SARS-COV-2 Triggers the Development of Class I and Class II HLA Antibodies in Recovered Convalescent Plasma Donors.

Various studies have shown that SARS-CoV-2 is a highly immunogenic virus. It is known that different types of immunogenic viral pathogens could trigger the formation of HLA antibodies. Therefore, there is a concern that the SARS-CoV-2 could also induce the development of HLA antibodies in volunteers, who donate convalescent plasma after their recovery from COVID-19. HLA antibodies have been identified as the main cause for transfusion-related acute lung injury (TRALI), a well-documented life-threatening complication of transfusions. The TRALI risk could be high in COVID-19 patients who need convalescent plasma, as such patients usually have already an impaired respiratory system affected by the SARS-CoV-2 infection. In this study, we screened 34 convalescent plasma donors on the presence of antibodies against HLA class I and II antigens. All included donors have no any history of sensitization events such as blood transfusions, pregnancy, or previous transplants. We found a high rate of HLA antibody formation in convalescent plasma donors. The frequency of positivity for HLA antibodies for class I, class II, class I and II, and the overall reactivity was 23%, 31%, 46%, and 76%, respectively. The presented data suggest a closed correlation between SARS-CoV-2 virus infection and the development of HLA antibodies in recovered convalescent plasma donors. This finding might have the potential to reduce the risk of TRALI and mortality rate in COVID-19 patients by implementing HLA diagnostic strategies before the administration of convalescent plasma.

Efficacy of ceftazidime-avibactam in the treatment of infections due to Carbapenem-resistant Enterobacteriaceae.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) represent an important global threat. The aim of this study is to describe the clinical course and outcomes of patients with CRE infections treated with ceftazidime-avibactam (CAZ-AVI) compared to patients treated with other agents. METHODS: A retrospective cohort study of patients with established CRE infections from January 2017 until August 2018 was conducted. All patients who received CAZ-AVI and all cultures with carbapenem-resistant isolates were screened. We compared patients who received CAZ-AVI for CRE infections with patients who received other agents. RESULTS: A total of 38 consecutive patients with CRE infections were identified. Age and baseline comorbidities were similar between the two groups. The median time from admission to isolation of CRE culture was 22.5 days in the CAZ-AVI group and 17 days in the comparative group (P = 0.7). The incidence of CRE bacteremia was similar between the two groups: 7 patients (70%) in the CAZ-AVI group and 15 patients (53.6%) in the comparative group (P = 0.47). The most common type of CRE infections in both groups was hospital acquired pneumonia (HAP). Klebsiella pneumoniae was the predominant pathogen in both groups. A carbapenemase gene was detected in 35 (92%) patients; the OXA-48 gene was the predominant gene identified in 28 (74%) isolates. Eight out of ten patients in the CAZ-AVI group and fifteen out of twenty-eight in the comparative group achieved clinical remission (P = 0.14). After thirty days, all-cause mortality was observed in five patients in the CAZ-AVI group and 16 patients in the comparative group, accounting for 50 and 57% respectively. CONCLUSIONS: In patients with established OXA-48-type CRE infection, CAZ-AVI is a reasonable alternative to standard therapy. These findings need to be confirmed in prospective studies.

Antibody Response and Disease Severity in Healthcare Worker MERS Survivors.

We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease.

Risk Factors for Middle East Respiratory Syndrome Coronavirus Infection among Healthcare Personnel.

Healthcare settings can amplify transmission of Middle East respiratory syndrome coronavirus (MERS-CoV), but knowledge gaps about the epidemiology of transmission remain. We conducted a retrospective cohort study among healthcare personnel in hospital units that treated MERS-CoV patients. Participants were interviewed about exposures to MERS-CoV patients, use of personal protective equipment, and signs and symptoms of illness after exposure. Infection status was determined by the presence of antibodies against MERS-CoV. To assess risk factors, we compared infected and uninfected participants. Healthcare personnel caring for MERS-CoV patients were at high risk for infection, but infection most often resulted in a relatively mild illness that might be unrecognized. In the healthcare personnel cohort reported here, infections occurred exclusively among those who had close contact with MERS-CoV patients.

Impact of Middle East Respiratory Syndrome coronavirus (MERS-CoV) on pregnancy and perinatal outcome.

BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a viral respiratory disease. Most people infected with MERS-CoV develop severe acute respiratory illness. It was first reported in Saudi Arabia in 2012 and has since spread to several other countries. We report the clinical course of MERS-CoV infection in a pregnant woman who acquired the infection during the last trimester. CASE PRESENTATION: The patient is a 33-year-old female working as a critical care nurse. She was 32 weeks pregnant when she presented with respiratory symptoms after direct contact with a MERS-COV patient. Although the patient was in respiratory failure, necessitated mechanical ventilation, and intensive care (ICU) admission, a healthy infant was delivered. The mother recovered. To the best of our knowledge, this is the first reported case of a laboratory-confirmed Middle East Respiratory Syndrome Coronavirus in a pregnant woman. CONCLUSIONS: Middle East Respiratory Syndrome coronavirus (MERS-CoV) known to cause severe acute respiratory illness associated with a high risk of mortality Various factors may have contributed to the successful outcome of this patient such as young age, presentation during the last stages of pregnancy, and possible differences in immune response.

Data-Driven Prediction for COVID-19 Severity in Hospitalized Patients.

Clinicians urgently need reliable and stable tools to predict the severity of COVID-19 infection for hospitalized patients to enhance the utilization of hospital resources and supplies. Published COVID-19 related guidelines are frequently being updated, which impacts its utilization as a stable go-to resource for informing clinical and operational decision-making processes. In addition, many COVID-19 patient-level severity prediction tools that were developed during the early stages of the pandemic failed to perform well in the hospital setting due to many challenges including data availability, model generalization, and clinical validation. This study describes the experience of a large tertiary hospital system network in the Middle East in developing a real-time severity prediction tool that can assist clinicians in matching patients with appropriate levels of needed care for better management of limited health care resources during COVID-19 surges. It also provides a new perspective for predicting patients' COVID-19 severity levels at the time of hospital admission using comprehensive data collected during the first year of the pandemic in the hospital. Unlike many previous studies for a similar population in the region, this study evaluated 4 machine learning models using a large training data set of 1386 patients collected between March 2020 and April 2021. The study uses comprehensive COVID-19 patient-level clinical data from the hospital electronic medical records (EMR), vital sign monitoring devices, and Polymerase Chain Reaction (PCR) machines. The data were collected, prepared, and leveraged by a panel of clinical and data experts to develop a multi-class data-driven framework to predict severity levels for COVID-19 infections at admission time. Finally, this study provides results from a prospective validation test conducted by clinical experts in the hospital. The proposed prediction framework shows excellent performance in concurrent validation (n=462 patients, March 2020-April 2021) with highest discrimination obtained with the random forest classification model, achieving a macro- and micro-average area under receiver operating characteristics curve (AUC) of 0.83 and 0.87, respectively. The prospective validation conducted by clinical experts (n=185 patients, April-May 2021) showed a promising overall prediction performance with a recall of 78.4-90.0% and a precision of 75.0-97.8% for different severity classes.

Revisiting Middle East Respiratory Coronavirus (MERS-CoV) Outbreak Chest Radiographic Initial Findings, Temporal Progression, and Correlation to Outcomes: A Multicenter Study.

Objectives Accounts of initial and follow-up chest X-rays (CXRs) of the Middle East respiratory coronavirus (MERS-CoV) patients, and correlation with outcomes, are sparse. We retrospectively evaluated MERS-CoV CXRs initial findings, temporal progression, and outcomes correlation. Materials and methods Fifty-three real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR)-confirmed MERS-CoV patients with CXRs were retrospectively identified from November 2013 to October 2014. Initial and follow-up CXR imaging findings and distribution were evaluated over 75 days. Findings were correlated with outcomes. Results Twenty-two of 53 (42%) initial CXRs were normal. In 31 (68%) abnormal initial CXRs, 15 (48%) showed bilateral non-diffuse involvement, 16 (52%) had ground-glass opacities (GGO), and 13 (42%) had peripheral distribution. On follow-up CXRs, mixed airspace opacities prevailed, seen in 16 (73%) of 22 patients 21-30 days after the initial CXRs. Bilateral non-diffuse involvement was the commonest finding throughout follow-up, affecting 16 (59%) of 27 patients 11-20 days after the initial CXRs. Bilateral diffuse involvement was seen in five (63%) of eight patients 31-40 days after the initial CXRs. A bilateral diffuse CXR pattern had an odds ratio for mortality of 13 (95% CI=2-78) on worst and 18 (95% CI=3-119) on final CXRs (P-value <0.05). Conclusion Initially, normal CXRs are common in MERS-CoV patients. Peripherally located ground-glass and mixed opacities are common on initial and follow-up imaging. The risk of mortality is higher when bilateral diffuse radiographic abnormalities are detected.

Characteristics and outcome of tertiary care critically ill COVID-19 patients with multiple comorbidities admitted to the intensive care unit.

PURPOSE: We conducted this study to evaluate the characteristics and outcomes exclusively in high-risk coronavirus disease 2019 (COVID-19) tertiary care patients with multiple comorbidities, as very few have reported outcomes in this specific cohort. METHODS: All patients, with two or more risk factors for COVID-19 and Charlson Comorbidity Index (CCI) of >2, who were admitted to intensive care unit (ICU) between March and December 2020 were included. Their characteristics, ICU course, and outcomes as well as differences between nonsurvivors and survivors were evaluated. The primary outcome was all-cause 28-day mortality. RESULTS: Out of 1152 COVID-19 patients, 101 met the inclusion criteria. The patients had an average of 4 or more comorbidities with a very high CCI of 5. The 28-day all-cause mortality was 23% and inhospital mortality was 32%. Among all risk factors, only age > 70 years, male gender, and chronic kidney disease were significant determinants of mortality (P < 0.03). Admission PaO2/FiO2 ratio and elevated inflammatory markers were same among survivors and nonsurvivors (P > 0.66). The mean time from presentation to ICU admission (59 vs. 38 h), APACHE II score (20.5 vs. 17), ICU length of stay (25 vs. 12 days), and hospital length of stay (28 vs. 20 days) were all higher in nonsurvivors as compared to survivors, respectively (P < 0.03). Fifty-four percent of the patients were intubated and had higher 28-day (40%) and inhospital (55%) mortality. CONCLUSION: Tertiary care patients with multiple comorbidities have higher mortality than what is reported for mixed populations. Further studies are needed to determine realistic mortality benchmarks for these patients.

De-isolation of vaccinated COVID-19 health care workers using rapid antigen detection test.

BACKGROUND: COVID-19 de-isolation guidelines of health care workers (HCW) were formulated based on evidence describing the duration of infectious viral shedding of the wild SARS-CoV-2 virus. During the periods of COVID-19 vaccination and variants, a test-based approach was recommended to end isolation of HCW, based on emerging data describing the viral kinetics of COVID-19 variants. While Rapid antigen detection tests (RADT) are increasingly used in the diagnosis of COVID-19, their use is limited in de-isolation. METHODS: We described the use of RADT in the de-isolation of COVID-19 vaccinated HCW with mild infection who were asymptomatic on day 7 post diagnosis in a single center retrospective cohort study during the Omicron surge. RESULTS: Of the 480 HCWs, 173 (36%) had positive RADT. The positivity rate of RADT was not different in HCW who received two doses versus three doses of vaccine (34.4% versus 40.3%, p = 0.239). CONCLUSIONS: A symptom based, test-based approach using RADT is a useful tool in the de-isolation of HCW, with mild disease, in the era of Omicron. Further studies are required to evaluate the role of RADT in de-isolation of patients with severe COVID-19 disease.

Early use of tocilizumab in solid organ transplant recipients with COVID-19: A retrospective cohort study in Saudi Arabia.

BACKGROUND: Tocilizumab was studied to reduce cytokine syndrome in patients with severe COVID-19 pneumonia in solid organ transplant (SOT) recipients with conflicting results. We aim to study the early use of tocilizumab in SOT with COVID-19 pneumonia on low flow oxygen. METHODS: This is a retrospective cohort study that was conducted in two transplant centers in Saudi Arabia among 46 SOT with COVID-19 comparing 21 patients who received tocilizumab to 25 patients who received standard of care. Their clinical characteristics and outcomes were described. RESULTS: Compared to patients who received standard of care, patients in the tocilizumab group were older (60.2 ± 12.8 vs. 48.6 ± 12.3, p = .003), had higher ferritin (862.1 ± 919.1 vs. 414 ± 447.3, p = .025) and C-reactive protein (CRP) (85 ± 83.1 vs. 42.9 ± 57.3, p = .012). More patients in the tocilizumab group required high flow oxygen (38.1% vs. 8.0%, p = .028) compared to patients on standard of care. There were no differences in mortality or mechanical ventilation requirement. Hospital stay was significantly shorter in the tocilizumab group than the standard of care group (9.6 ± 7.4 vs. 20.7 ± 11.7, p < .001). CONCLUSIONS: Early use of tocilizumab in SOT was associated with a shorter hospital stay. There was no difference in mortality rate and the requirement for mechanical ventilation in both groups.

Comparison of characteristics and ventilatory course between coronavirus disease 2019 and Middle East respiratory syndrome patients with acute respiratory distress syndrome.

BACKGROUND: Both coronavirus disease 2019 (COVID-19) and Middle East respiratory syndrome (MERS) can cause acute respiratory distress syndrome (ARDS); however, their ARDS course and characteristics have not been compared, which we evaluate in our study. METHODS: MERS patients with ARDS seen during the 2014 outbreak and COVID-19 patients with ARDS admitted between March and December 2020 in our hospital were included, and their clinical characteristics, ventilatory course, and outcomes were compared. RESULTS: Forty-nine and 14 patients met the inclusion criteria for ARDS in the COVID-19 and MERS groups, respectively. Both groups had a median of four comorbidities with high Charlson comorbidity index value of 5 points (P>0.22). COVID-19 patients were older, obese, had significantly higher initial C-reactive protein (CRP), more likely to get trial of high-flow oxygen, and had delayed intubation (P≤0.04). The postintubation course was similar between the groups. Patients in both groups experienced a prolonged duration of mechanical ventilation, and majority received paralytics, dialysis, and vasopressor agents (P>0.28). The respiratory and ventilatory parameters after intubation (including tidal volume, fraction of inspired oxygen, peak and plateau pressures) and their progression over 3 weeks were similar (P>0.05). Rates of mortality in the ICU (53% vs. 64%) and hospital (59% vs. 64%) among COVID-19 and MERS patients (P≥0.54) were very high. CONCLUSIONS: Despite some distinctive differences between COVID-19 and MERS patients prior to intubation, the respiratory and ventilatory parameters postintubation were not different. The higher initial CRP level in COVID-19 patients may explain the steroid responsiveness in this population.

Patient characteristics infected with Middle East respiratory syndrome coronavirus infection in a tertiary hospital.

BACKGROUND: In April 2014, a surge in cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was seen in Jeddah, Saudi Arabia. The aim of this study is to describe the demographic and clinical features, laboratory and radiological findings of MERS-CoV patients identified during this outbreak in a single tertiary hospital. METHODS: All laboratory-confirmed MERS-CoV cases who presented to King Faisal Specialist Hospital from March 1, 2014, to May 30, 2014, were identified. Patients' charts were reviewed for demographic information, comorbidities, clinical presentations, and outcomes. RESULTS: A total of 39 patients with confirmed MERS-CoV infection were identified. Twenty-one were male (54%), aged 40 ± 19 years and included 3 (8%) pediatric patients (<18-year-old). 16 (41%) patients were health care workers. Twenty-one (53%) patients were previously healthy whereas eighteen (47%) had at least one comorbidity. The predominant comorbidities included hypertension (31%), diabetes (26%), respiratory (23%), and renal disease (18%). Thirty patients (81%) were symptomatic at presentation, fever (69%) being the most common complaint. The overall mortality rate was 28%. In univariate analysis, older age, hypertension, and chronic kidney disease were associated with mortality. CONCLUSIONS: MERS-CoV presentation varies from asymptomatic infection to severe respiratory disease causing death. Future studies to identify the risk factors for worse outcome are needed.

Successful use of antitumor necrosis factor-alpha biological therapy in managing human immunodeficiency virus-associated arthritis: three case studies from Saudi Arabia.

Arthralgic disorders involving various rheumatic manifestations are commonly observed in HIV patients. Available therapies for HIV-associated rheumatic syndromes include non-steroidal anti-inflammatory drugs for pain management, disease-modifying antirheumatic drugs (e.g., methotrexate), and antitumor necrosis factor-alpha therapies. However, treatment of HIV-associated arthritis can be challenging, particularly in patients with co-infections like hepatitis viruses, and therapeutic strategies are not well defined. Here, we present three case reports on the use of antitumor necrosis factor-alpha agents for HIV-associated arthritis. We managed three cases of HIV-associated arthritis following initial presentation. All patients were on highly active antiretroviral therapy with stable HIV loads and CD4(+) cell counts. Data were reported for treatment of inflammatory arthritis using 5 months of etanercept followed by adalimumab for case 1, and 12 months of etanercept for case 2. In case 3, reactive arthritis was treated with 5 months of etanercept followed by adalimumab. In all three cases, significant improvement or resolution of arthritis was achieved following treatment with antitumor necrosis factor-alpha therapies. Moreover, these case studies demonstrated the safe and effective use of antitumor necrosis factor-alpha agents in HIV patients with hepatitis B and/or C virus co-infection. Our results indicate that antitumor necrosis factor-alpha therapies can be successfully used for HIV-infected patients with stable HIV loads and CD4(+) lymphocyte counts.

A case of erosive polyarthritis in a patient diagnosed with a suspicion of atypical mycobacteria.

In this report, we introduce a case of erosive polyarthritis in a 55-year-old female diagnosed with Mycobacterium abscessus pulmonary infection. Her arthritis has been worsened after use of DMARDs. The patient demonstrated a significant response to the antimicrobial regimen that was administered. We call special attention to the possibility of Mycobacterium abscessus being a cause of reactive polyarthritis, particularly if symptoms worsened after use of disease-modifying antirheumatic drugs (DMARDs), but further studies are necessary for clarification.

Novel influenza A (H1N1) virus-induced hemophagocytosis: first case reported in Saudi Arabia.

H1N1 is a novel subtype of the influenza A virus. Since its reemergence in 2008, it has been reported to cause a variety of illnesses ranging from mild flu-like symptoms to severe multiorgan failure. We report a case of a young immunocompetent man who presented with progressive shortness of breath and rapidly developed multiorgan dysfunction, including pancytopenia from H1N1 infection during the 2010-2011 influenza season. His H1N1 pneumonia caused severe acute respiratory distress syndrome, respiratory failure requiring mechanical ventilation, rhabdomyolysis, myocarditis, hepatitis, encephalitis, and renal failure. During the diagnostic workup, a bone marrow biopsy was performed, showing hemophagocytosis secondary to the H1N1 infection. Unfortunately the patient died despite aggressive measures. Published reports contain only a few records of H1N1-induced hemophagocytosis. This is the first case report from Saudi Arabia with H1N1-induced secondary hemophagocytosis. It also highlights the fact that the virus is still very virulent and will pose a major annual health risk along with the seasonal influenza for at least the next few years.