Discussion
In suspicious cases of Covid-19 PCR is used in the diagnosis and is the gold standard, in some patients suspicious of having pneumonia may have to undergo a CT scanning. Yet PCR and CT both are not availbale in every healtcare institution. Therefore, there is a need for simpler and more practical methods to detect Covid-19 cases and else more Covid-19 patients with pneumonia which may have to be internated or carefully followed.
Our study demonstrated that neutrophil levels decrease in Covid-19 patienets with and without pneumonia compared to healthy subjects (p <0.001 for both comparisons). The data on neutrophil levels in Covid-19 are incomplete and have not been widely studied. The available data suggest that neutrophilia is an expression of the cytokine storm and hyperinflammatory state which have an important pathogenetic role in COVID-19 and related infections. In previous studies neutrophilia is reported in patients treated in intensive care unit 5. Yet neutrophil levels may be effected by many secondary diseases. In our study we included previously totally healthy patients at admission before using any kind of medicine. In a study Gumus et al. demonstrated low neutrophil levels in pediatric Covid-19 patients6. Similar to our study Xie et al. reported low levels of neutrophils in Covid-19 patients 7 yet their study contained patients who had chnronic diseases like asthma, chronic obstructive pulmonry disease, coronary heart disease etc.
Lymphocytes play an important role in the maintenance of immune system function. After a viral infection, changes in total lymphocyte numbers varies with different virus types. Wang et al. reported decreased lymphocyte levels in patients with Covid-19 8. Similar to their study we found low lymphocyte levels in patients with Covid-19 pneumonia. Eventhough low lymphocyte levels have been demontrated previously our study demonstrated that lymphocyte levels decrease in preiously healthy Covid-19 patients but no statistically difference between those with and without pneumonia.
Monocytes and macrophages are the most enriched immune cell types in the lungs of Covid-19 patients and appear to have a central role in the pathogenicity of the disease 9. Current data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of Covid-19 patients 10.In our study we found lowe monocyte levels in Covid-19 patients with pneumonia compared to healthy controls (p <0.001) and patients without pneumonia (p <0.001). Zhang et al observed that during SARS-CoV-2 infection, there are morphological and inflammation-related phenotypic changes in peripheral blood monocytes that correlate with the patient’s outcome 11. Zhang et al. did not detect significant differences in the number of monocytes between patients with Covid-19 and normal healthy individuals. In a study Kos et al. reported reduced rate of activated monocytes mainly observed in patients with severe Covid-1912. Eventhough our study demonstrated that monocyte levels decrease in previously healthy Covid-19 pneumonia and in those without these results reflect begining of the disease before treatment. Levels may differ after progression of the disease and may be effected by drugs used in treatment.
Eosinophils are circulating and tissue-resident leukocytes that have potential of proinflammatory effects in some diseases. Eosinophils also have been shown to have various other functions like immunoregulation and antiviral activity. Yet their role in Covid-19 is not well known. Previosly it has been reported that Covid-19 patients had a decrease in circulating eosinophil counts, which was significantly more frequent than other types of pneumonia patients 7. Zhang et al. has previously reported eosinopenia in patients with acute respiratory deterioration during infection with SARS-CoV-213. Zhanh et al. included 140 Covid-19 patients with comorbidities which may effect eosinophil levels yet similar to their study we also found low levels of circulating eosinophils in patients with Covid-19. Our study demonstrated that circulating eosinophil counts decrease in preivously totally healthy patients with Covid-19 and much more in Covid-19 patients with pneumonia. These results may indicate involvement of the lungs is associated with decrease in eosinophil levels. So a treatment strategy which increases eosinophil levels or targeting reasons of eosinopenia may help in dealing with Covid-19.
Covid-19 causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. We found Covid-19 patients with pneumonia had the lowest platelet counts. Trombocytopenia is a big problem during Covid-19 because many patients need anticoagulant prophylaxy which implies that thrombocytopenia needs to be attached more importance in the follow-up of Covid-19 patients. The difficulty is to choose the apropriate anticoagulant while on the other side there is trombocytopneia.
Prveiosly it has been reported that increased MPV levels was associated with mortality in Covid-19 patients 14. In another study Ozcelik et al. compared Covid-19 patients with influenza pneumonia and reported low MPV levels in patients with Covid-1915. MPV levels also found significantly high in asymptomatic children infected with Covid-19 6. In this study we found no difference in MPV levels between groups. MPV can be effected from many diseases and conditions and the teqnique used which may effect the results. In this study similar to MPV levels we didnt find statistically differences between PDW and RDW levels. In a study Henry et al. found a progressive increase of RDW with advancing Covid-19 severity 16. The discrepency between two studies might be due to patients grops, Henry et al. included patients with comorbidities yet we aimed to see if RDW can be usefull in the early diagnosis of previously healthy Covid-19 patients.
In recent years, some ratios have been in use by researchers in the diagnosis and prognosis of many inflammatory conditions. Some of these are neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratio. In a study Seyit et al. Reported high NLR in patients tested positive for SARS-CoV-2 compared to controls 17. In our study we found no differences between NLR of three groups. In a study from Wuhan/China Yang et al. reported elevated NLR significantly associated with illness severity 18. Difference between our study and the study conducted by Seyit et al. migt be due to patient characteristics or to the heterogenisity of Covid-19. Seyit et al found high levels of PLR in patients with Covid-19. In acoordance with their study we also found high levels of PLR in patients with Covid-19 pneumonia compared to healthy subjects (p <0.013) and Covid-19 patients without pneumonia compared to healthy controls (p <0.005). Our study demonstrated that PLR is high in Covid-19 patients but it might not be associated with disease severity at least at the begining stage of the disease. Yang et al. investigated 93 Covid-19 patients and found out that lyphocyte to monocyte ratio (LMR) levels of severe patients were significantly higher than those of non-severe patients.18. In our study we aimed to observe if MLR could be used in the diagnosis of Covid-19 patients at the admmision before undergoing treatment. We found highest MLR in patients without Covid-19 pneumonia versus patients with pneumonia and healthy controls (both p <0.001). More studies are needed to obtain more detailed information.