Assessment of Th1/Th2 cytokines among patients with Middle East respiratory syndrome coronavirus infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a member of the beta-coronavirus genus of zoonotic origin that emerged in the Arabian Peninsula and is associated with significant morbidity and mortality. This study was conducted to assess the plasma levels of cytokines to evaluate the Th1/Th2 status among 46 MERS-CoV-infected patients (19 asymptomatic and 27 symptomatic) and 52 normal healthy controls using a customized luminex kit. Comparative analysis of data between MERS-CoV-infected patients and normal healthy controls revealed that although no difference was observed between asymptomatic MERS-CoV patients and controls, the mean plasma levels of interleukin (IL)-10 (44.69 ± 40.04 pg ml-1 versus 14.84 ± 6.96 pg ml-1; P < 0.0001), IL-4 (22.46 ± 8.02 pg ml-1 versus 16.01 ± 9.97 pg ml-1; P < 0.0001), IL-5 (10.78 ± 2.86 pg ml-1 versus 8.06 ± 1.41 pg ml-1; P < 0.0001) and IL-13 (14.51 ± 3.97 pg ml-1 versus 11.53 ± 4.16 pg ml-1; P < 0.003) in MERS-CoV symptomatic patients were significantly higher than the normal controls. The mean plasma levels of interferon (IFN)-γ and IL-12 were no different among the study groups. The cytokine profile among symptomatic MERS-CoV-infected patients was skewed to a Th2 type immune response.

Middle East Respiratory Syndrome Coronavirus and Pulmonary Tuberculosis Coinfection: Implications for Infection Control.

Coinfection of Middle East respiratory syndrome coronavirus (MERS-CoV) with tuberculosis (TB) has not been previously reported. Here, we present 2 cases with both MERS-CoV and pulmonary TB. The first case was a 13-year-old patient who was admitted with a 2-month history of fever, weight loss, night sweats, and cough. The second patient was a 30-year-old female who had a 4-week history of cough associated with shortness of breath and weight loss of 2 kg. The 2 patients were diagnosed with pulmonary TB and had positive MERS-CoV. Both patients were discharged to complete their therapy for TB at home. It is likely that both patients had pulmonary TB initially as they had prolonged symptoms and they subsequently developed MERS-CoV infection. It is important to carefully evaluate suspected MERS-CoV patients for the presence of other infectious diseases, such as TB, especially if cohorting is done for suspected MERS-CoV to avoid nosocomial transmission.

The First Reported Foodborne Botulism Outbreak in Riyadh, Saudi Arabia: Lessons Learned.

BACKGROUND: Botulism has not been previously reported in the Kingdom of Saudi Arabia. This rare and sometimes fatal foodborne illness is caused by neurotoxins and primarily results from consuming home-canned fruits, vegetables, dairy, and seafood products & it can lead to paralysis. OBJECTIVE: The purpose of this study was to evaluate the clinical features of patients who developed botulism in Riyadh in 2024 after consuming mayonnaise from a well-known local chain of restaurants in Riyadh, Saudi Arabia. METHODS: We conducted a retrospective analysis of medical records and interviewed patients or their attendants for all hospitalized cases of foodborne botulism at Riyadh First Health Cluster. For each patient, a standard case report form was completed, containing information on demographics, clinical aspects, botulinum test results, and type of exposure. Descriptive statistics were applied to assess the data. During the outbreak, nineteen patients with foodborne diseases were admitted to Riyadh First Health Cluster Hospitals. Following thorough physical examinations, botulism was suspected in each case. RESULTS: Eight of the 19 suspected foodborne illness patients fully satisfied the botulism case definition requirements set forth by the Saudi Arabian Public Health Authority (Weqaya). Among these eight patients, 2 (25%) were male and 6 (75%) were female, with a mean age of 23.25 ± 9.29 years (range: 12-38 years). The incubation period for our patients was 36.25 ± 26.26 h. Notable symptoms included dysphagia in all eight patients (100%), dysarthria, generalized weakness, nausea and vomiting in seven patients (88%), diplopia in four patients (50%), and stomach discomfort in three patients (38%). Of the eight cases, six required intubation, one mimicked brain death, and two were stable. The presence of Clostridium botulinum spores as the cause of the outbreak was confirmed by detecting botulinum spores in contaminated food. CONCLUSION: Diplopia and dysarthria were the most common early sign of botulism. Early manifestations may include respiratory symptoms without any musculoskeletal symptoms. or nausea, vomiting and disorientation.

