Atypical chest CT scan findings have higher mortality and ICU admission among older adults with COVID-19

doi:10.21203/rs.3.rs-3641113/v3

Introduction

: The global impact of the coronavirus pandemic has been particularly devastating among vulnerable populations, with a notably higher mortality rate observed among older adults. During this health crisis, chest computed tomography (CT) scans have emerged as a crucial diagnostic tool for identifying and assessing the severity of coronavirus disease (COVID-19). This study explored the significance of chest CT scan findings in predicting mortality and admission to the Intensive Care Unit (ICU) among older patients affected by COVID-19.

Materials and Methods

Conducted as a cross-sectional investigation, this study analyzed demographic characteristics such as age and gender, severity indicators (ICU admission, hospitalization outside the ICU) and outcomes (death or recovery) in a cohort of 411 COVID-19 patients aged 60 and above. Chest CT scan findings, categorized as normal, indeterminate, or abnormal, were scrutinized using SPSS ver. 24 software, with outcome analyses conducted through Chi-Square tests.

Results

Among the enrolled older patients, 52.3% were female, and 47.7% were male, with a mean age of 73.5 ± 8.75 years. The mortality rate reached 24.8%, and the ICU admission rate was 19%. Notably, 76.1% of subjects exhibited typical chest CT scan findings indicative of COVID-19, while 15.6% were classified as indeterminate and 8.3% as atypical. Mortality rates were 21.4% for typical findings, 28.1% for indeterminate results, and 50% for atypical findings. Furthermore, mortality among ICU-admitted patients stood at 78.2%. The incidence of atypical CT scan findings in ICU cases was 15.4%, compared to 6.6% in non-ICU cases.

Conclusion

The presence of atypical chest CT scan findings emerged as a significant predictor of heightened mortality and ICU admission among older individuals affected by COVID-19. This underscores the poor prognostic value associated with atypical findings in this demographic, emphasizing the importance of considering such indicators in the clinical management of older patients with COVID-19.

Geriatrics & Gerontology

COVID-19

SARS-CoV-2

Computed Tomography

Aged

Mortality

Prognosis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infiltrate the lower respiratory tract, resulting in severe lung damage and a high mortality rate from pneumonia. Different studies emphasized the diagnostic role of chest computed tomography (CT) scan; hence, it might help identify patients who will need ICU admission, require mechanical ventilation, and require a higher mortality expectancy [1]. Less common chest CT scan findings were found to be related to a higher risk of poor outcomes at earlier stages that could imply a need for close monitoring [2] or initiating treatment, especially in patients at higher risk since there are challenges for Coronavirus disease (COVID-19) treatment, including toxicity and drug reactions [3].

Older age and comorbidities (cardiovascular and cerebrovascular diseases) were associated with higher mortality in patients with COVID-19. Although the CT severity score of lung involvement was shown to be related to increased mortality, few studies have been done to compare the chest CT features between the survived and deceased patients [4]. The Radiological Society of North America (RSNA) classified the chest CT findings into three categories: typical, indeterminate, and atypical [5]. Standard features are reported to be frequently and more seen explicitly in COVID-19 pneumonia, while indeterminate features are not specific, and atypical features are uncommon in COVID-19 patients [6]. Typical CT findings of COVID-19 pneumonia are bilateral, multifocal, and lower lobe predominant involvement; grand glass opacity (GGO), and consolidations, while atypical chest CT findings are central and peri Broncho vascular involvement; isolated upper lobe involvement; solitary involvement; lobar consolidation; nodule formation, pleural and pericardial effusion that can be confused with other diseases [7].

The primary objective of this study was to assess the predictive significance of chest CT scan findings in determining mortality and intensive care unit (ICU) admission rates in older patients with COVID-19.

In this retrospective cross-sectional study, data extracted from the medical files of 411 COVID-19 patients (the diagnoses confirmed by RT-PCR or chest CT scan) aged over 60 years, admitted to Gharazi Hospital in Esfahan, Iran, from March 21 to June 21, 2021. All medical files related to older patients with a diagnosis of COVID-19 over 60 years old were studied. All patients had non-contrast CT chest imaging and positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) results for COVID-19. The information on the variables of demographic characteristics (age and gender) and categorized the outcomes. A radiologist skilled in chest CT was asked to review all CT scans and report again according to RSNA classification (typical, indeterminate, and atypical).

