INTRODUCTION

The coronavirus disease-2019 (COVID-19) presents mild-to-moderate upper and lower respiratory tract manifestations in most of the cases. However, particularly older patients or patients with underlying chronic disease progress to severe pneumonia associated with massive alveolar damage and acute respiratory failure. Moreover, as the pandemic progressed, various other systems like musculoskeletal system, central nervous system have been shown to be involved (1,2). Definitive diagnosis requires a positive real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) test on respiratory specimens (3). Although, chest computed tomography (CT) is not recommended in the diagnosis and screening of the patients due to its lower specifity, it plays an important role with a low rate of missed diagnosis by revealing the abnormalities immediately. Various chest CT findings have been reported in COVID-19 patients, of which some are typical and frequently observed findings while others are atypical and rare. As shown in many studies and our previous studies, multifocal ground glass opacities (GGOs) with peripheral/subpleural distribution and accompanying areas of consolidation are the most frequently observed scenerio in immunocompetent patients. Additionally, perilesional/intralesional microvascular dilatation, halo and reversed halo signs have been reported as quite characteristic CT features of COVID-19 pneumonia, observed more commonly than non-COVID-19 viral pneumonia (4-6). However, in immunodeficient patients the clinical manifestations and chest CT imaging findings may differ from these usual patterns and may cause mistakes in the diagnosis and management. In this study, we evaluated the chest CT imaging findings seen in patients with immunodeficiency from various causes and to compare with those seen in immunocompetent patients.

METHODS

Between 16 March-30 May 2020, 88 patients (44 immunodeficient and 44 immunocompetent) with positive rRT-PCR test for severe acute respiratory syndrome-coronavirus-2 having uspicious chest CT imaging findings of COVID-19 pneumonia (typical or atypical) were included in the study and the chest CT images were retrospectively evaluated. The exclusion criteria included a paucity of clinical or radiological data, a significant artifact on CT images and being under the age of 18. The radiological findings have been divided as typical findings including GGOs and/or consolidations (non-lobar/non-segmental), air bronchogram sign, crazy paving pattern, microvascular dilatation, halo sign and reverse halo sign and atypical findings including bronshiectasia, tree in bud appearance, pulmonary nodules, pleural effusion and cavitation. Additionally, the distribution of the pneumonic infiltration, presenting symptoms, underlying causes of the immunodeficiency and comorbidities of the patients were recorded. Mortality rates and the length of hospital stay were used as clinical markers. Chest CT images were evaluated in consensus by two experienced radiologists (NK and BE).

Statistical Analysis

Statistical significance level was set as p<0.05.

RESULTS

There were 28 male and 16 female patients in the immunodeficient group and 27 male 17 female patients in the control group. The mean age of the immunodeficient group was 58.6±12.17 versus 58.9±10.9 years in the control group. There was no significant difference between the two groups in terms of age and gender. Accompanying comorbidities in patients are shown in (Figure 1). Nineteen (43.1%) patients in the immunodeficient group and 3 (6.8%) patients in the immunocompetent group died during hospital stay and the rest of them were discharged. Additionally, the mean length of hospital stay was 16.13±14.15 days in immunodeficient patients and 10.18±5.87 in the control group. A statistically significant difference was found between the two groups in terms of the length of hospital stay and mortality (p=0.012 and p<0.001, respectively) The most frequent symptom was fever (54.5%) in immunodeficient patients, whereas it was dyspnea (84.1%) in the control group and there was a statistically significant difference in symptoms including fever, dyspnea, and confusion between the two groups (p=0.005, p=0.005, and p=0.049, respectively) (Table 1). The most common underlying cause for immunodeficiency was receiving chemo-radiotheraphy for cancer, and the lung &gastric cancers were the most common (13.6% and 9.1%, respectively) (Table 2). In terms of CT features, GGO was the most common finding and was detected in all chest CT scans (Figures 2, 3, 4). A significant difference was found in crazy paving pattern and peripheral-subpleural distribution of lesions between the two groups (p=0.031 and p=0.006, respectively) (Figure 3). Atypical findings, including bronchiectasis, pulmonary nodules, tree-in-bud appearance, and pleural effusion were detected statistically significantly higher in immunodeficient patients (p=0.002, p=0.047, p<0.001 and p=0.001, respectively) (Figures 2, 3, 5, 6, 7). When all patients were considered together, there was a significant association between mortality and tree-in-bud appearance, pleural effusion, bronchiectasis (each of p<0.05). In addition to these atypical findings, air bronchogram sign was associated with mortality (p<0.05) (Table 3).