Implementation of effective strategies to prevent Candida auris transmission in a Quaternary Care Center, Riyadh, Saudi Arabia.

This study outlines the results of an investigation of a large C. auris outbreak at King Saud Medical City (KSMC), a quaternary hospital in Saudi Arabia. We identified 122 cases of C. auris (colonization, 74; infection, 48) from June 2021 to June 2022. The mean patient age was 48.4 years, and the median duration of stay before diagnosis was 32.7 days. A significant proportion of patients (87.70%) were diagnosed with C. auris more than 3 days after admission to KSMC. The source of exposure was either nosocomial (from KSMC, 28.68%; from other hospitals, 16.39%) or unknown (54.91%). The hospitalization mortality rate was 45.90%. This report highlights the challenges in investigating and managing C. auris outbreaks, emphasizing the need for a comprehensive approach incorporating strategies for screening and early identification, effective environmental cleaning, and the implementation of stringent infection control measures such as hand hygiene, isolation of patient, standard and contact precaution and decolonization.

Assessment of Proinflammatory Cytokines Among Patients with Middle East Respiratory Syndrome Coronavirus Infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant morbidity and mortality. This study was performed to assess the proinflammatory cytokines profile among MERS-CoV patients. A total of 46 MERS-CoV-infected patients (27 symptomatic and 19 asymptomatic) were assessed and compared with 52 normal healthy controls for plasma levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-17, IL-7, IL-6, interferon (IFN)-α, and IL-15 using a customized luminex kit. Whereas asymptomatic MERS-CoV patients and controls were no different; the mean plasma levels among MERS-CoV symptomatic patients were significantly higher than the normal controls: IL-1ß (16.89 ± 1.23 vs. 12.80 ± 0.59 pg/mL; p < 0.001), TNF-α (14.04 ± 0.93 vs. 10.35 ± 0.29 pg/mL; p < 0.0001), IL-17 (14.3 ± 0.89 vs. 11.47 ± 0.61 pg/mL; p < 0.001), IL-7 (21.56 ± 1.00 vs. 16.31 ± 0.30 pg/mL; p < 0.0001), IL-6 (156.5 ± 37.90 vs. 18.60 ± 1.59 pg/mL; p < 0.0001), and IFN-α (68.73 ± 13.06 vs. 23.57 ± 1.05 pg/mL; p < 0.0001). The mean plasma levels of IL-7 (24.81 ± 1.63 vs. 19.79 ± 0.94 pg/mL; p < 0.01), IL-6 (312.7 ± 94.67 vs. 101.2 ± 25.67 pg/mL; p < 0.01), and IFN-α (89.00 ± 18.97 vs. 51.05 ± 8.68 pg/mL; p < 0.05) were significantly elevated among MERS-CoV symptomatic patients with fatal outcome compared with MERS-CoV symptomatic patients who survived. Only IL-7 was found to have a higher risk ratio of mortality (4.76, 95% confidence interval: 1.5-14.94; p < 0.01). No differences were observed in IL-15 levels among the groups. Significantly elevated proinflammatory cytokines among symptomatic MERS-CoV-infected patients may contribute to manifestations of cytokine storm frequently observed among critically ill MERS-CoV patients and IL-7 may serve as a marker for disease activity.

MERS-CoV Confirmation among 6,873 suspected persons and relevant Epidemiologic and Clinical Features, Saudi Arabia - 2014 to 2019.

