By Kamel, M; El-Shazly, M; Al-Zuabi, H; Al-Ameeri, S; Al-Asfoor, S; Al-Majdely, R; Almoosa, I (2023). Greener Journal of Epidemiology and Public Health, 11(1): 12-22.
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ISSN: 2354-2381
Vol. 11(1), pp. 12-22, 2023
Copyright ©2023, the copyright of this article is retained by the author(s)
DOI: https://doi.org/10.5281/zenodo.7755605
https://gjournals.org/GJEPH
1 MD, Consultant of Public Health, Department of Occupational Medicine, Ministry of Health, Kuwait & Professor of Community Medicine, Faculty of Medicine, Alexandria University, Egypt.
2 MD, Consultant of Public Health, Department of Planning, Ministry of Health, Kuwait & Professor of Health Statistics, Medical Research Institute, Alexandria University, Egypt.
3MRCGP, Consultant Family medicine, Head of Chronic Diseases Clinic Team, Head of the Non-communicable Disease Administration, Ministry of Health, Kuwait.
4 MRCGP, Family Medicine Specialist, Ministry of Health, Kuwait.
5 General practitioner, Ministry of Health, Kuwait.
6 MRCGP, Senior Specialist, Jaber Alahmad Quarantine, Mubarak Health Region, Ministry of Health, Kuwait
7 MRCGP, Consultant Family Medicine, Ministry of Health, Kuwait.
ARTICLE INFO
ABSTRACT
Type: Research
Full Text: PDF, HTML, PHP, EPUB
DOI: 10.5281/zenodo.7755605
Background: During hospitalization, 60.1% patients developed respiratory failure. Acute Respiratory Distress Syndrome (ARDS) is a common and devastating critical illness. It has been reported that 67% of COVID-19 patients with the severe illness have developed ARDS, which is the main cause of death.
Objectives: This study aimed at highlighting some factors that could be associated with severe respiratory complications of COVID-19 in admitted cases during the first wave of the disease.
Methods: This study is a retrospective case-control one that was conducted by reviewing records of all admitted COVID-19 patients in Jaber hospital in Kuwait during the period from February till May 2019. Analysis was initially carried on a series of univariate comparisons, followed by multiple logistic regression analysis.
Results: Male gender, older age as well as pre-existing conditions, such as hypertension, diabetes and pulmonary diseases, predispose patients to increased risk of severe respiratory complication. Such complications were associated with presenting fever, cough, lower blood oxygen level as well as longer hospital stay and ICU admission.
Conclusions:. Elderly males having fever, cough and shortness of breath and suffering hypertension, diabetes mellitus or other associated respiratory diseases at a higher risk for developing severe respiratory complications
Published: 21/03/2023
Prof. Dr. Medhat El-Shazly
E-mail: medshaz@ yahoo. com
Phone: +965/ 6612524
Introduction:
The coronavirus disease 2019 (COVID-19) is an acute infectious pneumonia. Spreading mainly through the droplet route and close contact, the virus causes mild symptoms in the majority of cases, the most common being: fever, dry cough, and fatigue. (Guan et al., 2020; Huang et al., 2020) The disease has rapidly developed into a worldwide pandemic. At the end of April, 2020, 217,769 people died of COVID-19 infection, (Xu W et al., 2021) and by the day of 11 February 2021, 2,369,067 million deaths were recorded.(WHO, 2021)
Despite the public health efforts aimed at delaying its spread; during the courses of treatment, due to the large increase in the demand for hospital beds and the shortage of medical equipment, coupled with the lack of specifc medicine, patients with basic diseases or old age are more likely to progress to severe disease, leading to death. Recent reports show that 14.1–33.0% of COVID-19 infected patients are prone to develop into severe cases, and the mortality rate of critical cases is 61.5%, increasing sharply with age and underlying comorbidities. (Yang X et al. 2020; Liu W et al. 2020; Zhao X-Y et al., 2020; Li K. et al., 2020). In a previous study, the author found that during hospitalization, 60.1% patients developed respiratory failure. (Becerra-Munoz, 2021) Acute Respiratory Distress Syndrome (ARDS) is a common and devastating critical illness (Bellani G. et al.; 2016). It has been reported that 67% of COVID-19 patients with the severe illness have developed ARDS, which is the main cause of death. However, in the early stage of onset, quite a few patients have no obvious clinical symptoms, so it is difcult to judge until ARDS occurs. (Yang X et al. 2020)
In the early phase of clinical observation, respiratory failure was attributed as a major cause of morbidity and mortality of COVID-19 patients. (Gacche et al., 2021) However, clinical and epidemiological data links it with patients having pre-existing history of hypertension, chronic obstructive pulmonary disease, diabetes, coronary heart disease, and kidney comorbidities have worse clinical outcomes when infected with SARS-CoV-2. (Lippi et al., 2020; Lippi and Henry, Cheng et al., 2020)
Certain demographic factors reported in the literature are associated with a higher rate of a respiratory failure and severe clinical course of COVID-19. Among these, older age is a major predictor of mortality. (Cecconi, et al., 2020) Data also suggest that male sex is a variable that is independently associated with COVID-19 severity. (Palaiodimos et al., 2020) Some other factors that could be associated, as hypoxemia with which worse clinical outcomes has been reported. (Duan et al., 2020)
Predicting which patients are more likely to develop ARDS, and thus face a greater risk of complications including death, is particularly important in a novel and accelerating outbreak. (Jiang X et al., 2020) The aim of the present study is to highlight certain factors that could be associated with the development of severe respiratory complications as ARDS or respiratory failure.
