- developed by Partridge et al.
- developed by Zhang et al. 

Cell Lines Used to Study COVID-19

While many animals have been used in laboratory studies of SARS-CoV-2, no model has been created that replicates the severity of the disease similar to hospitalized COVID-19 patients. In order to reduce COVID-19 morbidity and mortality, a reliable animal model is necessary to understand the biology of the infection as well as possible interventions. Animal models that produce severe infections, specifically pathogenesis of Covid-19 induced ARDS, are neccesary to develop reliable therapeutics. 

Potential animal models include:

- K18-hACE2 Mice
- AAV-hACE2 Mice
- HFH4-hACE2 Mice
- African Green Monkeys
- Rhesus Macaques

Animal Models Used to Study COVID-19

It is currently a problem that SARS-CoV-2 will not bind to animal model ACE2 receptor enzymes.  Instead of modifying the host organism, it was proposed that SARS-CoV-2 S protein could be remodeled to effectively bind to murine ACE2 (mACE2).  Recombinant SARS-CoV-2 viruses used to study COVID-19 include:

- SARS-CoV-2 MA

Genetically Engineered SARS-CoV-2 Used to Study COVID-19

- Animal models
- Cell lines
- Genetically engineered SARS-CoV-2

Michigan State University

Smith College

- Affected organs and organ systems
- Circadian Physiology in relation to COVID-19
- Exercise/Physical Activity and COVID-19
- Immune response to COVID-19
- Laboratory methods
- Pathogenesis
- Patient comorbidities 
- Symptomology 
- Genetic mechanisms in COVID-19
- The body's response to stress hormones






Focuses of Human physiology studies on COVID-19

Retrospective epidemiological studies using clinical data and experimental molecular biologies studies have revealed biomarkers of COVID-19.  These elements not only reveal how COVID-19 mechanistically affects the body, but they may also be risk factors for developing severe symptoms and act as targets for pharmacological intervention.  They include:

- A1AT protection
- ACE2 expression and activity
- ADAM17 sheddase activity
- Furin protease activity
- Irregular respiratory function
- Pro-inflammatory cytokine concentration in the plasma
- TMPRSS2 serine protease genetic variation
- Variation in genetic susceptibility to SARS-CoV-2
- Viral interactions with glycosaminoglycans
- Nsp (Non-specific Protein) Activity
- Neuropilin-1 expression


Pathogenesis of COVID-19

Current studies show that many organs that are heavily affected by COVID-19 have a high expression level of ACE2.

- Cardiovascular system
- Central nervous system (CNS)
- Gastrointestinal tract (GI)
- Kidney
- Liver 
- Lungs (Respiratory System)
- Peripheral nervous system (PNS)
- Testis

Organs and Organ Systems Affected by COVID-19

Laboratory Methods in COVID-19 Research

Infection by SARS-CoV-2, as is with other viral infections, induces a two-phased immune response in the human body, described in the figure below: 
- Innate (rapid, natural, non-specific) 
- Adaptive (slow, acquired, specific)

Those two branches of the immune system cooperate with one another, and can be distinguished based on the cell-types involved (immune response vs white blood cells). However, the adaptive system is further broken down by the type of mechanism:

- Cell-mediated
- Antibody-mediated

Current research around COVID-19 immunity aims at uncovering the interaction between SARS-CoV-2 and the host's immune response, with questions related to pathogenesis, severity, and intervention.

Immune Response to COVID-19 

Presence and severity of symptoms of COVID-19 depend largely on individual characteristics. COVID-19 produces both symptomatic and asymptomatic infection.

Symptomology of COVID-19 

- Pituitary gland: improper functioning of the hypothalamus in association with pituitary gland; changes the metabolism of ADH (regulates the amount of water in the kidneys); abnormal sodium levels
- Thyroid: sick euthyroid syndrome → decrease in size of thyroid gland; changes in TSH levels
- Adrenal gland: increased chance of COVID-19 infection if presented with Cushing’s syndrome (too much cortisol) or Addison’s disease (inadequate aldosterone and cortisol)
- Pancreas: those with diabetes are at higher risk of getting COVID-19
- Bone: low vitamin D and hypocalcemia

Dysfunctions/ diseases in endocrine glands/organs that could lead to greater susceptibility to COVID-19

Exercise and physical activity induce physiological changes on many levels, the effects of which are best understood using a biopsychosocial approach.  The bidirectional relationship between exercise and Covid-19 can be further broken down into different components:
- Exercise/PA and COVID-19 by geographical location
- Exercise/PA and COVID-19 by demographics


Exercise/Physical Activity (PA) and Covid-19

COVID-19 comorbidities are high risk conditions that put patients at greater risk for infection and negative outcomes. Some COVID-19 comorbidities have been found to be: 
- Cancer 
- Cardiovascular Disease
- Diabetes
- Digestive Diseases
- HIV
- Hypertension
- Immunological Disease
- Liver Injury
- Obesity
- Renal disease
- Respiratory System Disease

COVID-19 Patient Comorbidities

Circadian biology refers to any biological process that has a rhythmic component dependent on time of day.  Understanding the relation between COVID-19 and circadian rhythm could help improve clinical management in treating COVID-19.

Circadian Physiology in relation to COVID-19

ARTICLES RESEARCHED
- Genetic mechanisms of critical illness in Covid-19
- Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients

Genetic mechanisms in COVID-19

Levels of stress may increase in those diagnosed with COVID-19, resulting in an alteration in stress hormone levels and the body's ability to cope with the stress.

Learn Before

Related

Learn After