The only way to know for sure whether or not you have COVID-19 is to do an actual COVID-19 test. But are there other lab tests that can help doctors decide who needs testing when there are not enough tests for everyone? And are there tests that can help predict someone’s risk of hospitalization or severe complications? Read on to find out.
COVID-19 and Lab Tests
Coronaviruses are well-known triggers of respiratory infections. However, COVID-19 has emerged only recently and we are still in the early stages of learning about its effects on the human body.
One of the most important questions in this pandemic is what makes certain people fare better and others worse once they get infected?
- Severe obesity (BMI>35 kg/m2)
- Older age
- Being male
- High blood pressure (hypertension)
- Heart disease
- Lung disease
Obviously, the only way to know for sure whether or not you have COVID-19 is to do an actual COVID-19 test. But there are other lab tests that may help doctors decide who needs testing when there are not enough tests for everyone. Also, doctors and scientists are looking onto lab tests that could help them predict a person’s risk of hospitalization and severe complications. We’ve summarized them below.
Doctors can use lab tests to predict a COVID-19 diagnosis or to determine someone’s risk of hospitalization or severe disease complications.
In this post, we will go over the different labs that have been used to predict COVID-19 diagnosis and outcomes. However, as we talk about these labs and their link to COVID-19, keep in mind that:
- What we know is often based on a few small studies, which means that there is not enough research and that the studies are of limited quality.
- Many of the lab tests, with the exception of metabolic markers and vitamin D, are useful in hospital settings but are of little practical value to you at home when you are not infected.
- Correlation does not equal causation. This means that although there may be a link between a certain lab test and COVID-19 outcomes, that does not mean that the labs themselves are causing the outcome.
Therefore, take the following information with a grain of salt, because what we know will likely change as new information becomes available. We’ll keep you updated on all new significant findings.
The research into the usefulness of various lab tests in COVID-19 is still ongoing and there are a lot of uncertainties.
First, let’s discuss metabolic markers which are routinely used to estimate one’s overall metabolic health. If you are not already keeping track of these, now is probably a good time to start. You can read more about useful tests to evaluate your overall health here.
The important thing about these lab tests is that they are influenced by your day to day choices. That’s why, when they get out of balance, you can correct them by adjusting your lifestyle and your diet. Keeping these labs optimal is linked to the prevention of chronic diseases such as diabetes, obesity, and heart disease.
1. Blood Pressure
Blood pressure is an important indicator of your metabolic health and it’s especially important when it comes to COVID-19.
Early data from over 8700 patients from China and the United States suggest that high blood pressure is the most common condition among people admitted to hospitals with COVID-19. It’s found in 30 – 57% of patients [20, 21, 22].
Furthermore, based on available COVID-19 reports, scientists estimate that high blood pressure is associated with a nearly 2.5‑fold higher risk of severe COVID‑19 and a higher mortality .
To be clear, it’s not certain that it’s high blood pressure per se that has this negative effect. People with high blood pressure often also have other underlying health issues — and data has shown that people with multiple underlying issues fare worse .
Case in point, according to one set of data, high blood pressure was not independently associated with COVID-19 outcomes after adjusting for age. This means that older people tend to have higher blood pressure and also fare worse in COVID-19 [24, 25].
However, there are a couple of plausible mechanisms that could explain how high blood pressure could interact with COVID-19. These include blood vessel dysfunction (endothelial dysfunction) and a higher blood clotting risk seen in people with high blood pressure .
We’ll likely learn more soon as new studies are being released daily. In either case, managing your blood pressure will help you improve your overall health.
High blood pressure is the most common condition found in people admitted to the hospital for COVID-19. Having high blood pressure increases the risk of severe outcomes and dying of COVID-19.
Managing Blood Pressure
Although it was first speculated that certain drugs used to treat high blood pressure may worsen COVID-19 outcomes, new studies suggest the opposite may be true. A Chinese study reported that people with high blood pressure had a lower rate of severe diseases and a lower viral load when they took meds to decrease their blood pressure (RAS inhibitors) .
