Biographical Feature: Marie Louise Landry, M D

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Biographical Feature: Marie-Louise Landry, M.D.

Yi-Wei Tanga,b

a_{Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA}

b_{Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, USA}

T

hroughout her career, Dr. Marie-Louise Landry has brought a unique combination of actionable medical intelligence, charisma, and energy to the ﬁeld of clinical virology and infectious diseases. When asked whence her boundless energy and motivation stems, Marie states, “My father was a French-Canadian immigrant, 1 of 12 children, who left school at age 14 to work in the mills in New England during the Depression. My mother left school at 15 to work. I was the second of 5 children and, beginning at age 8, worked various jobs to earn money, including yard work, news-paper routes, and then ﬁeld work in shade tobacco farms in the summers. Even as a kid, work gave me a feeling of independence, and I took great pride in having my own money and being able to contribute to the family.”

Having been raised by parents who encouraged education and public service, Marie decided to become a physician when she was only 12 years old. Marie’s work ethic and energy undoubtedly helped her in pursuing her dream. She worked two or three jobs each summer while studying at the University of Massachusetts in Amherst. After graduation, she worked as a chemist at Pratt & Whitney Aircraft by day and worked

CitationTang Y-W. 2019. Biographical Feature:

Marie-Louise Landry, M.D. J Clin Microbiol 57:e01013-19.https://doi.org/10.1128/JCM .01013-19.

EditorErik Munson, Marquette University

Address correspondence to yiweitangmd@gmail.com.

Accepted manuscript posted online14

August 2019

Published

crossm

23 October 2019

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nights and weekends as a cocktail waitress to save for medical school. At Georgetown Medical School, Marie continued as a cocktail waitress evenings and weekends, until she secured jobs doing admission physicals at private hospitals to pay her expenses. When she started her internal medicine internship, Marie listed 26 jobs in her résumé. “My only regret is that I have no photos in my various cocktail waitress uniforms,” Marie quips with a smile.

After medical school, Marie trained in internal medicine at Yale and has never left. There, she met her husband, Peter Aronson, a physician scientist. Upon completion of residency training, she spent a year as an emergency room physician at the Department of Veterans Affairs (VA) Connecticut Medical Center and then began an infectious diseases fellowship, which required 2 years of laboratory research. Although she was initially reluctant to spend time away from patients, Marie says, “Viruses piqued my interest, so I sought out Edith G. D. Hsiung, Ph.D., a professor in laboratory medicine, who was doing work in clinical and diagnostic virology (1). I was accepted into her lab at the VA in 1979, and to my surprise, this experience opened doors to a new and exciting world and ultimately changed my career path. Dr. Hsiung’s enthusiasm for virology and every ‘discovery,’ no matter how small, was in itself infectious. In addition, at adult infectious disease case conferences, the faculty turned to me, a mere fellow, to ask virology questions. This was the ﬁrst time I had knowledge that the faculty did not, and I came to the realization that this was a transition period and that by staying in virology, I could provide a useful service.”

Forty years ago, when she started in virology, viral detection methods were conﬁned to virus isolation in embryonated eggs, suckling mice, or cell culture and acute- and convalescent-phase serology by complement ﬁxation. Marie recalls, “When I worked at the VA hospital as a fellow, the phone in the lab never rang. Many times, I had to solicit samples from my clinical colleagues, and by the time I isolated a virus and called the ward, no one cared because there was no treatment, and the patient was either dead or better.”

As a fellow, Marie worked to optimize isolation of viruses in cell culture and evaluated the efficacy of acyclovir, then a new antiviral, using the guinea pig model of genital herpes (2–4). After 2 years with Dr. Hsiung, Marie spent 2 years with William Summers, M.D., Ph.D., currently professor emeritus of therapeutic radiology and mo-lecular biophysics and biochemistry at Yale, learning about Southern blotting, DNA hybridization, and other pre-PCR molecular methods. In the New Haven area, there were three deaths from culture-proven herpes encephalitis in 3 weeks in December 1979, and a nurse caring for one of these patients developed a herpetic lesion on her nose. Using the restriction endonuclease mapping technique, Marie examined the viral isolates and disproved the possibility that a single strain of virus caused this cluster of cases (5). Summers recalled some 40 years later, “This paper was only the second in the literature to use DNA analysis to study an infectious disease outbreak and the first to bring the nascent field of molecular epidemiology to clinical virology. Marie experi-enced firsthand the swift revolution from the ‘classical’ virology of cell culture, cyto-pathic effects, Cowdry inclusion bodies, and embryonated eggs to the ‘molecular’ world of nucleic acid chemistry, monoclonal antibodies, and laboratory automation. She was prepared by experience, enthusiasm, and expertise to make important contributions as she moved on in her career as an independent scholar and clinician.”

