A Presentation By Ruby Shah Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic Authors: Eakachai Prompetcgara, Chutitorn Ketloy Tanapat Palaga
Quick Overview of Viruses and Viral Defenses Viruses are particles that have the ability to attach to cells and insert their genetic material through a receptor on the cell. This genetic material than takes over the cell which makes copies of the virus and eventually destroying the cell. The genetic material can also become a part of the cell’s own genetic material and changing the cells genome. Some viral defenses include vaccines (protein-derived, genetic material-derived, live virus, inactivated virus), washing hands, and various medicines that help with symptoms caused by viruses.
What is COVID-19? COVID-19 (name of disease), also known as novel coronavirus, SARS-CoV-2 (name of actual virus), and severe acute respiratory syndrome coronavirus 2 is a virus that has appeared in Wuhan, China in December 2019. COVID-19 is caused by a coronavirus that (currently) is thought to affect the respiratory system and be spread through respiratory droplets of those who are infected.
What is SARS and MERS? • MERS (also known as Middle East SARS (also known as Severe Acute Respiratory Syndrome) is a type of coronavirus that caused Respiratory Syndrome) is a type of an epidemic in China in 2002. coronavirus that caused an epidemic in the Middle East in 2012. It’s fatality rate is 9.19% and it’s natural • It’s fatality rate was 34.4% and it’s reservoir is the bat (intermediate host is palm natural reservoir is the bat civets). (intermediate host is the camel) It affects ACE2 which a receptor that’s located in • It affects DPP4 (Dipeptidyl peptidase 4) many cell types and especially cells that line which is an enzyme that’s in involved in specific tissues to create a barrier. (mainly increasing blood sugar. expressed in alveolar epithelium type 2 cells.)
Introduction Why use se i information a n about othe her v viruses t to st stop COVID-19? 19? In reality, it would take months to correctly determine the origins of COVID-19 and related coronaviruses. So, as a quicker alternative scientists decided to use previous information on how to make vaccines and Figure 1: TEM image of isolated COVID-19 treatments against MERS and SARS in order to stop viral particles (Credit: CDC Image Library) COVID-19.
Statistics on SARS, MERS, and COVID-19 As of February 20, 2020 the COVID-19 virus has a fatality rate of 2.8% vs the fatality rates of SARS: 9.19% and MERS: 34.4%. At the same date the number of cases of COVID-19 was 75,725 worldwide and the cases for SARS was 8,096 and MERS was 2,494. The main difference between COVID-19 and SARS/ MERS is that COVID-19 is a lot more contagious. This is the most probable reason why COVID-19 has a lot more cases than SARS or MERS.
Similarities of COVID-19 and SARS Both COVID-19 and SARS affect ACE2 but for COVID-19 it’s ability to attach to the ACE2 receptors on cells is higher than SARS. This is a probable reason for why the COVID-19 virus is a lot more contagious than SARS. The natural reservoirs for SARS and COVID-19 is bats. The reproductive number (or R-Naught) for SARS is 1.4-5.5 while COVID-19 is in the middle with 2.2-2.6. Any R-Naught above 1 can lead to continued transmission (as shown with both COVID-19 and SARS).
Immunopathology of COVID-19 This is still under investigation but it’s known that the COVID-19 virus is mainly a respiratory disease and for most patients it will only affect the lungs. The asymptomatic incubation period is between 2 and 14 days, which is also a reason for COVID-19’s rapid spread. A study of 41 hospitalized patients had high-levels of proinflammatory cytokines (mainly observed in the severe cases). High levels of cytokines can lead to a ‘cytokine storm’ which can initiate viral sepsis and cause lung injury (among many other complications)
Strategies Used on COVID-19 (Learned from SARS and MERS) Researchers and doctors recorded the numbers of total neutrophils,, lymphocytes and innate cytokines and compared the numbers of patients in ICU vs. non-ICU care. For those with COVID-19 there were an increase in total neutrophils and a decrease in total lymphocytes (separate study). Those in ICU care had higher plasma levels of many innate cytokines vs. those not in ICU care which can show how severe and deadly the virus is. Increased cytokines resulted in a proinflammatory condition and can cause a cytokine storm.
