Longevity of Middle East Respiratory Syndrome Coronavirus Antibody Responses in Humans, Saudi Arabia.

Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV-specific neutralizing antibodies were detected for 6 years postinfection.

Outcome of COVID19 in Patients With Osteogenesis Imperfecta: A Retrospective Multicenter Study in Saudi Arabia.

Background: Although genetic diseases are rare, children with such conditions who get infected with COVID-19 tend to have a severe illness requiring hospitalization. Osteogenesis imperfecta (OI) is a rare genetic disorder of collagen resulting in fractures and skeletal deformities. Kyphoscoliosis, restrictive lung disease, and pneumonia worsen the prognosis of patients with OI. The use of bisphosphonate improves bone mineral density (BMD) and reduces fractures in OI. There is no literature describing the impact of COVID-19 in patients with OI. Methodology: A retrospective multi-center study was performed in three hospitals in Jeddah and Riyadh, Saudi Arabia, from March 1st, 2020, until August 31st, 2021, aiming to evaluate the outcome of COVID-19 in patients with OI. Demographics, vaccination status, underlying kyphoscoliosis, functional status, use of bisphosphonate, BMD, and COVID-19 severity, and course were recorded for all patients. Results: Twelve cases of confirmed COVID-19 were identified among 146 patients with OI. 9 (75%) of patients were less than 18 years, 6 (50%) were male, 5 (41%) had kyphoscoliosis, and 5 (41%) were wheelchair-bound. 6 (50%) received bisphosphonate, and 7(58%) had normal BMD. All patients had mild disease and did not require hospitalization. None of OI the patients with COVID-19 were fully vaccinated before the infection, and some were ineligible for vaccination. Conclusion: Patients with OI and COVID-19 in our study recovered without complications, unlike patients with other genetic diseases. Young age and mild illness contributed to the favorable outcome. Half of the patients received bisphosphonate and had normal BMD.

T-cell responses to MERS coronavirus infection in people with occupational exposure to dromedary camels in Nigeria: an observational cohort study.

BACKGROUND: Middle East respiratory syndrome (MERS) remains of global public health concern. Dromedary camels are the source of zoonotic infection. Over 70% of MERS coronavirus (MERS-CoV)-infected dromedaries are found in Africa but no zoonotic disease has been reported in Africa. We aimed to understand whether individuals with exposure to dromedaries in Africa had been infected by MERS-CoV. METHODS: Workers slaughtering dromedaries in an abattoir in Kano, Nigeria, were compared with abattoir workers without direct dromedary contact, non-abattoir workers from Kano, and controls from Guangzhou, China. Exposure to dromedaries was ascertained using a questionnaire. Serum and peripheral blood mononuclear cells (PBMCs) were tested for MERS-CoV specific neutralising antibody and T-cell responses. FINDINGS: None of the participants from Nigeria or Guangdong were MERS-CoV seropositive. 18 (30%) of 61 abattoir workers with exposure to dromedaries, but none of 20 abattoir workers without exposure (p=0·0042), ten non-abattoir workers or 24 controls from Guangzhou (p=0·0002) had evidence of MERS-CoV-specific CD4+ or CD8+ T cells in PBMC. T-cell responses to other endemic human coronaviruses (229E, OC43, HKU-1, and NL-63) were observed in all groups with no association with dromedary exposure. Drinking both unpasteurised camel milk and camel urine was significantly and negatively associated with T-cell positivity (odds ratio 0·07, 95% CI 0·01-0·54). INTERPRETATION: Zoonotic infection of dromedary-exposed individuals is taking place in Nigeria and suggests that the extent of MERS-CoV infections in Africa is underestimated. MERS-CoV could therefore adapt to human transmission in Africa rather than the Arabian Peninsula, where attention is currently focused. FUNDING: The National Science and Technology Major Project, National Institutes of Health.

High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia.

Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.IMPORTANCE The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure. Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease. Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community.

Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study.

AIMS: The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome - coronavirus (MERS-CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS-CoV infection and represent a base of MERS-CoV histopathology. METHODS AND RESULTS: We analysed the post-mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33-year-old male patient of T cell lymphoma, who acquired MERS-CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles. CONCLUSION: The results highlight the pulmonary and extrapulmonary pathological changes of MERS-CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS-CoV in kidney.

Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses.

The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4+ and CD8+ T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT50) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4+ but not CD8+ T cell responses; patients with higher PRNT50 and CD4+ T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8+ T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8+ T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.

Acute respiratory distress syndrome complicating community-acquired pneumonia secondary to mycobacterium tuberculosis in a tertiary care center in Saudi Arabia.

OBJECTIVES: To discuss our center's experience with acute respiratory distress syndrome (ARDS) secondary to pulmonary tuberculosis (TB) in a major tertiary referral hospital in the Kingdom of Saudi Arabia. METHODS: A retrospective review of medical records of all patients with community-acquired pneumonia secondary to mycobacterium TB infection who were admitted for critical care in a single center of King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia from 2004 to 2013. RESULTS: In our review of 350 patients with community-acquired pneumonia admitted to Intensive Care Unit, 11 cases of TB complicated with ARDS were identified. The mean age of patients was 51.9 years. The median time from hospital admission to pulmonary TB diagnosis and start of therapy was 5 days, while the median time from onset of symptoms to initiation of treatment was 18 days. The mortality rate was 64%, and the median length of hospital stay before death was 21.4 days. Delayed treatment, as well as high acute physiology and chronic health evaluation II and CURB-65 scores at presentation, were independent risk factors for death.  CONCLUSION: Patients with pulmonary TB infrequently present to intensive care with acute symptoms that meet all criteria for ARDS. Such a presentation of TB carries a high mortality risk.

