Eighty health care providers at Peking University People’s Hospital contracted SARS in 2003. Two patients died of SARS in 2003, and seven patients declined to participate in the study. A total of 71 patients (57 female) completed a 15-year follow-up from 2003 to 2018 (Fig. 1).

Fig. 1 Flow diagram of the follow-up examinations Full size image

We surveyed the length of hospital stay and treatment regimes in 2018 and evaluated health utility via questionnaires. The results showed that the length of hospital stay ranged from 10 to 70 days in 2003, with a median of 33 days (30, 42.5), and daily methylprednisolone doses ranged from 0 to 800 mg, with a median of 160 mg per day (100, 400). Only 38 patients remembered their cumulative steroid dosage (methylprednisolone via intravenous injection) ranging from 0 to 20 000 mg with a median of 3 450 mg (2 285, 5 225 mg). A total of 53 out of 71 patients were still employed in 2018, nine were retired, and nine were on long-term sick leave. The enrolled patients had various comorbidities; three patients were complicated with anxiety and depression requiring treatment, sixteen had hypertension, five had diabetes, seven had peptic ulcers, and one had Sjogren’s syndrome. The characteristics of the patients are shown in Table 1.

Table 1 Characteristics of the 71 SARS patients included in the final analysis in 2003 Full size table

We performed pulmonary function tests in 2006 and 2018. The outcomes in 2006 revealed that 10 out of 46 (21.74%) patients had restrictive ventilation dysfunction. Sixteen out of 46 (34.78%) patients had reduced diffusion capacity with an ~70%–80% predicted value, indicating a mild reduction. In 2018, 15 years after being infected, we reperformed pulmonary function tests for the cohort. One out of 52 patients (1.92%) had obstructive ventilation dysfunction, while none had restrictive ventilation dysfunction. However, the number of patients with impaired FEF 25%–75% values increased (16/52, 40.38%). Eighteen patients (38.46%) had reduced diffusion capacity, indicating that the ratio slightly increased, but the difference was not statistically significant.

A total of 35 patients underwent pulmonary functional tests in both 2006 and 2018. The cohort was further divided into two groups (normal CT findings and abnormal CT findings group) based on their CT findings in 2003, 6 months after being infected. The pulmonary function test parameters were compared between the normal CT findings group (N = 22) and the abnormal CT findings group (N = 13). The results are shown in Table 2, and there were no substantial changes in pulmonary function in the abnormal CT finding group in the past few years. Between the two groups, only the forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC ratio) and the FEF 25%–75% value were significantly reduced (P = 0.04 and P = 0.01, respectively). The other parameters, including total lung capacity (TLC) and carbon monoxide diffusing capacity of the lungs (DLCO), did not significantly change 15 years after the initial infection. The pulmonary function in 2018 was better than that in 2006 for patients whose CT scans showed no abnormalities after recovery in 2003.

Table 2 Comparison of pulmonary function items in 2006 and 2018 in SARS patients with or without a pulmonary CT abnormity after recovery in 2003 Full size table

The pulmonary CT scans of the 71 SARS patients showed that 27 patients exhibited ground-glass opacities or cord-like consolidations during the 15-year follow-up. Two patients had no abnormalities on their pulmonary CT scans in 2003, but ground-glass-like changes were observed in both 2004 and 2007. We calculated the percentage of area with lesions on two sections of the CT scan and analyzed the overall variations in the proportion of lung area with lesions in 27 patients (Fig. 2a, b).

Fig. 2 Trends in percentage change of lesion area on pulmonary CT scan. a Changes in percentage in the injured lung CT. b Bubble plots and linear regression of changes in the percentage of injured lung on CT Full size image

The linear regression showed that in the 27 patients who underwent pulmonary CT scans from 2003 to 2018, the percentage of lesions gradually decreased (t = −2.56, P = 0.01). The mixed-model showed that the proportion of lesions differed every year during the follow-up period (F = 7.79, P < 0.001), with the proportion in 2004 being lower than that in 2003, and lower in 2013 than in 2012. No differences were observed between the last two remaining years. The results showed that the incidence of pulmonary lesions in SARS patients decreased annually. Lesion absorption and recovery occurred to a greater extent between 2003 and 2004 and then remained stable until 2018.

Fifteen out of 71 patients were confirmed to have femoral head necrosis by hip joint MRI in 2003. In the cohort, seven patients had unilateral osteonecrosis, and eight had bilateral osteonecrosis. The total number of patients with femoral head necrosis was 23, as some patients had bilateral lesions.

We determined the percentage of osteonecrotic volume by MRI and plotted the results from 2003 to 2018 (Fig. 3a, b).

Fig. 3 Trends in percentage change of osteonecrotic volume on hip MRI scan. a Change in the percentage of osteonecrotic volume. b Bubble plots and linear regression of the percentage of osteonecrotic volume Full size image

The linear regression showed that the proportion decreased during the follow-up period (P = 0.0011). The mixed-model showed that the percentage of necrotic volume differed each year from 2003 to 2018 (F = 5.62, P < 0.001). The volume of osteonecrosis decreased rapidly from 2003 (38.83 ± 21.01)% to 2005 (30.38 ± 21.23)% (P = 0.000 2), diminished slowly from 2005 to 2013 (28.99 ± 20.59)% and plateaued until 2018 (25.52 ± 15.51)%.

Among the 23 limbs in 15 patients with femoral head necrosis, the ARCO stage of 16 limbs in ten patients stabilized during the follow-up (three in stage IIA, eight in stage IIB, four in stage IIC, and one in stage IIIC). The stage of one limb, however, was downgraded from stage IIB to stage IIA, while the stages of six limbs in four patients were upgraded. In the worsened cohort, the ARCO stage of one limb progressed from stage IIC in 2003 to stage IIIC in 2007 and remained stable in 2018, one patient was upgraded from stage IIC in 2003 to stage IIIC in 2006 and progressed to stage IV in 2012, and one patient worsened from stage IIIC in 2004 to stage IV in 2007 within a short time. In addition, one limb was upgraded from stage IIC in 2003 to stage IIIC in 2006 and then progressed to stage IV in 2008 (Table 3).

Table 3 The ARCO stage of fifteen patients with femoral head necrosis and progression Full size table

In general, the clinical stage showed that femoral head necrosis progressed slightly from 2003 to 2007. Six limbs in four patients showed progressive worsening. The stages reached a plateau from 2007 to 2018, when we detected no progression. One patient improved in clinical stage, and the remaining 16 limbs of ten patients stabilized in clinical stage over the 15 years.

Forty patients underwent joint function assessments in March 2018. The average Harris hip score in patients with osteonecrosis of the femoral head on MRI was 69.69 ± 13.72 (n = 13), while the mean score in patients without necrosis was 78.70 ± 11.94 (n = 27). There was a significant difference between the two groups (t = −2.131, P = 0.04). Among the 40 patients, 29 (72.5%) had relatively stable hip joint function during the 15-year follow-up, seven (17.5%) had a mild decline, and four (10%) had severe deterioration.