BACKGROUND: Of the three lethal coronaviruses, in addition to the ongoing pandemic-causing SARS-CoV 2, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) remains in circulation. Information on MERS-CoV has relied on small sample of patients. We updated the epidemiology, laboratory and clinical characteristics, and survival patterns of MERS-CoV retrospectively with the largest sample of followed patients. METHODS: We conducted a retrospective review of line-listed records of non-random, continuously admitted patients who were suspected (6,873) or confirmed with MERS-CoV (501) admitted to one of the four MERS-CoV referral hospitals in Saudi Arabia, 2014-2019. FINDINGS: Of the 6,873 MERS-CoV suspected persons, the majority were male (56%) and Saudi nationals (83%) and 95% had no known history that increased their risk of exposure to MERS-CoV patients or vectors (95%). More confirmed cases reported history that increased their risk of MERS-CoV infection (41%). Among the suspected, MERS-CoV confirmation (7.4% overall) was independently associated with being male, known transmission link to MERS-CoV patients or vectors, fever, symptoms for 7 days, admission through intensive care unit, and diabetes. Among persons with confirmed MERS-CoV, single symptoms were reported by 20%, 3-symptom combinations (fever, cough and dyspnea) reported by 21% and 2-symptom combinations (fever, cough) reported by 16%. Of the two-thirds (62%) of MERS-CoV confirmed patients who presented with co-morbidity, 32% had 2-"comorbidities (diabetes, hypertension). More than half of the MERS-CoV patents showed abnormal chest X-ray, elevated aspartate aminotransferase, and creatinine kinase. About a quarter of MERS-CoV patients had positive cultures on blood, urine, or respiratory secretions. During an average hospital stay of 18 days (range 11 to 30), 64% developed complications involving liver, lungs, or kidneys. Ventilation requirement (29% of MERS-CoV cases) was independently associated with abnormal chest X-ray, viremia (Ct value <30), elevated creatinine, and prothrombin time. Death (21% overall) was independently associated with older age, dyspnea and abnormal chest X-ray on admission, and low hemoglobulin levels. INTERPRETATIONS: With two-thirds of the symptomatic persons developing multiorgan complications MERS-CoV remains the coronavirus with the highest severity (29%) and case fatality rate (21%) among the three lethal coronaviruses. Metabolic abnormalities appear to be an independent risk factor for sustained MERS-CoV transmission. The poorly understood transmission dynamics and non-specific clinical and laboratory features call for high index of suspicion among respiratory disease experts to help early detection of outbreaks. We reiterate the need for case control studies on transmission. FUNDING: No special funding to declare.

Middle East respiratory syndrome coronavirus intermittent positive cases: Implications for infection control.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to be reported from the Kingdom of Saudi Arabia. Data on the phenomenon of intermittent positive results for MERS-CoV on reverse-transcription polymerase chain reaction (RT-PCR) with negative results in between are lacking. Here we describe cases with intermittent positive MERS-CoV test results and highlight the required number of tests to rule out or rule in MERS-CoV infection based on a large retrospective cohort of patients with confirmed MERS-CoV. METHODS: This analysis included cases admitted between January 2014 and December 2017. The included patients had a minimum of 3 nasopharyngeal MERS-CoV RT-PCR tests for confirmation and needed 2 negative samples for MERS-CoV evaluated 48 hours apart with clinical improvement or stabilization apart to ensure clearance. RESULTS: A total of 408 patients with positive MERS-CoV test results were treated at the referring hospital. We excluded 72 patients who had only 1 swab result available in the system and were treated in the initial years of the disease. Of the remaining 336 patients, 300 (89%) had a positive result after 1 swab, 324 (96.5%) had a positive result after 2 consecutive swabs, and 328 (97.6%) had a positive result after 3 consecutive swabs. Of the total cases, 46 (13.7%) had a positive MERS-CoV test then a negative test, followed by positive test results. CONCLUSIONS: Our data indicate that 2 to 3 nasopharyngeal samples are needed to produce the highest yield of positive results for MERS-CoV. In addition, 2 negative results 48 hours apart with clinical improvement or stabilization are needed to clear patients from MERS-CoV. Evaluation of the yield of sputum samples is needed to assess the effectiveness against nasopharyngeal swabs.

Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia.

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%-60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April 19, 2016 reported 31 pediatric MERS-CoV cases. In this paper, we present the clinical and laboratory features of seven patients with pediatric MERS. Five patients had no underlying medical illnesses, and three patients were asymptomatic. Of the seven cases, four (57%) patients sought medical advice within 1-7 days from the onset of symptoms. The three other patients (43%) were asymptomatic and were in contact with patients with confirmed diagnosis of MERS-CoV. The most common presenting symptoms were fever (57%), cough (14%), shortness of breath (14%), vomiting (28%), and diarrhea (28%). Two (28.6%) patients had platelet counts of < 150 × 109/L, and one patient had an underlying end-stage renal disease. The remaining patients presented with normal blood count, liver function, and urea and creatinine levels. The documented MERS-CoV Ct values were 32-38 for four of the seven cases. Two patients (28.6%) had abnormal chest radiographic findings of bilateral infiltration. One patient (14.3%) required ventilator support, and two patients (28.6%) required oxygen supplementation. All the seven patients were discharged without complications.

Clinical predictors of mortality of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: A cohort study.

