Mehmet Kilic1, Kübra Saçar Kubuc1, Esra Gurbuz2, Abdusselam Ozdemir3

1Depertmant of Anesthesiology and Reanimation, University of Health Sciences, Van Training and Research Hospital, Van, Türkiye
2Department of Infectious Diseases and Microbiology, University of Health Sciences, Van Training and Research Hospital, Van, Türkiye
3Department of General Surgery, University of Health Sciences, Van Training and Research Hospital, Van, Türkiye

Keywords: COVID-19, Legionella infection, pandemic, pneumonia.

Abstract

During pandemics, certain uncommon diseases might manifest within vulnerable populations. An example is Legionella spp, an aerobic, gram-negative pathogen that can thrive intracellularly. This microorganism holds significance for public health, being responsible for both pneumonia acquired in community settings and healthcare settings. Among Legionella cases, Legionella pneumophila accounts for about 90% of them. When observing coronavirus disease 2019 (COVID-19) patients in the intensive care unit, it's crucial to consider Legionella as a possible alternative diagnosis due to its similar clinical manifestations. In this case report, we aim to highlight a 43-year-old male patient, previously without any chronic conditions, who was initially diagnosed with COVID-19 but later identified to have Legionella pneumonia, presenting with symptoms including confusion, dysarthria, weakness, pain, and respiratory failure upon hospital admission.

Introduction

The coronavirus SARS-CoV-2 is responsible for causing the disease known as coronavirus disease 2019 (COVID-19). The World Health Organization declared the COVID-19 pandemic in March 2020. COVID-19 typically presents with fever and various respiratory symptoms that are non-specific, leading to the need to consider other diseases in the differential diagnosis.[1,2] Legionella bacteria, which can be transmitted sporadically or through outbreaks, is a significant cause of pneumonia.[1-3] During a pandemic, the increased workload may result in the possibility of overlooking rare diseases, leading to potential delays in diagnosis and appropriate treatment.[2]

This case report highlights the significance of considering differential diagnosis in COVID-19 by presenting a patient with Legionella pneumophila infection initially managed as a COVID-19 case.

Case Report

A 43-year-old male who had any chronic disease before had been admitted to the hospital with complaints of confusion, dysarthria, weakness, and dyspnea. On laboratory tests, as serum sodium level was low (Na: 120 mmol/L) with detection of ground glass opacities on thorax computed tomography (CT) scan as shown in Figure 1a-d and Table 1, he had COVID-19 diagnosis. On magnetic resonance imaging of the brain, there was no pathological finding as shown in Figure 1e, f. He was internalized to COVID-19 intensive care unit (ICU) with severe hyponatremia and mild hypoxia.


He has been a worker at decontamination and air conditioning systems and he had stayed and worked at a hotel for seven days three weeks ago. He had contact with a COVID-19 patient at his work. He had diarrhea, nausea, weakness, and headache during the week. Then neurological symptoms like confusion, dysarthria, and walking difficulty developed. He is a smoker (4 pockets/day/22 years) and drinks alcohol (22 years). He had two doses of the BioNTech vaccine (last 3.5 months ago).

At physical examination; confusion, tremor in both hands, and muscle weakness in the lower extremities were detected. He was stabile hemodynamically, with 5L/min O2 mask SPO2: %95, respiratory rate: 22/min, blood pressure: 135/78 mmHg and heart rate: 85 beats/min. Saline infusion, empiric intravenous (IV) moxifloxacin 400 mg/day, and other symptomatic treatments were started after getting the cultures. COVID-19 polymerase chain reaction (PCR) test was negative at two tests one day apart. At the same time, we suspected Legionnaires' disease (LD) due to the history, clinical findings, and negative PCR tests. For LD diagnosis; blood, urine, and, sputum samples were collected. Legionella pneumophila serogroup-1 (Sg-1) antigen was positive in the urine sample as shown in Table 2. The other tests resulted after 12 days (Table 1). We also used moxifloxacin for LD treatment. During the follow-up serum sodium level: 130 mmol/L; dysarthria, tremors, and weakness got better. After four days in ICU, his all pathological neurologic findings were resolved completely. He got SPO2 %95 at room air. He externalized from ICU to a normal service room and after six days, he was discharged from the hospital.

