Marseille scoring system for empiric treatment of infective endocarditis.

Despite advances in medical, surgical, and critical care, infective endocarditis (IE) remains associated with considerable morbidity and mortality. We evaluated the performance of the Marseille score, including clinical data and biological tests obtained within 2 h, to identify patients at high risk of IE in order to initiate early antimicrobial treatment. This was secondarily confirmed using modified ESC criteria combined with molecular testing and (18)fluorodeoxyglucose-positron emission tomography/computed tomography as diagnostic tools. In a prospective cohort study, we enrolled 484 patients with cardiovascular predisposition and clinical suspicion of IE from 2011 to 2013. The final diagnosis was definite IE in 123 patients and possible IE in 107. Marseille score was calculated adding one point for each present parameter (range 0-9). This score includes clinical, epidemiological (male, fever, splenomegaly, clubbing, vascular disease and stroke) and biological criteria (Leucocytes >10,000/mm3, sedimentation rate (SR) > 50/mm or C reactive protein >10 mg/L and hemoglobin <100 g/l). A score of 2 or more performed best in predicting IE in patients with predisposing heart lesions. Sensitivity was better on left-side heart lesions (94%) than on right-side heart lesions (85%) (p = 0.04) and better for valvulopathy (94%) than intra cardiac devices (84%) (p = 0.02). The predictive positive value of prosthetic valves was greater than that of native valves (p = 0.02). Using our simple Marseille score combined with our standardized diagnostic procedures would help improve IE management by focusing on early empiric treatment within 2 h of admission for patients with cardiac predisposition factors.

Evaluation of empirical treatment for blood culture-negative endocarditis.

OBJECTIVES: Much progress has been made in understanding the main causes of blood culture-negative endocarditis (BCNE). Few studies concerning BCNE treatment (due to previous antibiotics used or fastidious pathogens) are available. We performed this study to evaluate the effectiveness of our therapeutic protocol in BCNE, based on compliance with the protocol, outcome and 1 year mortality. PATIENTS AND METHODS: We collected prospectively and analysed retrospectively cases of BCNE between 2002 and 2014, using a simplified and standardized protocol developed by our multidisciplinary team. We apply two kinds of protocols to treat BCNE, which include only four intravenous antimicrobial agents: amoxicillin, vancomycin, gentamicin and amphotericin B. RESULTS: We had 177 patients with definite BCNE. There were 154 (87.0%) patients treated with both appropriate antimicrobial agents and appropriate duration of treatment. We analysed the causes of inappropriate treatment in 13 (7.3%) cases and inappropriate duration in 10 (5.6%) cases. The treatment changes were justified in all cases except one of discharge against medical advice. The fatality rate was 5.1% (nine cases) and all deaths occurred in the group of patients who were treated with appropriate treatment; however, four deaths were not attributable to empirical treatment failure. Concerning the other deaths, the lack of surgical management, in association with empirical treatment, could explain our protocol's failure, such as poorly tolerated surgery. CONCLUSIONS: Our protocol is efficient and our mortality rate was low, compared with the literature review. This may result from a strategy that uses a sampling procedure and a standardized protocol at the same time.

Low antibodies titer and serological cross-reaction between Coxiella burnetii and Legionella pneumophila challenge the diagnosis of mediastinitis, an emerging Q fever clinical entity.

BACKGROUND: Coxiella burnetii is an intracellular and fastidious bacterium responsible of acute and persistent Q fever infection. Endocarditis and vascular infections are the most common serious complications of acute Q fever. CASE REPORT: We report the case of a 63-year-old man that presented a mediastinitis associated with a prosthetic vascular infection. Serological cross-reaction was observed between Coxiella burnetii, the agent of Q fever, and Legionella pneumophila with higher antibodies titer for L. pneumophila (IgG = 1:512) than for C. burnetii (phase I IgG = 1:400). We performed western blot with cross-adsorption that supports the diagnosis of C. burnetii infection. Two weeks later, a positive qPCR and culture for C. burnetii on swab taken from the mediastinal cutaneous fistula confirmed the definitive microbiological diagnosis of Q fever mediastinitis. CONCLUSION: Cross-reactivity between C. burnetii and Legionella spp. has long been known and should be considered in patients with persistent infections. It is important to establish the definite diagnosis because the antibiotic treatment regimens and duration are significantly different. To the best of our knowledge, we reported here the first case of mediastinitis associated to C. burnetii and we diagnosed this persistent infection despite low anti-C. burnetii phase I IgG levels.

