Most athletes are at low risk of significant symptoms from COVID-19 due to their age and state of cardiovascular health; however, some will experience symptoms and want to quickly recover and resolve any symptoms that do arise. Orreco recently described in this blog how point-of-care (POC) testing could be used to monitor inflammation in athletes in the COVID-19 era. Building on this, here we describe other hematological and biochemical biomarkers and a second POC test that has been associated with either COVID-19, or other respiratory illnesses that could help indicate an athlete at risk of COVID-19 infection. These include white blood cell count (WBC), neutrophil and lymphocyte count, neutrophil:lymphocyte ratio (NLR), creatine kinase (CK), serum ferritin, and oxidative stress (1). There is also evidence that Vitamin A and D (2), along with minerals, such as selenium, magnesium, copper, and zinc, are associated with the immune system’s general effectiveness. Avoiding deficiencies in these nutrients is one proactive step athletes can take to possibly ensure fast resolution ofCOVID-19, should they become infected.
COVID-19 and Immunity
All professional sports were abruptly halted due to the COVID-19 pandemic earlier this year. The resumption of play has been an arduous task for all professional leagues due to strict social distancing and quarantine rules. While some sports have successfully returned, it is clear that COVID-19 will not disappear quietly but will most likely be with us for a very long time. Current research has shown that individuals who contract COVID-19 generate an immune response (3-6).Briefly, specialized immune cells (i.e.,neutrophils) take up the virus and present part of the virus to lymphocytes called T-cells. Depending on the type of T-cell, they can either attack and kill the virus or help create other lymphocytes, called B-cells, that produce antibodies to neutralize the virus.
Most early COVID-19 research focused on B-cell antibodies because it is a hallmark of the immune system reacting to a novel virus (4, 5). It is well established that individuals infected with COVID‑19 generate antibodies; however, it is so far unclear how long these proteins remain circulating. In some studies, COVID-19 antibody levels have remained elevated for months, while other studies have reported undetectable levels after only a few weeks. Since the longevity of the antibody response appears to be varied, researchers have questioned if people create a long-lasting immunity to COVID-19. The generation of virus-specific T-cells in response to a novel virus is another hallmark of a well-functioning immune system. Research has shown that ‘helper’ T-cells, which assist in producing B-cells, and ‘killer’T-cells, which actively kill the virus, respond to COVID-19 infection (3, 6). Unfortunately, it is too early to show if ‘memory’ T-cells, which indicate long-lasting immunity to a novel virus, persist enough to respond to a secondary infection. In summary, the immune system in healthy people can generate a response to COVID-19 infection and likely have a ‘memory’ of the virus allowing fora quick immune response in case of reinfection. Here we describe biomarkers that are useful in either detecting an immune response or supporting the function of a healthy immune system.
Hematological & Biochemical Biomarkers
White blood cells, i.e., neutrophils, lymphocytes, and the NLR, have been commonly used to stratify COVID-19 patients (1, 7-9). All of these biomarkers are part of the immune system and help generate an effective immune response. Specifically, WBCs and neutrophils are significantly increased in COVID-19 patients, but lymphocytes are decreased (7-9). As mentioned previously, T-cells and B-cells are types of lymphocytes imperative to creating an immune response to COVID-19, so a decrease in lymphocytes indicates a weakened immune response among people infected with COVID-19. While neutrophils are essential for presenting the virus to lymphocytes and attacking the virus, they also release proteins called cytokines. Depending on the types of cytokines released, an inflammatory response can ensue. In the case ofCOVID-19 infection, the immune system can go awry by more neutrophils leading to increased inflammation and ultimately resulting in a deadly ‘cytokine storm.’ This increase in neutrophils and concurrent decrease in lymphocytes explains the increased NLR associated with COVID-19infection. These studies suggest that hematological biomarkers of the immune system should be essential in athlete testing.
Biochemical markers associated with inflammation, such as C-reactive protein, creatine kinase (CK), and serum ferritin, have all been associated with COVID-19 infection. Elevated CK levels were associated with poorer outcomes in COVID-19 patients, and a similar trend was observed with serum ferritin levels (1). Chronic inflammation is associated with a weakening immune response, which could exacerbate the symptoms of COVID-19 and or risk of infection (10). Therefore, healthcare practitioners could use signs of inflammation in athletes as an early indicator of COVID-19 infection, increased risk of infection, or the state of resolution of the infection in the recovery phase.
Several studies have shown that disruptions in oxidative stress can cause physiological problems leading to increased risk of infections and illness. COVID-19 is no exception and has been shown to induce severe oxidative stress and can potentially reduce antioxidant capacity (11). Therefore disruptions in oxidative stress and antioxidant capacity could be potential biomarkers to monitor COVID-19 infection, particularly recovery from the infection, and the athletes return to play. Importantly, redox homeostasis can be monitored through POC tests (FORT and FORD) which has been extensively validated in an athlete setting by Orreco scientists and others (12-15).
Vitamins and Minerals
Several studies have shown that multiple vitamins are important to a well-functioning immune system and could, therefore, play a protective role against COVID-19 infection (2, 16, 17). Crude relationships exist between Vitamin-D levels and COVID-19, with lower Vitamin-D levels associated with a greater number of cases and mortality (16). Also, patients with mild disease severity had significantly higher Vitamin-D levels than those with ordinary, severe, and critical disease severity (2). Suggesting that Vitamin-D is protecting people from poor outcomes after COVID-19 infection. There is an indication that Vitamin-D protects lung cells from being infected by COVID-19 and enhances the immune response to infections (2, 18). VitaminA and C have been implicated in the prevention and treatment of COVID-19 or other viral infections, indicating their importance in a normal functioning immune system (17).
It is well established that Vitamin D deficiency (25-OH <30 nmol/L) is associated with increased infection risk in athletes and soldiers. Additionally, Vitamin-D levels are associated with enhanced vaccine efficacy. Antibody titers were higher after hepatitis B vaccination in people with Vitamin-D levels>41nmol/L (19).Interestingly supplementation of Vitamin-D three days after vaccination did not help the vaccination response (19). Indicating that normal levels of Vitamin-D are imperative for a strong vaccine response at the time of vaccination. Overall, Vitamin-D is important for a strong immune system and should be monitored during future athlete testing.
Zinc, magnesium, copper, selenium levels are positively associated with a well-functioning immune system, but the specific role of these minerals in controlling or preventing COVID-19 is only loosely determined (17, 20). Simultaneously, deficiencies in these minerals are associated with an increased risk of viral and bacterial infections due to a weaker immune response, indicating they could be important biomarkers to monitor during the COVID-19 pandemic (21).
Conclusion
In summary, there has never been a more important time to monitor athletes health. Point of care tests to rapidly monitor inflammation and redox homeostatsis, as well as hematological, biochemical, and micronutrients associated with a well-functioning immune system could help prevent or reduce symptoms of COVID-19.
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