Binnicker, Matthew J.

The coronavirus disease (COVID-19) pandemic has placed the clinical laboratory and testing for SARS-CoV-2 front and center in the worldwide discussion of how to end the outbreak. Clinical laboratories have responded by developing, validating, and implementing a variety of molecular and serologic assays to test for SARS-CoV-2 infection. This has played an essential role in identifying cases, informing isolation decisions, and helping to curb the spread of disease. However, as the demand for COVID-19 testing has increased, laboratory professionals have faced a growing list of challenges, uncertainties, and, in some situations, controversy, as they have attempted to balance the need for increasing test capacity with maintaining a high-quality laboratory operation.

Abstract Background Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infection (LRTI) in immunocompromised children. There is no standard effective treatment, though ribavirin (inhaled or oral), pooled human intravenous immunoglobulin (IVIG), and monoclonal anti-RSV antibody (palivizumab) have been described. RI-002 (ADMA Biologics Inc.) is a pooled human polyclonal IVIG that contains standardized levels of neutralizing anti-RSV antibodies. It was recently FDA-approved for prophylaxis in primary immunodeficiency patients and has been used as compassionate treatment for RSV LRTI in stem cell transplant patients. Methods Two children with T-cell lymphoblastic lymphoma, both undergoing delayed intensification chemotherapy, were diagnosed with RSV LRTI. They were both treated with RI-002 under an emergency FDA Investigational New Drug protocol. Results Patient 1, a 4-year-old boy, was admitted with fever, neutropenia and nasal congestion, and diagnosed with RSV infection on hospital day (HD) 5. On HD17, he was intubated for respiratory failure. IVIG, palivizumab, and daily oral ribavirin were administered. On HD18, he required high frequency oscillator ventilation, nitric oxide, and paralysis. He was given RI-002 (1.5 g/kg on HD20 and 0.75 g/kg on HD22). He was placed on veno-venous extracorporeal membrane oxygenation (ECMO) on HD23. RSV PCR crossing point (Cp) values trended higher, but remained positive (table). On HD33, RI-002 was re-dosed (0.75 g/kg). Pulmonary compliance and chest CTs improved (figure). On HD52, ECMO support was discontinued. He was discharged on HD88, and currently requires no respiratory support. Patient 2, a 5-year-old boy, was admitted with fever, neutropenia, nasal congestion, cough, and stridor and diagnosed with RSV infection (HD1). He required nasal cannula oxygen. IVIG and daily oral ribavirin were administered. He was given RI-002 (1.5 g/kg on HD3 and 0.75 g/kg on HD5). By HD5, he was afebrile; oxygen was discontinued. He was discharged HD6. Conclusion Human polyclonal IVIG containing standardized levels of neutralizing anti-RSV antibodies may be useful in the treatment of RSV LRTI in immunocompromised children. Future studies on the role of RI-002 in treatment of RSV infection in immunocompromised children are warranted. Disclosures All authors: No reported disclosures.

Although U.S. Food and Drug Administration-approved and CLIA-waived point-of-care (POC) molecular systems are being implemented in routine clinical practice, instrument reliability, test performance in the hands of end users, and the potential for environmental contamination resulting from use of POC molecular systems have not been extensively evaluated.

Abstract The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

Abstract The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.