Fatal Neisseria macacae infective endocarditis: first report.

INTRODUCTION: Neisseria macacae is a Gram-negative diplococcus, found in the oropharynx of healthy Rhesus Monkeys. Infections caused by N. macacae in humans are extremely rare. CASE PRESENTATION: We present here the first case of N. macacae infective endocarditis in a 65-year-old man with a native aortic valve infection complicated by a peri-aortic abscess. N. macacae was isolated from blood culture and was found on the cardiac valve using 16S rDNA detection. Despite an appropriate antibiotic therapy, and aortic homograft replacement, and mitral repair, the patient died 4 days after surgery from a massive hemorrhagic stroke.

Impact of the SARS-CoV-2 Pandemic on the Management and Prognosis of Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) is a serious condition which is difficult to diagnose and to treat, both medically and surgically. OBJECTIVES: The objective of this study was to evaluate the impact of the SARS-CoV-2 pandemic on the management of patients with IE. METHODS: We conducted a single-centre retrospective study including patients hospitalized for IE during the pandemic (Group 2) compared with the same period the year before (Group 1). We compared clinical, laboratory, imagery, therapeutic, and patient outcomes between the two groups. RESULTS: A total of 283 patients were managed for possible or definite IE (164 in Group 1 and 119 in Group 2). There were more intravenous drug-related IE patients in Group 2 (p = 0.009). There was no significant difference in surgery including intra-cardiac device extraction (p = 0.412) or time to surgery (p = 0.894). The one-year mortality was similar in both groups (16% versus 17.7%, p = 0.704). The recurrence rate was not significantly different between the two groups (5.9% in Group 2 versus 9.1% in Group 1, p = 0.311). CONCLUSIONS: The SARS-CoV-2 pandemic did not appear to have had a negative impact on the management of patients with IE. Maintenance of the activities of the endocarditis team within the referral centre probably contributed to this result. Nevertheless, the high proportion of intravenous drug-addicted patients in the pandemic cohort suggests that the SARS-CoV-2 pandemic had a major psychosocial impact.

Atrioventricular conduction disorders in aortic valve infective endocarditis.

BACKGROUND: Aortic valve infective endocarditis may be complicated by high-degree atrioventricular block in up to 10-20% of cases. AIM: To assess high-degree atrioventricular block occurrence, contributing factors, prognosis and evolution in patients referred for aortic infective endocarditis. METHODS: Two hundred and five patients referred for aortic valve infective endocarditis between January 2018 and March 2021 were included in this study. A comprehensive assessment of clinical, electrocardiographic, biological, microbiological and imaging data was conducted, with a follow-up carried out over 1 year. RESULTS: High-degree atrioventricular block occurred in 22 (11%) patients. In univariate analysis, high-degree atrioventricular block was associated with first-degree heart block at admission (odds ratio 3.1; P=0.015), periannular complication on echocardiography (odds ratio 6.9; P<0.001) and severe biological inflammatory syndrome, notably C-reactive protein (127 vs 90mg/L; P=0.011). In-hospital mortality (12.7%) was higher in patients with high-degree atrioventricular block (odds ratio 4.0; P=0.011) in univariate analysis. Of the 16 patients implanted with a permanent pacemaker for high-degree atrioventricular block and interrogated, only four (25%) were dependent on the pacing function at 1-year follow-up. CONCLUSIONS: High-degree atrioventricular block is associated with high inflammation markers and periannular complications, especially if first-degree heart block is identified at admission. High-degree atrioventricular block is a marker of infectious severity, and tends to raise the in-hospital mortality rate. Systematic assessment of patients admitted for infective endocarditis suspicion, considering these contributing factors, could indicate intensive care unit monitoring or even temporary pacemaker implantation in those at highest risk.

Immunoglobulin G anticardiolipin antibodies and progression to Q fever endocarditis.

