Symptomatic MERS-CoV infection reduces the risk of future COVID-19 disease; a retrospective cohort study.

BACKGROUND: The general human immune responses similarity against different coronaviruses may reflect some degree of cross-immunity, whereby exposure to one coronavirus may confer partial immunity to another. The aim was to determine whether previous MERS-CoV infection was associated with a lower risk of subsequent COVID-19 disease and its related outcomes. METHODS: We conducted a retrospective cohort study among all patients screened for MERS-CoV at a tertiary care hospital in Saudi Arabia between 2012 and early 2020. Both MERS-CoV positive and negative patients were followed up from early 2020 to September 2021 for developing COVID-19 infection confirmed by RT-PCR testing. RESULTS: A total of 397 participants followed for an average 15 months during COVID-19 pandemic (4.9 years from MERS-CoV infection). Of the 397 participants, 93 (23.4%) were positive for MERS-CoV at baseline; 61 (65.6%) of the positive cases were symptomatic. Out of 397, 48 (12.1%) participants developed COVID-19 by the end of the follow-up period. Cox regression analysis adjusted for age, gender, and major comorbidity showed a marginally significant lower risk of COVID-19 disease (hazard ratio = 0.533, p = 0.085) and hospital admission (hazard ratio = 0.411, p = 0.061) in patients with positive MERS-CoV. Additionally, the risk of COVID-19 disease was further reduced and became significant in patients with symptomatic MERS-CoV infection (hazard ratio = 0.324, p = 0.034) and hospital admission (hazard ratio = 0.317, p = 0.042). CONCLUSIONS: The current findings may indicate a partial cross-immunity, where patients with symptomatic MERS-CoV have a lower risk of future COVID-19 infection and related hospitalization. The present results may need further examination nationally using immunity markers.

Serial cross-sectional estimation of vaccine and infection-induced SARS-CoV-2 sero-prevalence in children and adults, British Columbia, Canada: March 2020 to August 2022

BackgroundWe chronicle SARS-CoV-2 sero-prevalence through eight cross-sectional sero-surveys (snapshots) in the Lower Mainland (Greater Vancouver and Fraser Valley), British Columbia, Canada from March 2020 to August 2022. MethodsAnonymized-residual sera were obtained from children and adults attending an outpatient laboratory network. Sera were tested with at least three immuno-assays per snapshot to detect spike (S1) and/or nucleocapsid protein (NP) antibodies. Sero-prevalence was defined by dual-assay positivity, including any or infection-induced, the latter requiring S1+NP antibody detection from January 2021 owing to vaccine availability. Infection-induced estimates were used to assess the extent to which surveillance case reports under-estimated infections. ResultsSero-prevalence was [≤]1% by the 3rd snapshot in September 2020 and <5% by January 2021 (4th). Following vaccine roll-out, sero-prevalence increased to >55% by May/June 2021 (5th), [~]80% by September/October 2021 (6th), and >95% by March 2022 (7th). In all age groups, infection-induced sero-prevalence remained <15% through September/October 2021, increasing through subsequent Omicron waves to [~]40% by March 2022 (7th) and [~]60% by July/August 2022 (8th). By August 2022, at least 70-80% of children [≤]19 years, 60-70% of adults 20-59 years, but [~]40% of adults [≥]60 years had been infected. Surveillance case reports under-estimated infections by 12-fold between the 6th-7th and 92-fold between the 7th-8th snapshots. InterpretationBy August 2022, most children and adults had acquired SARS-CoV-2 vaccine and infection exposures, resulting in more robust hybrid immunity. Conversely the elderly, still at greatest risk of severe outcomes, remain largely-dependent on vaccine-induced protection alone, and should be prioritized for additional doses.

Risk of COVID-19 in healthcare workers working in intensive care setting.

