inhibition of the viral life cycle by inhibiting the above essential viral functions (Li &
De Clercq, 2020).
3. Pegylated Interferons -2b and -2a in combination with ribavirin: Ribavirin belongs to
the antiviral class of guanosine (ribonucleic) analogs while -2b and -2a belong to the
antiviral classes of interferons. Ribavirin exerts its mechanism of action by inhibiting
the functioning of RNA polymerases which in turn inhibits the replication of RNAs
which are essential for the survival of viruses. Additionally, ribivarin modulates the
functioning of interferons. Pegylated interferons exert their mechanism by stimulating
antiviral mechanisms within the body by facilitating infected cells to produce
antibodies against viral strains (Naggie et al., 2017). Thus, this combination can assist in
COVID-2019 treatment by inhibiting the replication of SARS-CoV-2 viral strains within
the host. Additionally, this combination can also assist in COVID-2019 treatment by
facilitating the immune responses of host against the novel SARS-CoV-2 viral strains (Li
& De Clercq, 2020).

In the review by Li and Clercq (2020), it’s mentioned that Remdesivir is one of the promising
antiviral drugs against a range of RNA virus and it’s currently being tested in the United
States. The authors mention that Remdesivir is a prodrug.
Question 4 — Explain how a prodrug is activated during the phases of metabolism in the
liver. Then, discuss how pharmacogenetic variations may alter the bioavailability of a
prodrug in different individuals and explain how an adjustment in dose and dosing
frequency is required for different types of metabolisers (300 words max). (10 marks)
Clinical manifestations
A prodrug is the name given to a compound with negligible amounts of pharmacological
activity. Prodrugs undergo metabolism to produce metabolites which can stimulate the
bioavailability of other medications to produce active pharmacological properties by the
cytochrome p450 enzyme during the stages of metabolism undergoing in the liver. Prodrugs
are generally metabolized by cytochrome p450 enzymes during phase I1 reactions of
metabolism in the liver. Cytochrome p450 oxidases via hydroxylation mechanisms, polarize
the prodrugs so that they can conjugate with polar compounds during phase II reactions
which then enhance the bioavailability of other medications (Lüpfert et al., 2018).
Genetics have been known to influence the bioavailability of drugs and prodrugs. This
means that individuals possessing genetic mutations of certain enzymes are likely to affect
the bioavailability of several drugs upon absorption (Lüpfert et al., 2018). For examples,
individuals who possess polymorphisms in gene expression of thiopurine S-
methyltransferase enzymes in the form of mutant alleles are likely to demonstrate
hematopoietic toxicity upon consumption of immunosuppressive drugs like azathioprine.
Thus it is likely that genetic variations will largely impact the absorption and metabolism of
prodrugs and drugs in individual possessing such polymorphisms in the genetic expression
of cytochrome p450 oxidases (Shu et al., 2017).
Thus, such polymorphisms in cytochrome p450 genetic enzyme can either contribute to an
elevation or a decrease in the individual functional activities of various cytochrome p450
enzymes. Individuals in whom these polymorphisms are expressed in higher levels are likely
to result in increased metabolic capacity (Shu et al., 2017). Such individuals are known are
‘hyper’ or ‘extensive’ metabolizers and thus, if prodrug dosages are not controlled, they are
likely to acquire higher bioavailability of drugs and thus encounter toxicity and overdose of
metabolites. Thus, as per pharmacogenetic variations, it is thus imperative to regulate and
adjust the dosages and dosing frequency of prodrugs to ensure regulation of optimum drug
bioavailability in different types of metabolizers (Cavallari & Obeng, 2017).