Zhi-Ming (Thomas) Zheng, M.D., Ph.D., a senior investigator and head of the tumor virus RNA biology section at the National Cancer Institute, NIH, recalled, “I have enjoyed a long friendship with Marie since 1981. I first met her at one of Dr. Hsiung’s lab meetings shortly after I arrived at Yale to begin my clinical virology training. My first impression of Marie was that her questions were always relevant to the rapid diagnosis of viral infections. Her enthusiasm for improving on classical virology diagnostics by using molecular and genotyping tools for viral infections was amazing in the early 1980s, when molecular biology in medicine was just starting. At that time, we took handwritten protocols from one lab to another. While she was back and forth from Bill Summers’s lab to Dr. Hsiung’s lab during my first year at Yale, Marie taught me

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molecular virology by hand— how to purify viral DNA, run agarose gel electrophoresis, clone a viral DNA fragment for probe preparation, and perform Southern blot hybrid-ization. She always had humor, making me laugh, and was encouraging and energetic when I felt lonely or tired.”

In 1984, Marie was appointed as an assistant professor of both laboratory medicine and internal medicine at Yale and worked with Dr. Hsiung to establish a virology reference laboratory to serve the VA system. Marie subsequently directed the lab for 15 years. Marie initially continued her research on the pathogenesis and treatment of genital herpes in the guinea pig model (6), spent many evenings meeting with patients at “herpes help groups,” ran the diagnostic virology lab at the VA, taught the virology course to Yale medical students, and attended on the infectious disease service. This was also the time that AIDS first was recognized, which greatly transformed both infectious disease practice and diagnostic virology. In 1987, Marie secured funding for the addition of a retrovirus diagnostic section to the VA virology reference laboratory, and Brigitte Griffith, as the new HIV section chief, then introduced HIV culture in human lymphocytes for both diagnosis and research (7). It was in this lab that HIV-2 was isolated from the second case of HIV-2 infection diagnosed in the country, from a patient at Yale. Due to her early experience with HIV culture, she served as chair of the national VA Biosafety Advisory Committee for Retrovirus Research from 1988 to 1990. Subsequently, through the Yale AIDS Clinical Trials Unit (ACTU), Marie was involved in developing a more rapid cytomegalovirus (CMV) resistance assay (8) as well as the first application of nucleic acid amplification testing (NAAT) for determining HIV viral load, a much safer and more rapid method than lymphocyte culture.

In the early years, Marie explored the use ofin situhybridization for detection and identification of herpes simplex virus (HSV) infection in cultured cells but found that immunologic methods using new monoclonal antibodies were more sensitive, simpler, and cheaper than nonamplified nucleic acid hybridization techniques (9). The advent of monoclonal antibodies was momentous, allowing for a rapid, accurate method of identification of viruses beyond detection of cytopathic effects (10). Marie reminisces, “I have been very fortunate to have witnessed the transition of viral diagnostics from the periphery to the mainstream of laboratory testing. It’s amazing to think of how far diagnostic virology has progressed, driven in particular by the rise of transplantation, the AIDS epidemic, herpes, hepatitis, and influenza virus therapies, as well as the repeated emergence of new viral pathogens.”

In 1989, Marie persuaded David Persing, M.D., Ph.D., then a sharp and energetic laboratory medicine resident, to prepare a perspective article on molecular diagnosis (11). In this 30-year-old article, which is still relevant today, David and Marie made a strong prediction: “if the potential problems of sample cross-contamination can be addressed and overcome, amplification methods may form the basis of a fully auto-mated nucleic acid detection system.” David, now executive vice president and chief medical and technology officer at Cepheid, said, “This has certainly proven to be correct after 30 years of practice, due, in part, to Marie’s own efforts. Technologies enabling fully automated PCR-based detection have been developed and used in tens of thousands of tests each day for infections due to HIV, tuberculosis, influenza, and many others.”