BACKGROUND: Immunoglobulin G (IgG) anticardiolipin (aCL) antibodies are associated with valvulopathy and endocarditis in patients with lupus and other diseases. During acute Q fever, high IgG aCL prevalence has been reported, but the clinical significance remains unknown. METHODS: To test if increased IgG aCL at acute Q fever diagnosis is associated with an increased risk of progression to endocarditis, all patients diagnosed in the French National Referral Center for Q fever from January 2007 to December 2011 were included and followed regularly until January 2013 in a 5-year prospective cohort study. Q fever endocarditis was defined according to recently updated criteria. RESULTS: Seventy-two patients were followed for a median time of 31 months (interquartile range, 18-47 months). Of these, 13 patients with valvulopathy without antibiotic prophylaxis progressed to endocarditis. IgG aCL levels were highly prevalent (57%) and significantly higher in the presence of a valvulopathy (P = .005). Using Cox regression analysis, highly increased levels of IgG aCL (adjusted hazard ratio [AHR], 12.95; 95% confidence interval, 2.85-58.95; P = .001) and high levels of phase II immunoglobulin M (IgM; AHR, 6.59; 95% CI, 1.37-31.62; P = .018) were the only independent predictors of progression to endocarditis. CONCLUSIONS: Rapid progression from acute Q fever to endocarditis is associated with high levels of IgG aCL and high levels of phase II IgM, findings that should be critical in the prevention of endocarditis.

Diagnostic yield of FDG positron-emission tomography/computed tomography in patients with CEID infection: a pilot study.

AIMS: Whole body imaging with (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) has proven useful in various infectious diseases. The purpose of this pilot study was to assess the diagnostic yield of FDG PET/CT in patients with cardiac implantable electronic device (CIED) infection. METHODS AND RESULTS: A total of 21 patients with CIED infection were prospectively included. Diagnosis of CIED infection was made in accordance with current criteria. It was classified in three categories, i.e. superficial skin infection, pocket site infection, or cardiac device-related infective endocarditis (CDRIE). All patients underwent FDG PET/CT. Scans were interpreted blindly, i.e. without prior knowledge of diagnosis, by experienced nuclear medicine physicians. The accuracy of FDG PET/CT was assessed for each diagnostic category. Findings demonstrated superficial skin infection in 1 patient, pocket site infection in 15, and CDRIE in 13 (definite: 7; possible: 6). In patients with pocket site infection, the sensitivity and specificity of FDG PET/CT were 86.7% [59.5-98.3, 95% confidence interval (CI)] and 100% [42.1-100, 95% CI]. The only patient with superficial skin infection was accurately identified by FDG PET/CT. The sensitivity and specificity of FDG PET/CT in patients with CDRIE were 30.8% [9.1-61.4, 95% CI] and 62.5% [24.5-91.5, 95% CI]. Most false-negative results occurred in patients who had undergone previous antimicrobial treatment. CONCLUSION: This study indicates that FDG PET/CT is highly accurate for the diagnosis of skin and pocket CIED infection but low for infective endocarditis. This suggests that the reliability of FDG PET/CT findings in management decision making varies according to the type of CIED infection.

Infectious endocarditis detected by PET/CT in a patient with a prosthetic knee infection: case report and review of the literature.

We report a case illustrating the potential use of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET/CT) for the diagnosis of infective endocarditis (IE) in an 84-y-old woman who had a history of chronic left knee osteitis and a mitral cardiac valve bioprosthesis replacement and a pacemaker. She developed a polymicrobial knee infection 15 days after her total knee replacement. Transoesophageal echocardiography showed a new mitral regurgitation, but no vegetation or abscess. PET/CT showed hypermetabolic hyperactivity around the mitral cardiac valve prosthesis and the intracardiac pacemaker leads. We found 17 case reports and 2 case series of IE in which PET/CT showed encouraging results for the detection of IE. PET/CT may be used in patients with a suspicion of IE who do not have echocardiographic evidence of IE. It may also be useful for identifying the portal of entry of an infection and for identifying secondary foci (mycotic aneurysm).

Multimodality imaging in marantic endocarditis associated with cancer: a multicentric cohort study.