2. Blood Sugar
Another important metabolic marker, when it comes to COVID-19 complications, is blood sugar (glucose). A group of scientists made an estimate that diabetes increases the risk of having severe/critical COVID-19 illness by about 4-fold, independent of one’s age, sex, obesity, blood pressure, or smoking .
A large investigation in China, with almost 45k cases, found that the mortality of COVID-19 patients with diabetes was around 7.3%, which was dramatically higher than the mortality in people without any underlying conditions (0.9%) .
A small scale Chinese study found that even in 69 non-diabetics, higher blood sugar levels were an early predictor for poor outcome and death in COVID-19 .
In addition, another Chinese study with 132 COVID-12 patients found that a measure of average blood sugar over three months, Hb1Ac, was associated with inflammation, blood clots and lower blood oxygen saturation .
Why do diabetes and higher blood sugar negatively impact covid19 outcomes? Scientists think that any of the following may be to blame :
- increased chronic inflammation
- increased clotting
- impaired immune response
- potential direct damage to the pancreas by SARS-CoV-2
Diabetes increases the risk of developing severe COVID-19 illness by about 4-fold. Even in people without diabetes, higher blood sugar levels have been linked to adverse outcomes.
Managing Blood Sugar
Monitoring glucose regularly and improving glucose control may improve the outcomes in COVID-19 .
Among diabetics, in particular, those who have well-controlled blood sugar levels seem to have a markedly lower risk of dying, compared to those with poor blood sugar control. This is based on a Chinese study with over 7.3k COVID-19 cases including over 900 diabetics .
If your blood sugar is elevated and you have prediabetes or diabetes, work with your doctor to find out what’s causing it and to zero in on the best strategies to bring your blood sugar levels under control. Read about ways to decrease blood sugar levels here.
Studies suggest that diabetics with better blood sugar control tend to have better COVID-19 outcomes.
3. TyG (The Triglyceride and Glucose Index)
Triglycerides are the scientific term for fats, including the fats you eat in your diet and the fat that is stored in your body. Your triglyceride levels in the blood get higher when you overeat and your diet is unhealthy, full of carbs and saturated fats, and when you have an inactive/sedentary lifestyle [35, 36, 37, 38, 39].
Alternatively, there are online calculators that can calculate it for you, such as this one.
In a Chinese study with 151 COVID-19 patients, TyG was significantly higher in people who developed severe disease and in those who eventually died .
This is potentially alarming because a lot of people in the US have high triglyceride levels and therefore high TyG. A National Health and Nutrition Examination Survey of 5.6k people found that about one-third of US adults had high triglyceride levels !
However, what we know about TyG in COVID-19 so far is based on a single study. Larger well-designed studies are needed to confirm the utility of this index in COVID-19.
You can read more about triglycerides and how to lower them here.
Higher TyG, calculated from triglyceride and blood sugar levels, has been linked to more severe disease and death in COVID-19.
So cholesterol, in this case, is used as a proxy of how serious the disease is. Therefore, measuring it to determine COVID-19 severity makes sense only in hospital settings.
Cholesterol levels decrease with more severe COVID-19.
White Blood Cells
Lymphocytes are a type of white blood cell. They produce antibodies, kill virus-infected cells, and help direct the immune response. Normally, lymphocytes account for 20 – 45% of white blood cells, or around 1 – 4 ×109/L [46, 47, 48, 49].
Based on a meta-analysis of 13 case-studies with a total of over 2.2k patients, having low lymphocytes was associated with a nearly 3-fold higher risk of developing severe COVID-19. The meta-analysis further suggests that a lymphocyte count of less than 1.5 × 109/L may be useful in predicting the severity of COVID-19 outcomes .
One of the studies suggests that patients could be classified at 10–12 days after symptom onset into :
- Lymphocytes > 20%: moderate and can recover quickly
- Lymphocytes < 20%: severe
And at 17-19 days after symptom onset into :
- Lymphocytes > 20%: in recovery
- 5% < Lymphocytes < 20%: still in danger and in need of supervision
- Lymphocytes < 5%: critically ill with a high mortality rate and in need of intensive care
More studies are needed, however, to establish how universal and useful these cut off values are.
