The COVID crisis response

The COVID-19 crisis is gripping the world, halting work and livelihood  for many, and killing thousands. In  the context of this we are publishing a review of the COVID-19 response by CRI student Morgane Opoix on the COVID crisis response.

This review was written using the pre-prints of 13 undergraduate students referring directly or indirectly to COVID-19 at the Center of interdisciplinary Research (CRI). In the context of the pandemic, their class have researched COVID-19, and published an open source textbook. This research is linked to the biological chapters they wrote this semester on an open source website

A Review of the COVID crisis and scientist’s response.

In December 2019, the COVID-19 outbreak emerged in the city of Wuhan, China named the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) virus. The virus then spread around the world resulting in a pandemic declared in March 2020. This bat derived infectious agent belongs to the coronaviruses group of viruses due to the halo of spike proteins that surround its surface. It is similar to two other viruses SARS-COV in 2002, and MERS-COV in 2012 (Middle East Respiratory Syndrome Coronavirus). Those too caused pandemics, however COVID-19 has already caused more than 200,000 deaths worldwide according to the World Health Organisation.  We are facing a big global health, social and economic crisis. 

Symptoms of COVID-19

In order to be able to detect the virus in the population, we need to understand how it develops and its effects on citizens. The most prevalent symptoms of COVID-19 are cough, fever, loss of smell and breathing difficulties. The worst cases may also have severe respiratory system disorders which can lead to Acute Respiratory Distress Syndrome (ARDS). The virus infects human cells by injecting it’s viral RNA genome which encodes the instructions for the host to replicate it.

During ARDS the virus first infects the trachea and then spreads through the bronchial tubes into the alveoli. Chemical mediators are involved to activate the immune system’s response (the cytokines) : interferons. The SARS-COV-2 virus is believed to attack the cytokine interferon 1 (IFN1). The attack on IFN1 weakens the body’s immune response to COVID-19 due to dysfunction of the interferon pathway. This leads to an uncontrolled inflammatory reaction that we call a cytokine storm.

It is important to note that during this pandemic many asymptomatic cases of COVID-19 have been reported, meaning that patients were tested positive for the virus with few or no symptoms. An analytical study comparing the characteristics of asymptomatic and symptomatic patients was conducted. Symptomatic patients were tested by real time RT-PCR to detect the amplified genes of the virus and to quantify its expression, asymptomatic patients were tested using the nucleic acid test (with small viral nucleic acid). For this study, the results were combined from publications using the same test for each case (asymptomatic and symptomatic) in order to have a larger sample size. The study concluded from this comparison of data the following statement : age could be a risk factor, women appear to be more asymptomatic than men, and patients with hypertension or cardiovascular disease have a higher risk of being symptomatic.  

The question of age in COVID-19 pathology was cited in several student papers and supported by immunological and neurological analysis. In fact, the question of neurological impact of the COVID-19 has also been raised, based on a publication of 214 patients testing positive and hospitalized (88 severe cases and 126 non severe cases). In this cohort, 36,4 % were affected by nervous system symptoms. The analysis is based on clinical observational studies and as the cohort remains quite small, the results are variable. Numerous further studies are ongoing.  Respiratory disorders remain at this time the leading cause of death. 

Treatments for COVID-19

An overview of the existing treatments to achieve sufficient oxygenation, particularly in cases of ARDS was carried out. Face mask oxygenation and flow nasal oxygenation are used to provide more concentrated oxygenated air, allowing the patient to breath on its own. But in the worst cases, mechanical ventilation, an artificial ventilation, is needed to assist the patient’s breathing. There are two types of artificial ventilation :  non-invasive ventilation, where no tubes are placed in the patient’s respiratory system and an invasive one which is binding and requires weeks of rehabilitation. However, these treatments don’t really address the underlying problems caused by the COVID-19.  

Clinical trials and observational studies are part of the research into COVID-19. Clinical trials are needed to measure the effectiveness and safety of a treatment or drug against the disease in volunteers. The example of clinical trials on hydroxychloroquine (HQC) used to fight against the COVID-19 as a treatment was discussed. Eight clinical trials were selected by the CRI students, seven from research and a recent french study for comparison. However, only two of these clinical trials were completed and came to two contradictory conclusions. A chinese trial concluded that HQC did not improve the patient’s health and a french trial pointed out that it could be more effective than standard care. It is impossible to tell at this time if this treatment would be really effective and the results of other clinical trials are needed to conclude. Furthermore the question of randomness of volunteer patients is important (controversies around the non-random nature of the patients chosen and the lack of peer review  in the french trial).  