Discussion

We presented a case who had an LD diagnosis at the time of COVID-19 peak on February 2022. Some rare diseases can appear in risk groups during the pandemic. Due to increased workload, they can be overlooked.

Legionella bacteria are aerobic, Gramnegative, and intracellular pathogens and are important causes of community-acquired and hospital-acquired pneumonia.[1] Legionella pneumophila is responsible for 90% of legionellosis cases.[1,4,5] Legionella infections can be transmitted sporadically or as epidemics. Transmission to humans is typically via inhalation from contaminated water or soil.[2]

Legionella spp. have been reported to be detected in the water systems of facilities such as hotels and hospitals that are not maintained.[1,3] Legionella spp. the incubation period is in the range of 2-14 days.[6] Legionella spp. Often cause LD and Pontiac fever.[1,6] Legionnaires' disease refers to pneumonia involving the lower respiratory tract and progressing mildly.[6,7] Pontiac fever, on the other hand, is an acute, self-limiting febrile illness that is usually seen during epidemics.[7] While Legionella species can cause serious illness in people with risk factors.[1] Risk factors for LD; elderly (especially ≥50 years old), smokers, those with chronic lung disease (chronic obstructive pulmonary disease, emphysema, etc.), immunocompromised patients (cancer, diabetes, kidney failure, etc.), and those using immunosuppressive drugs.[1,2,6,8]

During the COVID-19 pandemic, many hotels and dormitories around the world were closed. With the decrease of the COVID-19 pandemic, the risk of exposure to Legionella spp. has increased with the re-use of the water that has been stored in unused water systems.[7,9,10] Legionella pneumonia accounts for 3-8% of all pneumonia cases.[1,4,11] In a case report, they detected Legionella and SARS-CoV-2 as a co-infection.[1] Co-infection by these two microorganisms is very rare.

Symptoms and signs such as fever, headache, confusion, and shortness of breath are seen in COVID-19 and Legionella spp. Similarly, in both diseases, systemic diseases such as old age, diabetes, and chronic lung diseases are individual risk factors.[1,7] The incubation period of Legionella spp. is longer than the incubation period of SARS-CoV-2.[2,6] Thus determining the source of Legionella spp. may be more difficult than the source of COVID-19 disease.[6]

This case was at a peak period of the COVID-19 pandemic, had contact with a COVID-19 patient, and symptoms and findings like high ferritin, D-dimer, and serum lactate dehydrogenase. In addition to high laboratory tests such as C-reactive protein, white blood cell, procalcitonin, and low lymphocyte count, as there is no specific and specific definitive test and radiological image for COVID-19; It is undoubtedly acceptable to be evaluated as a COVID-19 patient.[13,14] In addition to the job of the case (being a water decontamination worker), staying in hotels that returned to full capacity, his travels during this period, bilateral ground-glass opacities in the lungs as well as more consolidated areas in the right lung in the thorax CT, less frequent infiltrations in the left lung are other factors in the differential diagnosis. It also paved the way for the consideration of diseases. The COVID-19 PCR two test results, which were examined from the nasopharynx swab sample taken with an interval of 24 hours, were negative. Due to the absence of a typical COVID-19 radiological lung image and the risk factors; LD was suspected in this case. The laboratory tests and radiological images mentioned are not specific to Legionella pneumonia, but can be seen in many clinical pictures.[1,15]

Patients followed up with suspected COVID-19 disease should be evaluated considering their symptoms, clinical findings, history of the case, and risk factors in case of suspected LD. If LD is suspected, laboratory tests used for diagnosis should be applied. In this case, samples taken from respiratory secretion, blood, and urine are studied in the laboratory. Detection of specific antigen in urine for Legionella pneumophila Sg-1 or antibody against Legionella pneumophila Sg-1 in specific single or double serum [(indirect fluorescence with a double serum sample antibody (IFA) or enzyme-linked immunosorbent assay (ELISA)] a significant increase in titers in IFA or ELISA gives definite results.[7] Searching for positivity of Legionella antigen in the urine is the most frequently used diagnostic method and its sensitivity is 70% and the specificity is 99%.[6,7,16-18] This test becomes positive in serotypes.[1] It should be kept in mind that other pathogenic Legionella spp. were not detected in this urinary antigen test.[6] The diagnosis was made by detecting a specific antigen in the urine for Legionella pneumophila Sg-1 after an average of one hour in the urine sample and after about one week in the patient's blood serum sample, in the sputum culture no growth was detected. According to the results of the research conducted by the local public health directorate, it is thought that the case LD was caught in the hotel where he stayed, most likely after a trip he made about two weeks ago. In this way, the Directorate of Public Health has taken the necessary measures for public health for this LD source.