All data was entered SPSS 24 (Armonk, NY: IBM Corp.), and the association between chest CT scan findings and outcomes was analyzed by Chi-Square (χ²). A P-value<0.05 was considered statistically significant.

Chest CT scan

Radiological Society of North America Chest CT Findings Related to COVID-19

The RSNA categorical system has four categories for standardized reporting of chest CT findings related to COVID-19, which were proposed by the RSNA Expert Consensus Statement (8): typical, indeterminate, atypical, and negative (Table 1).

Table 1: RSNA COVID-19 Pneumonia Imaging Classification

Typical appearance

Multifocal ground glass opacities

Ground glass and Consolidations

Crazy paving

Halo sign/Reversed halo

Bilateral peripheral and basal distribution

Indeterminate

appearance

Central or peri Broncho vascular

More apical distribution

Lymphadenopathy

Atypical

appearance

Cavitation – calcification

Bronchiolitis

Nodular pattern

Mass

Pleural effusion

Negative for pneumonia

No feature

CT Findings Related to COVID-19

The frequencies of typical, indeterminate, and atypical chest CT findings in the total population were determined.

CT scan findings are divided according to the RSNA COVID-19 Pneumonia imaging classification.

One radiologist skilled in chest CT was asked to review all CT scans and report again according to RSNA classification (typical, indeterminate, and atypical) without knowing the clinical features and laboratory findings.

Four hundred eleven patients entered the study, from which 309 subjects (75.2%) survived, while 102 cases (24.8%) deceased, which showed an overall mortality rate of 24.8% in this population of older adults.

Demographic Characteristics

215 patients (52.3%) were female, and 196 (47.7%) were male. Mortality rates in the male and female groups were not statistically significant (P-value: 0.98) (Table 2).

Table 2: Demographic frequencies by survival

Variables	Total population		survived		Non-survived		P-value
Male	196	47.7%	147	75.4%	49	24.6%	0.98
Female	215	52.3%	162	75%	53	25%	0.98

The average age of the total population was 73.5± 8.75 years (60-98) years, and it was divided into three age groups with the following frequencies: 60-75 (272, 66.2%); 76-80 (91, 22.1%); >80 years (48, 11.7%). The frequencies of death and the mortality rates of these groups were as follows, respectively: (54 cases) 19.8%, (31 cases) 34% (P-value: 0.006), and (17 cases) 35.4% (P-value: 0.017) (Table 3). Mortality rate increases with age in older adults.

Table 3: Demographic frequencies by survival

Variables	Total population		survived		Non-survived		P-value
60-75 years old	272	66.2%	218	80.2%	54	19.8%	Reference
76-80 years old	91	22.1%	60	66%	31	34%	0.006
>80 years old	48	11.7%	31	64.6%	17	35.4%	0.017

ICU admission

Seventy-eight patients were admitted to ICU and 333 to the general COVID-19 ward. The frequency of death cases and the mortality rate in the ICU admitted group was 61 cases (78.2%), and in general, in the COVID-19 ward were 41 cases (12.3%) (P-value<0,001). The chance of death was significantly associated with hospitalization in the intensive care unit (Table 4).

Table 4: The mortality rate and the frequencies by severity of disease

Variables	ICU	Non-ICU	P-value
Total population	78 (19%)	333 (81%)
survived Total population	17 (21.8%)	292 (78.7%)	<0,001
Non-survived	61 (78.2%)	41 (12.3%)	<0,001

Chest CT scan findings

The frequencies of chest CT scan findings in ICU and non-ICU admitted groups were as follows, respectively: typical: 57 (18.2%), 256(81.8%); indeterminate chest CT findings 9(14.1%), 55 (85.9%), and Atypical chest CT findings, 12 (35.3%), 22 (64.7%). The chance of death was significantly associated with atypical findings on CT scans. (P-value: 0.018). The possibility of death in older adults had no significant relationship with indeterminate chest CT scan findings (Table 5).

