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

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

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.

The Body's Physiological Response to Stress Hormones In COVID-19 Patients

- 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






Michigan State University

University of Michigan - Ann Arbor

Smith College

How human functions and mechanisms play a role in transmitting and fighting against COVID-19

Human physiology of COVID-19

Organization by Journal:
- American Heart Association
- American Journal of Neuroradiology
- American Journal of Perinatology
- American Journal of Physiology-Endocrinology and Metabolism
- American Journal of Physiology-Lung Cellular and Molecular Physiology
- American Journal of Respiratory and Critical Care Medicine
- American Journal of Roentgenology 
- Arthritis and Rheumatology
- BCN (Basic Clinical Neuroscience)
- BMC Medicine
- Biomedical and Biotechnology Research Journal (BBRJ)
- BioRxiv
- Brain: A Journal of Neurology
- Brain Sciences
- British Pharmacological Society (BPS)
- British Journal of Sports Medicine (BJSM)
- Cardiovascular Research
- Cell
- Cells
- Circulation
- Chronobiology International
- Clinical Neurology and Neurosurgery
- Clinical Immunology
- Cureus
- European Journal of Sports Science
- Frontiers in Immunology
- Gastroenterology
- Gerontology
- HHS Public Access
- Healthline
- Hypertension
- International Journal of Antimicrobial Agents 
- International Journal of Clinical and Laboratory Medicine (IJCLM)
- International Journal of Environmental Research and Public Health (IJCRPH)
- International Journal of Molecular Sciences (IJMS)
- International Journal of Molecular Medicine (IJMM)
- Intervirology
- Immunology
- JAMA Neurology
- Journal of Alzheimer's Disease
- Journal of Critical Care
- Journal of Clinical Medicine
- Journal of Clinical Neuroscience
- Journal of Experimental Medicine
- Journal of Infectious Diseases
- Journal of Medicinal Chemistry
- Journal of Medical Virology
- Journal of Microbiology, Immunology and Infection
- Journal of Sport and Health Science
- Journal of Stroke and Cerebrovascular Diseases
- Journal of Virology
- Mayo Clinic Proceedings
- MedCrave Online Journal of Immunology
- MedRxiv
- Medical Hypotheses
- Medical Science Monitor Basic Research
- Neurology
- Open Medicine
- Oxford
- Physiological Reviews
- PNAS
- PubMed Central (PMC)
- Radiological Society of North America (RSNA)
- Reviews in Medical Virology
- Science Bulletin
- Society of Critical Care Medicine
- Springer
- Stem Cell Reviews and Reports
- Stroke
- The American Journal of Cardiology
- The FEBS Journal
- The Journal of Antibiotics
- The Journal of Clinical Endocrinology & Metabolism
- The Lancet
- The New England Journal of Medicine (NEJM)
- The Neuroscientist
- The World Journal of Men's Health (WJMH)
- Translational  Psychiatry
- Vascular Health and Risk Management
- Virus Research
- Viruses
- World Neurosurgery
- World Health Organization (WHO)

Consolidation by Publisher:
- AAAS (Science Advances)
- ACS Publications (Pharmacology and Translational Science, Chemical Neuroscience)
- CDC (Emerging Infectious Diseases)
- Elsevier (Autoimmunity Reviews, Biochemical and Biophysical Research Communications, Brain, Behavior, and Immunity, Cytokine & Growth Factor Reviews, International Journal of Antimicrobial Agents, Journal of Autoimmunity, Life Sciences, Obesity Medicine, Pediatric Clinics of North America, Thrombosis Research)
- Karger (Intervirology)
- Nature (European Journal of Human Genetics,  Journal of Human Genetics, Nature Reviews Immunology, Nature Reviews Molecular Cell Biology, Nature Structural and Molecular Biology)
- Sage Journals (The Neuroscientist)
- Springer (Cellular and Molecular Neurobiology)
- Wiley (Journal of Medical Virology, Reviews in Medical Virology, Obesity)

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