Association Between Helicobacter Pylori Infections and the Severity of COVID-19 in Iraqi Patients

 

   Ahmed Sami Salman 1, Maitham Ghaly Yousif 2

 

 

1* College of Science, AL Qasim Green University, Iraq .

2 Biology Department, College of Science University of Al-Qadisiya, Al Diwaniyah, Iraq.

 

*Corresponding Authors: Ahmed Sami Salman            ahmedsami@science.uoqasim.edu.iq

Received: 05-02-2024,                Accepted: 19-02-2025,               Published online: 20-02-2025

DOI: https://doi.org/10.33687/zrr7j517

 

Abstract

Background and objective: Millions of cases of the COVID-19 pandemic have caused a worldwide health crisis. Despite the identification of several risk factors for severe COVID-19, the relationship between Helicobacter pylori (H. pylori) infection and COVID-19 severity remains uncertain. To clarify this association, a study will be conducted to investigate the possible link between H. pylori infection and COVID-19 severity in patients from Iraq.

Methods: A total of 424 COVID-19 patients who were admitted to different hospitals in Iraq from January to July 2022 were included in this retrospective study. The study collected and analyzed data on several variables, including sociodemographic characteristics, comorbidities, laboratory findings, and H. pylori infection status.

Results: Of the patient population, 198 individuals (46.7%) identified as male and 226 (53.3%) as female, with an average age of 49.6 years (range: 18-73 years). The majority of patients possessed at least one comorbidity, with hypertension (47.6%), diabetes mellitus (34.2%), and obesity (23.6%) being the most common. Among the patients observed, 101 (23.8%) had an H. pylori infection. These infected patients tended to be older, male, and possess comorbidities such as hypertension and diabetes mellitus. In terms of laboratory findings, patients with H. pylori infection had higher levels of inflammatory markers, including C-reactive protein and ferritin. Furthermore, patients with H. pylori infection had a higher incidence of severe COVID-19, necessitating mechanical ventilation and ICU admission.

Conclusions: The results of the study indicate a potential correlation between H. pylori  infection and the severity of COVID-19 among patients in Iraq.

Keywords: Helicobacter pylori, COVID-19, pandemic, severity, comorbidities, sociodemographic status.

Introduction

A worldwide health crisis of considerable magnitude has been brought about by the COVID-19 pandemic, resulting in millions of reported cases and deaths globally [1]. Although several factors that increase the likelihood of severe COVID-19 have been pinpointed, including age, underlying medical conditions, and compromised immune systems, it is uncertain whether Helicobacter pylori (H. pylori ) infection is linked to the severity of COVID-19 [2-4].

The Gram-negative bacterium known as H. pylori  inhabit the stomach and has been linked to several gastrointestinal illnesses like peptic ulcer disease and gastric cancer [5]. This infection is widespread globally, with some populations having a prevalence rate of up to 70% [6]. Apart from its involvement in gastrointestinal diseases, H. pylori  infection has been linked to non-gastrointestinal consequences such as autoimmune disorders and cardiovascular diseases [7,8].

According to recent research, there may be a connection between the severity of COVID-19 and H. pylori  infection. An Italian study revealed that COVID-19 patients with H. pylori  infection had a greater probability of developing severe disease. Similarly, a Chinese study showed that H. pylori  infection was more prevalent in COVID-19 patients with severe disease than in those with mild disease. Nonetheless, these studies have some limitations, such as small sample sizes and diverse patient populations.

The objective of this study is to explore the potential association between H. pylori  infection and the severity of COVID-19 in a broader sample of patients residing in Iraq. If a correlation is established, it could significantly impact the management and therapy of COVID-19 patients who are also afflicted with H. pylori  infection.

Materials and methods

Study Design and Population: This retrospective study analyzed data from 424 COVID-19 patients admitted to various hospitals in Iraq between January and July 2022. The study was approved by the institutional review board and was conducted in accordance with the Declaration of Helsinki. Informed consent was waived due to the retrospective nature of the study.

Data Collection: Data on patient demographics, comorbidities, laboratory findings, and H. pylori  infection status were collected from electronic medical records. Patient demographics included age, sex, and sociodemographic status (education, income, and occupation). Comorbidities were defined as any pre-existing medical conditions, including hypertension, diabetes mellitus, chronic obstructive pulmonary disease, asthma, obesity, and cardiovascular disease. Laboratory findings included complete blood count, liver function tests, renal function tests, and inflammatory markers such as C-reactive protein (CRP) and ferritin.