What’s the link between coronavirus and low lymphocyte levels? Scientists have several ideas :
- The virus might directly kill lymphocytes. Lymphocytes have the coronavirus receptor ACE2 and therefore may be a direct target for the virus.
- The virus might destroy organs that make lymphocytes, such as thymus and spleen.
- Inflammatory cytokines may cause lymphocyte death.
- Metabolic products, such as lactic acid, may interfere with the production of new lymphocytes.
It’s likely that multiple mechanisms, listed above and/or others not mentioned, work together to decrease lymphocyte levels in COVID-19 .
Having a low lymphocyte count has been linked to a 3 times higher risk of developing severe COVID-19.
Neutrophils are the first-responders at infection and inflammation sites. They help fight infection by ingesting microbes and releasing enzymes that kill them. Neutrophils usually account for 40 – 80% of white blood cells, or around 1.5 – 8 ×109/L [57, 58].
An Iranian study that looked at 200 people tested for COVID-19 found that those who were positive had significantly higher neutrophils .
Finally, in a Chinese study with 200 COVID-19 patients, having high neutrophils (neutrophilia) has been associated with a higher risk of death .
Why are elevated neutrophils bad in COVID-19? We know that neutrophils help clear the virus, but on the other hand, they can also cause an exaggerated immune response and inflammation that can harm the tissues, especially lungs [61, 62, 63].
Higher neutrophil levels have been linked to more severe disease and a higher risk of dying from COVID-19.
NLR is the ratio of neutrophils to lymphocytes in the blood. NLR has been previously studied as a predictor for various diseases, including infections, heart disease, inflammatory disease, and cancer .
According to a Chinese study of 245 people hospitalized for COVID-19, the risk of in-hospital death increased by 8% for each unit increase in NLR. Those with the highest NLR had a 15-fold higher risk of death compared to those with lower NLR .
According to an Italian study of 74 people with confirmed COVID-19, NLR of >4 was a predictor of admission to the ICU .
Higher neutrophil to lymphocyte ratio (NLR) has been associated with a higher risk of ICU admission and in-hospital death.
Eosinophils are white blood cells known for fighting parasite infections and for their involvement in allergies. However, newer studies suggest these white blood cells may also have a role in the antiviral response. Eosinophils usually account for 0 – 5% of white blood cells, or around 0 – 0.5 × 109/L [75, 76, 77].
According to a Chinese study of over 900 patients, a low eosinophil count (<0.02 109/L) was one of the features of COVID-19 and wasn’t present in those without this disease. The study suggests that the combination of low eosinophils and high hs-CRP may be used to triage suspected COVID-19 patients from other patients with COVID-19-like symptoms .
In another Chinese study with 140 hospitalized COVID-19 patients, eosinophils were lower in those who had severe disease .
However, according to a pooled analysis of a total of 3 studies with just under 300 patients, eosinophil count was not significantly different between patients with or without severe COVID-19 .
Larger studies are needed to verify if eosinophils can indeed be used to check for the presence and the severity of COVID-19.
A study suggests that eosinophils may be used to triage suspected COVID-19 patients in order to decide who gets tested. However, studies disagree on whether or not eosinophils are useful to determine disease severity.
C-reactive protein or CRP can tell whether your immune system is fighting an infection or experiencing chronic inflammation, which is closely tied to your metabolic health. Normally, hs-CRP levels are below 1 mg/L .
In an Iranian study with 200 people suspected of having COVID-19, those who turned out to be COVID-19 positive had significantly higher CRP levels .
Similarly, a Chinese study with over 980 suspected COVID-19 cases suggests that elevated hs-CRP (≥4 mg/L) could be used to effectively help triage likely COVID-19 patients from patients with COVID-19-like symptoms that didn’t have coronavirus .
For example, in a Chinese study with 27 COVID-19 positive patients, CRP levels at admission were correlated with the size of lung lesions and disease severity. They were highest in severe and lowest in mild cases. A cut off of 20.5 mg/L could be used to predict severe COVID-19 .
