Legionnaire's Disease Research Articles

Reduction of Legionella pneumophila and Pseudomonas aeruginosa bacteria in water using gamma irradiation

Pathogenic bacteria found in low levels in natural water systems can present a hazard to human health, such as through contraction of Legionnaires disease, if conditions are favourable for growth and there is potential to create an aerosol. In this study, gamma radiation using a60Co source was applied to Legionella pneumophila and Pseudomonas aeruginosa bacteria for 60 min at varying dose rates. All L. pneumophila bacteria were eliminated by irradiation at a dose of 1.86 kGy, and all P. aeruginosa at a dose of 0.70 kGy. Approximate D10 values for L. pneumophila and P. aeruginosa bacteria were 166.3 Gy and 70.9 Gy respectively.

Cerebellar syndrome associated with legionellosis: A case report and literature review

IntroductionLegionnaire's disease is a community-acquired pneumonia caused by the Gram-negative bacterium Legionella pneumophila. This disease is often associated with neurological symptoms, the clinical presentation of which can be very varied. Case reportWe report a 47-year-old female patient who developed Legionnaires’ disease with cerebellar symptoms (ataxia, dysarthria and hypermetria). Laboratory tests revealed a biological inflammatory syndrome. The cerebrospinal fluid was sterile. Urinary antigen test and serology were positive for L. pneumophila. An interstitial syndrome of the right upper lobe was detected on chest computed tomography (CT) scan. Brain imaging (magnetic resonance imaging and CT angiography) showed no abnormalities. The outcome was favourable after treatment with spiramycin, levofloxacin and corticosteroids. DiscussionFew cases only (n=110) of Legionnaires’ disease with cerebellar symptoms have been reported in the literature. The pathogenic mechanism behind neurological dysfunction in patients with Legionnaires’ disease is unknown. Neurological symptoms improve with antibiotic therapy and corticosteroids. Extra-pulmonary forms of Legionnaires’ disease are frequent, with neurological symptoms being the most common symptoms. Cerebellar dysfunction may be underestimated and requires appropriate management with antibiotic therapy and corticosteroid therapy. Recommendations for the management of Legionnaire's disease with severe extra-pulmonary symptoms are needed.

Presence of Viable, Clinically Relevant Legionella Bacteria in Environmental Water and Soil Sources of China.

ABSTRACTThe distribution of pathogenic Legionella in the environmental soil and water of China has not been documented yet. In this study, Legionella was detected in 129 of 575 water (22.43%) and 41 of 442 soil samples (9.28%) by culture. Twelve Legionella species were identified, of which 11 were disease-associated. Of the Legionella-positive samples, 109 of 129 (84.50%) water and 29 of 41 (70.73%) soil were positive for L. pneumophila, which accounted for about 75% of Legionella isolates in both water and soil, suggesting L. pneumophila was the most frequent species. Soil showed a higher diversity of Legionella spp. as compared with water (0.6279 versus 0.4493). In contrast, serogroup (sg) 1 was more prevalent among L. pneumophila isolates from water than from soil (26.66% versus 12.21%). Moreover, many disease-associated sequence types (STs) of L. pneumophila were found in China. Intragenic recombination was acting on L. pneumophila from both water and soil. Phylogeny, population structure, and molecular evolution analyses revealed a probable existence of L. pneumophila isolates with a special genetic background that is more adaptable to soil or water sources and a small proportion of genetic difference between water and soil isolates. The detection of viable, clinically relevant Legionella demonstrates soil as another source for harboring and dissemination of pathogenic Legionella bacteria in China. Future research should assess the implication in public health with the presence of Legionella in the soil and illustrate the genetic and pathogenicity difference of Legionella between water and soil, particularly the most prevalent L. pneumophila.IMPORTANCE Pathogenic Legionella spp. is the causative agent of Legionnaires’ disease (LD), and L. pneumophila is the most common one. Most studies have focused on L. pneumophila from water and clinical samples. However, the soil is another important reservoir for this bacterium, and the distribution of Legionella spp. in water and soil sources has not been compared and documented in China yet. Discovering the distribution of Legionella spp. and L. pneumophila in the two environments may help a deep understanding of the pathogenesis and molecular evolution of the bacterium. Our research systematically uncovered the distributions of Legionella spp. in different regions and sources (e.g., water and soil) of China. Moreover, phylogeny, population structure, and molecular evolution study revealed the possible existence of L. pneumophila with a special genetic background that is more adaptable to soil or water sources, and genetic difference may exist.

