COVID-19

Awareness

1. Epidemic vs Pandemic vs Endemic vs Outbreak

Epidemic, pandemic, endemic and outbreak are all terms related to the spread of an infectious disease. The definitions of these terms are fluid and changes as diseases become more or less prevalent over time.

However, we can still define these terms as follows:

Outbreak

An outbreak can be defined as the rapid increase of cases in one area over a short period of time that exceeds the normal expectancy
The hepatitis A outbreak that occurred in San Diego, California in 2017 was considered an outbreak because it happens locally although it was the biggest outbreak that the country has ever see

Epidemic

An epidemic is a rapid spread of disease that affects a large number of individuals within a community, a population or a region.
For example, a rapid increase and spread of COVID-19 cases in Wuhan, China was considered an epidemic before it was spread to the other parts of the world and turned into a pandemic.

Pandemic

A pandemic is an epidemic that has spread across a wide geographical area, affecting many countries and a large percent of the population.
An example of a pandemic is the H1N1 pandemic in 2009 that was declared as a pandemic in June 2009. Now, in 2020 we are facing another pandemic, COVID-19, that was declared as a pandemic in March.

Endemic

An endemic is the constant presence of a disease in a geographical area. It is often expected and occurs at a predictable rate.
For example, Malaria is endemic to certain parts of Africa and chickenpox is endemic to the young school children in parts of the United States.

2.What is COVID-19?

COVID-19 or Coronavirus disease is an infectious disease caused by a newly discovered coronavirus. From the name COVID-19, the CO' stands for corona, 'VI' for virus, and 'D' for disease. Formerly, this disease was referred to as '2019 novel coronavirus' or '2019-nCoV.' The COVID-19 virus is a new virus linked to the same family of viruses as Severe Acute Respiratory Syndrome (SARS), Middle East respiratory syndrome related coronavirus (MERS-CoV) and some types of common cold.

The symptoms of COVID-19 can include fever, cough and shortness of breath. Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment. But in more severe cases, infection can cause pneumonia or breathing difficulties. Older people, and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness. In rare cases, the disease can be fatal. The symptoms are similar to the flu (influenza) or the common cold, which are a lot more common than COVID-19. For this reason, testing is required to confirm if a person has been infected by COVID-19.

3. Source of the virus

The first human cases infected by SARS-CoV-2 was reported from Wuhan City, China in early December 2019. Earlier investigation found out that the earliest cases were linked with the wet market in Wuhan. The authorities took environmental samples from the market and it tested positive for SARS-CoV-2 and the market was closed on 1st January 2020.

The full genetic sequences of the SARS-CoV-2 from the early human cases shows that the virus has an ecological origin in bat population. All available evidence to date suggests that the virus has a natural animal origin and is not a manipulated or constructed virus. All available evidence for COVID-19 suggests that SARS-CoV-2 has a zoonotic source. Since there is usually limited close contact between humans and bats, it is more likely that transmission of the virus to humans happened through another animal species, one that is more likely to be handled by humans.

4. How it is transmitted?

The virus that causes COVID-19 is thought to spread mainly from person to person, mainly through respiratory droplets produced when an infected person coughs or sneezes. These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs. Spread is more likely when people are in close contact with one another (within about 6 feet).

COVID-19 is a new disease and there is limited information regarding risk factors for severe disease. Based on currently available information and clinical expertise, older adults and people of any age who have serious underlying medical conditions might be at higher risk for severe illness from COVID-19.

Based on what we know now, those at high-risk for severe illness from COVID-19 are:

People aged 65 years and older
People who live in a nursing home or long-term care facility

People of all ages with underlying medical conditions, particularly if not well controlled, including:

People with chronic lung disease or moderate to severe asthma
People who have serious heart conditions
People who are immunocompromised
- Many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation, immune deficiencies, poorly controlled HIV or AIDS, and prolonged use of corticosteroids and other immune weakening medications
People with severe obesity (body mass index [BMI] ≥40)
People with diabetes
People with chronic kidney disease undergoing dialysis
People with liver disease

5. How is it transmitted?

Currently, there are two methods to detect the SARS-CoV-2 virus, the cause of COVID-19 disease, a debilitating and potentially deadly viral pneumonia.