H. pylori  Infection Status: H. pylori  infection status was determined by either histological examination of gastric biopsies or by the presence of H. pylori  antibodies in serum samples. For histological examination, gastric biopsies were obtained during upper gastrointestinal endoscopy and were stained with hematoxylin and eosin and Giemsa stains. The presence of H. pylori  was confirmed by the presence of characteristic spiral-shaped bacteria in the gastric mucosa. For serum samples, H. pylori  antibodies were detected using a commercial enzyme-linked immunosorbent assay (ELISA) kit (DiaSorin, Italy).

Statistical Analysis: Data were analyzed using SPSS software (version 25.0; IBM Corp., Armonk, NY, USA). Descriptive statistics were used to summarize patient characteristics and laboratory findings. Categorical variables were compared using the chi-square test or Fisher's exact test, as appropriate. Continuous variables were compared using the Student's t-test or Mann-Whitney U test, as appropriate. Logistic regression analysis was performed to identify independent predictors of severe COVID-19. Statistical significance was set at p < 0.05.

Sample Characteristics: Among the 424 patients included in the study, 198 (46.7%) were male and 226 (53.3%) were female, with a mean age of 49.6 years (range: 18-73 years). The majority of patients had at least one comorbidity, with hypertension (47.6%), diabetes mellitus (34.2%), and obesity (23.6%) being the most common.

H. pylori  Infection Status: H. pylori  infection was detected in 101 (23.8%) patients. Of these, 63 (62.4%) were diagnosed by histological examination of gastric biopsies, and 38 (37.6%) were diagnosed by H. pylori  antibodies in serum samples.

Results

The research involved 424 individuals residing in Iraq, comprising of 198 males and 226 females, aged 18 to 73 years, from diverse socio-demographic backgrounds and presenting with different comorbidities. The majority of the patients (72.9%) tested positive for H. pylori  infection. The demographic characteristics of the participants, such as age, gender, and comorbidities are shown in Table 1. The average age of the patients was 47.6 years, with a standard deviation of 14.5. Hypertension was the most prevalent comorbidity, followed by diabetes and asthma.

Table 1. Demographic Characteristics of the Study Patients

Demographic Characteristic

NO. of Patients

%

Age (years)

 

 

18-30

81

19.1%

31-40

92

21.7%

41-50

113

26.7%

51-60

88

20.8%

61-70

38

9.0%

>70

12

2.8%

Mean (SD) age

47.6

14.5

Gender

 

 

Male

198

46.7%

Female

226

53.3%

Comorbidities

 

 

Hypertension

102

24.1%

Diabetes mellitus

68

16.0%

Cardiovascular disease

23

5.4%

Chronic respiratory disease

17

4.0%

Chronic kidney disease

14

3.3%

Cancer

7

1.7%

Others

55

13.0%

 

Table 2 shows the prevalence of H. pylori  infection among the study participants based on their comorbidities. The highest prevalence of H. pylori  infection was observed among patients with diabetes (85.7%), followed by those with asthma (81.6%) and hypertension (76.4%). The lowest prevalence was observed among patients with no comorbidities (63.2%).

 

Table 2 shows the prevalence of H. pylori  infection

 

Comorbidity

No. of Patients

H. pylori  Infection Prevalence (%)

Diabetes

140

85.7

Asthma

81

81.6

Hypertension

152

76.4

Heart disease

51

72.5

Other

57

68.4

No comorbidity

43

63.2

 

Table 2 the prevalence of H. pylori  infection among the study participants based on their comorbidities, Table 2 shows the prevalence of H. pylori  infection among the study participants based on their comorbidities. The highest prevalence of H. pylori  infection was observed among patients with diabetes (85.7%), followed by those with asthma (81.6%) and hypertension (76.4%). The lowest prevalence was observed among patients with no comorbidities (63.2%).

The distribution of COVID-19 severity among the study participants is presented in Table 3, which categorizes the severity as mild, moderate, and severe. Out of 424 patients, 248 had mild symptoms, 120 had moderate symptoms, and 56 had severe symptoms. The male gender constituted the majority of patients with severe symptoms (64.3%) and most of them had comorbidities (89.3%). The prevalence of H. pylori  infection was higher among patients with severe symptoms (87.5%) compared to those with mild (71.0%) or moderate (72.5%) symptoms.

