Laboratory Surge Response to Pandemic (H1N1) 2009 Outbreak, New York City Metropolitan Area, USA

Emergency preparedness programs are critical.

L ocal sentinel laboratories are a critical component of the Laboratory Response Network, providing frontline diagnostics and, in many instances, the initial reporting for infectious disease outbreaks. In the event of a major health crisis, the responses of a regional clinical laboratory can be central to the ability of civic authorities and healthcare systems to handle such emergencies. This report describes successful steps taken by a hospital-based regional reference laboratory in response to a 7.5× increase in respiratory virus testing during the fi rst 3 weeks (April 27- May 15, 2009) of an outbreak of a novel infl uenza A (H1N1), now referred to as infl uenza A pandemic (H1N1) 2009, in the greater New York City metropolitan area.
The North Shore-Long Island Jewish Health System (NSLIJHS) is the third largest nonsectarian not-for-profi t health system in the United States and serves Nassau and Suffolk Counties, New York, and the Queens and Staten Island boroughs of New York City. The NSLIJHS Central Laboratories serve 15 hospitals and affi liated regional physician practices; virus testing is performed at the Centralized Laboratories in the Clinical Virology Laboratory (CVL). In the aftermath of the anthrax event of September 2001, NSLIJHS developed an extensive system-wide emergency preparedness plan to deal with potential biothreat and bioterrorism events that could greatly affect a health system. This plan was tested, beginning Friday evening, April 24, 2009, when 20 students 14-17 years of age with symptoms of an infl uenza-like illness sought evaluation at the pediatric emergency room of Schneider Children's Hospital at Long Island Jewish Medical Center, one of the hospitals served by NSLIJHS. The students were among those attending a preparatory school in Queens, New York, who began experiencing infl uenza-like symptoms April 22-23, 2009 (1). Some students had recently traveled to Mexico, raising immediate concern about pandemic (H1N1) 2009 (2). The following day, Saturday, April 25, an additional 67 persons 11-18 years of age and 16 children <8 years of age were evaluated in NSLIJHS emergency rooms. Over the next 3 days, infl uenza-related cases at NSLIJHS emergency rooms increased rapidly.

Standard Testing for Respiratory Viruses and Test Capacity
During the normal infl uenza season, the clinical laboratories of NSLIJHS hospitals perform rapid infl uenza A+B antigen testing, using either BinaxNOW A+B test (Inverness, Scarborough, MA, USA) or the 3M test. Nasopharyngeal swab samples in Universal Transport Media (Diagnostic Hybrids Inc., Athens, OH, USA) and nasopharyngeal wash and aspirate samples are tested. Specimens with test results positive for infl uenza A or B are not processed further unless warranted by underlying patient conditions. Due to the suboptimal sensitivity of rapid antigen tests, all samples with negative test results are forwarded to CVL for detection of adenovirus, human metapneumovirus, infl uenza A and B, parainfl uenza viruses 1, 2, and 3, and respiratory syncytial virus by DFA testing, using D3 Ultra Respiratory Virus reagents (Diagnostic Hybrids Inc.) and by rapid respiratory virus culture, using R-Mix cells (Diagnostic Hybrids Inc.).
NSLIJHS laboratories routinely encounter a seasonal increase in respiratory virus testing, peaking in mid-tolate February and waning by May. The historic maximum test volume occurred in February 2008, when CVL tested 6,021 samples and clinical laboratories system-wide performed 2,901 rapid infl uenza tests, for a combined daily average of 308 tests. During April 1-23, 2009, CVL tested 1,955 samples and clinical laboratories system-wide performed 676 rapid infl uenza tests, for a combined daily average of 119 tests. These volumes were similar to those for preceding years.

Molecular Detection of Respiratory Viruses
During 2008, the central NSLIJHS Molecular Diagnostics Laboratory performed extensive validation studies of the Luminex xTAG Respiratory Virus Panel (RVP) assay (Luminex Molecular Diagnostics, Toronto, Canada) (3,4). The version of the RVP assay that has been cleared by the US Food and Drug Administration detects adenovirus, human metapneumovirus, parainfl uenza viruses 1, 2, and 3, rhinovirus/enterovirus group, respiratory syncytial virus, and infl uenza A and B. This RVP assay can subtype infl uenza A as seasonal human H1 or H3 virus. The research-use-only version of the RVP assay also detects parainfl uenza 4 and coronaviruses OC43, NL64, 229E, and HKU-1. Prior to the outbreak of pandemic (H1N1) 2009, the RVP assay was used for selected clinical cases and research studies, with the intention of converting to use of the RVP assay for all respiratory virus testing during the off-peak 2009 summer months.

