Pandemic COVID-19

What is COVID -19?

COVID-19 is an acronym for Corona Virus Disease 2019. It is caused by the virus SARS-CoV-2, an acronym for Severe Acute Respiratory Syndrome Coronavirus 2. The common symptoms of COVID-19 are

Less common symptoms:

aches and pains
sore throat
diarrhoea
conjunctivitis
headache
loss of taste or smell
a rash on skin, or discolouration of fingers or toes

What is a Virus?

A Virus outside the host body is just a particle made up of genetic material in the form of DNA or RNA encapsulated by lipid and protein layers.

Is a Virus living or non-living?

There is no clear classification of Virus as living or non-living. Virus shows some attributes of living organisms while some attributes are missing. Particularly the behaviour of Virus outside the host body are that of a non-living organism. Like outside the host body the Virus can’t replicate neither its active nor depending on its surroundings for nutrients. It is really the behaviour of the Virus inside the host body that qualifies it as living. Inside a host body the Virus replicates and mutates to different forms.

Discovery of Virus

Russian biologist Dmitri Ivanovsky in the year 1892 and Dutch microbiologist Martinus Beijerinck in the year 1898 are credited for the discovery of the first Virus, “Tobacco Mosaic Virus” using the technology invented by French microbiologist Charles Chamberland in the year 1884

Tobacco Mosaic Virus (TMV)

As the name indicates, the TMV primarily infects the Tobacco plant leaves and causes discoloration in some areas of the leaves turning them into a mosaic like pattern. The TMV is a positive sense single stranded RNA.

What is RNA?

RNA acronym for Ribonucleic Acid is a polymer ( Greek poly-, “many” + -mer, “part”) of nucleotides. Nucleotides are building blocks of Nucleic Acid or RNA. A nucleotide consists of a 5-carbon sugar molecule, a phosphate group and a nitrogenous base. The four bases used in nucleotide of RNA are Adenine (A), Cytosine (C), Guanine (G), and Uracil (U).

Positive Sense Virus

During protein synthesis process in cells the information in the DNA of the nucleus must travel to the protein synthesis sites of the cytoplasm and endoplasmic reticulum. The information in the DNA is transferred to a mRNA (messenger RNA) during transcription. This mRNA carries the genetic material or copy of the DNA which will in the end decide the protein synthesis from the cell. In short, the mRNA has message which can be directly used by the cell for protein synthesis.

Those type of viruses which carry a single stranded RNA as genetic material capable of acting like a mRNA and when these viruses enter a host body and the RNA from virus can directly be read by the host for protein synthesis are called as Positive Sense Virus. These viruses with positive sense are highly infectious as the protein synthesis in the host body need not wait for any other mechanism.

Baltimore classification

American biologist and Nobel Prize winner David Baltimore in the 1970s developed a method to classify Viruses based on the production method of mRNA.

SARS-CoV-2

SARS-CoV-2 (virus causing COVID-19) is a Baltimore class IV positive-sense single-stranded RNA virus(ssRNA) which is highly contagious to humans.

Taxonomical Classification:

Realm:	Riboviria
Kingdom:	Orthornavirae
Phylum:	Pisuviricota
Class:	Pisoniviricetes
Order:	Nidovirales
Family:	Coronaviridae
Genus:	Betacoronavirus
Subgenus:	Sarbecovirus
Species:	Severe acute respiratory syndrome–related coronavirus
Strain:	Severe acute respiratory syndrome coronavirus 2

History of SARS (Severe Acute Respiratory Syndrome) and Coronavirus

SARS or respiratory diseases are usually caused by Coronaviruses and affects both humans and animals. Coronaviruses were first discovered in the year 1930 affecting domestic poultry. In the year 1965 first human coronavirus was discovered. So far 7 coronavirus affecting humans are discovered:

229E (alpha coronavirus)
NL63 (alpha coronavirus)
OC43 (beta coronavirus)
HKU1 (beta coronavirus)
MERS-CoV (the beta coronavirus that causes Middle East Respiratory Syndrome, or MERS)
SARS-CoV (the beta coronavirus that causes severe acute respiratory syndrome, or SARS)
SARS-CoV-2 (the novel coronavirus that causes coronavirus disease 2019, or COVID-19)

229E, NL63, OC43, and HKU1 infections are very common and the symptoms are flu and common cold.

SARS-CoV 2003

SARS coronavirus (SARS-CoV) – virus identified in 2003. SARS-CoV is thought to be an animal virus from an as-yet-uncertain animal reservoir, perhaps bats, that spread to other animals (civet cats) and first infected humans in the Guangdong province of southern China in 2002. An epidemic of SARS affected 26 countries and resulted in more than 8000 cases in 2003.Implementation of appropriate infection control practices brought the global outbreak to an end.