In another Chinese study with 140 COVID-19 patients, those with CRP > 42 mg/L were more likely to have severe complications .
We don’t know, however, if any of these cut-offs would still be valid in the general population. While there definitely appears to be a trend of higher CRP in COVID-19, larger studies are needed before we can draw definite conclusions.
Higher CRP levels may help doctors decide on who needs a COVID-19 test. Furthermore, CRP levels seem to increase with lung damage and disease severity.
Interleukin-6 (IL-6) is a cytokine with both pro- and anti-inflammatory properties. The IL-6 test has been used a lot in research but not often in medical practice. It’s not standardized and the normal range is generally lower than 15, 5, or even 1.8 pg/mL, based on the laboratory that does the testing .
Scientists have known from before that IL-6 levels increase in people who have respiratory dysfunction or severe viral infections. Furthermore, IL-6 is high in cytokine storms, which also feature in COVID-19, in which inflammatory signals go haywire, and the immune system does more damage to the body than the infection itself [86, 87].
In a German study with 40 COVID-19 patients, elevated IL-6 was strongly associated with the need for mechanical ventilation. The risk of respiratory failure for patients with IL-6 levels of ≥ 80 pg/ml was 22 times higher compared to patients with lower IL-6 levels .
In one Chinese study with 140 COVID-19 patients, those with IL-6 > 32 pg/mL were more likely to have severe complications .
Interestingly, studies found that, unlike adults, children don’t seem to experience elevated IL-6 levels. Instead, their IL-6 levels remain within the normal range which is likely associated with their milder symptoms .
Higher IL-6 levels have been associated with severe COVID-19 and a higher risk of lung failure.
Tissue Damage Markers
Lactate dehydrogenase (LDH) is an enzyme found in most tissues of the body. When cells get damaged or destroyed, LDH leaks into the bloodstream. This makes LDH a useful marker of tissue damage due to injury or disease [91, 92].
In a Chinese study with 69 confirmed COVID-19 cases, those who had lower oxygen blood saturation also had higher LDH levels .
In another Chinese study of 94 discharged COVID-19 patients, a higher clearance of the virus (RNA) was linked to lower LDH levels .
There are only a few studies looking at LDH in COVID-19 and all of them look at a relatively small number of people. However, we can speculate that, by design, LDH can be used to estimate tissue damage in COVID-19. However, whether it’s a particularly useful tool remains to be seen.
Higher LDH has been linked to a positive COVID-19 diagnosis and less oxygen saturation in COVID-19 patients. Levels tend to decrease with the clearance of the virus.
12. Liver enzymes (ALT, AST)
Reports suggest that, apart from the lungs, the liver is the next most frequently affected organ in COVID-19 .
In an Iranian study with 200 people, those who tested positive for COVID-19 tended to have significantly higher levels of AST and ALT. Further, ALT had very good accuracy in predicting who was positive for COVID-19 .
Other studies have also reported higher ALT and AST in COVID-19. However, full-blown liver failure or severe liver damage is rare, except in people with pre-existing liver disease. Some reports suggest that ALT and AST levels increase with COVID-19 severity .
Liver injury in COVID-19 may be due to :
- Psychological stress
- Drug toxicity
- Progression of pre-existing liver diseases (e.g. fatty liver)
AST and ALT increase in COVID-19 and may increase with disease severity. However, at this point, there is no evidence that the virus directly infects and damages liver cells.
13. Vitamin D
Vitamin D, or the “sunshine vitamin”, plays an important role in the immune system. Studies have shown that vitamin D deficiency increases the risk of developing certain bacterial and viral infections and may be important for keeping excessive inflammation at bay [99, 100, 101, 102, 103, 104].
When it comes to the risk of getting COVID-19, a Swiss study with 100 patients found that lower vitamin D levels were associated with testing positive for COVID-19 .
However, a much larger UK Biobank study with over 348k people found that the link between vitamin D and COVID-19 was not significant after adjusting for other factors .
When it comes to disease severity, a study of 780 Indonesians with confirmed COVID-19 found that low vitamin D levels were strongly associated with dying from COVID-19, even when adjusting for age, sex, and the presence of other diseases .