Clinical predictors and outcomes for Legionnaire's disease versus bacteremic pneumococcal pneumonia

BackgroundLegionnaires' disease (LD) is a serious sometimes fatal pneumonia caused by Legionella pneumophila. The clinical manifestations of LD may be similar to those by caused by Streptococcus pneumoniae. As both conditions can be serious illnesses but requiring different antimicrobial therapies, factors that can help differentiate these types of pneumonias can be helpful in the clinical management of hospitalized patients with bacterial pneumonia. This study aimed to compare clinical features and indicators of disease progression in hospitalized patients with community-acquired pneumonia caused by L. pneumophila and bacteremic S. pneumoniae. MethodsWe conducted a retrospective case comparison study of adult patients hospitalized with LD or S. pneumoniae. Data collected included demographic, clinical characteristics, and comorbidities, and outcomes. Data were analyzed using SPS vs 24.0. Multivariable analysis was done using logistic regression with a forward stepwise algorithm. ResultsA total of 106 patients met study criteria. The incidence of LD peaked in summer months and S. pneumoniae peaked in the winter quarter. From multivariable analysis predictors of LD were male gender (OR=21.6, p < 0.001), diarrhea (OR=4.5, p = 0.04), body mass index (BMI) (OR=1.13, p = 0.02), hyponatremia (OR=5.6, p = 0.03 and Charlson weighted index of comorbidity (CWIC) score (OR=0.61, p = 0.01). Patients with S. pneumoniae had higher rates of mechanical ventilation, septic shock, and death than those with LD. ConclusionsOur data suggests that variables that may distinguish LD from S. pneumoniae include male gender, diarrhea, hyponatremia, higher temperature on admission, higher BMI and fewer comorbidities. Bacteremic S. pneumoniae was associated with poorer outcomes than LD including higher rates of septic shock, mechanical ventilation, ICU admission, and death.

A review of legionnaires' disease and public water systems - Scientific considerations, uncertainties and recommendations.

Legionella is an opportunistic premise plumbing pathogen and causative agent of a severe pneumonia called Legionnaires' Disease (LD). Cases of LD have been on the rise in the U.S. and globally. Although Legionella was first identified 45 years ago, it remains an 'emerging pathogen." Legionella is part of the normal ecology of a public water system and is frequently detected in regulatory-compliant drinking water. Drinking water utilities, regulators and public health alike are increasingly required to have a productive understanding of the evolving issues and complex discussions of the contribution of the public water utility to Legionella exposure and LD risk. This review provides a brief overview of scientific considerations important for understanding this complex topic, a review of findings from investigations of public water and LD, including data gaps, and recommendations for professionals interested in investigating public water utilities. Although the current literature is inconclusive in identifying a public water utility as a sole source of an LD outbreak, the evidence is clear that minimizing growth of Legionella in public water utilities through proper maintenance and sustained disinfectant residuals, throughout all sections of the water utility, will lead to a less conducive environment for growth of the bacteria in the system and the buildings they serve.

Rising Incidence of Legionnaires' Disease and Associated Epidemiologic Patterns, United States, 1992-2018.

Reported Legionnaires' disease (LD) cases began increasing in the United States in 2003 after relatively stable numbers for >10 years; reasons for the rise are unclear. We compared epidemiologic patterns associated with cases reported to the Centers for Disease Control and Prevention before and during the rise. The age-standardized average incidence was 0.48 cases/100,000 population during 1992-2002 compared with 2.71 cases/100,000 in 2018. Reported LD incidence increased in nearly every demographic, but increases tended to be larger in demographic groups with higher incidence. During both periods, the largest number of cases occurred among White persons, but the highest incidence was in Black or African American persons. Incidence and increases in incidence were generally largest in the East North Central, Middle Atlantic, and New England divisions. Seasonality was more pronounced during 2003-2018, especially in the Northeast and Midwest. Rising incidence was most notably associated with increasing racial disparities, geographic focus, and seasonality.