Country or region	Cases	Deaths	Fatality (%)
China	5,327	349	6.6
Hong Kong	1,755	299	17
Taiwan	346	73	21.1
Canada	251	43	17.1
Singapore	238	33	13.9
Vietnam	63	5	7.9
USA	27	0	0
Philippines	14	2	14.3
Thailand	9	2	2

MERS-CoV (the beta coronavirus that causes Middle East Respiratory Syndrome, or MERS)

Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a novel coronavirus (Middle East respiratory syndrome coronavirus, or MERS‐CoV) that was first identified in Saudi Arabia in the year 2012. The MERS coronavirus travels to humans from infected camels, the camels are infected by bats carrying the virus.

MERS has a very high mortality rate, out of 2519 cases 35 % people have died so far since 2012.

Country or region	Cases	Deaths	Fatality
Saudi Arabia	1029	452	0.44
South Korea	184	38	0.2
United Arab Emirates	74	10	0.14
Jordan	19	6	0.32
Qatar	10	4	0.4
Oman	5	3	0.6
Iran	5	2	0.4

Other historic pandemics:

1918 H1N1 (Spanish flu): Killed around 50 million people worldwide

1957 H2N2 (Asian flu): Killed around 4 million people worldwide

1968 H3N2 (Hong Kong flu): Killed 1 million people worldwide

2005 H5N1 (Bird flu): Which mostly affected more birds and few human causalities

2009 H1N1 (Swine flu): Killed around 18,000 people worldwide

How does the SARS-CoV-2 affects the host body?

Structure of SARS-CoV-2

The coronavirus has four structural proteins, Nucleocapsid (N) protein, Membrane (M) protein, Spike (S) protein and Envelop (E) protein and several non-structural proteins. The capsid is the protein shell, inside the capsid, there is nuclear capsid or N-protein which is bound to the virus single positive strand RNA that allows the virus to hijack human cells and turn them into virus factories. The N protein coats the viral RNA genome which plays a vital role in its replication and transcription.

The coronavirus spike (S) protein attaches to angiotensin converting enzyme 2 (ACE2) receptors that is found on the surface of many human cells, including those in the lungs allowing virus entry. From there, the virus makes its way down into the air sacs inside your lungs, known as alveoli.

Once inside the body the viral proteins begin making copies of the viral genetic instructions and new viral proteins using the virus’s genetic instructions and the cell’s enzyme machinery. Once the new viruses are made, they leave the host cell by breaking the cell membrane destroying the host cell in the process. Sometimes the virus travel inside the membrane coat and hence the body takes time to detect the foreign body. Once the host body detects the pathogen, it releases pyrogens which increases the body temperature and hence the fever that follows the viral infection. SARS-Cov2 virus affects both the lower and upper respiratory tracts.

Decease propagation:

Phase -1: Early Infection

Transmission: A healthy person inhales the virus through various means of transmission. The disease spreads primarily from person to person through small droplets from the nose or mouth, which are expelled when a person with COVID-19 coughs, sneezes, or speaks. These droplets are relatively heavy, do not travel far and quickly sink to the ground. People can catch COVID-19 if they breathe in these droplets from a person infected with the virus. Therefore, it is important to stay at least 1 meter) away from others. These droplets can land on objects and surfaces around the person such as tables, doorknobs and handrails. People can become infected by touching these objects or surfaces, then touching their eyes, nose or mouth. Therefore, it is important to wash your hands regularly with soap and water or clean with alcohol-based hand rub.
Infection: The virus enters and attaches itself to the human body as explained earlier.
Incubation: The virus keeps replicating inside the body without any signs like fever
Body defence and symptoms: 14 days from infection the body will start producing antibodies and symptoms will start to appear. At this stage hospitalization and medical care would be required to mage symptoms like lack of oxygen in blood due to lung infections and lung’s ability to supply oxygenated blood to the body.

Phase-2: Pulmonary phase: Due to puss filled in the air sacs of the lungs pneumonia onsets and blood oxygen levels fall and patient may require external oxygen supply.

Phase 2A: Pneumonia without hypoxia (acute lack of oxygen in body parts)

Phase 2B: Pneumonia without hypoxia. Hypoxia can show symptoms like change in colour of skin, wheezing, sweating etc.

Phase-3: Hyperinflammation phase: During this phase there is total loss of blood oxygen and hence patients will need ventilator support

Treatment of COVID-19

So far there is no approved drug for the treatment of COVID-19, however below drugs have been used worldwide with mixed results:

Dexamethasone

Dexamethasone is a corticosteroid used in a wide range of conditions for its anti-inflammatory and immunosuppressant effects.