The tests are:

Diagnostic Test: Genomic detection-based (molecular)
Antibody Test: Immunoglobulin detection-based (serology)

(Source: American Society For Microbiology)

Diagnostic Test:

Genomic detection-based (molecular)

The first and most prevalent method to detect the virus in individuals is based on detecting genetic material specific to SARS-CoV-2 viruses in a person’s nasopharyngeal secretions.

Procedure:

Swabs of oral and/or of nasal surfaces.
Swabbed tissue is loaded into a standard reaction vial.
Inside the standard reaction vial, some reagents will break open viruses to expose viral genome (RNA) to other reagents like synthesized RNA that binds to a specific small part of the viral RNA.
This small bound-up strand of viral genome and reagent is then replicated many times over minutes to hours.
At the same time, another reagent specifically binds to each replicated genetic complex to act as a marker.
Depending on the presence of viruses in the sample, positive results may occur in minutes to days.
Conversely, if the test detects no viral material after a fixed time (minutes to days), the result is a negative test.

The diagnostic test only shows whether the person is infected with SARS-CoV-2 and considered to be able to transmit the disease (a positive test) or is negative for the virus. However, this test cannot tell whether a person is immune from past infection or has yet to be exposed and is still in danger.

Bad Bacteria

Antibody Test:

Immunoglobulin detection-based (serology)

Immunoglobulin detection tests are based on the qualitative detection of IgM and IgG that are specifically generated by the body in response to SARS-CoV-2 infection. IgM is usually the first, specific antibody type generated by the body in response to infection. Then, the IgG antibody type is generated and replaces IgM as the predominant antibody in the response to infection.

IgM and IgG fight infections by targeting specific antigens on the surface of the SARS-nCoV-2 virus. In general, immunoglobulin tests use specific viral antigens to detect the IgM and/or IgG antibodies against those antigens.

Procedure:

Collect 2-3 drops of fresh blood/serum or plasma and place it in a sample container and place 2-3 drops of provided buffer in the same container (cassette).

The cassette allows the diluted sample to move through the cassette by capillary action.

The cassette has labeled SARS-CoV-2 antigen that may bind chemically with either IgM or IgG; thus, forming an antigen/antibody complexes of antigen/IgG and/or antigen/IgM.

After that reaction, the antigen/antibody product passes over anti-IgM and anti-IgG antibodies that are immobilized in a line within the cassette.

The anti-IgM and/or anti-IgG then will capture the specific complex and signal a result (a red line) if either complex is bound to the immobile anti-IgM or anti-IgG.

The results need to be read after 10 minutes and no more than 15 minutes (the test resembles a home pregnancy test in this respect.)

Negative Result: If only the quality control line (C) appears and the detection lines G and M are not visible, then no novel coronavirus antibody has been detected and the result is negative, the test indicates the person has not been recently exposed to the COVID-19 virus.

Positive Result, IgM only: If both the quality control line (C) and the detection line M appears, then the novel coronavirus IgM antibody has been detected and the result is positive for the IgM antibody, the person is likely in the early stage of the virus infection

Positive Result, IgG and IgM: If the quality control line (C) and both detection lines G and M appear, then the novel coronavirus IgG and IgM antibodies have been detected and the result is positive for both the IgG and IgM antibodies, the person is likely in the middle stage of infection.

Positive Result, IgG only: If both the quality control line (C) and the detection line G appears, then the novel coronavirus IgG antibody has been detected and the result is positive for the IgG antibody, then the person is either over the infection or in its last stage.

At the same point with diagnostic tests, antibody tests for COVID-19 also possess some limitations. It can only tell whether you have been exposed in the past or if you have never been exposed to SARS-CoV-2 but cannot confirm the presence of the virus in your system. Hence, diagnostic test and antibody test must be carried out together to get the best result.

6. Ways to prevent & possible treatment

WAYS TO PREVENT

Precautions to lower your risk of infection:

Wash your hands thoroughly with soap and water for at least 20 seconds.
Use hand sanitizer with at least 60 percent alcohol if soap isn’t available.
Avoid touching your face unless you’ve recently washed your hands.
Stay clear of people who are coughing and sneezing. The CDC recommends standing at least 6 feet away from anyone who appears to be sick.
Avoid crowded areas as much as possible.

Older adults are at the highest risk of infection and may want to take extra precautions to avoid coming into contact with the virus.