Table 5: The mortality rate and the frequencies by chest CT findings

Variables	ICU	Non-ICU	P-value
Typical chest CT findings	57 (73.1%)	256 (76.9%)	reference
indeterminate chest CT findings,	9 (11.5%)	55 (16.5%)	0.241
Atypical chest CT findings,	12 (15.4%)	22 (6.6 %)	0.018

The frequencies of typical, indeterminate, and atypical chest CT findings in the total population were as follows, respectively: 313 (76.1%), 64 (15.6%), and 34 (8.3%), and their mortality rates were as follows, respectively: Typical chest CT findings 21.4%, Indeterminate chest CT findings 28.1% (P-value: 0.24), and Atypical chest CT findings 50% (P-value<0.001) (Table 6).

Table 6: the frequencies of chest CT scan features and mortality

Variables	Total population	survived	Non-survived	P-value
Typical chest CT findings	313 76.1%	246 78.6%	67 21.4%	reference
Indeterminate chest CT findings	64 15.6%	46 71.9%	18 28.1%	0.24
Atypical chest CT findings	34 8.3%	17 50%	17 50%	<0.001

This study aimed to assess the predictive significance of chest CT scan findings in determining mortality and intensive care unit (ICU) admission rates in older patients with COVID-19. Mortality rates in male COVID-19 patients in most countries exceeded that of female cases [9]. However, the results of the present study showed no significant relationship between the gender of the subjects and the prevalence of COVID-19. The impacts of gender on some illnesses have been proved, such as coronary heart disease. Besides, in some societies, women are at higher risk of infection because of their role in providing care for others [9]. In a study on 168 COVID-19 cases, men tended to have a higher risk of mortality and a lower hospital discharge rate [10]. In other studies, there was no gender difference between severely and non-severely ill patients [11,12] that aligned with this study’s result.

Also, our study's mortality rate showed a statistically significant relationship with age. In a meta-analysis, mortality increased with age; the rise was exponential in cases aged>50 years. The most significant increase in mortality was detected in patients aged 60-79 years compared with 50-59-year age groups [13]. The increase in mortality with age can be attributed to the rise in the prevalence of comorbidities and frailty, both of which make an individual more vulnerable to infections [13]. In a study on 44 672 cases of COVID-19, the overall case-fatality rate (CFR) was 2.3%, but no deaths occurred in the group aged nine years and younger, while in those aged 70 to 79 years, was 8.0% CFR and in those aged 80 years and older was 14.8%. No deaths were reported among mild and severe cases; the CFR was 49.0% among critical issues [14]. In another study on 176 patients, the severity of COVID-19 was milder in those aged <60 years; in turn, the chance of implementing assisted ventilation was higher in those aged ≥60 years [15]. The findings from virtually all studies consistently demonstrated a rise in mortality associated with age, particularly among older individuals. Our study similarly observed a significant correlation between age and mortality rates.

In most studies, in-ICU mortality rates were higher than non-ICU cases. In a survey of 217 cases, the overall mortality rate was 27%, while the general ward and in-ICU mortality rates were 23% and 40% [16]. In this study, the in-ICU mortality rate showed a six-fold rise compared to that in non-ICU patients. One explanation for the higher mortality rate in ICU cases is that they needed more support that was not readily accessible in all centers, so mortality increased with higher ICU demand and overwhelmed ICU beds [17,18].