BACKGROUND: The higher risk of COVID-19 in health care workers (HCWs) is well-known. However, the risk within HCWs is not fully understood. The objective was to compare the COVID-19 risk in intensive care unit (ICU) vs non-ICU locations. METHODS: A prospective surveillance study was conducted among HCWs at a large tertiary care facility in Riyadh between March 1st to November 30th, 2020. HCWs included both clinical (provide direct patient care) and nonclinical positions (do not provide direct patient care). RESULTS: A total 1,594 HCWs with COVID-19 were included; 103 (6.5%) working in ICU and 1,491 (93.5%) working in non-ICU locations. Compared with non-ICU locations, ICU had more nurses (54.4% vs 22.1%, P < .001) and less support staff (2.9% vs 53.1%, P < .001). COVID-19 infection was similar in ICU and non-ICU locations (9.0% vs 9.8%, P = .374). However, it was significantly higher in ICU nurses (12.3% vs 6.5%, P < .001). Support staff had higher risk than other HCWs, irrespective of ICU working status (15.1% vs 7.2%, P < 0.001). The crude relative risk of COVID-19 in ICU vs non-ICU locations was 0.92, 95% confidence interval ( was 0.76-1.11 (P = .374). However, relative risk adjusted for professional category was significantly increased to 1.23, 95% confidence interval 1.01-1.50 (P = .036). CONCLUSIONS: ICU had a significantly higher risk of COVID-19 infection only after adjusting for the distribution and risk of different professional categories. The latter is probably determined by both exposure level and protection practices. The finding underscores the importance of strict implementation of preventive measures among all HCWs, including those performing nonclinical services.

Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada

BackgroundThe Canadian COVID-19 immunization strategy deferred second doses and allowed mixed schedules. We compared two-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in two of Canadas larger provinces. MethodsTwo-dose VE against infections and hospitalizations due to SARS-CoV-2, including variants of concern, was assessed between May 30 and October 2, 2021 using test-negative designs separately conducted among community-dwelling adults [≥]18-years-old in British Columbia (BC) and Quebec, Canada. FindingsIn both provinces, two doses of homologous or heterologous SARS-CoV-2 vaccines were associated with [~]95% reduction in the risk of hospitalization. VE exceeded 90% against SARS-CoV-2 infection when at least one dose was an mRNA vaccine, but was lower at [~]70% when both doses were ChAdOx1. Estimates were similar by age group (including adults [≥]70-years-old) and for Delta-variant outcomes. VE was significantly higher against both infection and hospitalization with longer 7-8-week vs. manufacturer-specified 3-4-week interval between doses. Two-dose mRNA VE was maintained against hospitalization for the 5-7-month monitoring period and while showing some decline against infection, remained [≥]80%. InterpretationTwo doses of mRNA and/or ChAdOx1 vaccines gave excellent protection against hospitalization, with no sign of decline by 5-7 months post-vaccination. A 7-8-week interval between doses improved VE and may be optimal in most circumstances. Findings indicate prolonged two-dose protection and support the use of mixed schedules and longer intervals between doses, with global health, equity and access implications in the context of recent third-dose proposals.

Comparative single-dose mRNA and ChAdOx1 vaccine effectiveness against SARS-CoV-2, including early variants of concern: a test-negative design, British Columbia, Canada

IntroductionIn randomized controlled trials, single-dose efficacy against SARS-CoV-2 illness exceeded 90% for mRNA vaccines (BNT162b2 and mRNA-1273), and 75% for ChAdOx1. In British Columbia (BC), Canada second doses were deferred up to 16 weeks and ChAdOx1 was only initially recommended for adults 55 years of age and older. We compared single-dose vaccine effectiveness (VE) during the spring 2021 wave in BC when Alpha and Gamma variants of concern (VOC) predominated. MethodsVE was estimated against infection and hospitalization by test-negative design: cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Adults 50-69 years old with specimen collection between April 4 and May 22 (weeks 14-20) were included. Variant-specific VE was estimated between weeks 17-20 when genetic characterization of all case viruses was performed, primarily through whole genome sequencing. ResultsVE analyses included 7,116 (10%) cases and 60,958 controls. Three-quarters of vaccinated participants received mRNA vaccine (60% BNT162b2, 15% mRNA-1273) and 25% received ChAdOx1. Half of genetically characterized viruses were Alpha, with 38% Gamma, 4% Delta and 8% non-VOCs. Single-dose VE against any infection was 75% (95%CI: 72-78) for BNT162b2, 82% (95%CI: 76-87) for mRNA-1273 and 61% (95%CI: 54-66) for ChAdOx1. VE against hospitalization was 83% (95%CI: 76-89), 85% (95%CI: 63-94) and 96% (95%CI: 86-99), respectively. VE against Alpha vs. Gamma infections did not differ among mRNA (78%;95%CI: 73-82 and 80%;95%CI: 74-85) or ChAdOx1 (66%;95%CI: 57-74 and 60%;95%CI: 48-69) recipients. ConclusionsA single dose of mRNA vaccine reduced the SARS-CoV-2 infection risk by at least 75%, including infections due to early VOC. Although effectiveness of a single dose of ChAdOx1 was lower at 60% against infection, just one dose of any vaccine reduced the hospitalization risk by more than 80%. In the context of constrained vaccine supplies, these findings have implications for global vaccine deployment to reduce the overall burden of infections and hospitalizations due to SARS-CoV-2.

