Background

The pandemic of coronavirus disease (COVID-19) has seriously struck those with underlying comorbidities [1]. This substantial group of patients with chronic comorbidities is at higher risk of acquiring a more severe COVID-19 and are more prone to rapid deterioration as well as unfavorable disease outcomes including the development of complications and death [2].

It is of note that the majority of hospitalized COVID-19 patients have self-reported a minimum of one underlying chronic health condition, with hypertension, diabetes, malignancy, and chronic obstructive pulmonary disease (COPD) being the most commonly reported comorbidity [3].

Patients with any comorbid lung condition especially COPD have a higher risk for severe illness and are likely to have a worse prognosis and poor outcomes such as ARDS leading to an increased risk of mortality. The risk of SARS-CoV-2 infection and mortality in COPD patients is observed to be fourfold exceeding patients without COPD [2, 4]. Accordingly, it is of particular importance to identify COVID-19 patients with underlying comorbid pulmonary disease, especially patients with COPD. Mucus overproduction, systemic inflammation, and bacterial colonization, in addition to inhaled steroid intake, and smoking status are all acknowledged factors contributing to weakening immune responses in those patients [5].

Knowledge gathered concerning this susceptible group of patients with poor pulmonary reserve is still limited regarding their vulnerability to COVID-19 infection and its effect on its course. So, the authors of this research aim to identify the influence of COVID-19 on patients with comorbid lung disease regarding disease severity and outcome, hopefully aiding the medical sector while developing policies regarding those who would benefit the most from the vaccines.

Methods

Study design and participants

This is a retrospective cohort study of 587 SARS-CoV-2-infected patients identified with real-time polymerase chain reaction swabs, seeking medical help at the Kasr Al-Ainy Hospital, an authorized center to treat COVID-19 patients between June 1, 2020, and June 30, 2021.

COVID-19 severity is determined via the World Health Organization (WHO) classification as mild, moderate, severe, and critical with mild and moderate being the non-severe forms of the disease. The defining criteria for mild, moderate, severe, and critical COVID are as follows: mild in patients demonstrating clinically no signs of consolidation and hypoxemia, moderate COVID-19 in those with signs of consolidation but still no hypoxemia, and severe in those with signs of severe consolidation, with signs of severe respiratory distress, or tachypnea more than 30 breaths/min or their saturation of oxygen on room air is less than 90%, whereas critical infection in patients in need of life support measures as mechanical ventilation and/or vasopressors in their management [6].

Data collection

By referring to the hospital records, the extracted data from hospital medical records included patients’ demographics, presenting symptoms, comorbidities as reported by the patient on admission and confirmed by the patient’s previous medical records, oxygen saturation, laboratory results on admission including CBC (complete blood count), CRP (C-reactive protein) with titer, ferritin, and D-dimer, chest radiological findings upon admission. Also, data regarding whether the patient is hospitalized or not, ICU (intensive care unit) admitted or not, and the length of hospital stay, as well as the development of complications and mortality, is gathered from the medical records.

Comorbidities are sorted based on the system affected, and this permits grouping of chronic pulmonary diseases and merging them all into a single category.

The study population is initially categorized based on the presence or absence of comorbidities and then subcategorization of patients with comorbidities into three groups: group 1: patients with comorbid lung disease not associated with other comorbidities, group 2: patients with comorbid lung disease associated with other comorbidities, and group 3: patients with comorbidities other than comorbid lung disease.

Statistical analysis

The Statistical Package for Social Science version 24 is used for the analysis of data. Mean and standard deviation are used for the numerical variables, while frequencies and percentages are applied for categorical ones. Analysis of variance (ANOVA) is used to compare between groups. Post hoc test is applied for normally distributed quantitative variables, while the Kruskal–Wallis test and Mann–Whitney test were used for non-normally distributed quantitative variables. For comparing categorical data, a chi-square (χ2) test was performed. P-values less than 0.05 were considered statistically significant.

Ethics approval

This research is revised by the institutional review board and accepted by the research ethics committee, at Cairo University (no. 101–2022) dated 24 December 2022. The policy of data confidentiality is firmly followed.

Results

Demographics of the studied patients

This research included 587 COVID-19 patients. Their mean age is 51 ± 15 years. The study included 375 males (63.9%) and 212 females (36.1%). Four-hundred thirty-five (74.1%) had nonsevere SARS-CoV-2 infection, and 152 (25.9%) had a severe and critical infection. Three-hundred sixty-four (62%) patients were hospitalized, and the length of hospital stay was 8 ± 4 days. One-hundred fifty (25.5%) patients needed intensive care unit (ICU) admission (Table 1).

Table 1 Demographics and clinical characteristics of the study population
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Patients with chronic comorbid pulmonary diseases represented 113 patients among the whole study population as shown in Table 2.

Table 2 Frequency of comorbidities among the whole study population
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Frequency of comorbidities among the whole study population

Hypertension represented the most common comorbidity in our patients 157 (26.7%), followed by diabetes (25.4%), then obesity (15.5%), and COPD (11.4%). The distribution of other comorbidities among the whole study group is shown in Table 2.

Characteristics of patients with comorbid pulmonary disease associated or not with other comorbidities as compared to patients without comorbidities concerning the severity of COVID-19

Patients with comorbid chronic lung disease associated or not with other comorbidities had a significantly higher COVID-19 severity when compared to patients without comorbidities (p < 0.001) (Fig. 1) (Table 3).