DISCUSSION

Immunodeficiency is one of the important underlying conditions that may be associated with a more severe course of most viral infectious pneumonia, including influenza (7). It could also be pre prepared for COVID-19. However, there are currently limited data on the prognosis, clinical presentations and the CT imaging findings of the disease in immunodeficient patients, which may differ from those seen in immunocompetent adults. Reported studies also have conflicting results. Some studies have shown that the mortality and morbidity of COVID-19 is higher in immunodeficient patients due to the higher levels of viral load (8-10), while other studies reported no statistically significant risk of more severe COVID-19 in these patients (11). Previously, some viral respiratory infections were shown to be associated with more severe manifestations in patients on long-term immunosuppressive medications (12,13). A prospective cohort monitoring COVID-19 cases throughout China revealed poorer outcomes from COVID-19 in patients with cancer with a higher risk of severe events including admission to the intensive care unit, requiring invasive ventilation, and death compared with patients without cancer (14). However, any significant differences were not found in the study by Miyashita et al. (15) regarding COVID-19 mortality among 334 patients with cancer compared with those without cancer. Moreover, as the pandemic progresses corticosteroids decreases mortality in patients with severe COVID-19 pneumonia, implying a favorable effect of suppressed immune response during the disease (16). In COVID-19, a hyperinflammatory state with increased levels of cytokines, including IL-6, is generated and suggested as an endogenous pathway in the pathophysiology of both pulmonary damage and multiorgan complications of the disease, which is known as a cytokine storm. This could be expected to be less likely and milder in severity in immunodeficient patients (17-20). Similarly, the evaluation of 110 immunodeficient patients with COVID-19 obtained from a systematic review of 16 articles revealed that immunodeficient patients seemed to have a favorable course (21). Additionally, a statistically significant risk of severe COVID-19 was not found among immunodeficient patients in a meta-analysis from China (22). However, the lack of a normal immune response can also be associated with the lack of protective antiinflammatory effects and higher possibility of developing co-infections in this patient group, which may be associated with higher mortality. A large retrospective national cohort study from Spain showed that immunodeficient patients hospitalized with COVID-19 have higher odds of in-hospital death and complications than immunocompetent patients. These groups were reported as the vulnerable population for complicated COVID-19 and suggested to be closely monitored (23). Similarly, our study revealed a significantly higher mortality rate in immunodeficient patients than in the immunocompetent patients, regardless of the age. When we looked at the underlying causes for immunodeficiency in our patients, the most common were being under treatment for cancer, which may be the reason for this higher mortality. Some recent reports revealed a similarly high mortality rate in cancer patients with COVID-19 (24). Reports regarding the chest CT imaging findings in immunodeficient patients with COVID-19 pneumonia are scarce in the current literature. Severe pulmonary sequelae has been reported in a 12-year-old child with primary immunodeficiency during the follow-up of COVID-19 pneumonia (25). Bilateral GGOs with multiple nodules complicated with pneumothorax, pneumomediastinum and pneumopericardium has been reported in a 28-year-old woman with a medical history of combined variable immunodeficiency under treatment with intravenous immune globulin (26). In the study by Abrishami et al. (27) most chest CT findings in kidney transplant recipients on immunosuppression were found to be similar to those from other adult studies for the general population. They only reported unilateral involvement and consolidation as slightly more frequent in their patients (27). In our study, the most common chest CT finding was also GGO with or without accompanying consolidations, which is the most frequent imaging finding of COVID-19 in general population reported in the literature. However, in our study, the crazy paving pattern, which is consistent with the progressive phase of the disease was observed statistically significantly higher in the immunocompetent group. Peripheral/subpleural distribution of the infiltration was also observed significantly higher in immunocompetent patients. A significant correlation was found between the immunodeficient patient group and atypical radiological findings, including bronshiectasia, tree in bud appearance, pulmonary nodules, and pleural effusion. Our study also revealed a significant association between mortality and atypical findings, which were statistically significantly more frequent in immunodeficient patients.

Study Limitations

The limitations of our study included, the limited number of patients, the retrospective nature of the study, not being able to evaluation in terms of superinfection, which may be a confounder of the chest CT findings observed, particularly immunodeficient patients who may be more susceptible to secondary bacterial infections.

CONCLUSION

In our study, it was determined that there was an increased risk of more severe COVID-19 disease and a higher mortality rate in immunodeficient patients. Radiologists should consider COVID-19 pneumonia in cases of rare, atypical and vague CT findings in immunodeficient patients. Since the course of COVID-19 pneumonia may be more severe in immunodeficient patients, the detection of chest CT findings of the diagnosed patients and knowing the typical and atypical findings will decrease morbidity and mortality rates with a more accurate interpretation.

Ethics

Ethics Committee Approval: This study was approved by the Clinical Research Ethics Committee of University of Health Sciences Turkey, Prof. Dr. Cemil Taşcıoğlu City Hospital (no: 48670771-514.10).

Informed Consent: Retrospective study.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Concept: N.K., H.K.Y., F.Ş., H.Ö., Design: N.K., B.E., H.K.Y., F.Ş., H.Ö., Data Collection or Processing: N.K., B.E., M.K.T., Analysis or Interpretation: N.K., B.E., H.Ö., Literature Search: N.K., B.E., Writing: N.K., B.E., M.K.T.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.