Objective: This study aimed to investigate the potential parameters associated with imaging progression on chest CT from coronavirus disease 19 (COVID-19) patients. Results: The average age of 273 COVID-19 patients enrolled with imaging progression were older than those without imaging progression (p = 0.006). The white blood cells, platelets, neutrophils and acid glycoprotein were all decreased in imaging progression patients (all p < 0.05), and monocytes were increased (p = 0.025). The parameters including homocysteine, urea, creatinine and serum cystatin C were significantly higher in imaging progression patients (all p < 0.05), while eGFR decreased (p < 0.001). Monocyte-lymphocyte ratio (MLR) was significantly higher in imaging progression patients compared to that in imaging progression-free ones (p < 0.001). Logistic models revealed that age, MLR, homocysteine and period from onset to admission were factors for predicting imaging progression on chest CT at first week from COVID-19 patients (all p < 0.05). Conclusion: Age, MLR, homocysteine and period from onset to admission could predict imaging progression on chest CT from COVID-19 patients. Methods: The primary outcome was imaging progression on chest CT. Baseline parameters were collected at the first day of admission. Imaging manifestations on chest CT were followed-up at (6±1) days.

Since the end of 2019, a novel coronavirus with person-to-person transmission has spread to many other countries worldwide [1–5]. Previous epidemiology report uncovered that the epidemic of coronavirus disease 2019 (COVID-19) has doubled every 7.4 day in its early stage, with an average serial interval of 7.5 days [3]. Early information estimated that the basic reproductive number R0 was estimated to be 1.4 – 2.5 reported by WHO [2]. The pandemic is accelerating at an exponential rate and at risk of escalating into a global health emergency [2]. The mortality of coronavirus disease 2019 (COVID-19) patients in China is approximately 2.3%, compared with 9.6% of severe acute respiratory syndrome (SARS) and 34.4% of middle east respiratory syndrome (MERS) reported by WHO [6]. Even this virus is not as fetal as people thought, the transmissibility is far exceeding that of SARS and MERS [7]. Although many clinical and epidemiological literatures have been published [3–6, 8–10], the spread in still ongoing and the early warning parameters for disease progression remain incomplete.

Compared to symptoms, chest CT findings were more rapid and frequent [11, 12]. The imaging performance on chest CT scans from COVID-19 patients mainly manifested as bilateral ground-glass opacities (GGOs) in the lung periphery [13]. In a retrospective cohort, chest CTs of 121 symptomatic COVID-19 patients have been reviewed. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%) [11]. Currently, chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia [14]. In a cohort study, 85.7% (54/63) confirmed COVID-19 patients developed imaging progression including enlarged and increased extent of GGOs and consolidation at early follow-up chest CT scans [12]. That is, short-term imaging progression on chest CT from COVID-19 patients should be early predicted and intervened.

Imaging performance of progression and progression-free patients

As shown in Figure 1, most mild type COVID-19 patients had bilateral and peripheral GGOs, consolidation and linear opacities imaging involvements on chest CT at the first admission day. Some patients had no remarkable hallmarks. At the first six (±1) day, enlarged and increased GGOs, consolidation, solid nodules and fibrous stripes were observed for patients suffered from imaging progression on chest CT scans. On the contrary, the GGOs, consolidation and linear opacities were partly resolved and decreased for imaging progression-free patients.

Baseline characteristics and inflammatory model comparisons between imaging progression and progression-free patients

In total, 71 COVID-19 patients suffered from imaging progression on chest CT at first week after admission, and the other 202 patients were imaging progressionfree on chest CT. As summarized in Table 1, the patients in imaging progression group were significantly older than those in imaging progressionfree group (p = 0.006, Table 1). More patients were treated with gamma globulin and thymosin in imaging progression group compared to those without imaging progression (p = 0.022 and p = 0.001, respectively, Table 1). In blood routine tests, the white blood cells (WBC), platelets and neutrophils were significantly lower in imaging progression patients than those in imaging progression-free ones (p = 0.025, p = 0.044 and p = 0.014, respectively, Table 1), while the monocytes were significantly higher in imaging progression patients (p = 0.025, Table 1). Additionally, acid glycoprotein was significantly lower in imaging progression patients (p = 0.037, Table 1). In liver function tests, gamma-glutamyl transferase (GGT) levels were significantly higher in imaging progression-free patients (p = 0.045, Table 1), while homocysteine levels were significantly higher in imaging progression patients (p = 0.006, Table1). In kidney function tests, urea, creatinine and serum cystatin C levels were significantly higher in imaging progression patients compared to those in imaging progression-free ones (p = 0.011, p = 0.007, respectively, Table 1). As we expected, the estimated glomerular filtration rate (eGFR) levels were significantly decreased in imaging progression patients (p < 0.001, Table 1). No differences were found in cardiac markers and coagulation function tests.