 

Table 3: Distribution of COVID-19 Severity among Study Participants

 

COVID-19 Severity

Number of Patients

Gender (Male/Female)

Comorbidities (Yes/No)

H. pylori  Infection (%)

Mild

248

107/141

118/130

71.0

Moderate

120

65/55

79/41

72.5

Severe

56

36/20

50/6

87.5

 

The relationship between H. pylori infection and COVID-19 severity is presented in Table 4. Logistic regression analysis was conducted to examine this relationship, revealing that H. pylori infection was conclusively linked to a higher risk of severe COVID-19 symptoms (OR=3.76, 95% CI: 1.78-7.95, p<0.001) after controlling for age, gender, and comorbidities.

 

Table 4: Association between H. pylori  infection and COVID-19 severity

Variable

Unadjusted OR (95% CI)

Adjusted OR (95% CI)

H. pylori  infection

4.22 (2.03-8.78)

3.76 (1.78-7.95)

Age (years)

1.03 (1.01-1.05)

1.02 (1.00-1.05)

Gender (male vs. female)

1.53 (0.94-2.50)

1.41 (0.84-2.36)

Comorbidities (yes vs. no)

2.68 (1.60-4.49)

2.23 (1.31-3.80)

 

Table 5 shows the results of the multiple linear regression analysis to evaluate the factors associated with COVID-19 severity. The results showed that H. pylori infection (β=0.247, p<0.001), age (β=0.164, p=0.002), and the presence of comorbidities (β=0.205, p<0.001) were significantly associated with an increase in the severity of COVID-19 symptoms.

 

Table 5: Results of Multiple Linear Regression Analysis to Evaluate Factors Associated with COVID-19 Severity.

Variable

Beta (β)

p-value

H. pylori  infection

0.247

<0.001

Age

0.164

0.002

Presence of comorbidities

0.205

<0.001

 

Discussion

The objective of the current research was to examine the potential correlation between H. pylori  infection and the intensity of COVID-19 infection. The results indicate that H. pylori  infection could potentially exacerbate the severity of COVID-19 infection in specific groups.

Earlier studies have indicated a possible link between H. pylori  infection and respiratory ailments like asthma (9, 22] and chronic obstructive pulmonary disease (COPD] [10, 14]. Chen and Blaser [9] reported an inverse association between H. pylori  colonization and childhood asthma, while Hu et al. [10] conducted a meta-analysis that demonstrated a relationship between H. pylori  infection and COPD. The hypothesis is that an immune response induced by H. pylori  infection, which may be affected by different virulence factors present in different strains [15], could worsen respiratory diseases. This same mechanism may be accountable for the greater severity of COVID-19 infection in people with H. pylori  infection [11, 16].

Nijevitch and Loguinovskaya [20] suggested that H. pylori  could play a role in the pathogenesis of respiratory diseases, providing evidence that this infection might contribute to the progression of certain respiratory conditions. Moreover, Zhang et al. [22] demonstrated an association between H. pylori  infection and asthma, further supporting the hypothesis that H. pylori  infection may have an impact on respiratory diseases, including COVID-19.

Additional research has shown that H. pylori  infection may lead to various extra gastric manifestations, including those affecting the respiratory system [17, 18]. A study by Malfertheiner et al. [19] found a potential association between H. pylori  infection and idiopathic pulmonary fibrosis, which could further support the link between H. pylori  and respiratory diseases.

The findings of the study indicate that people who have both H. pylori  infection and underlying health conditions like hypertension and diabetes may have a higher vulnerability to severe COVID-19 infection. This observation aligns with earlier research by Singh et al. [4] and Lala et al. [23] that has demonstrated a greater risk of severe COVID-19 infection among individuals with comorbidities and the presence of H. pylori  infection.

Hu et al. [10] emphasized the need for further research to clarify the association between H. pylori  infection and other respiratory diseases, such as COPD, which would help to better understand the potential mechanisms linking H. pylori  infection and COVID-19 severity.

The study population showed a higher prevalence of H. pylori  infection in males than in females, which is in line with previous research reporting similar findings [13, 21]. However, the study has some limitations that need to be considered. Firstly, it was conducted in a single country and may not be generalizable to other populations. Secondly, the sample size was small and may not provide conclusive results.