Although the use of empirical antibiotics in mild to moderate COVID-19 patients reaches 70%, there is not enough evidence to show that it is beneficial.[1,20] Beta-lactam antibiotic group drugs, which are generally used as the first choice in the treatment of bacterial pneumonia, do not affect Legionella pneumonia. Macrolides and new-generation quinolones are effective in the treatment of Legionella. [1,10,21] In this case, in addition to oxygen support, IV moxifloxacin, and other symptomatic treatments were given for 10 days. The patient was discharged home with full recovery after being treated in the hospital for 10 days.

In studies, in Europe between 2006 and 2010, the annual incidence of LD was 1/100,000 and the mortality rate was 6.6% and the mortality rate was 25-40% in Legionella pneumonia. [1,7,12,13,19]

In our country Cesur et al.[23] presented an LD case who had Legionella antigen positivity in the urine. They suspected Legionella pneumophila in the patient who applied to the emergency department with high fever and dyspnea. COVID-19 PCR was negative. The patient was discharged home after ceftriaxone and levofloxacin treatment.

In conclusion, LD should be considered in the differential diagnosis of critically ill COVID-19 patients admitted to the ICU, as well as other diseases that cause a similar clinical picture. The patient's anamnesis, clinical symptoms, test results, and imaging examinations should be thoroughly examined; We believe that early diagnosis and initiation of treatment by performing rapid and reliable tests in suspicion of LD will be an important step to reduce the mortality in the ICU, as well as to prevent unnecessary health expenditures and inappropriate antibacterial drug use.

Cite this article as: Kilic M, Saçar Kubuc K, Gurbuz E, Ozdemir A. Infections that may be missed during the COVID-19 pandemic, legionella pneumophila infection: A case report. D J Med Sci 2023;9(2):72-77. doi: 10.5606/fng. btd.2023.119.

Author Contributions

Analyzed and interpreted the patient data, performed the physical examination, and was a major contributor in writing the manuscript: M.K.; Major contributor in writing and reading and correcting any misspellings in the manuscript: K.S.K.; Major contributor in writing the manuscript: A.O.; Major contributor in writing the manuscript: E.G.; All authors read and approved the final manuscript.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/ or publication of this article.

Financial Disclosure

The authors received no financial support for the research and/or authorship of this article.

