Discussion
This research aims to inquire about the association between lymphopenia and lung involvement in the outcome of hospitalized patients with COVID-19. Here, the lymphocyte percentage was calculated as 20.35 ±10.16, it was significantly associated with more severe lung involvement (P= 0.00). The lymphopenia was observed in 312 patients (52.3%) and 284 patients lied within the normal range. Of the 596 hospitalized patients, 84 (14%) died and 515 cases were discharged. We observed that CRP and ESR may not a predictable inflammation marker in patients with COVID-19. Of the 596 patients, 260 (43.6%) showed bilateral ground‐glass and consolidative opacities, 253 (42.4%) had bilateral ground-glass opacities, and 50 (8.4%) had bilateral consolidation on chest CT. While the pleural effusion, consolidation, GGO was seen in COVID-19 cases, 24 patients (4.1%) had exclusively unilateral lung involvement. The bilateral ground-glass opacities and consolidation were the major pulmonary CT findings of COVID-19 patients.
In the same conclusion as ours, other studies reported lymphopenia as a reliable indicator for COVID-19 severity. Tan et al were shown that there is a reverse association between lymphocyte count and COVID-19 severity and its prognosis 14. The lymphocyte count < 20% was reported in severe clinical illness; lymphopenia at the level <5% was found in patients who died14. In another study, lymphopenia at the level of 40% was demonstrated within 191 patients 26. It was also presented that 48% of included patients experienced underlying non-communicable diseases including hypertension, diabetes, and coronary heart disease 26. Several symptoms of coronavirus infection were also described in Iranian children and were defined as a less serious disease with a good prognosis 27. Zhenget al compared the laboratory features of COVID-19 pneumonia to non- COVID-19 pneumonia. They stated that COVID-19 pneumonia- derived lymphopenia negatively affect the biochemical indicators of organ dysfunction 28. A study done on 221 hospitalized COVID-19 patients confirmed leukopenia (33%), lymphopenia (73.8%), and more susceptibility to fungal and bacterial infections29. Chinese research explained that bilateral pneumonia, shorter duration of onset to admission, lymphopenia, and disease severity are regarding as risk factors of prolonged hospitalization of COVID-19 30. Lymphopenia may occur along with an increased level of cytokine, disease severity, mortality, and impaired immune response 31.
Tan et al showed the inverse relationship between lymphocyte count and disease severity and its prognosis in 92 COVID-19 patients32. It was disclosed that LYM% lower than 20% was seen in severe cases and it fell under 5% in dead patients32. Comparison of laboratory variations of 88 patients with COVID-19 pneumonia and 22 non-COVID-19 pneumonia cases revealed that lymphocyte depletion, not neutrophil, and monocyte, inversely affect biochemistry disorder and organ failure 33. Lymphopenia and augmentation of cytokine are accompanied by increased disease severity, death, and disrupted immune response31. Despite that some studies found higher levels of ESR and CRP as inflammatory indicators in severe patients of COVID-1934-36, our results did not show increased ESR and CRP levels in severe cases. It was also shown by Peng et al37.
The chest CT scan plays a crucial role in the early diagnosis and evaluation of patients with COVID-19 pneumonia likewise, lymphopenia and thrombocytopenia were the verified markers for disease detection38. The sensitivity of a chest CT imaging was examined among 1014 patients who had negative RT-PCR 19. Their results showed high sensitivity of lung CT (75% of the included population were positive for COVID-19) and suggested it as a reliable detection method in epidemic regions 19. Subgroup analysis revealed that COVID-19 patients with severe pulmonary lung involvement and lymphopenia had 9.2-fold increased odds of in-hospital mortality. The mortality rate was also calculated in patients with severe lung involvement and patients with lymphopenia, these groups had a mortality rate of 3.4 and 3.6 times greater than those without lung involvement and lymphopenia (Table 3). In other words, the mortality in the case of lymphopenia along with severe lung involvement was deeply different compared with patients with neither lymphopenia nor lung involvement (OR 9.2, [95% CI 4.3- 19.7]) (Table 3). We found that the incremental effect of lymphocyte count and lung involvement tracks the multiplicative model, no additive model.
Assessment of RT-PCR positive COVID-19 cases showed leukopenia, lymphopenia, and high CRP concentration as hematological and biochemical parameters. The most involved segments were lung segments 6 and 8 with peripheral pulmonary localized lesions 39. The sensitivity of the CT scan was inspected in mild COVID-19 reach to a high level after 10 days of infection 40. It was examined that the most frequent CT Manifestations and Clinical Features were GGO (86%) and consolidation (62%) 41. Similarly, we found that bilateral distribution of GGO and consolidation are the main pulmonary lesions of COVID-19 patients.
The inflammatory marker of platelet to lymphocyte ratio (PLR) was suggested as a predictive indicator for disease severity and mortality in infectious disease and cancer 42,43. Rong et al noted the value of PLR for predicting the clinical outcome of COVID-19 and patients’ observing. They found out a high PLR is associated with more severity and longer hospitalization44. Conversely, our study showed no significance and it was not correlated to mortality (p= 0.16). The PLR was not correlated with the LOS (p= 0.06; r= 0.07). Notably, we found that LOS in patients with lymphopenia and severe lung involvement was remarkably higher than others (p <0.05). Likewise, a Chinese study represented that bilateral pneumonia in a lung CT scan, a short period from symptoms onset to hospitalization, lymphopenia, and disease severity were the main factors in prolonged LOS (ProLOS) 45.