Single-dose mRNA vaccine effectiveness against SARS-CoV-2, including P.1 and B.1.1.7 variants: a test-negative design in adults 70 years and older in British Columbia, Canada

IntroductionRandomized-controlled trials of mRNA vaccine protection against SARS-CoV-2 included relatively few elderly participants. We assess singe-dose mRNA vaccine effectiveness (VE) in adults [≥]70-years-old in British Columbia (BC), Canada where the second dose was deferred by up to 16 weeks and where a spring 2021 wave uniquely included co-dominant circulation of B.1.1.7 and P.1 variants of concern (VOC). MethodsAnalyses included community-dwelling adults [≥]70-years-old with specimen collection between April 4 (epidemiological week 14) and May 1 (week 17). Adjusted VE was estimated by test-negative design through provincial laboratory and immunization data linkage. Cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Vaccine status was defined by receipt of a single-dose [≥]21 days before specimen collection, but a range of intervals was assessed. In variant-specific analyses, test-positive cases were restricted to those genetically-characterized as B.1.1.7, P.1 or non-VOC. ResultsVE analyses included 16,993 specimens: 1,226 (7.2%) test-positive cases and 15,767 test-negative controls. Of 1,131 (92%) viruses genetically categorized, 509 (45%), 314 (28%) and 276 (24%) were B.1.1.7, P.1 and non-VOC lineages, respectively. VE was negligible at 14% (95% CI 0-26) during the period 0-13 days post-vaccination but increased from 43% (95% CI 30-53) at 14-20 days to 75% (95% CI 63-83) at 35-41 days post-vaccination. VE at [≥]21 days was 65% (95% CI 58-71) overall: 72% (95% CI 58-81), 67% (95% CI 57-75) and 61% (95% CI 45-72) for non-VOC, B.1.1.7 and P.1, respectively. ConclusionsA single dose of mRNA vaccine reduced the risk of SARS-CoV-2 in adults [≥]70-years-old by about two-thirds, with protection only minimally reduced against B.1.1.7 and P.1 variants. Substantial single-dose protection in older adults reinforces the option to defer the second dose when vaccine supply is scarce and broader first-dose coverage is needed.

High Burden of Resistant Gram Negative Pathogens Causing Device-associated Healthcare Infections in a Tertiary Care Setting in Saudi Arabia, 2008-2016.

OBJECTIVES: There is local and regional deficiency in the data examining the contribution of resistant pathogens to device-associated healthcare-associated infections (DA-HAIs). The objective was to examine such data in a multi-hospital system in Saudi Arabia in comparison with the US National Health Surveillance Network (NHSN). METHODS: Surveillance of DA-HAIs was prospectively conducted between 2008 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Consecutive NHSN reports were used for comparisons. Definitions and methodology of DA-HAIs and bacterial resistance were based on NHSN. RESULTS: A total 1260 pathogens causing 1141 DA-HAI events were included. Gram negative pathogens (GNPs) were responsible for 62.5% of DA-HAIs, with a significantly higher Klebsiella, Pseudomonas, Acinetobacter, and Enterobacter than NHSN hospitals. Approximately 28.3% of GNPs and 23.5% of gram positive pathogens (GPPs) had some type of resistance. Nearly 34.3% of Klebsiella were resistant to third/fourth generation cephalosporins, 4.8% of Enterobacteriaceae were carbapenem-resistant (CRE), 24.4% of Staphylococcus aureus were methicillin-resistant (MRSA), and 21.9% of Enterococci were vancomycin-resistant (VRE). Multidrug resistance (MDR) was 65.0% in Acinetobacter, 26.4% in Escherichia coli, 23.0% in Klebsiella, and 14.9% in Pseudomonas. Resistant GNPs including cephalosporin-resistant Klebsiella, MDR Klebsiella, and MDR Escherichia coli were significantly more frequent while resistant GPPs including MRSA and VRE were significantly less frequent than NHSN hospitals. CONCLUSION: The current findings showed heavier and more resistant contribution of GNPs to DA-HAIs in Saudi hospitals compared with American hospitals. The higher resistance rates in Klebsiella and Escherichia coli are alarming and call for effective antimicrobial stewardship programs.