The Use of Culture, Molecular Methods and Whole Genome Sequencing to Detect the Source of an Outbreak of Legionnaire's Disease in New York State

The Use of Culture, Molecular Methods and Whole Genome Sequencing to Detect the Source of an Outbreak of Legionnaire's Disease in New York State

Legionella pneumophila in Municipal Shower Systems in Stavanger, Norway; A Longitudinal Surveillance Study Using Whole Genome Sequencing in Risk Management.

Following an incidence of Legionnaires disease (LD) in 2007, where a municipal shower system was the likely source of infection, Stavanger municipality initiated a surveillance program for Legionella as part of establishing internal risk evaluation and prevention routines. More than 250 shower systems were examined for cultivatable Legionella pneumophila. The prevalence and diversity of serogroups (sg) and sequence types (STs) of L. pneumophila were mapped using available typing techniques over a period of more than 10 years (2010–2021). The surveillance showed an overall reduction in the L. pneumophila colonisation rate in municipal systems from 11 to 4.5% following prevention measures during the period, with the highest colonisation rate in complex systems (e.g., larger nursing homes and sports complexes). Further, an approximately even distribution between sg1 and 2–14 was seen. Whole genome sequencing (WGS) revealed that only a limited number of STs were detected, and they were consistent at specific locations over time. This study showed that environmental surveillance data in combination with available typing techniques and WGS can give the municipality a better tool for risk management and an overview of ST distributions that can be a valuable asset in future source investigations.

SARS-CoV-2-Legionella Co-Infections: A Systematic Review and Meta-Analysis (2020-2021).

Legionnaires’ Disease (LD) is a severe, sometimes fatal interstitial pneumonia due to Legionella pneumophila. Since the inception of the SARS-CoV-2 pandemic, some contradictory reports about the effects of lockdown measures on its epidemiology have been published, but no summary evidence has been collected to date. Therefore, we searched two different databases (PubMed and EMBASE) focusing on studies that reported the occurrence of LD among SARS-CoV-2 cases. Data were extracted using a standardized assessment form, and the results of such analyses were systematically reported, summarized, and compared. We identified a total of 38 articles, including 27 observational studies (either prospective or retrospective ones), 10 case reports, and 1 case series. Overall, data on 10,936 SARS-CoV-2 cases were included in the analyses. Of them, 5035 (46.0%) were tested for Legionella either through urinary antigen test or PCR, with 18 positive cases (0.4%). A pooled prevalence of 0.288% (95% Confidence Interval (95% CI) 0.129–0.641), was eventually calculated. Moreover, detailed data on 19 co-infections LD + SARS-CoV-2 were obtained (males: 84.2%; mean age: 61.9 years, range 35 to 83; 78.9% with 1 or more underlying comorbidities), including 16 (84.2%) admissions to the ICU, with a Case Fatality Ratio of 26.3%. In summary, our analyses suggest that the occurrence of SARS-CoV-2–Legionella infections may represent a relatively rare but not irrelevant event, and incident cases are characterized by a dismal prognosis.

Global Perspective of Legionella Infection in Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Observational Studies.