GGOs, whether in isolation or coexisting with other lesions like consolidations, interlobular septal thickening, or crazy paving, were uniformly the most common lesions among all the studies. All 138 patients included in the study had GGOs in one large case series. The patients with severe or critically severe pneumonia had more extensive involvement with consolidations, effusions, atelectasis, “white out” lungs, and ARDS. [19]. In a study on 120 patients, CT scan features of multiple multilobar peripheral GGO, white lung, and pleural effusion were related to the need for ICU admission and mechanical ventilation [1]. In another study on 281 patients, pleural effusion and higher CT scores were associated with poor prognosis in patients with COVID-19. Although consolidation opacity was frequently observed in patients in the severe group, it was not found to be a predictor of poor prognosis in this study. In the case of Middle East respiratory syndrome (MERS) and SARS, pleural effusion has also been reported to be a significant prognostic factor [20]. In a study on 298 cases, most patients (73.1%) developed typical chest CT features, and only 21.1% showed atypical features. A significant positive correlation between chest CT severity score and atypical findings and age was observed, indicating that with increased age, there was an increase in the chest CT severity score and atypical CT features [21]. In a retrospective study on 476 COVID-19 inpatients, pleural effusion was significantly accompanied by more severity, higher mortality, and longer hospital stay times than their counterparts without pleural effusion [22]. However, in another study, a crazy-paving pattern, vascular enlargement (over 3 mm diameter), bronchiolar dilatation, and peribronchovascular consolidation were associated with disease progression [23]. In a study, patients older than 50 years had more extensive lung involvement with more consolidation as compared with patients younger than 50, and they had more architectural distortion, bronchiectasis, mediastinal and hilar lymphadenopathy, and pleural effusions and worse outcomes than younger patients [24]. In a retrospective study on 72 patients with COVID-19, the ratio of sub-pleural line and pleural thickness was higher in older patients than in young patients. This may indicate that older patients show a more severe inflammatory response. At the same time, whole lung lobes were more likely to be involved in older patients. This may indicate that disease progression in older patients was faster in the same disease course than in young patients [25]. In a study comparing chest CT features in the young with cases aged 50 and above, the younger patients had more GGOs, while older patients tended to have more areas of lung involvement and more consolidation. Therefore, the finding of consolidation lesions would serve as an alert in treating patients [26]. A study of stratifying chest CT scans by age showed a higher proportion of pleural effusions, bronchiectasis, and pulmonary nodules, which are not typically associated with COVID-19 pneumonia [27]. A study comparing serial chest CT features of cases showed that consolidation patterns have been more common in non-survivors of COVID-19 cases compared to survivors. In survivors, consolidation patterns drastically reduced in the fourth week compared to those in the first week. This study proved a significant association between the severity score and the number of involved lung lobes with fatality in COVID-19 [28]. In a survey of chest CT findings on admission, the typical results of chest CT images of ICU patients on admission were bilateral multiple lobular and sub-segmental areas of consolidation. In contrast, non-ICU patients showed bilateral ground-glass opacity and sub-segmental areas of consolidation [29].

Identifying less common chest CT scan findings plays a crucial role in the early detection of high-risk patients, enabling closer monitoring to swiftly recognize any signs or symptoms of deterioration, thereby facilitating prompt and appropriate care. Despite existing challenges in COVID-19 treatment, such as concerns regarding toxicity and potential drug reactions, the imperative of mitigating poor outcomes in high-risk patients supersedes these obstacles. Identifying individuals at higher risk significantly aids clinicians in preserving more lives. As chest CT scans are routinely utilized as a diagnostic tool for suspected COVID-19 cases, understanding the significance of their findings empowers clinicians to predict patient outcomes without necessitating further invasive investigations.

Healthcare providers working with older adults should be aware that older patients diagnosed with COVID-19 and exhibiting atypical chest CT findings often experience a more unfavourable prognosis and elevated mortality rates. Consequently, these individuals necessitate expedited and intensified treatment alongside comprehensive supportive care to improve their clinical outcomes and enhance their chances of recovery.

Acknowledgments

This article has been extracted from the thesis written by Mr. Mehdi Hasanzadeh. We also appreciate the staff of Gharazi Hospital in Esfahan, Iran, for their participation.

Authors’ contributions

MH, SVJ, MN, ZZ, AD, and NZ contributed to the conceptual design of the study. MH and SN contributed to the data collection. MH, ZZ, and RB contributed to the data analyses and interpretation. SVJ and SN drafted the manuscript. ZZ reviewed the core manuscript. ZZ and MN supervised the study and provided intellectual comments. All authors reviewed and approved the last version of the manuscript.

Funding

Not applicable.

Availability of data and materials

The datasets generated and analyzed during the current study are not publicly available. Still, data can be retrieved from the authors, Zhale Zandieh, by E-mail at [email protected] or Mehdi Hasanzadeh at [email protected] on reasonable request.

Declarations

Ethics approval and consent to participate in this study were approved by the ethical committee of Social Welfare and Rehabilitation Sciences University by the code of IR.USWR.REC.1401.073. All the study protocols and methods were carried out following relevant guidelines and regulations.

Consent for publication

Not applicable.

Competing interests

Not applicable.

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Atypical chest CT scan findings have higher mortality and ICU admission among older adults with COVID-19

Status:

Version 3

Abstract

Introduction

Materials and Methods

Results

Conclusion

Introduction

Materials and Methods

Results

Discussion

Conclusion

Declarations

References

Status:

Version 3