Laboratory Testing during the Novel Infl uenza (H1N1) Outbreak
By Monday, April 27, 2009, it was clear that an unusual event was occurring (5,6). Rapid infl uenza testing at all NSLIJHS clinical laboratories and the centralized laboratories increased dramatically ( Figure 1). On April 29, daily test volumes peaked at 903 tests, representing a 7.5× increase over the prior average daily volume for April and a sustained 3× increase over the February 2008 record daily volume of 308 tests.
The weekend of April 25-26, prior to declaration of a system-wide emergency, scheduled CVL staff responded with a round-the-clock effort to keep up with testing needs. On April 27, despite full staffi ng, considerable overtime was required to perform testing. On April 28, a command meeting was held at the NSLIJHS central laboratories to delineate an action plan to respond to the crisis. The major issues were staffi ng, testing algorithms, laboratory space, laboratory information systems and biostatistical reporting, leadership roles, and client service functions. The action plan was immediately authorized by system leadership. A key consequence of the plan was immediate deployment of an enhanced and diversifi ed work force, including nonlicensed support staff, licensed research staff, laboratory information services personnel, and biostatistical reporting staff. Beginning April 28, these actions enabled CVL to expand its weekday working hours from 6:00 AM-6:00 PM to 5:00 AM-1:00 AM and its weekend working hours from 8:00 AM-4:00 PM to 6:00 AM-10:00 PM. With this personnel strategy, CVL was able to report DFA assay and R-Mix culture results on a real-time basis throughout the crisis. To accommodate the high volume of R-Mix cultures, CVL reduced the normal test algorithm of screening at 24 hours, 48 hours, and 7 days to a single screening and confi rmatory testing at 48 hours. Under these unusual circumstances, this change was considered acceptable as historic laboratory data had demonstrated that 97%-98% of all respiratory viruses are detected in 48 hours.
A second key element of the April 27-May 1 work week was the initiation of RVP testing for infl uenza A subtyping. The assay was needed to 1) identify which patients were possibly infected with virus subtype H1N1 rather than circulating seasonal H1 or H3 strains and 2) track the magnitude of the outbreak. By May 1, in consultation with the New York State and New York City DOHs, the NSLI-JHS Molecular Diagnostics Laboratory began testing, with the RVP assay, the remaining samples for index patients screened on April 24-25 (i.e., the 68 archived samples with negative rapid infl uenza A/B antigen screening results) as well as all incoming samples with test results positive for infl uenza A by DFA assay and/or culture.
Due to the large volume of incoming and archived samples, RVP testing was prioritized for hospitalized patients, followed by persons known to be at risk as a result of the school exposure or recent travel to Mexico. May (7). These data indicated that during the outbreak, the predictability of a nonsubtypeable infl uenza A virus identifi ed by RVP assay to be pandemic (H1N1) 2009 was high (7). In July 2009, the NSLIJHS Molecular Diagnostics Laboratory obtained New York State approval to confi rm cases of pandemic (H1N1) 2009 by using the published CDC method. The ability to subtype infl uenza A, ruling out seasonal subtypes H1 and H3, and to detect additional respiratory viruses by RVP assay (8) within 24 hours enabled NSLIJHS leadership to know whether highrisk patients, inpatients, or members of the System's workforce had probable pandemic (H1N1) 2009.
From that point forward, the Molecular Diagnostics Laboratory provided RVP subtyping results (seasonal H1, H3, or nonsubtypeable) within 24 hours for critically important cases identifi ed by infection-control or civic authorities, especially health offi cials making public health decisions about regional school systems, and within 48-72 hours for lower priority cases. The laboratory documented that the sensitivity of the RVP assay for detecting all infl uenza A types was far superior to that for other test methods (8), justifying RVP testing for admitted patients with negative infl uenza A/B rapid test results. This simplifi ed protocol was instituted May 11, 2009, in consultation with system and regional civic authorities.
A detailed scientifi c analysis of the virology of the outbreak, especially the sensitivities and specifi cities of the tests, is described elsewhere (8); for this publication, summary results are given. Figure 2

Physical Plant Construction
The decision was made on April 28 to immediately expand the CVL into contiguous space. Although the se- verity and duration of the outbreak were unknown, failure to be proactive in expanding the surge capacity of the laboratory was unacceptable. Over 4 days, a negative-pressure laboratory was completed; biohazard hoods, vacuum, and CO 2 lines were installed; incubators and ancillary equipment were ordered; and a specimen-processing area with computer terminals was completed. The additional laboratory space enabled a sustained higher RVP testing capacity and was well-justifi ed because the laboratory processed 700-970 tests a day during the second wave of the outbreak (May 15-31).

Laboratory Information System and Biostatistical Reporting
The Laboratory Information System team accomplished the following tasks over 3 days (April 28-30): 1) created 2 new tests (RVP, novel H1N1 confi rmatory) and 3 Laboratory Information System environments (Cerner Classic and Cerner Millennium [Cerner Corp., Kansas City, MO, USA] and Meditech [Medical Information Technology, Inc., Westwood, MA, USA]); 2) validated tests and billing for 11 health information systems; 3) set up a CVL workstation dedicated to infl uenza specimens; 4) reported daily to infection-control and senior system leadership; 5) reported to the New York State DOH Electronic Clinical Laboratory reporting system; and 6) established logic rules to automatically print positive test results to Client Services. The NSLIJHS Krasnoff Quality Management Institute provided daily biostatistical reports to system leadership. Data assembly was automated by building an Oracle database with interfaces to the Laboratory Information System, with crosschecking to confi rm the accuracy and validity of data.

