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I’m writing this the day after the Passover seder, which includes a retelling of the biblical story of the 10 plagues of Egypt. Like many others who carry on this ancient tradition, even this year when it had to be done with different households of the family linked in Zoom chat, I usually get pretty hungry by this point of the ceremony, so my thoughts are increasingly focused on the upcoming meal. Even so, some parallels between this story and the modern plague of COVID-19 were hard to ignore. For instance, there is the quarantine and social distancing phenomenon; in the Passover story, the Israelite slaves must remain locked in their homes, or else risk becoming plague victims themselves. That parallel was the elephant in the room, but last night I was also thinking about antibodies –proteins of the immune system that are present in body fluids, especially in blood, the substance that forms the first plague of the story.
Not all of the Egyptian plagues, but a couple of them, sound like infectious diseases, and thus more like plagues of recorded history. Those affected directly, whether cattle or people, would thus be under biological attack, and their immune systems would be responding. Acting as a defense force within your body, the immune system responds as soon as some substance gets into you that is not supposed to be there. As explained in a recent Pregistry post, such an invader can be parasitic, fungal, bacterial, or viral. Inside the body, a foreign substance is first detected by special immune cells called macrophages. The word macrophage is Greek for “big eater” (yet another connection with the Passover seder), because macrophages are basically large cells that engulf stuff, so they can break it into smaller pieces, which they then present to another class of immune cells called T lymphocytes. Through a series of events, this leads other immune cells, called B lymphocytes, to reproduce and multiply into more specialized cells called plasma cells, which manufacture what we are here to discuss: antibodies.
At this point, we’re going to get a little bit detailed and you’ll be wondering why, but bear with me, because we’ll need the information later when we discuss the prospect of utilizing antibodies from recovered COVID-19 patients as treatment for others who have the disease.
Antibodies are made with instructions from just a few genes, but the genes are shuffled around in ways that enable the immune system to create billions, and possibly trillions, of different variations of the basic antibody structure. Antibodies are proteins that possess particular 3-dimensional shapes, like keys, or the locks into which keys fit. A substance that your immune system considers to be “foreign” –meaning not part of the body– is called an antigen. One particular antigen, such as a new virus, typically triggers the creation of many different antibodies. These antibodies all can attach to the antigen, but not all to the same spot on the antigen and not all antibodies that attach to the same spot of an antigen attach with the same strength. It’s like having a locksmith make you keys for a few different locks on a door, and multiple keys for each lock, with some keys working better than other keys. Rather than designing from scratch the perfect key for the most important lock, the locksmith has instead made all of these different keys, hoping that at least some of them will do an adequate job. Those that work better will be produced later, in greater numbers, so that next time you can open the door more quickly.
Your immune system takes a similar trial-and-error approach with varying degrees of success in fighting off an infection, such as a disease-causing virus. In many cases, including the case of the SARS-CoV-2 virus that causes COVID-19, the success varies greatly among infected people. With the current pandemic, many people who are infected do such a good job fighting off the virus that they never even develop symptoms. Such people probably produce the best antibodies against SARS-CoV-2. It is hard to know who the asymptomatic people are, since they are much less likely to be tested than people who develop COVID-19 with symptoms, but people with symptoms also have trillions of antibodies against SARS-CoV-2 in their blood. Consequently, researchers are investigating the effectiveness of using antibodies from recovering COVID-19 patients to treat others with the same disease who have not recovered. The process involves creation of what’s called an anti-serum, but before we delve into what this means, let’s talk a little about how antibodies relate to pregnancy.
Starting right at the beginning, if you are pregnant, you likely found out with a take-home pregnancy test, a test at your obstetrician’s office, or both. And guess what; the pregnancy test itself, which measures the presence of the hormone beta human chorionic gonadotropin (β-hCG), actually uses antibodies to find the hormone in your urine or blood. That’s because antibodies can be extremely precise in recognizing and attaching to an antigen, in this case the pregnancy hormone. Such tests can be made to be extremely precise, because researchers have methods to find the best antibodies that can be made against an antigen, or even just the needed genetic arrangements for making those antibodies. The same methods are used to make various medicines, consisting of billions of copies of the same antibody. Known as monoclonal antibodies (MAbs), these much more precisely engineered locks and keys could eventually include treatments against COVID-19, but they take a lot of time to develop. Thus, for now, a bigger focus is on the mixtures of many different types of antibodies –called polyclonal antibodies– that the immune systems of COVID-19 patients are making.
Thinking about immunology and pregnancy, you may now be wondering about what a mother’s immune system makes of the embryo and its development into a fetus. Is it not foreign, and, if foreign, why is it not attacked? This is actually a question that has come up every now and then, and researchers think that in many cases the fetus, or earlier in pregnancy the embryo, may indeed be attacked, leading to its demise. This could be the reason for some miscarriages. Additionally, there is a pregnancy condition called Rh incompatibility in which the mother’s immune system can attack the blood cells of her fetus, because the cells have antigens on them that the mother’s immune system considers foreign. Especially now, with the COVID-19 crisis in full swing, there also are concerns that pregnant women might be more vulnerable to infection than others, partly because the strength of their immunity fluctuates throughout pregnancy, due to the need to keep the embryo/fetus from being rejected as a foreign substance.
Now, when it comes to an antiserum, you may have heard about it in relation to other conditions, such as to treat a bite a venomous snake. A rattlesnake bite victim, for instance, is given antiserum, which contains antibodies (usually made by the immune system of animal that is large enough to survive a rattle snake bite, such as a horse) that neutralize the venom. In the case of COVID-19, we want to neutralize the SARS-CoV-2 virus in order to slow and stop the spread of the virus through the respiratory system and other areas of the body. Earlier, we noted that antibodies are in the blood. Some antibodies are literally attached to the plasma cells that make them as they circulate in the blood, while other antibodies circulate freely. After you draw blood out of a blood vessel, usually a vein, if you put the tube containing the blood in a centrifuge (a machine that spins around, subjecting the spinning sample to a force many times the pull of gravity) the blood cells collect at the bottom of the tube while the liquid above is called plasma. If you add chemicals that prevent clotting, the liquid portion remains plasma, but otherwise it clots, which consumes proteins present in the blood that cause the clotting. This remaining liquid is called serum and it contains the various freely circulating antibodies. Although plasma also contains these antibodies, for various applications, including utilizing the antibodies for therapy, serum is better. And thus, one major focus in the search for COVID-19 therapies is to take serum that is rich in a variety of anti-SARS-C0V-2 antibodies –notably serum from recovering COVID-19 patients– purify it, and give it, or the antibodies from it, to people who are in an earlier stage of the disease. Although the patients would be receiving, not only the antibodies useful against the virus, but also a bunch of other antibodies, the treatment could very well prove to be effective and would be a start toward more accurate treatments.
While research advances toward the goal of using antibodies for COVID-19 therapy, health authorities around the world are also taking antibody approaches increasingly in connection with COVID-19 testing. In contrast with the test for an active infection with the SARS-CoV-2 virus, which uses a method called RT-PCR , antibody tactics can identify people who have been infected with the virus and have fought it off, because the body keeps making antibodies long after the virus has been put down. Consequently, health authorities believe that antibody testing could contribute greatly toward the goal tracking the spread of the virus among people who have not become seriously ill –which is the main way that the virus has been spreading.