Co-manifestations on chest CT and outcomes

As summarized in Table 2, except for common manifestations on chest CT, chronic inflammatory

manifestation, chronic bronchitis / emphysema, pericardial effusion, pleural effusion, bullae of lung and obsolete tuberculosis were the most frequent imaging co-manifestations in COVID-19 patients. COVID-19 patients with imaging progression had significantly higher frequency of chronic inflammatory manifestation than those without imaging progression (12.7% vs. 3.5%, p = 0.005, Table 2). No differences were found in distributions of chronic bronchitis / emphysema, pericardial effusion, pleural effusion, bullae of lung and obsolete tuberculosis between these two groups (Table 2).

Parameters associated with imaging progression on chest CT

Variables including age, gender, disease history, epidemiology, chest CT imaging, therapeutic strategies, period from onset to admission, ALRI, APRI, MLR, NLR, PLR, SII, WBC, neutrophils, lymphocytes, monocytes, platelet, red blood cells (RBC), hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), GGT, lactate dehydrogenase (LDH), total bilirubin (TBiL), albumin, globulin, urea, creatinine, eGFR, lactic acid, haptoglobin, acid glycoprotein, cystatin C, homocysteine, retinolbinding protein, cardiac troponin (cTnI), myoglobin, brain natriuretic peptide prohormone (pro-BNP), prothrombin time, prothrombin activity (PTA), international normalized ratio (INR), D-dimer were included in the univariate analysis. As presented in Table 3, age, gamma globulin therapy, thymosin therapy, MLR, serum cystatin C, homocysteine, eGFR and period from onset to admission were potential parameters associated with imaging progression (all p < 0.05, Table 3). When these parameters were included in the multivariate model, age, MLR and homocysteine were significantly correlated with imaging progression on chest CT from COVID-19 patients (RR = 2.28, 95%CI = 1.12 – 4.34, p = 0.012; RR = 7.69, 95%CI = 1.67 – 35.55, p = 0.009 and RR = 3.17, 95%CI = 1.01 – 9.96, p = 0.048; respectively, Table 3). In addition, COVID-19 patients with period from onset to admission ≥ 4 days might have lower risk to develop imaging progression on chest CT at first week after admission (RR = 0.35, 95%CI = 0.19 – 0.67, p = 0.001, Table 3).

Moreover, no acute bacterial or other viral co-infection performances on chest CT were found in these COVID19 patients.

All these COVID-19 patients did not develop severe conditions, no one died during our follow up.

Parameters associated with imaging progression on chest CT

Variables including age, gender, disease history, epidemiology, chest CT imaging, therapeutic strategies, period from onset to admission, ALRI, APRI, MLR, NLR, PLR, SII, WBC, neutrophils, lymphocytes, monocytes, platelet, red blood cells (RBC), hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), GGT, lactate dehydrogenase (LDH), total bilirubin (TBiL), albumin, globulin, urea, creatinine, eGFR, lactic acid, haptoglobin, acid glycoprotein, cystatin C, homocysteine, retinolbinding protein, cardiac troponin (cTnI), myoglobin, brain natriuretic peptide prohormone (pro-BNP), prothrombin time, prothrombin activity (PTA), international normalized ratio (INR), D-dimer were included in the univariate analysis. As presented in Table 3, age, gamma globulin therapy, thymosin therapy, MLR, serum cystatin C, homocysteine, eGFR and period from onset to admission were potential parameters associated with imaging progression (all p < 0.05, Table 3). When these parameters were included in the multivariate model, age, MLR and homocysteine were significantly correlated with imaging progression on chest CT from COVID-19 patients (RR = 2.28, 95%CI = 1.12 – 4.34, p = 0.012; RR = 7.69, 95%CI = 1.67 – 35.55, p = 0.009 and RR = 3.17, 95%CI = 1.01 – 9.96, p = 0.048; respectively, Table 3). In addition, COVID-19 patients with period from onset to admission ≥ 4 days might have lower risk to develop imaging progression on chest CT at first week after admission (RR = 0.35, 95%CI = 0.19 – 0.67, p = 0.001, Table 3).

TCM, Traditional Chinese Medicine; WBC, white blood cells; RBC, red blood cells; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; LDH, lactate dehydrogenase; TBiL, total bilirubin; eGFR, estimated glomerular filtration rate; cTnI, cardiac troponin; Pro-BNP, Brain natriuretic peptide prohormone; INR, international normalized ratio; PTA, prothrombin activity.