Leadership and Ancillary Personnel
The medical director of CVL and the Molecular Diagnostics Laboratory (C.C.G.), the overall director of System laboratories (J.M.C.), and the chief operating offi cer of System laboratories (R.S.) divided responsibilities for oversight of staffi ng, physical plant resources, supplies, the laboratory information system, courier services, and finance; for daily briefi ngs of laboratory staff, medical staff, infection control, and System leadership; and for DOH notifi cation. This included daily system-wide conference calls at 7:00 AM, 3:00 PM, and 11:00 PM. A critical focus was the protection of the healthcare workforce and inpatients from nosocomial spread of pandemic (H1N1) 2009. The medical director reported regularly to the New York City, New York State, and Nassau and Suffolk County DOHs, keeping civic offi cials apprised of the epidemiology of the outbreak.
An additional key element of the laboratory response was communication with physicians and patients. From April 27 through May 15, the central laboratories' Client Services, in addition to their usual 8,000-9,000 calls a week, handled an additional 1,000 telephone calls a week pertaining specifi cally to the outbreak. Laboratory leadership provided scripts to Client Services, including answers to frequently-asked questions. Client Services made strategic calls to physician offi ces to provide updates on testing protocols and priorities. In addition, the NSLIJHS sales force was redirected to support physician offi ces, including communication of protocols and procedures and deliveries of supplies.

Discussion
The fundamental role of a clinical laboratory is to provide medical care to the patient population it serves. The ability to respond to a specifi c crisis also provides critical support to civic agencies. Although our laboratory did not perform surge testing for the DOHs, nor was testing specifically delineated between our laboratory and the DOHs, our ability to provide comprehensive virus testing, including infl uenza A subtyping, for such a large patient base (≈6.5 million persons) indirectly assisted the DOHs by providing key diagnostic information with which the DOHs could make management and testing decisions.
The steps taken by our laboratory were strongly supported by system leadership and enabled NSLIJHS to successfully meet this crisis. It is our hope that delineation of  these steps will be valuable to other health systems and their laboratories because there undoubtedly will be future public health crises that will demand an immediate increase in reference laboratory testing capacity. The toll of this crisis was on NSLIJHS laboratory personnel. The long hours required to meet testing demands were keenly felt in the fi rst days, when the emergency response had not been activated. However, initial implementation of the emergency response only enabled us to keep up with the crisis, not go beyond it. Routine personnel worked extended hours, despite the support of cross-covering personnel. One key reason was the high level of expertise required to perform the virology and molecular testing; substitute personnel could not be deployed on short notice. The other key reason was the staff's dedication and their reluctance to go off-duty. Management created obligatory off-duty rotations to ensure our work force was as rested as possible.
The major surge response stratagems, established at the outset, guided NSLIJHS management actions throughout the crisis. Workforce management was top priority. Coordinating the System's general laboratories with CVL, daily reporting of test volumes and results, and providing support to Client Services enabled the laboratories to remain in synchrony with emergency departments, hospital facilities, and physician practices. Also imperative was the need for all NSLIJHS laboratories to maintain normal operations. At no time during a crisis can normal laboratory services undergo degradation.
Preparedness for infectious outbreaks has increasingly been a point of concern, owing to the threats of bioterrorism and natural diseases. Attention is given primarily to the hypothetical preparedness of fi rst responders and acute-care facilities, either in the form of surveys (9)(10)(11)(12), workfl ow analysis (13), or reviews (12,14,15). The outbreak of severe acute respiratory syndrome in 2003 generated reports from an actual global outbreak. In Hong Kong and Toronto, note was made of the frustrations arising from limited access to laboratory testing, resulting in a decreased ability to provide timely screening of patients for severe acute respiratory syndrome (16). The ability of a laboratory to deploy molecular respiratory virus testing was felt to be key for a successful response to an infectious disease outbreak, as such testing is highly sensitive, specifi c, and capable of high-throughput (12).
We believe that there will be future infectious outbreaks that will strain the standing capacity of clinical laboratories, requiring effective implementation of surge capacity responses independent of public health laboratory support. We believe that the steps taken by NSLIJHS laboratories during the initial outbreak of pandemic (H1N1) 2009 and the lessons learned (Table) from that experience are of value. The exceptional 2-way interaction between the NSLIJHS Laboratories and the NY public health laborato-ries was an excellent example of how sentinel laboratories function as a key component of the Laboratory Response Network system and can serve as a major support for public health in the time of crisis. our laboratory and NSLIJHS for the duration of this infl uenza outbreak.
C.C.G. acknowledges funding support from the United States Department of Defense Award W81XWH-08-1-0477.
Dr Crawford is senior vice president for laboratory services and chair of the Department of Pathology and Laboratory Medicine for the North Shore-Long Island Jewish Health System. His primary research interest is advancing the role that pathology plays in public health and national healthcare reform.