It was tested in hospitalized patients with COVID-19 in the United Kingdom’s national clinical trial RECOVERY and was found to have benefits for critically ill patients.

According to preliminary findings shared with WHO (and now available as a preprint), for patients on ventilators, the treatment was shown to reduce mortality by about one third, and for patients requiring only oxygen, mortality was cut by about one fifth.

Chloroquine/Hydroxychloroquine and Azithromycin

Hydroxychloroquine and chloroquine have been shown to kill the COVID-19 virus in the laboratory dish. The drugs appear to work through two mechanisms. First, they make it harder for the virus to attach itself to the cell, inhibiting the virus from entering the cell and multiplying within it. Second, if the virus does manage to get inside the cell, the drugs kill it before it can multiply.

Azithromycin is never used for viral infections. However, this antibiotic does have some anti-inflammatory action. There has been speculation, though never proven, that azithromycin may help to dampen an overactive immune response to the COVID-19 infection.

Remdesivir

Remdesivir is an investigational nucleotide analog with broad-spectrum antiviral activity – it is not approved anywhere globally for any use. Remdesivir has demonstrated in vitro and in vivo activity in animal models against the viral pathogens MERS and SARS, which are also coronaviruses and are structurally like COVID-19. The limited preclinical data on Remdesivir in MERS and SARS indicate that Remdesivir may have potential activity against COVID-19. Remdesivir is an experimental medicine that does not have established safety or efficacy for the treatment of any condition.

Drugs not so effective on COVID-19

Kaletra: A combination of lopinavir and ritonavir used as an antiviral drug for HIV patients has been proposed initially as a treatment of COVID-19. Later studies have proven that Kaletra is no so effective in managing the symptoms of COVID-19.

Myths: Antibacterial drugs do not work on COVID-19 as COVID-19 is caused due to the virus SARS-CoV-2 and not a bacteria. Viruses change the molecular programming of the body while bacteria work by attacking the cells by various means.

Plasms Transfusion: Convalescent Plasma: Convalescent refers to anyone recovering from a disease. Plasma is the yellow, liquid part of blood that contains antibodies. Antibodies are proteins made by the body in response to infections. Convalescent plasma from patients who have already recovered from coronavirus disease 2019 (COVID-19) may contain antibodies against COVID-19. Giving this convalescent plasma to hospitalized people currently fighting COVID-19 may help them recover.

COVID-19 Vaccination

There are at least 50 vaccine trials going on worldwide for COVID-19.