AIMS: We aimed to assess the role of multimodality imaging (MMI) in the diagnosis of marantic endocarditis (ME) associated with cancers and to describe the clinical characteristics, management, and outcome of these patients. METHODS AND RESULTS: In a retrospective multicentric study including four tertiary centres for the treatment of endocarditis in France and Belgium, patients with a diagnosis of ME were included. Demographic, MMI [echocardiography, computed tomography (CT), and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)], and management data were collected. Long-term mortality was analysed. Between November 2011 and August 2021, 47 patients with a diagnosis of ME were included. Mean age was 65 ± 11 years. ME occurred in 43 cases (91%) on native valves. Vegetations were detected by echocardiography in all cases and in 12 cases (26%) by CT. No patient had an increased cardiac 18F-FDG valve uptake. The most common cardiac valve involved was aortic (34 cases, 73%). Twenty-two patients (46%) had a known cancer before ME, and 25 cases (54%) were diagnosed thanks to multimodality imaging. 18FDG PET/CT was performed in 30 patients (64%) and allowed a new diagnosis of cancer in 14 patients (30%). Systemic embolism was frequent (40 patients, 85% of cases). Forty-one patients (87%) were treated medically with anticoagulation therapy. One-year mortality was 55% (26 patients). CONCLUSION: ME remains associated with a high risk of complications and death.

Clinical and Echocardiographic Features of Patients With Infective Endocarditis and Bicuspid Aortic Valve According to Echocardiographic Definition of Valve Morphology.

BACKGROUND: The influence of different bicuspid aortic valve (BAV) morphology in the clinical course of infective endocarditis (IE) has not yet been investigated. This study aimed to describe the clinical and echocardiographic features of IE in patients with BAV (BAVIE) according to valve morphology. METHODS: Patients with definite BAVIE prospectively enrolled in 4 high-volume referral centers from 2000 to 2019 were evaluated and divided into 2 groups according to the echocardiographic definition of fused BAV morphology: right-left coronary (RL type) and right noncoronary or left noncoronary (non-RL type) cusp fusion. All patients were followed up for 1 year. RESULTS: One hundred thirty-eight patients with BAVIE were included (77.7% male; median age, 52 [36.83-61.00] years): 112 patients with RL type (81%) and 26 patients with non-RL type BAV (19%), with no significant differences in age, sex, and comorbidities between groups. Although 43% of the cohort had known BAV, the referral was late after symptom onset, particularly for the RL phenotype; time from symptom onset to hospitalization >30 days (31.3% vs 11.5%; P = .032) and New York Heart Association class ≥ II (64.3% vs 42.3%; P = .039) were more frequent in patients with RL type BAV than in patients with non-RL type BAV. Conversely, patients with non-RL type BAV had a higher incidence of hemorrhagic stroke (19.2% vs 5.4%; P = .034) and high-grade atrioventricular block (11.5% vs 0.9%; P = .021). Streptococcus viridans was more frequently isolated in patients with non-RL type BAV than in patients with RL type BAV (44% vs 24.1%; P = .045). No difference in short- and intermediate-term mortality was observed between groups. CONCLUSIONS: Clinical profile and echocardiographic features in BAVIE patients may differ according to valve morphology, and patients with BAVIE appear to be referred late, even when BAV disease is previously known.

Legionella longbeachae and endocarditis.

We report a case of infectious endocarditis attributable to Legionella longbeachae. L. longbeachae is usually associated with lung infections. It is commonly found in composted waste wood products. L. longbeachae should be regarded as an agent of infectious endocarditis, notably in the context of gardening involving handling of potting soils.

Excess mortality and morbidity in patients surviving infective endocarditis.

BACKGROUND: Mortality and morbidity associated with infective endocarditis may extend beyond successful treatment. The primary objective was to analyze rates, temporal changes, and predictors of excess mortality in patients surviving the acute phase of endocarditis. The secondary objective was to determine the rate of recurrence and the need for late cardiac surgery. METHODS: An observational cohort study was conducted at a university-affiliated tertiary medical center, among 328 patients who survived the active phase of endocarditis. We used age-, sex-, and calendar year-specific mortality hazard rates of the Bouches-du-Rhone French district population to calculate expected survival and excess mortality. The risk of recurrence and late valve surgery was also assessed. RESULT: Compared with expected survival, patients surviving a first episode of endocarditis had significantly worse outcomes (P = .001). The relative survival rates at 1, 3, and 5 years were 92% (95% CI, 88%-95%), 86% (95% CI, 77%-92%), and 82% (95% CI, 59%-91%), respectively. This excess mortality was observed during the entire follow-up period but was the highest during the first year after hospital discharge. Most of the recurrences and late cardiac surgeries also occurred during this period. Women exhibited a higher risk of age-adjusted excess mortality (adjusted excess hazard ratio, 2.0; 95% CI, 1.05-3.82; P = .03). Comorbidity index, recurrence of endocarditis, and history of an aortic valve endocarditis in women were independent predictors of excess mortality. CONCLUSIONS: These results justify close monitoring of patients after successful treatment of endocarditis, at least during the first year. Special attention should be paid to women with aortic valve damage.