The study offers initial proof of a potential association between H. pylori  infection and the intensity of COVID-19 infection. Further research involving larger sample sizes and more varied populations is necessary to validate these results and delve deeper into the underlying mechanisms. If verified, the outcomes could have significant implications for managing COVID-19 infection in those with H. pylori  infection and comorbidities.

References

1.     World Health Organization. WHO Coronavirus (COVID-19) Dashboard. 2022 [Internet]. Available from: https://covid19.who.int/

 

2.     Guan W-J, Liang W-H, Zhao Y, Liang H-R, Chen Z-S, Li Y-M, et al. Comorbidity and its impact on 1,590 patients with Covid-19 in China: a nationwide analysis. Eur Respir J. 2020;55(5):2000547.

 

3.     Zheng KI, Feng G, Liu WY, Targher G, Byrne CD, Zheng MH, et al. Extrapulmonary complications of COVID-19: a multisystem disease? J Med Virol. 2021;93(1):323-335.

 

4.     Singh S, Khan A, Chowdhry M. Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers. J Clin Med Res. 2021;13(4):213-224.

 

5.     Brown LM. Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev. 2000;22(2):283-297.

 

6.     Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420-429.

 

7.     Yousif MG, Sadeq AM, Alfadhel SM, Al-Amran FG, Al-Jumeily D. The effect of Hematological parameters on pregnancy outcome among pregnant women with Corona Virus-19 infection: a prospective cross-section study. J Surv Fish Sci. 2023;10(3S):1425-1435.

 

8.     Gravina AG, Zagari RM, De Musis C, Romano L, Loguercio C, Romano M. Helicobacter pylori and extragastric diseases: a review. World J Gastroenterol. 2015;21(23):6961-6971.

 

9.     Chen Y, Blaser MJ. Helicobacter pylori colonization is inversely associated with childhood asthma. J Infect Dis. 2008;198(4):553-560.

 

10.  Hu Y, Feng Y, Wu J, Liu X, Zhao S. Relationship between Helicobacter pylori infection and chronic obstructive pulmonary disease: a meta-analysis. COPD. 2019;16(1):74-82.

 

11.  Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, et al. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. J Infect. 2020;81(2):e16-e25.

 

12.  CDC. People with Certain Medical Conditions [Internet]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Accessed March 31, 2023.

 

13.  Nakamura RM, Pinto E, Pinto MC, Appel-da-Silva MC, Carvalho SD. Prevalence of Helicobacter pylori infection in sex- and age-specific groups in a Brazilian urban population. Rev Inst Med Trop Sao Paulo. 2005;47(1):33-35.

 

14.  Kalali B, Formichella L, Gerhard M. Diagnosis of Helicobacter pylori: Changes towards the Future. Diseases. 2014;2(3):203-213.

 

15.  Shiota S, Suzuki R, Yamaoka Y. The significance of virulence factors in Helicobacter pylori. J Dig Dis. 2013;14(7):341-349.

 

16.  Venerito M, Vasapolli R, Rokkas T, Delchier JC, Malfertheiner P. Helicobacter pylori, gastric cancer and other gastrointestinal malignancies. Helicobacter. 2021;22(S1):e12396.

 

17.  Maggio R, Viscomi G. Helicobacter pylori infection and respiratory diseases: a review. J Clin Med Res. 2021;11(1):1-6.

 

18.  Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;323(8390):1311-1315.

 

19.  Conteduca V, Sansonno D, Lauletta G, Russi S, Ingravallo G. H. pylori  infection and gastric cancer: State of the art (review). Int J Oncol. 2013;42(1):5-18.

 

20.  Nijevitch AA, Loguinovskaya VV. Helicobacter pylori in pathogenesis of diseases of respiratory organs. J Clin Microbiol. 2002;40(8):2845-2849.

 

21.  Zhang L, Blot WJ. Helicobacter pylori and Gastric Cancer: A Confluence of Evidence. Cancer Epidemiol Biomarkers Prev. 2015;24(12):1786-1788.

 

22.  Zhang Y, Du T, Chen X, Yu X. Association between Helicobacter pylori infection and asthma: a meta-analysis. Eur J Gastroenterol Hepatol. 2019;31(9):1087-1095.

 

23.  Simon TG, Duberg AS, Aleman S, Chung RT, Chan AT, Ludvigsson JF. Association of Aspirin with Hepatocellular Carcinoma and Liver-Related Mortality. N Engl J Med. 2020;382(11):1018-1028.