COVID-19 and the human immune response
In order to understand how Sars-Cov-2 escapes the initial powerful immune defense we must first review the components of the human immune system. My colleagues and I seriously regret sleeping through the ‘boring’ immunology lectures in medical school. It has come back to haunt us. ( To all my colleagues in healthcare, click “thumbs up” if you are guilty as charged). ☺️
Sorry for the digression. The human immune system has two major components namely innate and acquired immunity. Innate immunity refers to the initial barriers mounted by the body which includes physical barriers such as skin, mucus membranes and alike that tries to ward off the germ. Think about how you feel when you catch a cold. Within 1-2 days of getting exposed to another person with a cold, you start feeling a runny nose, runny eyes, sore throat, and maybe a little bit of sinus drainage and maybe a wet cough. Your body is trying to prevent the virus from getting in the respiratory tract. You cant go through enough tissues and you feel a little miserable. After that initial attempt to block the virus by shedding it in your secretions, inevitably some virus gets into the systemic circulation and internalizes in the upper respiratory tract.
At that point, your body recognizes that it must signal your cytotoxic T cells and T helper cells to recognize that there is a foreign object ( called an antigen). The cells release chemokines and cytokines that are messenger proteins that alert those T cells to ‘phagocytize’ the virus, that is like Pac-man eating the bad guys ( remember that game?). T cells which are stored in the thymus gland are nondiscriminatory and eat anything foreign to them .
By the way the chemokine and cytokine proteins give you the fever and mild aches and pains and lack of appetite and your taste for a hearty soup.
In the interim more cytokines and chemokines alert the B cells coming from the bone marrow. B cells are part of the acquired immunity. We have millions of B cells each with a specific type of surface protein. One of these surface proteins will match the virus and attach to it. Once that happens the specific B cell proliferates into millions. Those memory B cells and plasma cells then neutralize the virus but stick around ready for the next time the virus dares enter the body. That is when the host starts getting better. It is important to mention that woman have a stronger innate immunity than men which may be one reason why the mortality is lower in women than men with COVID-19. Children also have very powerful innate immunity. Remember our babies with their runny noses.
Now we come to COVID-19. Sars-Cov-2’s incubation period is about 5 days. That means the host carries the virus for 5 days before exhibiting any symptoms. The virus completely escapes detection by the innate immune response. No runny nose or runny eyes, no sinus drainage, no productive cough. The human host doesn’t shed the virus through secretions. No tissues. This allows for a high viral load to get into the lower respiratory tract.
Then insidiously the viral spike proteins binds the ACE-2 receptor of the cells of the lung and gains entry into cell where it replicates into millions. Then the viral army in its full maniacal might exits the cell and enters the circulation.
It is only then that the dormant soldiers recognize the gravity of the situation and in a frenzy starts producing chemokines and cytokines to alert those T cells and B cells to act. But the response is dramatic and uncoordinated resulting in a cytokine storm resulting in production of large amount of inflammatory and clot producing molecules that devastate the invaded tissues and cause secondary effects. The result is severe inflammation of the lungs into what is termed acute respiratory distress syndrome and production of clots. This is why the host goes from feeling ok to extremely sick in a matter of 1-2 days while harboring the virus quietly for 5 days. We are seeing pulmonary embolism, stroke, heart attacks as a result of this immune system gone wild.
The treatment of COVID-19 has to be tailored towards antiviral agents but also towards agents that suppress the powerful inappropriate cytokine storm.
What is fascinating about this is that COVID-19 has made us realized the powerful intersection of immunology, cardiology, cancer medicine and infectious disease all secondary to cytokines.