I. Study design and patient selection
This retrospective case-control observational study involved 38 COVID-19 confirmed cases using nasopharyngeal swab RT-PCR at King Abdullah Medical City (KAMC), Makkah-Saudi Arabia. Patients were recruited from the Post-COVID-19 interstitial lung disease (ILD) clinic. Referral to this clinic was based on a pulmonologist’s assessment of hospitalized patients suspected of developing COVID-19-related ILD changes during hospitalization.
At the Post-COVID ILD clinic, detailed medical history and physical examination were performed. Laboratory and physiological assessments were requested for all patients; however, follow-up chest CT was requested for patients with significant residual disease, such as patients with severe symptoms who still required oxygen at home in order to maintain oxygen saturation for more than two months after discharge and those in whom the prednisolone dose could not be tapered down. According to evidence of persistent COVID-19-related parenchymal lung changes, the 38 selected patients were divided into two groups. Those patients who had undergone follow-up chest CT, at least 10 weeks after the first positive RT-PCR swab, and had residual parenchymal lung diseases were included in the case group "Group 1". The control group included patients with earlier clinical and/or radiological resolution.
Inclusion criteria included all adults (age >12 years) and RT-PCR-confirmed COVID-19 infection with radiological evidence of pneumonia. We excluded patients diagnosed with fibrotic or other structural lung diseases prior to having COVID-19 infection. Patients who were lost to follow-up after discharge or judged to need a follow-up chest CT and missed their radiology appointments were also excluded.
Baseline patient characteristics, including age, sex, smoking history, and obesity, comorbidities, and other clinical variables related to acute COVID-19 disease, such as inflammatory markers, treatment intervention, and intensive care unit (ICU) admission, were collected from electronic the patients’ records.
II. Chest CT image protocol and interpretation
CT scans were acquired without ECG gating on a 64-slice multidetector CT (Siemens SOMATOM Sensation 64) with a 64 × 0.625 mm collimation and a spiral pitch factor of 1.3. Scans were obtained in the craniocaudal direction, supine position, and during end-inspiration without the administration of an intravenous contrast agent with a standard dose scanning protocol. For patients who had a clinical suspicion of pulmonary embolism (PE), additional CT pulmonary angiography was conducted. Axial reconstructions were performed with a slice thickness of 1.5 mm.
Two radiologists, each with 6 years of experience, reviewed all chest CT images. The images were reviewed independently, and any discrepancies were resolved by consensus. There was no major disagreement between the radiologists’ interpretations.
For each of the two patient groups, the CT examinations were evaluated for the following characteristics: (1) CT severity scores (CT-SS) for initial and follow-up CT as described by Li et al. ; (2) ground-glass opacities and consolidations; and (3) presence of fibrotic lesions (traction bronchiectasis, parenchymal bands, honeycombing, and reticulations).
The CT severity scores were based on a visual quantitative evaluation of the percentage of involvement in each lobe as well as the overall lung. The severity scores were classified as none (0%), minimal (1–25%), mild (26–50%), moderate (51–75%), or severe (76–100%), with corresponding scores of 0, 1, 2, 3, or 4, respectively. The CT-SS was reached by summing the five lobe scores (ranging from 0 to 20).
In the “case group,” the CT performed during acute illness was termed “the initial CT,” and CT performed 10 weeks after the first RT-PCR was termed “the follow-up CT.” However, follow-up CT images were not obtained in most patients in the “control group” as they showed significant clinical improvement; thus, the first CT performed during acute illness was termed as “the initial CT,” and the latest CT subsequently performed (not necessarily after 10 weeks of the acute illness) was termed “the follow-up CT.”
III. Definitions of clinical status
1. Disease severity
- Moderate: RT-PCR-confirmed COVID-19 pneumonia without any severe or critical criteria
- Severe: RT-PCR-confirmed COVID-19 pneumonia with any of the following: respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO2/FiO2 ratio <300, or radiological lung infiltration > 50% of the lung field as judged on chest CT
- Critical: RT-PCR-confirmed COVID-19 pneumonia with any of the following: respiratory failure requiring non-invasive or invasive ventilation, sepsis or septic shock, altered consciousness, or multi-organ failure
IV. Statistical analysis
Statistical analyses were performed using STATA/IC version v16.1 software (StataCorp LLC, TX, USA). For normally distributed variables, means and standard deviations (SDs) were used to describe continuous variables, and frequencies and percentages were used for categorical variables. Non-normally distributed variables were described using median and interquartile ranges. Comparisons across groups were made using chi-square or Fisher's exact test for categorical variables and one-way ANOVA or Kruskal-Wallis test as appropriate for continuous variables.
Logistic regression was used to evaluate risk factors associated with post-COVID-19 ILD. Multivariate models were adjusted for age, sex, smoking history, body mass index (BMI) >30, and asthma to eliminate possible confounding factors. The variables were selected based on previous studies and clinical relevance. Statistical significance was set at P < 0.05.