Subjects and methods:
Setting and design:
This study is a part of a larger one that was conducted in Jaber Al-Ahmed hospital. The time interval of the study was set as four months from April to July 2021. The details of the study design, sampling and research tool were described elsewhere. (Al-Zuabi et al., 2022) Studied patients were classified into 2 groups: cases (with respiratory complications ) and control (free from respiratory complications). Research tool included personal characteristics, associated co-morbid conditions, presenting symptoms, investigations and vital signs on admission, COVI-19 complications, as well as outcome parameters. The study was approved by the Ethics Committee of the Kuwaiti Ministry of Health. The permission of the Deputy Ministry of Health in Kuwait as well as head of Jaber hospital were obtained.
Statistical analysis:
Analysis was initially carried out based on a series of univariate comparisons. In order to control simultaneously for possible confounding effect of the variables, multiple logistic regression was used for the final analysis. In the univariate analysis Chi-square test was used to detect the association between respiratory comlications and explanatory variables. In multiple logistic regression analysis, the association between exposure and outcome was expressed in terms of odds ratio (OR) together with their 95% confidence intervals (95% CIs).
All the explanatory variables included in the logistic model were categorized into two or more levels (R = reference category): gender: maleR, female; age (years): < 40R, 40 – 49, 50 – 59, > 60; nationality: KuwaitiR, non-Kuwaiti; Governorate: CapitalR, Hawally, Farwaniya, Ahmadi, Jahar, Mubarak; smoking: noR, yes; history of hypertension: noR, yes; history of cardiovascular disease: noR, yes; history of diabetes mellitus: noR, yes; history of pulmonary disease: noR, yes; history of dyslipidemia: noR, yes; SpO2 level: ≤ 95R, > 95; lymphocytic count: normalR, low, high; FBS: normalR, prediabetic, diabetic; creatinine level: normalR, high; ICU admission: noR, yes; days of hospital stay: <10R, 10-14, 15-19, ≥20. All presenting symptoms were also categorized as noR, yes. Analysis was performed using SPSS package 22.
Results:
Reviewing the medical records of the cases admitted to the selected hospital during the defined period resulted in inclusion of 1482 positive cases for COVOD-19. Among them, 79 cases suffered from ARDS or respiratory failure.
Table 1 describes the personal characteristics of the included patients according to the presence of ARDS or respiratory failure. The proportion of males in the control group was significantly higher than in cases group (77.0% versus 88.6%, p = 0.02). The mean age of the control group (42.7±12.9) was insignificantly lower than that of the case group (54.8±12.8), p < 0.001.
Table 2 shows the frequency of co-morbid chronic diseases among patients with respiratory complications and the control group. The proportions of hypertension, cardiovascular diseases, diabetes mellitus, and respiratory diseases were significantly higher in cases than controls (χ2 = 12.20, 14.94, 31.82, and 1.22, p<0.001) respectively.
As shown in table 3, only the percentages of fever and cough were significantly higher in cases than control (51.9% versus 25.9%, and 50.6% versus 32.4%, p<0.001)
Low blood oxygen level on admission was significantly more encountered among cases than controls (29.1% versus 3.8%, p < 0.001), as well as lymphocytoenia (40.5% versus 11.9%, p < 0.001). Also, creatinine level was higher in cases than controls signifivcantly (Median (IQR): 86(48) versus 75(2), p <0.001. The percentage of diabetic patients as indicated by elevated fasting blood glucose was more encountered in cases than controls (74.7% versus 24.9%, p <0.001). Higher levels of other laboratory paraeters were significantly more encountered in cases than control as D Dimer, CRP, LDH, troponin and ferritin.