The timing of surgery influences mortality and morbidity in adults with severe complicated infective endocarditis: a propensity analysis.

AIMS: To determine whether the timing of surgery could influence mortality and morbidity in adults with complicated infective endocarditis (IE). METHODS AND RESULTS: In 291 consecutive adults with definite IE who underwent surgery during the active phase, we compared those operated on within the first week of antimicrobial therapy (n=95) to those operated on later (n=191). The impact of the timing of surgery on 6-month mortality, relapses, and postoperative valvular dysfunctions (PVD) was analysed using propensity score (PS) analyses. After stratification of the cohort into quintiles based on the PS, ≤1st week surgery was associated with a trend of decrease in 6-month mortality in the quintile of patients with the most likelihood of undergoing this early surgical management [quintile 5: 11% vs. 33%, odds ratio (OR)=0.18, 95% CI (confidence interval) 0.04-0.83, P=0.03]. Patients of this subgroup were younger, were more likely to have Staphylococcus aureus infections, congestive heart failure, and larger vegetations. Besides, ≤1st week surgery was associated with an increased number of relapses or PVD (16% vs. 4%, adjusted OR=2.9, 95% CI 0.99-8.40, P=0.05). CONCLUSION: Surgery performed very early may improve survival in patients with the most severe complicated IE. However, a greater risk of relapses and PVD should be expected when surgery is performed very early.

Control of common viral epidemics but not of SARS-CoV-2 through the application of hygiene and distancing measures.

BACKGROUND: We systematically survey respiratory and gastrointestinal infections of viral origin in samples sent to our university hospital institute in Marseille, southern France. Here, we evaluated whether the measures implemented to fight COVID-19 had an effect on the dynamics of viral respiratory or gastrointestinal infections. METHODS: We analysed PCR performed and positive for the diagnoses of viral respiratory and gastrointestinal infections over five years (January 2017-February 2021). Data were collected from our epidemiological surveillance system (MIDaS). Dates and contents of French measures against SARS-CoV-2 were collected from: https://www.gouvernement.fr/info-coronavirus/les-actions-du-gouvernement. RESULTS: Over the 2017-2021 period, 990,364 analyses were carried out for respiratory infections not including SARS-CoV-2, 510,671 for SARS-CoV-2 and 27,719 for gastrointestinal infections. During winter 2020-2021, when the most restrictive lockdown measures were in place in France, a marked decrease of infections with influenza viruses (one case versus 1,839-1,850 cases during 2017-2020 cold seasons) and with the RSV (56 cases versus 988-1,196 cases during 2017-2020 cold seasons) was observed, demonstrating the relative effectiveness of these measures on their occurrence. SARS-CoV-2 incidence seemed far less affected. Rhinoviruses, parainfluenza 3 virus, and the coronavirus NL63 remained at comparable levels. Also, the norovirus winter season positivity rates decreased continuously and significantly over time from 9.3% in 2017-2018 to 2.0% in 2020-2021. CONCLUSION: The measures taken to control COVID-19 were effective against lower respiratory tract infections viruses and gastroenteritis agents, but not on the agents of the common winter cold and SARS-CoV-2. This suggests that more specific measures to prevent COVID-19 and upper respiratory tract infections need to be discovered to limit the spread of this epidemic.

A Massive Number of Extracellular Tropheryma whipplei in Infective Endocarditis: A Case Report and Literature Review.

Whipple's disease (WD) is a chronic multisystemic infection caused by Tropheryma whipplei. If this bacterium presents an intracellular localization, associated with rare diseases and without pathognomonic signs, it is often subject to a misunderstanding of its physiopathology, often a misdiagnosis or simply an oversight. Here, we report the case of a patient treated for presumed rheumatoid arthritis. Recently, this patient presented to the hospital with infectious endocarditis. After surgery and histological analysis, we discovered the presence of T. whipplei. Electron microscopy allowed us to discover an atypical bacterial organization with a very large number of bacteria present in the extracellular medium in vegetation and valvular tissue. This atypical presentation we report here might be explained by the anti-inflammatory treatment administrated for our patient's initial diagnosis of rheumatoid arthritis.