Legionnaires’ disease (LD) (Legionella) is a common cause of community-acquired pneumonia (CAP) in those requiring hospitalization. Geographical variation in the importance of Legionella species as an aetiologic agent of CAP is poorly understood. We performed a systematic review and meta-analysis of population-based observational studies that reported the proportion of Legionella infection in patients with CAP (1 January 1990 to 31 May 2020). Using five electronic databases, articles were identified, appraised and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of the included studies was assessed using the Newcastle–Ottawa Scale. Univariate and multivariate meta-regression analyses were conducted using study design, WHO region, study quality and healthcare setting as the explanatory variables. We reviewed 2778 studies, of which 219 were included in the meta-analysis. The mean incidence of CAP was 46.7/100,000 population (95% CI: 46.6–46.8). The mean proportion of Legionella as the causative agent for CAP was 4.6% (95% CI: 4.4 to 4.7). Consequently, the mean Legionella incidence rate was 2.8/100,000 population (95% CI: 2.7–2.9). There was significant heterogeneity across all studies I2 = 99.27% (p < 0.0001). After outliers were removed, there was a decrease in the heterogeneity (I2 = 43.53%). Legionella contribution to CAP has a global distribution. Although the rates appear highest in high income countries in temperate regions, there are insufficient studies from low- and middle-income countries to draw conclusions about the rates in these regions. Nevertheless, this study provides an estimate of the mean incidence of Legionella infection in CAP, which could be used to estimate the regional and global burden of LD to support efforts to reduce the impact of this infection as well as to fill important knowledge gaps.

Decreasing Pasteurization Treatment Efficiency against Amoeba-Grown Legionella pneumophila-Recognized Public Health Risk Factor.

Legionellae are gram-negative bacteria most commonly found in freshwater ecosystems and purpose-built water systems. In humans, the bacterium causes Legionnaires’ disease (LD) or a Pontiac fever. In this study, the different waters (drinking water, pool water, cooling towers) in which Legionella pneumophila has been isolated were studied to assess the possible risk of bacterial spreading in the population. The influence of physical and chemical parameters, and interactions with Acanthamoeba castellanii on L. pneumophila, were analyzed by Heterotrophic Plate Count, the Colony-forming units (CFU) methods, transmission electron microscopy (TEM), and Sequence-Based Typing (SBT) analysis. During the study period (2013–2019), a total of 1932 water samples were analyzed, with the average annual rate of Legionella-positive water samples of 8.9%, showing an increasing trend. The largest proportion of Legionella-positive samples was found in cooling towers and rehabilitation centers (33.9% and 33.3%, respectively). Among the isolates, L. pneumophila SGs 2–14 was the most commonly identified strain (76%). The survival of Legionella was enhanced in the samples with higher pH values, while higher electrical conductivity, nitrate, and free residual chlorine concentration significantly reduced the survival of Legionella. Our results show that growth in amoeba does not affect the allelic profile, phenotype, and morphology of the bacterium but environmental L. pneumophila becomes more resistant to pasteurization treatment.

Legionnaires disease: history of the discovery, the main stages of the study pathogen and infection

The article discusses main directions and stages of the 45 years of Legionnaires disease study. Analysis of epidemiology and laboratory diagnostics of infection show as unknown until 1976 microorganism occupied a notable niche in the etiology of severe pneumonia. Control and monitoring of potential dangerous water systems, generating water aerosol containing Legionella in high concentration, plays a major role in the prevention of Legionnaires disease.

TNF-α response in macrophages depends on clinical Legionella pneumophila isolates genotypes

ABSTRACT Legionnaires’ Disease (LD) is a severe pneumonia mainly caused in Europe by Legionella pneumophila serogroup 1 (Lp1). Sequence-based typing methods reveal that some sequence types (ST) are overrepresented in clinical samples such as ST1 and ST47, suggesting that some strains are more fit for infection than others. In the present study, a collection of 108 Lp1 clinical isolates were used to evaluate the strain-dependent immune responses from human macrophages. Clinical Lp1 isolates induced differential TNFα secretion from macrophages. ST1 isolates induced a significantly higher TNF-α secretion than non-ST1, whereas ST47 isolates induced a significantly lower TNF-α secretion than non-ST47 isolates. ST1 isolates induced a significantly higher cell death than ST47 isolates evaluated by lactate dehydrogenase activity (cytotoxicity) and caspase-3 activity (apoptosis). Treatment of macrophages with anti-TNF-α antibodies significantly reduced the cell death in macrophages infected with ST1 or ST47 strains. The TNF-α secretion was neither explained by a differential bacterial replication nor by the number or type (bystander or infected) of TNF-α producing cells following infection but by a differential response from macrophages. The Paris ST1 reference strain elicited a significantly higher TNF-α gene transcription and a higher induction of NF-κB signaling pathway than the Lorraine ST47 reference strain. Clinical Lp1 isolates induce a diverse immune response and cell death, which could be related to the genotype. The two predominant sequence-types ST1 and ST47 trigger opposite inflammatory response that could be related to the host susceptibility.