As the need for diagnostic virology services grew, in 1991 Marie was recruited to establish a new clinical virology laboratory within the laboratory medicine department at Yale New Haven Hospital. Marie insisted on unifying all virology diagnostic testing within one laboratory and, together with David Ferguson, M.T.(ASCP), former clinical virology laboratory manager, was at the forefront of adopting new methods for clinical diagnosis. In the early 1990s, CMV pp65 antigenemia revolutionized patient manage-ment, allowing for rapid quantification of CMV viral load in blood (12–15). Marie’s laboratory at Yale was the first clinical laboratory in the United States to offer the test as a routine diagnostic test. Marie and her colleagues then applied the cytocentrifu-gation technique to direct fluorescent antibody (DFA)-based detection of viruses directly in clinical samples to provide a more sensitive and specific result, first for HSV

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and varicella-zoster virus (VZV) in lesion swabs and then for respiratory viruses (16). When pooled monoclonal antibodies with dual fluorescent labels became available in 1998 and 1999, the lab conducted the initial clinical studies and was the first to introduce the test into routine clinical use (17, 18). Multiple respiratory viruses could now be efficiently detected within 1 to 2 hours with sensitivity similar to that of culture, with an immediate impact on patient care. “Marie worked tirelessly to ensure that sample quality, test utilization, and interpretation were optimal and well understood. Her efforts made a huge difference in how DFA testing was deployed and used at Yale New Haven,” commented Ferguson. While virology had been appreciated by services caring for transplant recipients, HIV patients, and pediatric patients, the impact of rapid on-demand respiratory virus DFA testing caught the attention of hospital administra-tion and the clinical virology laboratory, and Marie’s work was suddenly recognized as a valued resource for infection prevention and bed management, especially in flu season. Over the years, the virology laboratory grew from 3 to 18 staff.

Initially, NAAT was confined to viruses that were dangerous, slow, or difficult to grow in culture, and there were few commercial products. In 2000, Marie’s laboratory began to offer laboratory-developed conventional PCR for herpesviruses with gel-based am-plicon detection in the clinical laboratory, followed by nucleic acid sequence-based amplification (NASBA) for enteroviruses (19–22). Then, the floodgates opened when the laboratory transitioned to real-time TaqMan PCR (23–28). Marie implemented the real-time assays, using protocols originally from the CDC as well as those published by other international experts. Marie credits the generous guidance of many experts, especially Fred Lakeman, Greg Storch, Christine Ginocchio, Dean Erdman, and Rick Hodinka, and the friendly, collaborative atmosphere of the Annual Clinical Virology Symposium in Clearwater Beach, FL, instituted by Steve Specter in 1985 and cospon-sored by the Pan American Society for Clinical Virology. Within a few years, the clinical virology laboratory at the Yale New Haven Hospital was offering testing for all common viral pathogens. Even today, as better, faster, and simpler commercial NAATs have become available, advantages remain for lab-developed tests, including lower cost, excellent performance characteristics, efficient use of a single platform, the ability to estimate viral load in real-time qualitative assays, and the ability to update quickly in response to pathogen diversity and change (29). “We now have many rapid and accurate tests for viruses, but some are quite expensive,” Marie notes. “The challenge is discerning how we can best impact patient outcomes and then implement the most cost-effective approach.” The wealth of clinical samples arriving in the Yale laboratory also allowed collaborations with other researchers that led to the detection of new viruses and the development of new methods, including, most recently, with Ellen Foxman, M.D., Ph.D., an assistant professor of laboratory medicine and immunobiology at Yale, the recognition of virus infections by identification of an antiviral host response rather than by detection of a specific virus (30–33).

Those of you who know Marie only through clinical microbiology may not be aware of her extraordinary career as a medical educator. For almost 40 years, in addition to being director of medical studies for the department, she has essentially single-handedly taught the virology course within the preclinical curriculum at Yale School of Medicine. She has been an extraordinarily successful and beloved teacher, the only two-time winner so far of the Bohmfalk award for basic science teaching at Yale, and her evaluations glow with the students’ praise of her. In addition to being extremely organized and clear, her lectures are distinguished by her use of personal reﬂections and anecdotes, particularly of viral illnesses that have affected her and her family. When she received her ﬁrst Bohmfalk award, she was traveling, so she sent her young sons to accept it on her behalf, since many of her slides of viral illnesses included pictures of them as affected children. She now includes stories from the next generation, her grandchildren, to help students remember the plethora of viral pathogens.

In addition to her academic career, Marie has been active in her community as a Little League baseball coach and a Cub Scout den leader and assistant scoutmaster. She hosted in her home a Fresh Air Fund child in the summer and high school students in

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the town of Guilford’s “A Better Chance” (ABC) program during the school year. For 14 years, she served on the Guilford ABC board of directors as secretary and as academic advisor and mentor to a number of talented young women of color from inner cities who attended the town’s high school as ABC scholars and went on to obtain college and graduate degrees.