Antiviral Responses of COVID-19 There are downstream cascades that help limit viral replication and start effective adaptive immune responses. At the moment, it’s hypothesized that the COVID-19 could stop certain steps in the downstream cascade. This could cause the COVID-19 virus to increase in severity.
Dampening Properties of SARS There has been evidence that SARS does stop certain steps on downstream cascades that limit viral replication in cells. These are specifically called pathogen-associated molecular patterns or PAMPs. AMPs are innate forms of viral defenses where when the cell starts transcribing viral genetic material, it starts another transcription process that can suppress viral replication. SARS limited downstream cascades by suppressing type 1 IFN (type 1 IFN is the starting point that helps initiate the transcription of certain genes that suppress viral replication) which lead to its increased severity.
Adaptive Immune Responses Using Th1 type immune response can help find ways to stop and treat COVID-19 by creating an adaptive response while cytotoxic T cells are killing viral infected cells. Humoral immune response helps in the production in making antibodies which will protect the host from getting infected from the same virus. By initiating the humoral immune response or increasing the rate of production of antibodies, the host can be protected from the COVID-19 virus for a long period of time. For SARS, long lasting specific IgG antibodies were found and by initiating the production of these specific IgG antibodies, protection from COVID-19 can be created.
Potential Immune Evasion Mechanisms Observations show that coronaviruses have adapted to evade immune detection which also increases their severity and explains why they have a longer incubation period. These immune evasion mechanisms can include: viral mutations, immune exhaustion and immune deviation: Th2 biased. Most of these mechanisms rely on the inhibition of innate immune responses so instead of increasing the strength of innate immune responses, the rate of adaptive immune responses can be increased.
Prophylactic Vaccines There are various vaccines that can be made to stop COVID-19 (by inducing an adaptive immune response. By using what researchers learned about making vaccines for SARS and MERS, similar vaccines can be developed in order to make an effective vaccine for the COVID-19 virus. Vaccines used for SARS and MERS: DNA (Advantage: Rapid production, Disadvantage: Efficient delivery system required); Viral Vector (Advantage: Excellence in immune induction, Disadvantage: various inoculation routes may produce different immune responses).
Prophylactic Vaccines (Continued) Subunit Vaccine (Full-length Spike): Advantage- High Safety profile, Disadvantage- Cost-effectiveness may vary Virus-like particles (RDB): Advantage- Preserve virus particle structure, Disadvantage- Require optimum assembly condition Inactivated (whole virus): Advantage- Preserve virus structure, Disadvantage- Possible cause of hypersensitivity Live-attenuated virus (mutant virus): Advantage- excellence in induction of T and B cells responses, Disadvantage- Risk of reversion to a virulent strain.
Conclusions COVID-19 is caused by a type of coronavirus and previous coronaviruses such as SARS and MERS can teach us how to defend against COVID-19. Using statistics on all three coronaviruses, COVID-19 seems mild in terms of fatality rate compared to SARS and MERS but it is a lot more contagious due to its enhanced ability to attach to the ACE2 receptor (and the high number of ACE2 receptors in the human body). It’s currently unknown if the COVID-19 virus can suppress antiviral responses. It’s also known that the COVID-19 virus can evade the immune system. By using adaptive immune responses such as the Th1 immune response and prophylactic vaccines (as learned from SARS and MERS), a vaccines and treatments can be made.
Any Questions?
Blog Post The COVID-19 virus have shown to be a very contagious virus that has the ability to cause a pandemic. But, it’s also known that the COVID-19 virus is also a coronavirus such as SARS and MERS which are two viruses that we have developed vaccines and treatments for. By using what we’ve learned from SARS and MERS, we can make viral defenses against COVID-19. Coronaviruses are known to evade immune detection and SARS and MERS can specifically inhibit innate immune responses. The human body has another form of immune response known as: adaptive immunity (this is where immune system uses specific antibodies to stop pathogens). Adaptive immunity has been used to stop SARS and MERS in the form of DNA, viral vector, etc. vaccines. By knowing this, these types of vaccines and treatments that involve adaptive immunity can stop COVID-19.
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