Knowledge to Predict Pathogens: Legionella pneumophila Lifecycle Systematic Review Part II Growth within and Egress from a Host Cell.

Legionella pneumophila (L. pneumophila) is a pathogenic bacterium of increasing concern, due to its ability to cause a severe pneumonia, Legionnaires’ Disease (LD), and the challenges in controlling the bacteria within premise plumbing systems. L. pneumophila can thrive within the biofilm of premise plumbing systems, utilizing protozoan hosts for protection from environmental stressors and to increase its growth rate, which increases the bacteria’s infectivity to human host cells. Typical disinfectant techniques have proven to be inadequate in controlling L. pneumophila in the premise plumbing system, exposing users to LD risks. As the bacteria have limited infectivity to human macrophages without replicating within a host protozoan cell, the replication within, and egress from, a protozoan host cell is an integral part of the bacteria’s lifecycle. While there is a great deal of information regarding how L. pneumophila interacts with protozoa, the ability to use this data in a model to attempt to predict a concentration of L. pneumophila in a water system is not known. This systematic review summarizes the information in the literature regarding L. pneumophila’s growth within and egress from the host cell, summarizes the genes which affect these processes, and calculates how oxidative stress can downregulate those genes.

Evaluation of Serotyping of Environmental and Clinical Isolates of Legionella pneumophila using MALDI-TOF MS.

Legionella pneumophila (L. pneumophila) is responsible for most Legionnaire's disease cases diagnosed worldwide. The species includes 16 serogroups, but most Legionnaire's disease cases (85.7% in Europe, 87.0% in Japan) are caused by L. pneumophila serogroup 1. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can be used to identify the L. pneumophila serogroup. In this study, we compared three sample preparation methods that are compatible with MALDI-TOF MS: the direct colony transfer method (DCTM), on-target extraction method (OTEM), and in-tube extraction method (ITEM). The aim was to improve the low identification rates for L. pneumophila, and establish and validate a simple, rapid and robust MALDI-TOF MS-based method for routine use in microbiological laboratories for assignment of L. pneumophila isolates to serogroups and identification of reliable peak biomarkers. Using ITEM, 100.0% (29/29) of hot spring water samples and clinical isolates were correctly identified at the species level. Augmented reference spectra correctly identified all 29 strains at the species level and 29 isolates at the serogroup level, displaying sensitivity, specificity and accuracy of 100.0% for serogroup assignment. MALDI-TOF MS is a relatively inexpensive method for assignment of L. pneumophila serogroups that can serve as a first-line tool for rapid prospective typing.

Impact of lockdown and non-pharmaceutical interventions on the epidemiology of Legionnaires' disease.

Background and aim.In order to cope with the requirements of COVID-19 pandemic and prevent overwhelming of the healthcare systems, during 2020 social distancing measures were proposed, and generalized lockdown. Aim of our study is to ascertain whether non-pharmaceutical intervention did have any impact on the epidemiology of Legionnaires’ disease (LD), a respiratory infectious disease without interhuman spreading.Methods.Official national reports from 4 index countries in European Union (i.e. Germany, France, Italy, and Spain) were retrieved. The study included all cases notified during 2020 COVID-19 outbreak, versus the cases referred during the same period in 2019. Subgroup analyses for hospital-associated and travel-associated LD cases, as well as for lethality estimates were performed.Results.A sustained drop for incidence rate was confirmed, at EU-level (3.5 per 100,000 vs. 5.3 per 100,000) as well as in the national estimates. The decrease was particularly evident in Italy (RR 0.880, 95%CI 0.839 to 0.905), despite a transient surge in notification rates during the month of June, 2020. Subgroup analyses demonstrated a fall in travel-associated cases (-66.8% at EU level), while hospital-associated cases decreased in absolute number when compared to 2019, but where substantially stable in terms when compared to EU estimates. While Case Fatality Ratio increased in comparison with 2019, no significant trend was similarly identified in comparison to EU estimates.Conclusions.Lockdown measures have impacted on the epidemiology of LD in Europe during 2020, but some heterogeneities were identified both across the assessed countries, and the various subgroup. Even though the absolute number of total cases did substantially decrease in 2020 compared to 2019, the effect of non-pharmaceutical interventions was mostly indirect, through a reduced interaction of individuals with environments at potentially high-risk for human infections (e.g. hospitals, accommodation sites, etc.). (www.actabiomedica.it)