References

  1. Shimizu M, Chihara Y, Satake S, Yone A, Makio M, Kitou H, et al. Co-infection with Legionella and SARS-CoV-2: A case report. JA Clin Rep 2021;7:62. doi: 10.1186/s40981-021-00467-3.
  2. Alkan S, Sener A, Güçlü Kayta SB, Kayta G, Akça A. Q fever in the differential diagnosis of COVID 19 infection. Turk J Intern Med 2021;3:145-6. doi: 10.46310/tjim.905105.
  3. Dey R, Ashbolt NJ. Legionella Infection during and after the COVID-19 Pandemic. ACS ES&T Water 2020:acsestwater.0c00151. doi: 10.1021/ acsestwater.0c00151.
  4. Shoar S, Musher DM. Etiology of community-acquired pneumonia in adults: A systematic review. Pneumonia (Nathan) 2020;12:11. doi: 10.1186/s41479-020- 00074-3.
  5. Miyashita N, Higa F, Aoki Y, Kikuchi T, Seki M, Tateda K, et al. Distribution of Legionella species and serogroups in patients with culture-confirmed Legionella pneumonia. J Infect Chemother 2020;26:411-7. doi: 10.1016/j.jiac.2019.12.016.
  6. Cassell K, Davis JL, Berkelman R. Legionnaires' disease in the time of COVID-19. Pneumonia (Nathan) 2021;13:2. doi: 10.1186/s41479-020- 00080-5.
  7. Şener A, Alkan Çeviker S, Önder T, Karaduman N. Ghost in opera: Are Legionella bacteria really rare pathogens for hospital plumbing? D J Med Sci 2021;7:26-9. doi: 10.5606/fng.btd.2021.25042.
  8. Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev 2020;36:e3319. doi: 10.1002/dmrr.3319.
  9. Phin N, Parry-Ford F, Harrison T, Stagg HR, Zhang N, Kumar K, et al. Epidemiology and clinical management of Legionnaires' disease. Lancet Infect Dis 2014;14:1011-21. doi: 10.1016/S1473- 3099(14)70713-3.
  10. Lejyoner hastalığı kontrol programı rehberi. Ankara: T.C. Sağlık Bakanlığı, Türkiye Halk Sağlığı Kurumu; 2016.
  11. Rello J, Gattarello S, Souto J, Sole-Violan J, Valles J, Peredo R, et al. Community-acquired Legionella Pneumonia in the intensive care unit: Impact on survival of combined antibiotic therapy. Med Intensiva 2013;37:320-6. doi: 10.1016/j.medin.2012.05.010.
  12. Miyashita N, Higa F, Aoki Y, Kikuchi T, Seki M, Tateda K, et al. Distribution of Legionella species and serogroups in patients with culture-confirmed Legionella pneumonia. J Infect Chemother 2020;26:411-7. doi: 10.1016/j.jiac.2019.12.016.
  13. Arashiro T, Nakamura S, Asami T, Mikuni H, Fujiwara E, Sakamoto S, et al. SARS-CoV-2 and Legionella co-infection in a person returning from a Nile cruise. J Travel Med 2020;27:taaa053. doi: 10.1093/jtm/ taaa053.
  14. Keane T. COVID-19 and Legionella: Preparations to consider for municipal and building potable water systems. Available at: https://legionellae. org/wp-content/uploads/COVID-19-and-LegionellaPreparations-to-Consider-4-23-2020.pdf. 2020. [Accessed: 23.04.2020].
  15. Yu C, Lei Q, Li W, Wang X, Liu W, Fan X, et al. Clinical characteristics, associated factors, and predicting COVID-19 mortality risk: A retrospective study in Wuhan, China. Am J Prev Med 2020;59:168- 75. doi: 10.1016/j.amepre.2020.05.002.
  16. Fiumefreddo R, Zaborsky R, Haeuptle J, Christ-Crain M, Trampuz A, Steffen I, et al. Clinical predictors for Legionella in patients presenting with community-acquired pneumonia to the emergency department. BMC Pulm Med 2009;9:4. doi: 10.1186/1471-2466- 9-4.
  17. External communications. European Centre for Disease Prevention and Control publishes Annual epidemiological report 2011. Euro Surveill 2011;16:20012.
  18. C.D.C. Closes Some Offices Over Bacteria Discovery - The New York Times. Available at: https://www. nytimes.com/2020/08/08/health/cdclegionnairescoronavirus.html. [cited 2020 aug 8].
  19. Shimada T, Noguchi Y, Jackson JL, Miyashita J, Hayashino Y, Kamiya T, et al. Systematic review and metaanalysis: Urinary antigen tests for Legionellosis. Chest 2009;136:1576-85. doi: 10.1378/chest.08- 2602.
  20. Gacouin A, Le Tulzo Y, Lavoue S, Camus C, Hoff J, Bassen R, et al. Severe pneumonia due to Legionella pneumophila: Prognostic factors, impact of delayed appropriate antimicrobial therapy. Intensive Care Med 2002;28:686-91. doi: 10.1007/s00134-002-1304-8.
  21. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: A systematic review and meta-analysis. J Infect 2020;81:266-75. doi: 10.1016/j.jinf.2020.05.046.
  22. Phin N, Parry-Ford F, Harrison T, Stagg HR, Zhang N, Kumar K, et al. Epidemiology and clinical management of Legionnaires’ disease. Lancet Infect Dis 2014;14:1011-21. doi: 10.1016/S1473- 3099(14)70713-3.
  23. Cesur S, Siyah Ü, Kaya Kılıç E, Sarı M, Ataman Hatipoglu C, Kınıklı S. Covid-19 pandemisi döneminde tanı konan bir toplum kaynaklı Legionella pneumophila pnömonisi olgusu. TJCL 2021;12:116-9.