In 212 Philippinos with confirmed COVID-19, vitamin D levels were lowest in critical cases and highest in mild cases. A higher vitamin D level improved the odds of having a mild rather than a severe outcome .
In addition, a small Irish study of 33 people with COVID-19 related pneumonia found that those who progressed to ARDS had lower vitamin D levels at admission. A baseline vitamin D below 30 nmol/L was associated with about 3 times higher risk of intubation .
Lower vitamin D levels have been linked to more severe disease and a higher risk of death in COVID-19.
Similarly, in Chicago, more than half of COVID-19 cases and around 70% of COVID-19 deaths were observed in African-Americans, who are at a greater risk for vitamin D deficiency .
However, it’s important to stress here that correlation does not equal causation. Vitamin D is lower in people who are older, obese, smokers, and have underlying health issues – all of which are known risk factors for severe COVID-19 .
There is an indication that vitamin D deficiency contributes to acute respiratory distress syndrome (ARDS) and cytokine storms, both features of severe COVID-10 disease. Studies in animals showed that pretreatment with vitamin D was beneficial in ARDS. However, there are no studies to confirm that this also works in humans [113, 114, 111, 115, 116].
Either way, it would make sense to megadose with vitamin D just in case, right? Wrong.
It’s definitely important to make sure you have enough vitamin D, which can be accomplished by getting more sun or regularly taking low-dose supplements. However, high-dose vitamin D didn’t have any effect in a clinical study with critically ill people, and even had negative effects in some trials where it increased the risk of fractures and falls in the elderly. Long-term supplementation with vitamin D in excess of 4000 IU/day is considered possibly unsafe and can be toxic, because it dangerously increases blood calcium levels [117, 118, 111, 119, 120, 121, 122].
All of the above is why vitamin D levels and supplementation are currently such a popular and debated topic during this pandemic.
At this point, we still don’t know if vitamin D deficiency is directly responsible for the adverse outcomes, or if it’s just related to other COVID-19 risk factors such as obesity, old age, and chronic diseases.
As vitamin D deficiency is especially common in the US and can get depleted if you haven’t been leading the healthiest lifestyle or you are suffering from chronic health issues, we think it’s a good idea to check your levels regularly. And if your levels are low, discuss how to supplement safely and effectively with your doctor.
Red Blood Cells
14. Blood Type
In a recent preprint (not yet peer-reviewed) scientists from Columbia University investigated this link in 1,559 subjects, of which 682 were coronavirus-positive. They also found a higher frequency of the A group and a lower frequency of the O group among the infected people. However, the results were significant only for those with a positive Rh factor (Rh+) .
Interestingly, back in 2005, scientists observed that people with the O group were more resistant to SARS coronavirus, which is similar to the new SARS-CoV-2 causing COVID-19 .
In 2008, French researchers found that the anti-A antibodies inhibited the binding of SARS to ACE-2 receptors, thus preventing the virus from entering the cells .
When a group from Belgium reanalyzed the Chinese data, they found that whereas both blood group O and B patients possess circulating anti-A antibodies, it appears that the protection from COVID-19 was limited to the O blood type. This is likely related to the fact that in people with blood group B the anti-A bodies are mostly IgM, which offer short-lived protection, while in the O group they are IgG, the most prevalent antibodies in the body .
Bear in mind that if you have the O blood type, you may be less likely to get infected, but you are by no means immune to the infection. To stay as safe as possible, you still need to follow all CDC guidelines, including social distancing, washing your hands, and wearing a mask in public.
There is some research suggesting that the A blood group may increase susceptible to COVID-19 infection, while the O group is likely somewhat protective.
Doctors have used the following lab tests to predict a COVID-19 diagnosis or to determine the risk of hospitalization or severe complications:
- Blood Pressure
- Blood Sugar
- Triglycerides (TyG)
- Liver enzymes (ALT, AST)
- Vitamin D
In addition, there has been research into the link between different blood types and COVID-19.
However, the research into the usefulness of these tests in COVID-19 is still ongoing and there are a lot of uncertainties.