Influence of the healthcare pathway on the outcome of patients with infective endocarditis.

AIMS: To determine the prognosis of patients treated for infective endocarditis (IE) according to their healthcare pathway. To assess how the ESC guidelines are implemented concerning the performance of transoesophageal echocardiography, the use of antibiotic therapy, and the performance of valve surgery; and to compare the epidemiological profile of IE according to the type of centres in which the patients are hospitalized. METHODS AND RESULTS: In a prospective multicentric study including 22 hospitals in the South-East of France, 342 patients were classified into three groups according to their healthcare pathway: 119 patients diagnosed and taken care entirely in a reference centre or hospital with cardiac surgery [Referral Center (RC) group], 111 patients diagnosed and initially taken care in a non-RC (NRC), then referred in a centre including cardiac surgery [transferred to the Referral Center (TRC) group] and 112 patients totally taken care in the NRC (NRC group). One-year mortality was 26% (88 deaths) and was not significantly different between Groups 1 and 2 (20 vs. 21%, P = 0.83). Patients in the NRC group had a higher mortality (37%) compared with patients in the RC and TRC groups (P < 0.001). ESC guidelines were not implemented similarly depending on the healthcare pathway (P = 0.04). Patients in the NRC group were significantly older (P < 0.001) and had more comorbidities (P < 0.001) than patients treated in referral centres. CONCLUSION: Prognosis of patients with IE is influenced by their healthcare pathway. Patients treated exclusively in NRC have a worse prognosis than patients treated in referral or surgical centres.

Mitral valve repair is better than mitral valve replacement in native mitral valve endocarditis: Results from a prospective matched cohort.

BACKGROUND: In native mitral valve infective endocarditis (NMIE), the respective values of mitral valve repair (MVRep) and replacement (MVR) are still debated. AIM: To compare MVRep and MVR in a large prospective matched cohort. METHODS: Between 2010 and 2017, all consecutive patients operated on for NMIE in our centre were included prospectively. Clinical and outcome features were compared between the two groups. Primary endpoint was event-free survival, including death, reoperation and relapse. Univariate and multivariable survival analyses and a propensity score analysis were performed. RESULTS: Among 152 patients, 115 (75.7%) underwent MVRep, and 37 (24.3%) MVR. Median follow-up was 28±22months. Surgery was performed during the active phase in 75.0% of patients (25.7% on an urgent basis). Compared with the MVRep group, patients in the MVR group were more frequently intravenous drug abusers (10.8% vs. 0.9%; P=0.016), had a more frequent history of rheumatic fever (13.5% vs. 0%; P=0.001), more aortic abscesses (16.7% vs. 3.5%; P=0.018), larger vegetations (16.6±8.1mm vs. 12.6±9.9mm; P=0.042) and poorer New York Heart Association status (P=0.006). Overall mortality was lower in the MVRep group than in MVR group (11.3% vs. 29.3%; P=0.018). Event-free survival was better in the MVRep group than in the MVR group in univariate analysis (hazard ratio: 2.72, 95% confidence interval: 1.34-5.52; P=0.004). Survival analysis in the propensity-matched cohort showed that MVRep was safer than MVR (log rank test: P=0.018). Multivariable analysis using the Cox proportional hazard model confirmed this finding (hazard ratio: 3.48, 95% confidence interval: 1.15-10.61; P=0.03). CONCLUSIONS: MVRep is feasible in most cases of NMIE and, when technically possible, should be preferred, even in urgent surgery.

Low blood zinc concentrations in patients with poor clinical outcome during SARS-CoV-2 infection: is there a need to supplement with zinc COVID-19 patients?

Among 275 patients with COVID-19, we found that median blood zinc level was significantly lower in patients with poor clinical outcome (N = 75) as compared to patients with good clinical outcome (N = 200) (840 µg/L versus 970 µg/L; p < 0.0001), suggesting that zinc supplementation could be useful for patients with severe COVID-19.