POTENTIAL TREATEMT

There currently isn’t a vaccine against developing COVID-19. Antibiotics are also ineffective because COVID-19 is a viral infection and not bacterial.

If the symptoms are more severe, supportive treatments may be given by doctor or at a hospital. This type of treatment may involve:

fluids to reduce the risk of dehydration
medication to reduce a fever
supplemental oxygen in more severe cases

People who have a hard time breathing on their own due to COVID-19 may need a respirator.

Here are some treatment options that are currently being investigated for protection against SARS-CoV-2 and treatment of COVID-19 symptoms.

Remdesivir: Remdesivir is an experimental broad-spectrum antiviral drug originally designed to target Ebola. Researchers have found that remdesivir is highly effective at fighting the novel coronavirus in isolated cells. This treatment is not yet approved in humans, but two clinical trials for this drug have been implemented in China. One clinical trial was recently also approved by the FDA in the United States.

Chloroquine : Chloroquine is a drug that’s used to fight malaria and autoimmune diseases. It’s been in use for more than 70 yearsTrusted Source and is considered safe. Researchers have discovered that this drug is effective at fighting the SARS-CoV-2 virus in studies done in test tubes. At least 10 clinical trialsTrusted Source are currently looking at the potential use of chloroquine as an option for combating the novel coronavirus.

Lopinavir and ritonavir: Lopinavir and ritonavir are sold under the name Kaletra and are designed to treat HIV.In South Korea, a 54-year-old man was given a combination of these two drugs and had a significant reductionTrusted Source in his levels of the coronavirus. According to the World Health Organization (WHO), there could be benefits to using Kaletra in combination with other drugs.

APN01 : A clinical trial is set to start soon in China to examine the potential of a drug called APN01 to fight the novel coronavirus. The scientists who first developed APN01 in the early 2000s discovered that a certain protein called ACE2 is involved in SARS infections. This protein also helped protect the lungs from injury due to respiratory distress. From recent research, it turns out that the 2019 coronavirus, like SARS, also uses the ACE2 protein to infect cells in humans. The randomized, dual-arm trial will look at the effect of the medication on 24 patients for 1 week. Half of the participants in the trial will receive the APN01 drug, and the other half will be given a placebo. If results are encouraging, larger clinical trials will be done.

Favilavir : China has approved the use of the antiviral drug favilavir to treat symptoms of COVID-19. The drug was initially developed to treat inflammation in the nose and throat. Although the results of the study haven’t been released yet, the drug has supposedly shown to be effective in treating COVID-19 symptoms in a clinical trial of 70 people.

7. COVID-19 Vaccine

Vaccine or antivirals are the only things we can rely on to truly end this pandemic. However, antivirals are very hard to develop because they have a high risk of destroying our cells when trying to kill the virus. So, vaccines are still the best solution. As of now, dozens of companies around the world are racing to find COVID-19 vaccine. But, developing a vaccine is also not an easy task and requires a lot of time, effort, and money, too. To understand this, we need to look into how vaccines are being developed.

Vaccine Development

Vaccine development can be summarized into three parts

So, vaccines targeted for humans will need to undergo “human trials” to confirm their safety and efficacy in humans. Of course, safety is always first when developing a vaccine that, if successful, will be distributed around the world and hopefully administered to the entire human population! The human clinical trials involve 4 phases. Take a look at the following chart.

i-feel-like-its-been-forever-since-i-mad

So when the experts says vaccines take YEARS to develop, they are not lying! Even before they start researching vaccines, researchers normally need years to secure funding, get approvals and study results piece by piece. And in the end, approximately only less than 10% of drug trials are ultimately approved. Then what about the current outlook of COVID-19 vaccines? We never even had a vaccine for a coronavirus before. Do we still need to wait for another 10 years for a coronavirus?

Let’s take a look at the COVID-19 vaccine development landscape.