Table 5, showed that caes of respiratory complication were significantly more in need of oxygen therapy than control (72.2% versus 7.4%, p<0.001) and stayed for longer duration in hospital (median = 23 versus 8 , p <0.01), and significantly more proportions of cases were admitted to the ICU than control (89.9 versus 3.7, p<0.001)
After adjustment for the confounding effects between variables, table 6 illustrated variables that retained as significant determinants for the outcome of interest (severe respiratory complications). Female gender was proved to be a protective factor against the out come on interest (OR = 1.4, CIs: 0.1 – 0.8). Older age seemed to be at higher risk among admitted COVID-19 cases as patient in the age group 40-49, and 50-59 years old were more prone to severe respiratory complications as compared to those in the age group < 40 years (OR = 5.6, CIs: 2.8 – 9.5), and (OR = 3.1, CIs: 1.4 – 4.9) respectively.
Regarding chronic co-morbid conditions, patients with hypertension were 2.9 folds liable for severe respiratory complications during hospital stay (CIs: 1.7 – 4.6), and patients with diabetes mellitus were 2.3 folds (CIs: 1.2 – 5.2). Also, pulmonar diseases patients disease were significantly more liable to severe respiratory complications during their hospital stay (OR = 3.9, CIs: 1.9 – 8.1).
Regarding the presenting symptoms, only fever and cough were proven to be positively associated with sever respiratory complications (OR = 5.4, CIs: 2.9 – 11.7) and (OR = 3.0, CIs: 1.4 – 5.5) respectively. Those patients with low blood oxygen level on admission were 9.4 folds at risk of severe respiratory complications (CIs: 4.9 – 17.6). Severe respiratory complications were significantly associated with ICU admission (OR = 163.3, CIs: 68.9 – 389.9) and hospital stay > 20 days (OR = 5.5, CIs: 2.0 – 14.8).
Table (1): Distribution of hospitalized COVID-19 patients according to personal characteristics and respiratory complications.
( p )
(n=1403)
(n=79)
*: missing 941 cases
**: missing 987 cases
Table (2): Distribution of hospitalized COVID-19 patients according to chronic co-morbid diseases and respiratory complications.
No
5
1.9
Table (3): Distribution of hospitalized COVID-19 patients according to symptoms on admission and respiratory complications
Table (4): Distribution of hospitalized COVID-19 patients according to investigations and vital signs on admission and respiratory complications.
( p.)
Table (5): Distribution of hospitalized COVID-19 patients according to oxygen therap, hospital stay, ICU admission and and respiratory complications
Table (6): Factors associated with respiratory complications among admitted COVID-19 patients.
15-19
R = Reference category, OR = Odds ratio, CI = Confidence interval
Discussion:
Extra-pulmonary organ systems including the cardiac, gastrointestinal, hepatic, renal, ocular, and dermatologic are affected by COVID-19, however the most commonly affected organ system by COVID-19 is the pulmonary system, with the most frequent clinical manifestations including cough, dyspnea, fever, and sore throat. (Huang et al., 2020; Chen et al., 2020) In the severe disease state, the patient’s clinical course is complicated by the development of pneumonia with acute respiratory distress syndrome (ARDS), acute hypoxic respiratory failure, and/or death. (Rodriguez-Morales et al., 2020) The current study was designed to reveal the risk factors leading to severe forms of the respiratory tract affection of COVID-19 (acute respiratory distress syndrome or respiratory failure) in the main hospital established to receive all forms of COVID-19 cases requiring hospitalization.