Risk assessment and quantitative measurement along with monitoring of Legionella in hospital water sources

Legionella spp. as a causative agent of Legionnaires' disease (LD) and an opportunistic pathogen creates a public health problem. Isolation and quantification of this bacteria from clinic water sources are essential for hazard appraisal and sickness avoidance. This study aimed at risk assessment and quantitative measurement along with Legionella monitoring in educational hospital water sources in Tehran, Iran. A cross-sectional study was carried out in 1 year. The conventional culture method was used in this study to isolate Legionella from water samples. The polymerase chain reaction (PCR) technique was used to confirm the identity of the isolates and ensure that they were all Legionella. Quantitative PCR (qPCR) was used to determine the count of bacteria, and HeLa cell culture was used to determine the invasion of isolates. A total of 100 water samples were collected and inoculated on GVPC (glycine, vancomycin, polymyxin, and cycloheximide) agar; 12 (12%) and 42 (42%) cases were culture and PCR positive, respectively. Percentage of Legionella presence in PCR-positive samples by the qPCR method in <103 GU/L, in about 103 and lower than 104 GU/L, and in 104 GU/L was 40.47 (17 cases), 4.76% (two cases), and 54.76% (23 cases), respectively. Invasion analysis revealed that five and four isolates had invaded HeLa cells more than twice and equally, respectively, and the others had a lower invasion than the reference strain. The findings revealed that the spread of LD in hospitals was linked to the water system. Given the importance of nosocomial infections in the medical community, establishing a hospital water monitoring system is the most effective way to control these infections, particularly Legionella infections.

Clinical features of patients with Legionnaires disease showing initial clinical improvement but radiological deterioration: A retrospective single-center analysis.

Patients with Legionnaires disease occasionally experience initial clinical improvement but radiological progression. However, data on this issue are so far limited. The aim of this study was to investigate changes in chest radiograph findings in patients with Legionnaires disease who showed initial clinical improvement and to identify risk factors and outcomes in these patients.All patients diagnosed with Legionnaires disease at a tertiary hospital in South Korea between March 2011 and May 2020 were retrospectively enrolled. Legionnaires disease was defined as abnormal chest radiographs accompanied by a positive finding on at least one of the following tests: urinary antigen test, sputum Legionella polymerase chain reaction, and sputum Legionella culture. Clinical improvement was defined as defervescence and decreased C-reactive protein level. Clinical and radiological records were reviewed on treatment days 7 and 14 and at discharge. We describe the characteristics of patients with clinical improvement but radiological deterioration on treatment for Legionnaires disease and compared them with patients with initial clinical improvement and stable or resolving chest radiograph findings.Of 140 patients with Legionnaires disease, 33 (24%) showed initial clinical deterioration, while the remaining 107 (76%) showed initial clinical improvement on day 7. The latter 107 patients were analyzed in this study; 22 (21%) showed radiological progression despite the clinical improvement. Risk factors for these patients were a high pneumonia severity index score and the use of mechanical ventilation. Mortality did not significantly differ between those with initial clinical improvement but radiological deterioration and those with both initial clinical and radiological improvement (28% vs 12%, P = .49).About one-fifth of patients with Legionnaires disease, especially those who had a high pneumonia severity index score and underwent mechanical ventilation, showed radiological deterioration despite of clinical improvement 1 week after appropriate treatment, while outcomes were not significantly worse in these patients. Therefore, our findings support that close monitoring without modification of antibiotics use is warranted in those who have clinical improvement regardless of radiologic findings.