Fig. 1
figure 1

Comparative statistical analysis between COVID-19 patients without comorbidities and patients with comorbid chronic lung disease associated or not with other comorbidities regarding the severity of COVID-19 and outcome

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Table 3 Comparative statistical analysis between COVID-19 patients without comorbidities and patients with comorbid chronic lung disease associated or not with other comorbidities
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Characteristics of patients with comorbid pulmonary disease associated or not with other comorbidities as compared to patients without comorbidities concerning the frequency of complications

Patients with comorbid chronic lung disease associated or not with other comorbidities had a statistically significant higher frequency of complications in comparison to patients without comorbidities (P < 0.001). ARDS and mechanical ventilation, chest infection, and acute kidney injury were significantly higher in patients with comorbid chronic lung disease associated or not with other comorbidities as compared to patients without comorbidities (p 0.003, p < 0.001, p < 0.001, p < 0.001) (Fig. 1) (Table 3).

Characteristics of patients with comorbid pulmonary disease associated or not with other comorbidities as compared to patients without comorbidities concerning mortality

Patients with comorbid chronic lung disease associated or not with other comorbidities had a significantly higher mortality rate when compared to patients without comorbidities (p < 0.001) (Fig. 1) (Table 3).

Characteristics of patients with comorbid pulmonary disease associated or not with other comorbidities as compared to patients without comorbidities concerning laboratory data

Patients with comorbid chronic lung disease (CLD) associated or not with other comorbidities had significantly higher CRP, ferritin, and d-dimer serum levels when compared to patients without comorbidities (p 0.003, p 0.003, p < 0.001) respectively. Other labs showed no significance as outlined in Table 3.

Characteristics of patients with different comorbidities concerning the severity of infection, complications, and mortality

Patients with preexisting diabetes, hypertension, COPD, and chronic kidney disease have a significantly higher risk of severe and critical infection (p-value < 0.001, 0.001, 0.001, < 0.001, respectively), complications (p-value 0.038, 0.005, < 0.001, < 0.001, respectively), and mortality (p-value 0.021, 0.001, < 0.001, < 0.001, respectively). On the contrary, other comorbidities such as autoimmune, hepatic or thyroid diseases, bronchial asthma, pulmonary hypertension (PHTN), and malignancy did not show significant severity of infection, complications, and mortality (Table 4).

Table 4 Characteristics of patients with different comorbidities in relation to the severity of COVID-19 infection, complications, and mortality
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Discussion

Several comorbid diseases increase the severity and risk of mortality in COVID-19 [7]. The presence of diabetes, hypertension, malignancies, cardiovascular diseases (CVD), and COPD, besides other comorbid diseases, places COVID-19 patients in a life-threatening situation [8].

It is of vital importance to recognize those at risk of developing severe and critical COVID-19 to implement an efficient strategy to hinder SARS-CoV-2 infection through patient isolation and early vaccination [9]. Researchers still enquire about the relationship between the presence of various comorbidities including chronic pulmonary diseases and the COVID-19 severity and outcome. Hence, the authors of this study tackled this point of research.

In the present study, hypertension is the most common comorbidity in our patients (26.7%), followed by diabetes (25.4%), then obesity (15.5%), COPD (11.4%), pulmonary hypertension (3.9%), and bronchial asthma (3.6%). This percentage is surprisingly striking as one might expect that patients with chronic pulmonary diseases, particularly COPD and asthma, would be at increased risk of COVID-19 owing to their poor pulmonary reserve and greater angiotensin-converting enzyme 2 (ACE2) receptors’ expression in their lungs [10]. However, chronic pulmonary diseases are underrepresented in the studies registering comorbidities for patients with COVID-19 as compared to the global estimated prevalence of chronic pulmonary diseases in the general population [11].

Several explanations are postulated. First, this vulnerable community of patients conformed to the general lockdown measures applied during most of the study period as well as following strict preventive procedures leading to a significant reduction in SARS-CoV-2 infection [12]. Also, it is noticed that medications utilized by patients with chronic lung diseases can lessen disease manifestations as was observed in in vitro models that inhaled steroids and bronchodilators suppress viral replication and cytokine production [13].

Consistent with several previous studies, the current study shows that patients with preexisting chronic lung disease associated or not with other comorbidities have severe and critical COVID-19, ICU admission, and longer hospital stays compared to patients without preexisting comorbidities [14,15,16,17].

It is well-known that the frequent coexistence of comorbidities is associated with compromised baseline health conditions contributing to a poor prognosis as compared with no or single comorbidity [17]. The present study reveals that patients with preexisting chronic lung disease associated or not with other comorbidities have more frequent complications compared to patients without comorbidities with ARDS, mechanical ventilation, secondary bacterial infection, and acute kidney injury being the most significant complications.

The current study reveals that the mortality rate is significantly higher in patients with preexisting chronic lung disease associated or not with other comorbidities as compared to those without comorbidities. This echoes the latest report stating that patients with comorbidities such as chronic lung disease or patients with multiple comorbid diseases have an increased risk of death [18]. This indicates that those patients have sustained lung injury, bronchial hyperactivity, and impaired natural airway immune responses [19].

In our study, the frequency of SARS-CoV-2-infected COPD patients is higher as compared to other comorbid chronic lung diseases. This could be explained by the increase of ACE2 receptors’ expression in the epithelial cells mediating viral entry [20]. This finding came in line with Singh et al., who reported that COPD patients have increased COVID-19 susceptibility when compared to other comorbid lung diseases such as asthma and pulmonary hypertension [21].

Our finding that COPD patients present with a more severe infection and with significantly higher rates of complications and mortality is attributed to the lowered antiviral defense mechanisms together with the impaired natural immune responses [22].

The most important limitations of our study are its retrospective nature and the comorbidities being self-reported, so few patients might have missed reporting other comorbid conditions that they were not aware of.

Conclusion

Patients with comorbid pulmonary diseases are susceptible to a more severe COVID-19 with higher complications and mortality rates. Thus, precautions should be directed to limit SARS-CoV-2 infection along with directing future research regarding the usefulness of implementing an annual vaccination program for those patients if needed.