Candidate	Mechanism	Sponsor	Trial Phase	Institution
Ad5-nCoV	Recombinant vaccine (adenovirus type 5 vector)	CanSino Biologics	Phase 3	Tongji Hospital; Wuhan, China
AZD1222	Replication-deficient viral vector vaccine (adenovirus from chimpanzees)	The University of Oxford; AstraZeneca; IQVIA; Serum Institute of India	Phase 3	The University of Oxford, the Jenner Institute
CoronaVac	Inactivated vaccine (formalin with alum adjuvant)	Sinovac	Phase 3	Sinovac Research and Development Co., Ltd.
JNJ-78436735 (formerly Ad26.COV2-S)	Non-replicating viral vector	Johnson & Johnson	Phase 3	Johnson & Johnson
mRNA-1273	mRNA-based vaccine	Moderna	Phase 3	Kaiser Permanente Washington Health Research Institute
No name announced	Inactivated vaccine	Wuhan Institute of Biological Products; China National Pharmaceutical Group (Sinopharm)	Phase 3	Henan Provincial Center for Disease Control and Prevention
NVX-CoV2373	Nanoparticle vaccine	Novavax	Phase 3	Novavax
Bacillus Calmette-Guerin (BCG) vaccine	Live-attenuated vaccine	University of Melbourne and Murdoch Children’s Research Institute; Radboud University Medical Center; Faustman Lab at Massachusetts General Hospital	Phase 2/3	University of Melbourne and Murdoch Children’s Research Institute; Radboud University Medical Center; Faustman Lab at Massachusetts General Hospital
BNT162	mRNA-based vaccine	Pfizer, BioNTech	Phase 2/3	Multiple study sites in Europe and North America
Covaxin	Inactivated vaccine	Bharat Biotech; National Institute of Virology	Phase 2
No name announced	Recombinant vaccine	Anhui Zhifei Longcom Biopharmaceutical, Institute of Microbiology of the Chinese Academy of Sciences	Phase 2
ZyCoV-D	DNA vaccine (plasmid)	Zydus Cadila	Phase 2	Zydus Cadila
AG0301-COVID19	DNA vaccine	AnGes, Inc.	Phase 1/2	AnGes, Inc.; Japan Agency for Medical Research and Development
BBIBP-CorV	Inactivated vaccine	Beijing Institute of Biological Products; China National Pharmaceutical Group (Sinopharm)	Phase 1/2	Henan Provincial Center for Disease Control and Prevention
GX-19	DNA vaccine	Genexine	Phase 1/2
INO-4800	DNA vaccine (plasmid)	Inovio Pharmaceuticals	Phase 1/2	Center for Pharmaceutical Research, Kansas City. Mo.; University of Pennsylvania, Philadelphia
LUNAR-COV19 (ARCT-021)	Self-replicating RNA vaccine	Arcturus Therapeutics and Duke-NUS Medical School	Phase 1/2	Duke-NUS Medical School, Singapore
No name announced	Self-amplifying RNA vaccine	Imperial College London	Phase 1/2	Imperial College London
No name announced	Protein subunit vaccine	Sanofi; GlaxoSmithKline	Phase 1/2	Various
Sputnik V	Non-replicating viral vector	Gamaleya Research Institute, Acellena Contract Drug Research and Development	Phase 1/2	Various
EpiVacCorona	Peptide vaccine	Federal Budgetary Research Institution State Research Center of Virology and Biotechnology	Phase 1/2	Federal Budgetary Research Institution State Research Center of Virology and Biotechnology
AdimrSC-2f	Protein subunit vaccine	Adimmune	Phase 1	Adimmune
COVAX-19	Monovalent recombinant protein vaccine	Vaxine Pty Ltd.	Phase 1	Royal Adelaide Hospital
CVnCoV	mRNA-based vaccine	CureVac	Phase 1	CureVac
GRAd-COV2	Adenovirus-based vaccine	ReiThera; Leukocare; Univercells	Phase 1	Lazzaro Spallanzani National Institute for Infectious Diseases
No name announced	Plant-based adjutant vaccine	Medicago; GSK; Dynavax	Phase 1	Medicago
No name announced	Protein subunit vaccine	CSL; The University of Queensland	Phase 1
SCB-2019	Protein subunit vaccine	GlaxoSmithKline, Sanofi, Clover Biopharmaceuticals, Dynavax and Xiamen Innovax	Phase 1	Linear Clinical Research (Australia)
V590	Recombinant vaccine (vesicular stomatitis virus)	Merck; IAVI	Phase 1
V591	Measles vector vaccine	University of Pittsburgh’s Center for Vaccine Research	Phase 1	University of Pittsburgh; Themis Biosciences; Institut Pasteur
UB-612	Multitope peptide-based vaccine	COVAXX	Phase 1	United Biomedical Inc. (UBI)
AAVCOVID	Gene-based vaccine	Massachusetts Eye and Ear; Massachusetts General Hospital; University of Pennsylvania	Pre-clinical
AdCOVID	Intranasal vaccine	Altimmune	Pre-clinical	University of Alabama at Birmingham
bacTRL-Spike	Monovalent oral vaccine (bifidobacteria)	Symvivo	Pre-clinical	Symvivo Corporation
ChAd-SARS-CoV-2-S	Adenovirus-based vaccine	Washington University School of Medicine in St. Louis	Pre-clinical	Washington University School of Medicine in St. Louis
HaloVax	Self-assembling vaccine	Voltron Therapeutics, Inc.; Hoth Therapeutics, Inc.	Pre-clinical	MGH Vaccine and Immunotherapy Center
HDT-301	RNA vaccine	University of Washington; National Institutes of Health Rocky Mountain Laboratories; HDT Bio Corp	Pre-clinical
LineaDNA	DNA vaccine	Takis Biotech	Pre-clinical	Takis Biotech
No name announced	Ii-Key peptide COVID-19 vaccine	Generex Biotechnology	Pre-clinical	Generex
No name announced	Recombinant vaccine	Vaxart	Pre-clinical	Vaxart
No name announced	Protein subunit vaccine	University of Saskatchewan Vaccine and Infectious Disease Organization-International Vaccine Centre	Pre-clinical	University of Saskatchewan Vaccine and Infectious Disease Organization-International Vaccine Centre
No name announced	Adenovirus-based vaccine	ImmunityBio; NantKwest	Pre-clinical
No name announced	Recombinant vaccine	Sanofi, Translate Bio	Pre-clinical
No name announced	mRNA-based vaccine	Chulalongkorn University’s Center of Excellence in Vaccine Research and Development	Pre-clinical
No name announced	gp96-based vaccine	Heat Biologics	Pre-clinical	University of Miami Miller School of Medicine
PittCoVacc	Recombinant protein subunit vaccine (delivered through microneedle array)	UPMC/University of Pittsburgh School of Medicine	Pre-clinical	University of Pittsburgh
T-COVIDTM	Intranasal vaccine	Altimmune	Pre-clinical
No name announced	Inactivated vaccine	Shenzhen Kangtai Biological Products	Pre-clinical
No name announced	mRNA lipid nanoparticle (mRNA-LNP) vaccine	CanSino Biologics, Precision NanoSystems	Early research

How is a Vaccine developed?