The scientific community is also boiling over to create a vaccine against this coronavirus. Immune reaction activation allows for the elimination of the virus. However, the replication of the infectious agent SARS-COV-2 leads to immunosuppression (weakening of the immune system). Therefore, in order to develop a vaccine, the good equilibrium between the SARS-COV-2 virus and the immune system must be determined. It is also necessary to find the appropriate dose of virus to be contained in the vaccine. A comparison of the techniques used and the target antigens selected for the previous SARS-COV and MERS-COV vaccines was performed. In fact, it has only been a few months since the disease emerged and the vaccine development process is a long one requiring research, production, pre-clinical studies and clinical trials. The COVID-19 vaccine could be developed based on these other coronaviruses according to this comparison. It was concluded that the full length spike proteins were the most used as target antigens and DNA vaccine was the best vaccine technique for other coronaviruses.

Epidemiological modelling and COVID-19 prediction

Modelling an outbreak is a necessity to understand and predict its expansion, simplifying reality to help policy makers make decisions about the evolution of the pandemic. In order to build a model that is closest to reality, the data on epidemics must be reliable. Therefore, for coronavirus disease, sharing hospital data with the scientific community is important to build the models. 

“The basic reproductive rate”, R0, is an important indicator for modelling the epidemic. In short, it is based on the contact rate, the probability of transmission of the virus upon contact and the time a person can infect others and is therefore spatially dependent. When it is greater to 1, the epidemic is likely to spread. R is the number of secondary cases generated by an infectious case once an epidemic is underway. The combination of these two parameters allows us to estimate the number of people infected! 

Various strategies and measures have been implemented worldwide to limit the pandemic and thus to bring R0 down to values below 1. At this time, in the absence of effective drugs and vaccines, measures have had to be taken in order to not exceed the capabilities of national healthcare systems. However, many countries around the world have already reached this limit and health services are being saturated. Healthcare workers are at a higher risk of being infected and are under extreme pressure. 

A neurobiological study has been conducted to analyze the mental health consequences of infectious disease on healthcare workers. Many of them have a higher risk to develop post-traumatic stress disorder (PTSD) through exposure to psychological traumatic environmental events. Therefore, in the event of a prolonged epidemic we must be prepared to adopt the best strategies to maintain global health security and avoid hospital overcrowding. 

Epidemiological models can be used to analyse the political decisions already taken and expose the most strategic ones. Indeed, three distinct strategies to fight against the outbreak were compared by one student : not doing anything for a certain amount of time (USA), testing a lot and confining only infected/exposed people (South Korea) and quarantining a whole population (China). For this purpose, among the numerous models used, the classical SEIR epidemiological model was chosen, defined by these variables: Susceptible individuals (S), Infected (I), Recovered (R), Exposed (E). The model used in this case was not complete and was not sufficiently appropriate. It was concluded that Chinese and South Korean were more efficient than the USA, but a comparison between the strategies of the first two countries was not possible.  More complex models can be used in order to get closer to reality adding new variables or even using variables with sub-categories. The data is incomplete due to the ongoing crisis however.

Society’s response to COVID-19

Based on each student’s work I have tried to get an overview of the society’s reaction to COVID-19. The research community is currently working on many major challenges, but focuses on detection of the virus, treatment and epidemiological models and analysis. I have made a schematic that describes society’s effort in fighting the virus through the work of students. I have tried to take into account the systemic view of the issues, but this schematic is a simplified view of reality as with all models, thus it is not exhaustive. This schematic focuses on the scientific community to facilitate, produce and contribute knowledge, and shows how this community interacts with the rest of society, in the context of the COVID-19 pandemic. For those of us who don’t have a scientific background, it is important to make the link between science and society. Especially as citizen science projects related to biohacking to fight the virus are developing and allow citizens to help the science community. 

The important role of the population during the pandemic hasn’t been mentioned in this review. Many countries have decided to quarantine people at home, in addition to the basic rules of social distancing. It is up to citizens to respect these rules to limit the spread of the infection. Therefore, the risk of social isolation is high and can lead to multiple effects on the endocrine system that were described in one of the student essays. Social isolation can lead to a high concentration of cortisol (stress hormone) and citizens have a higher risk of contracting an inflammatory disease. Thanks to social media we can get still connected with people and the outside world to avoid social isolation. However, high exposure to social media can have impacts on mental health according to another literature analysis conducted. It has been proven that emotional contagion can easily occur through social media. Especially in the context of a pandemic, where citizens are subject to overexposure of information, which can lead to stress and anxiety. Furthermore, while the actual lockdown is already a big challenge for teaching and education, these different stress levels (in duration or intensity) are known to affect concentration and learning. Studies show that stress impairs synaptic plasticity and neurochemical systems and thus impede learning and memories consolidation. 

Schematic : Society’s response to COVID-19 @Morgane Opoix

Picture 1

The CRI open-source COVID-19 Essays/Bibliography: 

Written by Morgane Opoix-  CRI Undergraduate Student.

Author: Chris LB Graham

A biochemist and microbiologist studying a PhD at Warwick University since 2018. Creator and writer/editor of articles. Co-founder of human swarm; Helpful Engineers COVID-19 response charity. Launched the worlds first prototype open peer review systems and grant application systems with ‘JOGL’ the future of collaborative science networks.

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