COVID-19 Vaccine Development

Under normal circumstances, vaccines would take a decade or longer to develop. But of course, this pandemic is not what we would call a “normal circumstance”. Which is why COVID-19 vaccine development has been “fast-tracked”, so that we could hopefully gain access to COVID-19 vaccines by 2021. But how do we fast-track a development? According to Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, to get a COVID-19 vaccine within the 18 months timeframe, one way to do that is “to put as many horses in the race as you can”. Now biotech companies all over the world are racing like horses to develop an effective COVID-19 vaccine, and even applied new methods as a basis for the vaccine. As of 8 April 2020, there are 115 COVID-19 vaccine candidates, of which 78 are confirmed as active and 37 are unconfirmed

(Source: Nature Reviews)

So far, vaccines that have been approved to fight against viral diseases in humans are either live vaccine, inactivated vaccine, or recombinant antigen vaccine (Hepatitis B). But now some companies proposed novel bases for the vaccine such as DNA, RNA, and adenovirus vector vaccines, which developers claim to be able to be manufactured more quickly. Let’s take a look at some of the most promising candidates to date.

RNA Vaccine - BNT162 by BioNTech & mRNA-1273 by Moderna

In each cell of a living organism, DNA is the molecule that contains the genetic information of the organism. It is composed of a series of four building blocks (A, C, G, & T), whose sequence gives the instructions to fabricate proteins. This process requires a transient intermediary called messenger RNA (mRNA) that carries the genetic information to the cell machinery responsible for protein synthesis. As an analogy, one can see the DNA as a cookbook in a library: the recipe is stored here but cannot be used. The chef’s assistant first makes a copy (the RNA) of a specific recipe and brings it to the kitchen (the ribosome in the cell). The information is now ready-to-use by the chef, who can add the ingredients in the order specified by the recipe and create a cake (the protein).

BNT162 is a vaccine candidate based upon mRNA developed by BioNTech and Pfizer. The mRNA-1273 vaccine developed by Moderna also uses the same concept. The mRNA used in the vaccine codes for the SARS-CoV-2’s infamous spike protein, more specifically called Spike glycoprotein (S). The mRNA is transported into the cell in pockets of lipid nanoparticle (LNP). Once inside an antigen presenting cell (APC), the mRNA will be translated into the SARS-CoV-2's spike protein, which serves as an antigen. When the antigen is presented by APC, T cells recognize the antigen and initiate a humoral immune response. The primary immune response will result in the production of memory cells, which “remembers” the SARS-CoV-2's spike protein so that the next time the virus invades the body, the memory cells can initiate a stronger and rapid response towards the virus.

The vaccine is currently on phase I/II trials. On May 30, 2020, Global pharmaceutical Pfizer CEO Albert Bourla said he believes that a vaccine could be available in the fall of 2020.

Adenovirus (AdV) Vector Vaccine - Ad5-nCov by CanSinoBIO & AZD1222 by Oxford University

AZD1222 coronavirus vaccine candidate is developed by Oxford University’s Jenner Institute, formerly known as ChAdOx1 nCoV-19, and is made from a virus (ChAdOx1), which is a weakened version of Adenovirus (a common cold virus) that causes infections in chimpanzees, that has been genetically changed so that it is impossible for it to grow in humans. The same goes for Ad5-nCoV, a vaccine candidate developed by a Chinese biotech company, CanSinoBIO, is a genetically engineered vaccine candidate with the replication-defective adenovirus type 5 as the vector to express SARS-CoV-2 spike protein.

Unlike mRNA vaccine which sends mRNA into the cells, AdV vector vaccine has been modified to contain a genetically engineered double stranded DNA. The engineered DNA contains a gene that codes for the SARS-CoV-2’s Spike glycoprotein (S). The modified AdV will inject its DNA into the cell as shown in the diagram below, so that the cell can express the Spike glycoprotein (S). Once in the cell AdVs also don’t integrate their DNA with the host’s genome, but transfer episomal DNA to the host cell’s nucleus, unlike many other viruses (of course we don’t want to risk altering our DNA!). It is basically a DNA vaccine. The concept is similar to the mRNA vaccine, but instead of mRNA, its DNA. The cell will eventually transcribe the DNA into mRNA to be translated into the Spike glycoprotein (S), which initiates an immune response. The rest of the story is the same.

Source: https://www.ncbi.nlm.nih.gov/pubmed/27286566

Both Ad5-nCov and AZD1222 are now undergoing phase II/III clinical trials, with 508 and 1090 participants respectively.

There are many other COVID-19 vaccine candidates out there, and their approaches are quite innovative and intriguing. This pandemic has sparked a massive development in the world of vaccines, and we hopefully can learn how to develop vaccines more quickly in the future. For now, we must do all that we can do to prevent the spread of COVID-19, like by maintaining physical distance and keeping good hygiene!