key: cord-0966215-kgjr5w9m
authors: Zaboli, Ehsan; Majidi, Hadi; Alizadeh‐Navaei, Reza; Hedayatizadeh‐Omran, Akbar; Asgarian‐Omran, Hossein; Vahedi Larijani, Laleh; Khodaverdi, Vahid; Amjadi, Omolbanin
title: Lymphopenia and lung complications in patients with coronavirus disease‐2019 (COVID‐19): A retrospective study based on clinical data
date: 2021-05-13
journal: J Med Virol
DOI: 10.1002/jmv.27060
sha: 4d76f7907c5342e2185f86abc4e3621dbe139a8d
doc_id: 966215
cord_uid: kgjr5w9m

A rapid outbreak of novel coronavirus, coronavirus disease‐2019 (COVID‐19), has made it a global pandemic. This study focused on the possible association between lymphopenia and computed tomography (CT) scan features and COVID‐19 patient mortality. The clinical data of 596 COVID‐19 patients were collected from February 2020 to September 2020. The patients' serological survey and CT scan features were retrospectively explored. The median age of the patients was 56.7 ± 16.4 years old. Lung involvement was more than 50% in 214 COVID‐19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ± 10.16 (normal range, 20%–50%). Although the levels of C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in more than 80% of COVID‐19 patients; CRP, ESR, and platelet‐to‐lymphocyte ratio (PLR) may not indicate the in‐hospital mortality of COVID‐19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio, 9.24; 95% confidence interval, 4.32–19.78). These results indicated that lymphopenia < 20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in‐hospital mortality rate of this group was significantly higher than other COVID‐19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (p = .00). Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient's mortality. These could act as laboratory and clinical indicators of disease severity, mortality, and outcome.

receptor ACE2 infect lymphocytes that lead to lymphocyte death 13 ;

(b) the possible role of coronavirus in the destruction of lymphoid organs 14 ; (c) induction of lymphocyte apoptosis by the production of tumor necrosis factor-α and interleukin-6, 15 and (d) inhibition of lymphocyte production during metabolic acidosis. 16 Although the pathogenesis of COVID-19 remains unclear, lymphopenia was observed in most of the patients. 17 Aging and chronic illness lead to endothelial dysfunction that dismounts cell-cell adhesions, promotes endothelial cell death, extravasation that resulted in lymphopenia. 18 The infection of COVID-19 is diagnosed and confirmed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and gene sequencing of the blood and lung samples. In the early phase of the disease, positive nasopharyngeal RT-PCR results ranged between 30% and 60%. 19 In emergency cases, the low sensitivity of RT-PCR missed diagnoses of COVID-19 patients who failed to receive appropriate medications and upended outside spreading of COVID-19.

In contrast with RT-PCR, chest computed tomography (CT) has sufficient sensitivity for atypical radiographic manifestations of COVID-19 cases who are asymptomatic and/or negative on the initial RT-PCR test. 20, 21 According to the Chinese reports, chest CT is adequately sensitive (97%) in the early detection of COVID-19 patients compared with RT-PCR. 22 Bilateral lung involvement was observed in 98% of patients and lobular and subsegmental areas of consolidation were considered as the most typical findings of CT. 4 Besides this, several COVID-19 cases demonstrated ground-glass opacities (GGOs) and pulmonary consolidation with round morphology. 23 The main CT findings of COVID-19 pneumonia are the shape of GGO, crazy paving pattern, and consolidation. 24 Iran is one of the worst affected countries by the coronavirus and Mazandaran province is considered one of the most impacted areas. 25 The paucity of evidence on the relationship between lymphopenia, chest CT examination, and mortality rate in COVID-19 patients made us ascertain this possibility. As Imam Khomeini hospital in Mazandaran was considered as the main referral center for the management of COVID-19 cases, we aimed to retrospect and evaluate the lymphopenia in COVID-19 patients and its association with lung involvement. Complete Blood Count, CRP, and ESR were evaluated within a 7 days monitoring period. All medical data including epidemiological, demographic, laboratory data, and patient's discharge and/or death were extracted via the hospital information system. 

A total of 596 patients were included. With the same conclusion as ours, other studies reported lymphopenia as a reliable indicator for COVID-19 severity.

Tan et al. 14 showed that there is a reverse association between lymphocyte count and COVID-19 severity and its prognosis.

Lymphocyte count < 20% was reported in severe clinical illness; lymphopenia at the level <5% was found in patients who died. 14 In another study, lymphopenia at the level of 40% was demonstrated in 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 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 detection. 37 The sensitivity of 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 to be 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 ( and biochemical parameters. The most involved segments were lung segments 6 and 8 with peripheral pulmonary localized lesions. 38 The sensitivity of the CT scan was inspected in mild COVID-19 reaching a high level after 10 days of infection. 39 It was found that the most frequent CT manifestations and clinical features were GGO (86%) and consolidation (62%). 40 Similarly, we found that bilateral distribution of GGO and consolidation are the main pulmonary lesions of COVID-19 patients.

The inflammatory marker of PLR was suggested as a predictive indicator for disease severity and mortality in infectious disease and cancer. 41, 42 Rong et al. noted the value of PLR for predicting the clinical outcome of COVID-19 and patients' observation. They found a high PLR is associated with more severity and longer hospitalization. 43 Conversely, our study showed no significance and it was not correlated to mortality (p = .16). The PLR was not correlated with the LOS (p = .06; r = .07). Notably, we found that LOS in patients with lymphopenia and severe lung involvement was remarkably higher than others (p < .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). 44 ZABOLI ET AL.

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Lymphopenia and lung complications in patients with coronavirus disease-2019 (COVID-19): A retrospective study based on clinical data