A Theory on the Impact of Copper and Micronutrients Against COVID-19 in Humans

Copper (Cu) has a strong impact on the function of the immune system through several different pathways. These impacts include helping the function of monocytes, neutrophils, and macrophages, and enhancing Natural Killer cells’ activities. Cu also has a role in antimicrobial properties and inflammatory response. It is also important for IL-2 production and response, which is a component of adaptive immune cells. Additionally, Cu has multiple roles in both proliferation and differentiation of T cells and is involved in the production of antibodies. Cu deficiency can even lead to "increased viral virulence"1. Copper has a long history of use in medicine, and has continued to be used for purification of water, including use in hospitals to prevent legionnaires disease. The CDC pre released information on a study completed in March 2020 on the lifespan of COVID-19 on different surfaces which included its lifespan on copper, where it was completely dead within 4 hours. In addition, "Several reports demonstrated that Cu deficiency weakens the human immune response" 2. Given the multiple avenues of impact, it has been suggested that Cu supplementation, within recommended levels, be given to individuals who are low in Cu to help them fight off COVID-19. It is also possible that Cu supplementation, within recommended levels, may help prevent COVID-19 infection, or help individuals who are not low in Cu to fight off COVID-19 infection. However, dosage would have to be carefully managed, as excess levels of Cu can lead to both neurodegenerative and neurodevelopmental diseases.

COVID-19 and Legionella Co-Infection

Introduction Concurrent infections or co-infections in patients diagnosed with Coronavirus Disease-19 (COVID-19) are not uncommon and predict a pejorative prognosis. A co-infection accounts for 1 out of every 5 cases of COVID-19 and increases the likelihood of adverse health outcomes such as mechanical ventilations, ICU admissions, and death. Specifically, Legionella spp. co-infection presents additional challenges in COVID-19 patients because of its rarity, similar clinical presentation to SARS-CoV-2, and poorer outcomes without prompt treatment. Cases Presentation Case 1. A 62-year-old female presented with a 3-day history of subjective fever and worsening shortness of breath. Room air saturation (saO2) was 70% and improved to 100 % on noninvasive positivepressure ventilation (NIPPV). Lung auscultation revealed rales BL. Chest X –Ray (CXR) showed patchy airspace opacities bilaterally (BL), SARS-CoV-2 PCR and urine legionella antigen tests were positive. The diagnosis of hypoxic respiratory failure secondary to COVID-19 and Legionella pneumonia was made. Patient was admitted to intensive care unit (ICU) and managed with decadron, remdesivir, one unit of convalescent plasma for COVID-19 and Azithromycin for Legionella. Patient subsequently developed acute respiratory distress syndrome (ARDS). ARDS protocol was initiated. 13 days after, the patient was compassionately extubated. Case 2. A 41-year-old male presented with 5-day history of fever, worsening shortness of breath, cough and diarrhea. Patient admitted history of ethanol abuse. SaO2 was 88% and improved on oxygen canula. Lung auscultation revealed rhonchi BL. CXR showed extensive left lung consolidation. Urine test for legionella antigen was positive. COVID-19 PCR was negative, but SARS-CoV-2 IgG was reactive. The diagnosis of Legionnaire disease was made. Despite initial treatment with Azithromycin, patient's hypoxia continued to worsen requiring NIPPV, and subsequently mechanical ventilation in the ICU. The adjunction of empiric treatment for COVID-19 with convalescent plasma, remdesivir and steroids improved both clinicals and laboratory findings. Discussion The cases illustrated the practical challenges of managing COVID-19 and legionella coinfection. Legionella spp and SARS-CoV-2 overlapping incubation periods and similar clinical presentations and complications. In the absence of diagnosis and treatment, legionella pneumonia has an intrinsic mortality rate of up to 80%. As some COVID-19 mitigation strategies, such as the closure of businesses, have enhanced the conditions for Legionella spp proliferation, the incidence of Co-infection with COVID-19 may increase. We recommend clinicians to have high-indexed suspicion of COVID-19 and Legionella co-infection in order to obtain complete work up at patient’s initial presentation.