Low SARS-CoV-2 sero-prevalence based on anonymized residual sero-survey before and after first wave measures in British Columbia, Canada, March-May 2020

BackgroundThe province of British Columbia (BC) has been recognized for successful SARS-CoV-2 control, with surveillance data showing amongst the lowest case and death rates in Canada. We estimate sero-prevalence for two periods flanking the start (March) and end (May) of first-wave mitigation measures in BC. MethodsSerial cross-sectional sampling was conducted using anonymized residual sera obtained from an outpatient laboratory network, including children and adults in the Greater Vancouver Area (population [~]3 million) where community attack rates were expected to be highest. Screening used two chemiluminescent immuno-assays for spike (S1) and nucleocapsid antibodies. Samples sero-positive on either screening assay were assessed by a third assay targeting the S1 receptor binding domain plus a neutralization assay. Age-standardized sero-prevalence estimates were based on dual-assay positivity. The May sero-prevalence estimate was extrapolated to the source population to assess surveillance under-ascertainment, quantified as the ratio of estimated infections versus reported cases. ResultsSerum collection dates spanned March 5-13 and May 15-27, 2020. In March, two of 869 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.28% (95%CI=0.03-0.95). Neither specimen had detectable neutralizing antibodies. In May, four of 885 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.55% (95%CI=0.15-1.37%). All four specimens had detectable neutralizing antibodies. We estimate [~]8 times more infections than reported cases. ConclusionsLess than 1% of British Columbians had been infected with SARS-CoV-2 when first-wave mitigation measures were relaxed in May 2020. Our findings indicate successful suppression of community transmission in BC, but also substantial residual susceptibility. Further sero-survey snapshots are planned as the pandemic unfolds. Key pointsCross-sectional sampling of anonymized residual sera at the start and end of first-wave mitigation measures in British Columbia, Canada shows SARS-CoV-2 sero-prevalence below 1% throughout the winter-spring 2020. Findings indicate successful suppression of community transmission but also substantial residual susceptibility.

Ten-year resistance trends in pathogens causing healthcare-associated infections; reflection of infection control interventions at a multi-hospital healthcare system in Saudi Arabia, 2007-2016.

BACKGROUND: Studying temporal changes in resistant pathogens causing healthcare-associated infections (HAIs) is crucial in improving local antimicrobial and infection control practices. The objective was to describe ten-year trends of resistance in pathogens causing HAIs in a tertiary care setting in Saudi Arabia and to compare such trends with those of US National Health Surveillance Network (NHSN). METHODS: Pooled analysis of surveillance data that were prospectively collected between 2007 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Definitions and methodology of HAIs and antimicrobial resistance were based on NHSN. Consecutive NHSN reports were used for comparisons. RESULTS: A total 1544 pathogens causing 1531 HAI events were included. Gram negative pathogens (GNP) were responsible for 63% of HAIs, with a significant increasing trend in Klebsiella spp. and a decreasing trend in Acinetobacter. Methicillin-resistant Staphylococcus aureus (27.0%) was consistently less frequent than NHSN. Vancomycin-resistant Enterococci (VRE, 20.3%) were more than doubled during the study, closing the gap with NHSN. Carbapenem resistance was highest with Acinetobacter (68.3%) and Pseudomonas (36.8%). Increasing trends of carbapenem resistance were highest in Pseudomonas and Enterobacteriaceae, closing initial gaps with NHSN. With the exception of Klebsiella and Enterobacter, multidrug-resistant (MDR) GNPs were generally decreasing, mainly due to the decreasing resistance towards cephalosporins, fluoroquinolones, and aminoglycosides. CONCLUSION: The findings showed increasing trends of carbapenem resistance and VRE, which may reflect heavy use of carbapenems and vancomycin. These findings may highlight the need for effective antimicrobial stewardship programs, including monitoring and feedback on antimicrobial use and resistance.