Lilly goes on to investigate the clinical manifestation of the Corona viruses. Different types
of corona viruses usually cause respiratory clinical manifestations, varying from common
cold and pneumonia, and sometimes mild gastrointestinal symptoms. Although the
infections are usually not severe, there are exceptions such as SARS, MERS and the COVID-
19. The signs of COVID-19 are usually fever, cough and shortness of breath, sometimes
escalating to pneumonia, kidney failure and death.
Lilly has just learned in her Pathophysiology class that pneumonia involves inflammation of
the lungs. She also learned how inflammation can cause pain.
Question 5 – Describe the pathophysiology of acute inflammation induced by a viral
infection. Suppose that the natural mechanism of acute inflammation was not successful in
healing the tissue area damaged by the virus and necrotic patches developed in the lungs.
Explain how inflammation could progress to necrosis (up to 300 words). (10 marks)
Question 6 — Explain how inflammation could cause somatic pain in the throat (describe
the somatosensory pain pathways involved). Outline one drug group that could be
Upon entry of a viral strain, the functioning of the innate immune systems of the body is
facilitated which facilitates production of pro-inflammatory substances like cytokines. The
rapid production of cytokines at the point of viral infection is the key contributor to the
pathophysiology of inflammation. Innate immune system cells like macrophages and
monocytes, in response to the virus, stimulate the production of the cytokine tumour
necrosis factor (TNF) (Beyer et al., 2016). TNF facilitates the production of antibodies and
stimulate capillaries in the vicinity to allow the entry of white blood cells required to combat
the viral infection. However, prolonged activation of these processes without any change
induced in the viral strain is likely to contribute to inflammation induced cell necrosis, via
mainly four inflammatory mechanisms: pain, heat, erythema and swelling (Williams et al.,
2020). Pain is causes due to the proliferation of pro-inflammatory substances like
prostaglandins erythema is caused as a result of constriction of capillaries which results in
capillary engorgement and increased influx of blood flow and phagocytic cells which damage
viral as well as surrounding cell and tissues. The combined effect of capillary constriction,
increased blood flow and pain mechanisms stimulate the inflammation side effects of
swelling. Such inflammatory mechanisms coupled with the production of free radicals
contribute to injury in cells and resultant cell death, apoptosis and overall necrosis (Cai et al.,
2016). Such long term processes of coagulation ultimately contribute to coagulation. In
coagulation, the proteins in healthy cells are likely to become acidified in the presence of
such inflammatory mechanisms resulting in the breakdown of cellular proteins and cell
death. Increased rates of coagulation and apoptosis due to cell death thus contribute to
necrosis of cells and tissues as a result of inflammation caused to the infection by viral
strains (De Visser et al., 2017).

prescribed to control both inflammation and pain and describe its mechanism of action (up
to 200 words). (10 marks)
The key neurons which are responsible for pain perceptions are known as nociceptors.
Inflammation causes pain the throat via the stimulation of A and C nociceptor fibers as a result of
depolarization in the presence of noxious chemical or thermal factors such as swelling and heat
produced due to inflammation. Upon stimulation these nerve fibers transmit the nerve impulse to
the spinal cord’s dorsal horn which in turn results in the stimulation of glutamate and associated
neurotransmitters. These contribute to the transmission of the impulse across post synaptic
neurons to the brain, where the overall pain sensation is localized, perceived and interpreted (Duan
et al., 2018). Non-steroidal anti-inflammatory drugs (NSAIDS) are a key group of drugs which can be
used to treat both inflammation and pain. Examples of drugs include aspirin and ibuprofen. NSAIDs
exert their mechanisms of actions via inhibition of enzymes known as cyclooxygenases, such as
COX-2 and COX-1. This is because these enzymes facilitate the release of key pro-inflammatory
substances which are responsible for facilitating inflammation, swelling and pain. The inhibition of
such enzymes by NSAIDs thus assists in the alleviation of symptoms like fever and pain which occur
due to inflammation as a result of infections (Gupta & Bah, 2016).

APA referencing list:
Aiello, A. E., Simanek, A. M., Eisenberg, M. C., Walsh, A. R., Davis, B., Volz, E., ... & Osgood, N.
(2016). Design and methods of a social network isolation study for reducing respiratory
infection transmission: The eX-FLU cluster randomized trial. Epidemics, 15, 38-55.
https://doi.org/10.1016/j.epidem.2016.01.001.
Beyer, M., Abdullah, Z., Chemnitz, J. M., Maisel, D., Sander, J., Lehmann, C., ... & Trebicka, J.
(2016). Tumor-necrosis factor impairs CD4+ T cell–mediated immunological control in
chronic viral infection. Nature immunology, 17(5), 593. https://doi.org/10.1038/ni.3399.
Cai, J., Han, T., Nie, C., Jia, X., Liu, Y., Zhu, Z., & Gao, Y. (2016). Biomarkers of oxidation stress,
inflammation, necrosis and apoptosis are associated with hepatitis B-related acute-on-
chronic liver failure. Clinics and research in hepatology and gastroenterology, 40(1), 41-
50. https://doi.org/10.1016/j.clinre.2015.06.009.
Cavallari, L. H., & Obeng, A. O. (2017). Genetic determinants of P2Y12 inhibitors and clinical
implications. Interventional cardiology clinics, 6(1), 141.
https://dx.doi.org/10.1016%2Fj.iccl.2016.08.010.
De Visser, L., de Boer, J. H., Rijkers, G. T., Wiertz, K., van den Ham, H. J., de Boer, R., ... & de Groot-
Mijnes, D. F. (2017). Cytokines and chemokines involved in acute retinal
necrosis. Investigative ophthalmology & visual science, 58(4), 2139-2151.
https://doi.org/10.1167/iovs.16-20799.
Duan, Z., Su, Z., Wang, H., & Pang, X. (2018). Involvement of pro-inflammation signal pathway in
inhibitory effects of rapamycin on oxaliplatin-induced neuropathic pain. Molecular
pain, 14, 1744806918769426. https://doi.org/10.1177%2F1744806918769426.
Gondrie, I. P., Bastiaans, D. E., Fraaij, P. L., Driessen, G. J., Van Der Knaap, L. C., Visser, E. G., ... &
van Rossum, A. (2017). Sustained viral suppression in HIV-infected children on once-daily
lopinavir/ritonavir in clinical practice. The Pediatric infectious disease journal, 36(10), 976-
980. https://doi.org/10.1097/INF.0000000000001627.
Gupta, A., & Bah, M. (2016). NSAIDs in the treatment of postoperative pain. Current pain and
headache reports, 20(11), 62. https://doi.org/10.1007/s11916-016-0591-7.
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., ... & Cheng, Z. (2020). Clinical features of
patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223),
497-506. https://doi.org/10.1016/S0140-6736(20)30183-5.