End-of-life practices in a tertiary intensive care unit in Saudi Arabia.

Our aim was to evaluate end-of-life practices in a tertiary intensive care unit in Saudi Arabia. A prospective observational study was conducted in the medical-surgical intensive care unit of a teaching hospital in Riyadh, Saudi Arabia. Over the course of the one-year study period, 176 patients died and 77% of these deaths were preceded by end-of-life decisions. Of these, 66% made do-not-resuscitate decisions, 30% decided to withhold life support and 4% withdrew life support. These decisions were made after a median time of four days (Q1 to Q3: 1 to 9) and at least one day before death (Q1 to Q3: 1 to 4). The patients' families or surrogates were informed for 88% of the decisions and all decisions were documented in the patients' medical records. Despite religious and cultural values, more than three-quarters of the patients whose deaths were preceded by end-of-life decisions gave do-not-resuscitate decisions before death. These decisions should be made early in the patients' stay in the intensive care unit.

Eosinophilic pneumonia: experience at two tertiary care referral hospitals in Saudi Arabia.

BACKGROUND AND OBJECTIVES: Eosinophilic lung diseases are a diverse group of disorders characterized by pulmonary opacities associated with tissue or peripheral eosinophilia. DESIGN AND SETTING: A retrospective study conducted at two tertiary care hospitals from January 1999 to December 2009. METHODS: All cases with the diagnosis of pulmonary eosinophilia were reviewed over a period of 10 years. Data on demographic, clinical, and radiologic characteristics were collected. RESULTS: Thirty-five patients with a mean age of 33.9 (16.2) years, of which 20 (57.1%) were male and meeting the criteria of eosinophilic lung disease were identified. Cough and dyspnea were the most frequent symptoms at presentation in 29 (82.9%) and 27 (77.1%) patients, respectively. Reticulonodular and airspace patterns were the most common radiographic findings in 17 (48.6%) and 15 (42.9%) patients, respectively. Peripheral eosinophilia was present in 33 (94.3%) patients. Twenty-four patients (68.6%) were labeled as having idiopathic pulmonary infiltrate with eosinophilia. Complete remission was achieved in 13 (54.2%) of 24 patients, while 10 (41.7%) patients relapsed within a few months of discontinuation of therapy. Specific therapy for a specific disease was administered in 8 patients: 2 patients for pulmonary tuberculosis, 2 for Churg-Strauss syndrome, 1 for lymphoma, 1 for schistosomiasis, 1 for acute eosinophilic pneumonia, and 1 for Wegener granuloma; 3 patients were treated as allergic bronchopulmonary aspergillosis. CONCLUSIONS: Pulmonary eosinophilia remains rare but challenging, and it can have the same diverse clinical and radiographic presentations seen with other common pulmonary conditions. Clinicians should be alert to these syndromes and must think of them in any lung disease differential diagnoses.

In-hospital mortality among a cohort of cirrhotic patients admitted to a tertiary hospital.

BACKGROUND/AIM: To determine the mortality rate in a cohort of hospitalized patients with cirrhosis and examine their resuscitation status at admission. MATERIALS AND METHODS: A retrospective chart review was conducted of patients with cirrhosis who were admitted to a tertiary care hospital in Riyadh, Saudi Arabia, from January 1, 2009, to December 31, 2009. RESULTS: We reviewed 226 cirrhotic patients during the study period. The hospital mortality rate was 35%. A univariate analysis revealed that worse outcomes were seen in patients with advanced age or who had worse child-turcotte-pugh (CPT) scores, worse model for end-stage liver disease (MELD) scores, low albumin and high serum creatinine. Using a multivariate analysis, we found that advanced age (P=0.004) and high MELD (P=0.001) scores were independent risk factors for the mortality of cirrhotic patients. The end-of-life decision were made in 34% of cirrhotic patients, and the majority of deceased patients were "no resuscitation" status (90% vs. 4%, P<0.001). CONCLUSIONS: The relatively high mortality in cirrhotic patients admitted for care in a tertiary hospital, Saudi Arabia was comparable to that reported in the literature. Furthermore, end-of-life discussions should be addressed early in the hospitalization of cirrhotic patients.

Factors associated with decision-making about end-of-life care by hemodialysis patients.

The current cross sectional study is based on a questionnaire database on patients with end-stage renal disease (ESRD) to determine their preferences about end-of-life care and differences of certainty regarding the application of cardiopulmonary resuscitation and life sustaining measures in case of cardiac arrest. The study was performed on 100 patients on hemodialysis for at least 2 years and not on the transplant list in two tertiary hospitals in Saudi Arabia; King Fahad National Guard in Riyadh and King Faisal Specialist Hospital in Jeddah in March 2007. More than two thirds of the surveyed patients were willing to make decisive decisions. Having more than 5 children was the only factor significantly associated with the ability to make decisive decisions; there was an insignificant association with factors such as marital status or non-Saudi nationality. Factors such as self-perception or disease curability, previous admissions to hospital or intensive care units, prior knowledge of mechanical ventilation, or cardiopulmonary resuscitation did not have any influence on making certain decisions on end-of-life care. There was a significant lack of knowledge in our study patients of cardiopulmonary resuscitation, mechanical ventilation, and disease outcome.

Septic arthritis of the knee joint secondary to Prevotella bivia.

Prevotella bivia is an obligatory anaerobic, gram-negative rod, which often produces a detectable beta-lactamase. To date, there has been only 3 descriptions of septic arthritis secondary to this microorganism in a patients pre-existing sever joint disease like rheumatoid arthritis and osteoarthritis or after joint prosthesis. We are reporting the first case of septic arthritis due to Prevotella bivia in a patient with no pre-existing joint symptoms.