Appropriateness of antimicrobial use among septic patients managed by the critical care response team: an opportunity for improvement through de-escalation.

Background: Most septic patients managed by critical care response teams (CCRT) are prescribed antimicrobials. Nevertheless, data evaluating their appropriateness are lacking both locally and internationally. The objective was to assess antimicrobial use among septic and non-septic patients managed by CCRT. Setting: Case-control design was used to compare septic (cases) and non-septic (controls) CCRT patients at tertiary care setting. The frequency of antimicrobial use was assessed before and after CCRT activation. The appropriateness of antimicrobial use was assessed at day four post-CCRT, based on standard recommendations, clinical assessment, and culture results. Main results: A total of 157 cases and 158 controls were included. The average age was 61.1 ± 20.4 years, and 54.6% were males, with minor differences between groups. The use of any antimicrobial was 100.0% in cases and 87.3% in controls (p < 0.001). The use of meropenem (68.2% versus 34.8%, p < 0.001) and vancomycin (56.7% versus 25.9%, p < 0.001) were markedly higher in cases than controls. The overall appropriateness was significantly lower in cases than controls (50.7% versus 59.6%, p = 0.047). Individual appropriateness was lowest with meropenem (16.7%) and imipenem (25.0%), and highest with piperacillin/tazobactam (87.1%) and colistin (78.3%). Only 48.5% of antimicrobials prescribed by CCRT were de-escalated by a primary team within four days. Individual appropriateness and de-escalations were not different between groups. Conclusions: Empiric use and inadequate de-escalation of broad-spectrum antimicrobials were major causes for inappropriate antimicrobial use in CCRT patients. Our findings highlight the necessity of urgent implementation of an antimicrobial stewardship program, including training and auditing of antimicrobial prescriptions.

Identified Transmission Dynamics of Middle East Respiratory Syndrome Coronavirus Infection During an Outbreak: Implications of an Overcrowded Emergency Department.

A total 130 cases of Middle East respiratory syndrome coronavirus were identified during a large hospital outbreak in Saudi Arabia; 87 patients and 43 healthcare workers. The majority (80%) of transmission was healthcare-acquired (HAI) infection, with 4 generations of HAI transmission. The emergency department was the main location of exposure.

Description of a Hospital Outbreak of Middle East Respiratory Syndrome in a Large Tertiary Care Hospital in Saudi Arabia.

BACKGROUND Since the first isolation of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in 2012, sporadic cases, clusters, and sometimes large outbreaks have been reported. OBJECTIVE To describe the recent (2015) MERS-CoV outbreak at a large tertiary care hospital in Riyadh, Saudi Arabia. METHODS We conducted an epidemiologic outbreak investigation, including case finding and contact tracing and screening. MERS-CoV cases were categorized as suspected, probable, and confirmed. A confirmed case was defined as positive reverse transcription polymerase chain reaction test for MERS-CoV. RESULTS Of the 130 suspected cases, 81 (62%) were confirmed and 49 (38%) were probable. These included 87 patients (67%) and 43 healthcare workers (33%). Older age (mean [SD], 64.4 [18.3] vs 40.1 [11.3] years, P<.001), symptoms (97% vs 58%, P<.001), and comorbidity (99% vs 42%, P<.001) were more common in patients than healthcare workers. Almost all patients (97%) were hospitalized whereas most healthcare workers (72%) were home isolated. Among 96 hospitalized cases, 63 (66%) required intensive care unit management and 60 (63%) required mechanical ventilation. Among all 130 cases, 51 (39%) died; all were patients (51 [59%]) with no deaths among healthcare workers. More than half (54%) of infections were believed to be caught at the emergency department. Strict infection control measures, including isolation and closure of the emergency department, were implemented to interrupt the chain of transmission and end the outbreak. CONCLUSION MERS-CoV remains a major healthcare threat. Early recognition of cases and rapid implementation of infection control measures are necessary. Infect Control Hosp Epidemiol 2016;1-9.