Li, G., & De Clercq, E. (2020). Therapeutic options for the 2019 novel coronavirus (2019-nCoV).
https://www.nature.com/articles/d41573-020-00016-0.
Li, L., Yu, X., Zhang, H., Cheng, H., Hou, L., Zheng, Q., & Hou, J. (2019). In vitro antiviral activity of Griffithsin
against porcine epidemic diarrhea virus. Virus genes, 55(2), 174-181. https://doi.org/10.1007/s11262-
019-01633-7.
Lüpfert, C., Dyroff, M., von Richter, O., Gallemann, D., El Bawab, S., Dolgos, H., ... & Johne, A. (2018). A Novel
PBPK Modeling Approach to Assess Cytochrome P450 Mediated Drug Drug Interaction Potential of‐
the Cytotoxic Prodrug Evofosfamide. CPT: pharmacometrics & systems pharmacology, 7(12), 829-837.
https://doi.org/10.1002/psp4.12360.
Marintcheva, B. (2016). Modeling Influenza Antigenic Shift and Drift with LEGO Bricks. Journal of microbiology
& biology education, 17(2), 300. https://dx.doi.org/10.1128%2Fjmbe.v17i2.1096.
Naeem, A., Elbakkouri, K., Alfaiz, A., Hamed, M. E., Alsaran, H., AlOtaiby, S., ... & Alosaimi, B. (2020). Antigenic
Drift of Hemagglutinin and Neuraminidase in seasonal H1N1 influenza Viruses from Saudi Arabia in
2014 2015.‐ Journal of Medical Virology. https://doi.org/10.1002/jmv.25759.
Naggie, S., Marks, K. M., Hughes, M., Fierer, D. S., Macbrayne, C., Kim, A., ... & McHutchison, J. G. (2017).
Sofosbuvir plus ribavirin without interferon for treatment of acute hepatitis C virus infection in HIV-1–
infected individuals: SWIFT-C. Clinical Infectious Diseases, 64(8), 1035-1042.
https://doi.org/10.1093/cid/cix025.
Pawar, A., Garg, S., Mehta, S., & Dang, R. (2016). Breaking the chain of infection: dental unit water quality
control. Journal of clinical and diagnostic research: JCDR, 10(7), ZC80.
https://dx.doi.org/10.7860%2FJCDR%2F2016%2F19070.8196.
Shu, W., Chen, L., Hu, X., Zhang, M., Chen, W., Ma, L., ... & Zhang, Y. (2017). Cytochrome P450 Genetic
Variations Can Predict mRNA Expression, Cyclophosphamide 4 Hydroxylation, and Treatment‐
Outcomes in Chinese Patients With Non Hodgkin's Lymphoma.‐ The Journal of Clinical
Pharmacology, 57(7), 886-898. https://doi.org/10.1002/jcph.878.
Wang, C., Horby, P. W., Hayden, F. G., & Gao, G. F. (2020). A novel coronavirus outbreak of global health
concern. The Lancet, 395(10223), 470-473. https://doi.org/10.1016/S0140-6736(20)30185-9.
Williams, A. M., Nguyen, V. Q., Botsford, B. W., & Eller, A. W. (2020). Bilateral acute retinal necrosis caused by
two separate viral etiologies. American Journal of Ophthalmology Case Reports, 100636.
https://doi.org/10.1016/j.ajoc.2020.100636.
Wu, F., Zhao, S., Yu, B., Chen, Y. M., Wang, W., Song, Z. G., ... & Yuan, M. L. (2020). A new coronavirus
associated with human respiratory disease in China. Nature, 579(7798), 265-269.
https://doi.org/10.1038/s41586-020-2008-3.
Zhou, P., Yang, X. L., Wang, X. G., Hu, B., Zhang, L., Zhang, W., ... & Chen, H. D. (2020). A pneumonia outbreak
associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270-273.
https://doi.org/10.1038/s41586-020-2012-7.
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., ... & Niu, P. (2020). A novel coronavirus from patients
with pneumonia in China, 2019. New England Journal of Medicine.
https://www.nejm.org/doi/full/10.1056/NEJMoa2001017.