Your White Blood Cells During Pregnancy and COVID-19

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White blood cells (WBCs) are a group of cells within blood that help protect you against infection and other conditions. They are called white cells, because, when blood is placed in a tube and spun in a centrifuge, they form a thin white layer above a much thicker layer consisting of red blood cells (RBCs). Along with WBCs, the white layer also contains cell-like entities called platelets, which are important in clotting the blood, but in this post we’re focused on the WBCs. Another name for WBCs is leukocytes (derived from the Greek roots leuk for white and cyt for cell). In old movies from the 1940s and 50s, you may also hear people refer to WBCs as white corpuscles. WBCs differ from their RBC counterparts in many ways. For instance, WBCs do not contain hemoglobin, so they do not transport oxygen around the body. Also, whereas mature RBCs lack nuclei (special compartments containing chromosomes with most of your genes) and lack mitochondria (power plants that consuming oxygen to generate energy and reproduce with their own special chromosomes), each WBC contains mitochondria and a nucleus. Under a microscope, certain WBCs appear as if they contain more than one nucleus, but this is only because the nucleus of such cells has an irregular shape, consisting of multiple lobes connected by narrower regions. For the most part, WBCs are a little bit bigger than RBCs. However there is some overlap in size between RBCs and a group of WBCs called lymphocytes. When stained with special dyes and viewed within a sample of blood under the microscope, WBCs stand out among the much more numerous RBCs.

When a sample of blood is taken from you, often the tests that are performed include what is called a complete blood count (CBC). A CBC provides various measurements of various components of the blood, including the WBCs. Such measurements include a count of the number of WBCs in a given volume of blood and a count of the numbers of the different types of WBCs and the percentages that they comprise of the total WBC count.

The count of total white blood cells and the counts and percentages of the different types of WBCs can come out within ranges that are considered normal, or any of the numbers or percentages can come out abnormally low or abnormally high. Abnormal values are associated with various disease conditions, such as infections, but also with conditions that are not diseases. Studies have suggested, for instance, that mild changes in body temperature from activities such as exercise or cold showers, and even strong emotions, can increase the WBC, generally by increasing the number of a type of WBC called neutrophils. Furthermore, more definitely, the WBC count also increases moderately in women over the course of pregnancy, also generally driven by an increase in the number of neutrophils.

Neutrophils play a very important role in what immunologists call innate immunity, meaning defending the body against a range of agents to which the immune system has not adapted. When you have a bacterial infection, for example, the number of neutrophils in your blood spikes up, boosting the total WBC count, since neutrophils are part of that count. Neutrophils are further categorized based on how mature they are. Neutrophils of different stages of maturity circulate in the blood, but the most abundant type of immature neutrophils are called bands. The nuclei of these cells have a banded appearance, but as neutrophils mature their nuclei transform in the kind of multi-lobed shape that earlier we said characterizes certain WBCs. Such nuclei are also called segmented, and so, for short, the mature neutrophils are called segs. When the body is in a hurry to make more neutrophils, the bands become increasingly abundant in the blood. Consequently, in addition to an increase in the number of neutrophils, there is also an increase in the ratio of bands versus segs. This is called a left shift and usually it suggests a bacterial infection, but the rise in neutrophils during pregnancy often is also a left shift, meaning that it is dominated by a rise in bands.

In contrast with neutrophils rising up, another group of WBCs, called lymphocytes, tends to decrease its numbers in blood during pregnancy. Lymphocytes are immune cells that work together to find things that are foreign to the body and then learn to find them increasingly better in order to neutralize them. There are different flavors of lymphocytes, each with a different function. They all appear similar when examined under a microscope, exhibiting a single-lobed nucleus, but the different kinds of lymphocytes can be distinguished and counted by laboratory machines based on different proteins that sit their surfaces. Because the number of lymphocytes in a given volume of blood decreases during pregnancy while the number of neutrophils increases, doctors often put the neutrophil value and the lymphocyte value together into a measurement called the neutrophil-to-lymphocyte ratio (NLR). The NLR will increase if the number of neutrophils goes up, if the number of lymphocytes goes down, or a combination of both.

Currently, the NLR is of particular interest, because it also frequently increases in people suffering from COVID-19. Increasingly, doctors and scientists are finding that people experiencing particularly severe reactions to infection with SARS-CoV2 (the virus that causes COVID-19) have an abnormally high neutrophil count. At the same time, people with COVID-19 who experience a drop in the lymphocyte count tend to suffer more severe illness. Putting the two measurements together as the NLR, there is growing evidence of a correlation between the magnitude of the NLR and the likelihood that a person with COVID-19 will develop life-threatening complications. Although the details of the phenomenon are under study, the overall picture makes sense, because reduced lymphocytes suggests an immune system that’s having trouble targeting the virus to neutralize it, while elevated neutrophils suggest an immune system tuning up its overall defense, which can produce side effects that can worsen disease.

Depending on which study you read, the numbers indicating a good or bad prognosis vary. Some have reported that COVID-19 patients are likely to suffer only mild to moderate symptoms if the NLR is 3 or less, while an NLR above 10 has generally been associated with an elevated risk of bad complications. There is more of a gray area above 3 and below 10, with some reports suggesting that an NLR of 6 puts a person in the high-risk zone. The issue becomes still more complicated when we weave pregnancy into the picture, since most of the data are from people who are not pregnant. Moreover, while the NLR has been reported to increase moderately as a normal consequence of pregnancy, there is evidence that it may increase more in connection with various complications of pregnancy, such as gestational diabetes, ectopic pregnancy (pregnancy in the wrong part of the body), hyperemesis gravidarum (a condition involving sever nausea and vomiting and liver problems), preterm delivery, and preeclampsia (a condition characterized by high blood pressure and problem with an organ, usually the kidney). These factors could make it very challenging for doctors to interpret the changes in WBC measurements for those who are pregnant and also have COVID-19.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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