Preclinical Stage: How will this vaccine work?

This research-intensive stage is designed to find natural or synthetic antigens—foreign substances that induce an immune reaction in your body—that trigger the same reaction an actual virus or bacteria would. Identifying the right antigen or antigens can often take up to four years.

Phases 1/2a and 2b: Is it safe, and what’s the right dose?

Phase 1 testing marks the first time the vaccine is tested in a small group of adults, usually between 20 to 80 people, to evaluate its safety and measure the immune response it generates. Phase 2a studies aim to determine the most effective dose and expand the safety experience with the vaccine. Phase 1 and 2a clinical trials normally last several months to even a year before proceeding to Phase 2b or Phase 3 trials, in which the pool of people receiving the vaccine increases.

Phase 3: How effective is the vaccine?

In this stage of the clinical trial, even more volunteers receive the vaccine to study whether it’s effective. Before volunteers are vaccinated, they will be tested to make sure they currently do not have the SARS-CoV-2 virus. Half of the group will be assigned to receive the vaccine; the other half will receive a placebo. Then they will all be followed closely for up to two years to see if they do develop COVID-19-related symptoms, such as fever, headache, shortness of breath, dry cough or gastrointestinal distress.

Phase 4: Regulatory approval and licensure: Is it ready for the world?

After a successful Phase 3 trial, vaccine manufacturers apply to regulatory bodies such as the European Commission or the U.S. Food and Drug Administration (FDA). At this stage, clinical trial data is reviewed to make sure the vaccine is safe and effective. the manufacturing process is also reviewed.

Phase 5: Will it stay safe down the road?

Even after the vaccine is approved and licensed, regulatory agencies stay involved, continuing to monitor production; inspecting manufacturing facilities; and testing vaccines for potency, safety and purity.

Note: Typically, a vaccine development cycle takes 10 -14 years. In the case of COVID-19 the goal is to identify a potential mass-produced vaccination in next 2 years and get people vaccinated for less cost or free.

Socio-Economic Impact of COVID-19

World economy/ global GDP may shrink by a baseline of 5.2 % in 2020 due to COVID-19
Global airlines have taken a big hit on revenue due to reduced number of flight and travel restrictions. Daily flights have shrunk by 48 %.
Crude Oil: Crude oil is stabilized at 5-year low levels.

Poverty projections suggest that the social and economic impacts of the crisis are likely to be

quite significant. Estimates based on growth projections from the June 2020 Global Economic

Prospects report show that, when compared with pre-crisis forecasts, COVID-19 could push 71

million people into extreme poverty in 2020 under the baseline scenario and 100 million under the

downside scenario. As a result, the global extreme poverty rate would increase from 8.23% in 2019

to 8.82% under the baseline scenario or 9.18% under the downside scenario, representing the first

increase in global extreme poverty since 1998, effectively wiping out progress made since 2017.

While a small decline in poverty is expected in 2021 under the baseline scenario, projected impacts

are likely to be long-lasting.

Under the baseline scenario, COVID-19 could generate 176 million additional poor at $3.20 and 177 million additional poor at $5.50. This is equivalent to an increase in the poverty rate of 2.3 percentage points compared to a no-COVID-19 scenario. Almost half of the projected new poor will be in South Asia, and more than a third in Sub-Saharan Africa. Under the baseline scenario, the number of extreme poor in IDA, Blend and FCV countries is projected to increase by 21, 10 and 18 million, respectively

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112118/

https://en.wikipedia.org/wiki/Baltimore_classification

https://en.wikipedia.org/wiki/David_Baltimore

https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2

https://www.who.int/ith/diseases/sars/en/

https://www.msdmanuals.com/professional/infectious-diseases/respiratory-viruses/coronaviruses-and-acute-respiratory-syndromes-covid-19-mers-and-sars

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098031/

https://www.cdc.gov/coronavirus/types.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1925312/pdf/brmedj02979-0032.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196923/

https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/donate-covid-19-plasma

https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker