Patients were admitted to ICU after a median (Q1, Q3) of 9days (4, 13) from the onset of symptoms with an admission SOFA score median (Q1, Q3)of 11 (6.5, 12). vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 13) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with Ractopamine HCl faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy. Subject terms:Immunology, Diseases, Pathogenesis, Signs and symptoms == Introduction == Over Ractopamine HCl 2 decades, there has been 3 emerging coronavirus causing human outbreaks. In 2003, the severe acute respiratory syndrome coronavirus (SARS-CoV-1) spread from China to at least 26 countries in less than a week1. In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and continues to appear sporadically causing a severe form of acute respiratory distress syndrome and multiorgan failure that is associated with a mortality of 67%2,3. Since December 2019, the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the largest known pandemic in recent history. Data on the antibody response in MERS patients are limited. Existing data suggest that antibody response MERS-CoV typically is detected in the second and third Ractopamine HCl week after the onset of the infection4,5, but little is known about antibody response among critically ill patients and its association with viral shedding and clinical outcomes6,7. The objective of this study is to examine the IgG antibody response in critically ill patients with MERS and to examine the association of early antibody response with mortality and viral clearance. Data on the kinetics of antibody response in critically ill patients with the MERS can be critical for understanding diagnostic testing, seroepidemiology, pathogenesis and possibly passive immunotherapy. == Methods == == Settings and patients == In this prospective cohort study, we enrolled consecutive critically ill patients with MERS confirmed by real-time reverse transcription-polymerase chain reaction (rRT-PCR) and admitted to the Intensive Care Unit (ICU) at King Abdulaziz Medical City, Riyadh, Saudi Arabia between April 2015 to January 2016. == Clinical data == Clinical data was collected using standardized case report forms developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)8. We documented patients’ demographic features, underlying comorbidities, duration from the onset of symptom to presentation to the Emergency Room (ER), ICU and intubation. In addition, physiologic parameters and clinical outcomes including mortality (at ICU and hospital discharge, 90 days, 28 days), mechanical ventilation duration, length of stay in the ICU and hospital were also included. == Laboratory procedures == rRT-PCR and enzyme-linked immunosorbent assay (ELISA) for MERS-CoV were performed at the King Abdulaziz Medical City laboratory. Diagnostic testing for MERS followed the guidelines set by the Saudi Arabian Ministry of Health; nasopharyngeal swabs or sputum samples, if possible, in non-intubated patients and tracheal aspirates or bronchoalveolar lavage in intubated patients were tested by MERS-CoV rRT-PCR which targeted amplification of the upstream E protein (upE gene) and open reading frame 1a9,10. In patients with suspected MERS and negative rRT-PCR, testing was repeated at the discretion of the treating teams. For MERS-CoV positive patients, follow-up respiratory samples were collected approximately 12 times per week to assess the clearance of viral RNA for infection control purposes. We defined the time to MERS-CoV RNA clearance in respiratory samples in patients as the time from the first performed rRT-PCR after ICU admission until the test was negative on two occasions, without a positive test afterward3. Blood samples were Kif2c collected prospectively on days 1, 3, 7, 14 and 28 while the patient was in ICU. MERS-CoV antibodies were measured using ELISA (Euroimmun AG, Lubeck, Germany) using wells coated with.
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