BACKGROUND: Since the emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, the virus had caused a high case fatality rate. The clinical presentation of MERS varied from asymptomatic to severe bilateral pneumonia, depending on the case definition and surveillance strategies. There are few studies examining the mortality predictors in this disease. In this study, we examined clinical predictors of mortality of Middle East Respiratory Syndrome (MERS) infection. METHODS: This is a retrospective analysis of symptomatic admitted patients to a large tertiary MERS-CoV center in Saudi Arabia over the period from April 2014 to March 2018. Clinical and laboratory data were collected and analysis was done using a binary regression model. RESULTS: A total of 314 symptomatic MERS-CoV patients were included in the analysis, with a mean age of 48 (±17.3) years. Of these cases, 78 (24.8%) died. The following parameters were associated with increased mortality, age, WBC, neutrophil count, serum albumin level, use of a continuous renal replacement therapy (CRRT) and corticosteroid use. The odd ratio for mortality was highest for CRRT and corticosteroid use (4.95 and 3.85, respectively). The use of interferon-ribavirin was not associated with mortality in this cohort. CONCLUSION: Several factors contributed to increased mortality in this cohort of MERS-CoV patients. Of these factors, the use of corticosteroid and CRRT were the most significant. Further studies are needed to evaluate whether these factors were a mark of severe disease or actual contributors to higher mortality.

Middle East respiratory syndrome coronavirus transmission among health care workers: Implication for infection control.

BACKGROUND: Many outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in health care settings and involved health care workers (HCWs). We describe the occurrence of an outbreak among HCWs and attempt to characterize at-risk exposures to improve future infection control interventions. METHODS: This study included an index case and all HCW contacts. All contacts were screened for MERS-CoV using polymerase chain reaction. RESULTS: During the study period in 2015, the index case was a 30-year-old Filipino nurse who had a history of unprotected exposure to a MERS-CoV-positive case on May 15, 2015, and had multiple negative tests for MERS-CoV. Weeks later, she was diagnosed with pulmonary tuberculosis and MERS-CoV infection. A total of 73 staff were quarantined for 14 days, and nasopharyngeal swabs were taken on days 2, 5, and 12 postexposure. Of those contacts, 3 (4%) were confirmed positive for MERS-CoV. An additional 18 staff were quarantined and had MERS-CoV swabs. A fourth case was confirmed positive on day 12. Subsequent contact investigations revealed a fourth-generation transmission. Only 7 (4.5%) of the total 153 contacts were positive for MERS-CoV. CONCLUSIONS: The role of HCWs in MERS-CoV transmission is complex. Although most MERS-CoV-infected HCWs are asymptomatic or have mild disease, fatal infections can occur and HCWs can play a major role in propagating health care facility outbreaks. This investigation highlights the need to continuously review infection control guidance relating to the role of HCWs in MERS-CoV transmission in health care outbreaks, especially as it relates to the complex questions on definition of risky exposures, who to test, and the frequency of MERS-CoV testing; criteria for who to quarantine and for how long; and clearance and return to active duty criteria.

Predictors of MERS-CoV infection: A large case control study of patients presenting with ILI at a MERS-CoV referral hospital in Saudi Arabia.

BACKGROUND: A case control study to better characterize the clinical features, laboratory, and radiological abnormalities associated with MERS-CoV infection in order to help with early identification of this syndrome from other respiratory infections. METHODS: Eighty patients admitted to a hospital in Riyadh, diagnosed with MERS-CoV infection based on RT-PCR were matched on age, sex, and the presence of a co-morbid condition on a basis of 1:2 to other patients admitted with respiratory symptoms and tested negative for MERS-CoV on RT-PCR. RESULTS: None of the reported MERS-CoV presenting symptoms was significantly associated with being infected with MERS-CoV. On the other hand, WBC count was significantly lower in patients with confirmed MERS-CoV infection (median 5.7 vs 9.3, P: 0.0004). Neutrophil count was as well significantly lower in MERS-CoV patients (median 3.7 vs 6.7, P: 0.0001). Both AST, and ALT values were significantly higher in MERS-CoV infected group (AST median 42 vs 36, P: 0.03, and ALT median 33 vs 28, P: 0.003). Overall our MERS-CoV mortality rate was (10%) below the national figure of (40%). CONCLUSIONS: None of the presenting symptoms are specific for MERS-CoV infection. And out of all the investigations WBC, neutrophil counts, AST and ALT values have some predictive utility.