Notes from the Field: Nosocomial Outbreak of Middle East Respiratory Syndrome in a Large Tertiary Care Hospital--Riyadh, Saudi Arabia, 2015.

Since the first diagnosis of Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia in 2012, sporadic cases and clusters have occurred throughout the country (1). During June-August, 2015, a large MERS outbreak occurred at King Abulaziz Medical City, a 1,200-bed tertiary-care hospital that includes a 150-bed emergency department that registers 250,000 visits per year.

Acute intermittent porphyria caused by novel mutation in HMBS gene, misdiagnosed as cholecystitis.

BACKGROUND: Acute intermittent porphyria (AIP) is an autosomal dominant neurovisceral inherited disorder due to a defect in the heme biosynthesis pathway. Misdiagnosis of the porphyrias is not uncommon. CASE REPORT: We present a case of a 26-year-old female with suspected acute cholecystitis, mental status changes, and seizures. Biochemical and molecular investigations confirmed the diagnosis of AIP by findings of elevated urinary porphobilinogen, 5-aminolevulinic acid, and total porphyrins. DNA molecular testing showed a novel heterozygous mutation (c. 760delC p.L254X) in the exon11 of the HMBS gene. To the best of our knowledge, this is the first report of a misdiagnosis of AIP presenting with acute cholecystitis. CONCLUSION: Clinicians are alerted to consider the possibility of AIP in an adult presenting with an acute abdomen, features of cholecystitis, and neuropsychiatric manifestations.

Single-room infant care: future trends in special care nursery planning and design.

For the past several years, health care providers specializing in the treatment of neonates have been working steadily to improve the environment for premature and sick neonates in order to optimize outcomes. They have also begun to recognize that involving the family in every aspect of care not only has positive value for the family, but can improve outcomes for neonates as well. This article examines how the staff at one hospital closely utilized and married these two concepts, developmentally supportive care and family-centered care, to design a Level II special care nursery that embraces parents as partners in treatment. Each phase of design development is described, including space programming, schematic design, environmental design, and design development, as well as the successful use of a multidisciplinary team.

Predictors of outcome in hospitalized patients with severe hyponatremia.

UNLABELLED: Severe hyponatremia is associated with increased morbidity and mortality. Clinicians treating patients with severe hyponatremia are often torn between a desire to promptly raise serum sodium concentration to a "safe range," and at the same time, to avoid excessively rapid correction of hyponatremia. The aim of this study was to assess the prevalence of severe hyponatremia in hospitalized patients, the etiologic factors involved, as well as treatment and outcome of the patients using a retrospective case series. METHODS: Retrospective study of 168 patients with severe hyponatremia (< 115mmol/L) seen at Grady Memorial Hospital, a tertiary teaching hospital, in Atlanta, Georgia, from 1997-2001. The main outcome measures of interest were death during admission or occurrence of neurologic symptoms before, during or after therapy. RESULTS: One hundred sixty-eight patients met the inclusion criteria out of a total of 5994 patients with hyponatremia treated at our hospital over the study period. Eighty-nine patients (52.9%) were symptomatic. The mean absolute serum sodium at 48-hours of therapy was 120.02 +/- 8.31 mmol/L. Respiratory failure and/or hypoxia was present in 28 patients (16.7%); sepsis was documented in 16 patients (9.5%). Mortality rate was high, 34 patients died (20.2%). On multivariate analysis factors with strong association with mortality of patients with severe hyponatremia were hypoxia, presence of neurologic symptoms, slow correction rates and a diagnosis of sepsis. CONCLUSIONS: The mortality associated with severe hyponatremia remains high. Sepsis, respiratory failure and the presence of symptoms predict poor outcome in hospitalized patients with severe hyponatremia. More aggressive therapy with 3% saline may improve outcome in symptomatic patients. Our data suggest that a slow rate of correction in severe hyponatremia is associated with higher mortality than rapid correction, at least in the short-term.