It is important to reveal the extent to which COVID-19 leads to severe forms of respiratory tract complications which are the main cause of deaths in such cases and the risk factors, at hospital admission, that can predict such severe complications. The current study included 1482 hospitalized COVID-19 patients to study clinical, laboratory and outcome differences between those suffering or not from ARDS/respiratory failure. The study revealed that 79 (5.3%) patients developed ARDS or failure. Early studies reported an incidence rate ranging from 15.6–31% for ARDS. (Huang et al., 2020; Chen et al., 2020; Wang et al., 2020; Guang et al., 2019; Zhou et al., 2020)
A met-analysis of observational studies and case reports showed that nearly one third (32.8%) of patients with COVID-19 developed ARDS during their hospital admission. (Rodriguez-Morales et al., 2020) Similarly, in a retrospective analysis of clinical findings in 85 patients with confirmed COVID-19, 74.1%of patients developed ARDS during their hospitalization. Lai and his colleagues. identified that about 20% developed ARDS and >25% of patients with COVID-19 required intensive care unit (ICU) admission. (Lai et al., 2020) The figures revealed by these studies are higher than that revealed by the current study however, the lower frequency rate of ARDS of the current study may be attributed to several factors mainly that any case of positive test for COVID-19 was admitted in the hospital under study however the severity of the disease. That is many cases were admitted inspite of being minor symptoms. Other factors may include the small number of cases in some studies and the different population characteristics as well as the differences in the study approach. Also, the decreasing virulence of COVID-19 virus with progress of the epidemic combined with weaker mutant strains of the virus may be behind this difference.
The most common perceived manifestations on hospital admissions were those related to the respiratory system in addition to fever (51.9% compared with 25.9%). Cough (50.6% compared with 32.4%) and shortness of breath (55.7% compared with 7.8%) were several folds higher among patients suffering from ARDS compared to those non suffering from ARDS. Several previous studies revealed a similar pattern of manifestations characterized by dry cough, fever and respiratory failure. (Zhang et al., 2020; Chu et al., 2020; Iwasawa et al., 2020) The study of Huang and his colleagues pointed that the most common symptoms were fever (98%) followed by cough (76%), with over half (55%) of the patients developing dyspnea. (Huang et al., 2020)
Although there is no clear risk factor for COVID-19, several factors have an impact on the prognosis of respiratory illness including sex, age, positive smoking history, and coexisting underlying disease(s). The current study revealed that elderly males were at a higher risk of developing ARDS, not only that but the risk of developing ARDS gradually increases with progress of age. Those at or above 60 years of age were at around three fold likely to develop ARDS compared to those less than 40 years. Also hypertension (36.7% compared with 17.5%), diabetes mellitus (43.0% compared with 15.1%) and existence of other pulmonary diseases (12.7% compared with 3.6%), the most common comorbidities on hospital admission were significant predictors of developing ARDS. Numerous studies reported that a significant proportion of patients had at least one underlying disease. Based on Chih-Cheng Lai and his associate, hypertension is the most underlying disease (14.9%) followed by diabetes mellitus (7.4%) and cardiovascular disease. (4.2%)(Lai et al., 2020) A literature review by Pramath Kakodkar and his associates showed that 28% of the patients had comorbidity (s), the most underlying disorders were hypertension (55.3%), coronary artery disease/cerebrovascular accident (31.5%) and diabetes mellitus (30.6%) respectively. Guan and his colleagues showed that any underlying condition was more common among patients with severe COVID-19. (Kakodkar et al., 2020; Guan et al., 2020)
Laboratory investigations provide valuable information about both the clinical status and severity of hospitalized COVID-19 patients. Consistent with other studies, the current research revealed significant differences among multiple laboratory investigations between those with and without ARDS.( Li X et al., 2020; Li X et al., 2020; Yazdanpanah et al., 2020) Also, as expected patients with ARDS were more likely to stay in the hospital (with a median of 23 days compared with 14 days) and to be admitted to the intensive care unit (89.9% compared with 3.7%). Also they suffered from a higher mortality rate (51.9% compared with just only 1.1%).
The main limitations of the current study is being hospital based and depending mainly on secondary data (records of hospitalized patients) however, the large number of recruited cases and a selection of the only specialized hospital to deal with COVID-19 cases from all districts of Kuwait can provide both power and advantage for carrying out this study.
Conclusions:
Thus, this study demonstrates a difference of COVID-19 presentation and associated comorbidities between those suffering from ARDS/failure. Overall, this renders elderly males having fever, cough and shortness of breath and suffering hypertension, diabetes mellitus and to other associated respiratory diseases at a higher risk for developing severe respiratory complications. Hospital physicians should be aware of these differences to guide the diagnosis and subsequent management decisions. These results would help in developing specific and effective management strategies.
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Cite this Article: Kamel, M; El-Shazly, M; Al-Zuabi, H; Al-Ameeri, S; Al-Asfoor, S; Al-Majdely, R; Almoosa, I (2023). Predictors of severe respiratory complications among hospitalized COVID-19 patients. Greener Journal of Epidemiology and Public Health, 11(1): 12-22. https://doi.org/10.5281/zenodo.7755605.
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