What Changes in the Blood Profile Can Teach Us About Covid-19
“When you visit a GP’s [general practitioner’s] office or emergency department with an unknown illness, a doctor will commonly draw some blood to gain a better idea of what’s going on inside your body,” said Karen Dwyer, a professor of medicine, nephrologist, transplant physician, and dean of Deakin University. “Blood is perhaps the most important window through which we can peer into a person’s health or illness.”
As the blood transverse all organs, it picks up biochemicals or proteins that reflect the state of the overall organ systems. Thus, what happens in the blood of Covid-19 patients says a lot about how the disease affects the body.
“Blood is perhaps the most important window through which we can peer into a person’s health or illness.”
There are three meta-analyses published in August and September — from separate research groups in China, Belgium, and New York— that examined biomarkers of severe Covid-19. These papers synthesized clinical data from 40, 32, and 31 studies, respectively. And all arrived at the same biomarkers that could tell apart severe from non-severe cases of Covid-19.
Only two pro-inflammatory biomarkers — procalcitonin and C-reactive protein (CRP) — were found at higher levels in severe compared to non-severe cases.
Covid-19 also increases levels of other pro-inflammatory biomarkers, such as monocyte chemoattractant protein 1 (MCP-1), interleukins (IL-2, IL-6, and IL-7), and tumor necrosis factor-alpha (TNF-a). But these biomarkers do not increase any further as Covid-19 worsens.
↑ C-reactive protein (CRP)
Levels of CRP can rise to 1000-fold during an infection. Most of it came from the liver, but other types of cells (e.g., the muscle, immune, fat, or endothelial cells) can produce CRP to some degree. CRP then tells other cells to secrete inflammatory cytokines. Next, CRP activates several defense systems — such as the complement system, phagocytosis, or programmed cell death — to help clear the infection.
The high procalcitonin in Covid-19 (a viral disease), therefore, either means a bacterial co-infection or unwanted inflammation.
Procalcitonin is primarily made by the thyroid to adjust calcium levels. But how calcium regulation helps fight infections remains unclear. Increased procalcitonin levels usually diagnose bacterial (and sometimes fungi or parasitic) infections, but not viruses. The high procalcitonin in Covid-19 (a viral disease), therefore, either means a bacterial co-infection or unwanted inflammation.
The meta-analyses also calculated that severe Covid-19 patients have lower counts of platelets and lymphocytes — but a higher white blood cell (WBC) count— than their non-severe counterparts.
↓ Platelets (also called thrombocytes)
Platelets form blood clots to stop bleeding from injured blood vessels. And researchers have suggested three reasons for Covid-19 thrombocytopenia (i.e., abnormally low platelets):
- Direct infection of the bone marrow where platelets are made.
- Increased production of autoantibodies or immune complexes by the immune system that mistakenly destroys platelets.
- Increased injury in the lungs’ blood vessels where platelets concentrate, so fewer platelets are available in the blood circulation.
Killing lymphocytes is a smart move, especially when B-cells and T-cells make up the adaptive immune system… that determines if a serious infection is successfully eradicated.
Lymphocytes are a subset of white blood cells that live in the lymph nodes. Lymphocytes include NK cells (that kill abnormal cells), B-cells (that make antibodies), and T-cells (that kill abnormal cells and boost functions of other types of immune cells). Abnormal cells mean cells that are cancerous or infected with pathogens.
Lymphocytopenia (i.e., abnormally low lymphocytes) is not unique to Covid-19, as it is a common way how viruses fight back. Viruses can infect lymphocytes, which causes its destruction. Indeed, lymphocytes express the ACE2 receptor that SARS-CoV-2 uses for cell invasion. Serious infections also induce a cytokine storm that makes it difficult for the lymphocytes to thrive.
Killing lymphocytes is a smart move, especially when B-cells and T-cells make up the adaptive immune system that mounts immune responses designed for a specific pathogen and forms immune memory. As the adaptive immune system is more specialized, it takes time to prepare. This is in contrast to the innate immune system that is the first responder to foreign invaders, but its activities are more generalized and less effective. And it is ultimately the adaptive immune system that determines if a serious infection is successfully eradicated.
Therefore, a high WBC-to-lymphocyte ratio in patients signifies a cytokine storm or hyper-inflammation.
↑ White blood cell (WBC)
WBC refers to immune cells in general, including cells of the adaptive (B-cells and T-cells) and the innate (e.g., neutrophils, macrophages, phagocytes, etc.) immune system.
The high WBC but low lymphocyte counts in more severe cases of Covid-19 indicate an imbalance in the immune system. The innate immune system (responsible for the generalized inflammation and killing of pathogens) is on overdrive, while the adaptive immune system is suppressed.
Indeed, patients with severe Covid-19 had higher levels of neutrophils — a highly inflammatory immune cell that kills both foreign invaders and healthy cells — than mild cases. Therefore, a high WBC-to-lymphocyte ratio in patients signifies a cytokine storm or hyper-inflammation.
III. Other biochemical biomarkers
In the blood of patients with greater Covid-19 severity, the meta-analyses also identified many other biomarkers informing of multi-organ damage:
- Heart injury: ↑ troponin I, creatine kinase-MB, and lactate dehydrogenase levels.
- Lung injury: ↑ lactate dehydrogenase levels (other biomarkers were not tested because chest CT scans quickly diagnose lung injury).
- Abnormal blood clots: ↑ D-dimer levels and prothrombin time.
- Liver injury: ↑ bilirubin, gamma-glutamyltransferase, and alanine and aspartate aminotransferases levels.
- Kidney injury: ↑ creatine, myoglobin, and urea nitrogen levels.
- Muscle injury: ↑ creatine kinase and myoglobin levels.
- Brain injury: Brain biomarkers are usually measured from the cerebrospinal fluid, not the blood.
At least 40 studies have examined biomarkers of Covid-19 severity, which were synthesized by three recent meta-analyses. And the pooled results revealed a hyper-inflammation (possibly with bacterial co-infection), imbalanced immune systems (an overactive innate but subdued adaptive immunity), and multi-organ complications (of the heart, lungs, blood vessels, liver, kidney, and muscle). All in all, these blood profile data shed some light on how severe Covid-19 ravages through the body, or what the body is facing as Covid-19 worsens.