Marie has also been an invaluable mentor to young Yale faculty, giving guidance, support, and the occasionally needed push. In the Department of Laboratory Medicine, where she is vice chair, her inﬂuence extends far beyond clinical virology to other areas of the laboratory-clinical interface. Marie brings the same attention to detail and thoroughness to her administrative and director roles, including as cochair of the hospital system Laboratory Formulary Committee, as she does to her academic en-deavors. She will review guidelines, internal data, and internal and external expert opinions to determine best practices for moving forward. David Peaper, M.D., Ph.D., and Sheldon Campbell, M.D., Ph.D., other Yale clinical microbiologists, are only half-joking when they say they wear bracelets with the abbreviation “WWMD,” for “What would Marie do?” David and Sheldon emphasize, “When confronted with a difﬁcult adminis-trative, educational, clinical, or quality problem in the laboratory, asking ‘WWMD?’ may not lead to the easiest, most expedient, or simplest answer, but it will almost always lead to thebestanswer.” The quality of the work being done around Marie is elevated to her high standards by dint of her leadership and the example she sets.

Marie states, “I have been very fortunate to have participated in the transformation of viral diagnostics over the past 4 decades. In the past, virology was distinct from the rest of microbiology due to the need for cell culture expertise. As cell culture has been increasingly abandoned in routine labs, I am concerned that NAAT testing for viral pathogens may be dispersed to molecular labs, core labs, or to the point of care (34) and viral serology dispersed to chemistry or immunology labs, and as a result, expertise in use and interpretation of viral diagnostics as a whole may be lost. So I am grateful that I have been able to specialize in clinical virology during a very exciting and transformative time.” Marie’s contributions to the ﬁeld include recognition and early adoption of new methods in routine clinical practice and, by starting new virology laboratories, building laboratory capacity to support patient care.

During her career in diagnostic virology, she has received the Diagnostic Virology Award from the Pan American Society for Clinical Virology in 2005 and the Outstanding Teacher Award, Yale Pathology and Laboratory Medicine Residents in 2012. She has served as councilor, secretary-treasurer, and then president of the Pan American Society of Clinical Virology. She relates that she has particularly enjoyed being the virology volume editor of theManual of Clinical Microbiology from ASM Press for the past 4 editions, because she gets to carefully read, and then reread, all the virology chapters (35). She is the quintessential academic physician, exhibiting the same boundless energy and conviction as when I ﬁrst met her at the Annual Clinical Virology Sympo-sium in 1997 at Clearwater Beach; may her living legacy continue.

ACKNOWLEDGMENTS

I express sincere gratitude to Marie Landry for her provision of time and biblio-graphic items to this biobiblio-graphical feature and for liberally sharing her wealth of experience and insight. I thank and acknowledge the following colleagues who pro-vided tremendous assistance to this biography: Sheldon Campbell, David Ferguson, David Peaper, David Persing, Bill Summers, and Thomas Zhi-Ming Zheng.

REFERENCES

1. Landry ML. 1989. G.D. Edith Hsiung, Ph.D.: virologist and teacher. Yale J Biol Med 62:62–77.

2. Landry ML, Mayo DR, Hsiung GD. 1982. Comparison of guinea pig embryo cells, rabbit kidney cells, and human embryonic lung ﬁbroblast cell strains for isolation of herpes simplex virus. J Clin Microbiol 15:842– 847. 3. Landry ML, Madore HP, Fong CK, Hsiung GD. 1981. Use of guinea pig

embryo cell cultures for isolation and propagation of group A coxsacki-eviruses. J Clin Microbiol 13:588 –593.

4. Landry ML, Lucia HL, Hsiung GD, Pronovost AD, Dann PR, August MJ, Mayo DR. 1982. Effect of acyclovir on genital infection with herpes simplex virus types 1 and 2 in the guinea pig. Am J Med 73:143–150. https://doi.org/10.1016/0002-9343(82)90080-8.

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5. Landry ML, Berkovits N, Summers WP, Booss J, Hsiung GD, Summers WC. 1983. Herpes simplex encephalitis: analysis of a cluster of cases by restriction endonuclease mapping of virus isolates. Neurology 33: 831– 835.https://doi.org/10.1212/wnl.33.7.831.

6. Landry ML, Zibello TA. 1988. Ability of herpes simplex virus (HSV) types 1 and 2 to induce clinical disease and establish latency following pre-vious genital infection with the heterologous HSV type. J Infect Dis 158:1220 –1226.https://doi.org/10.1093/infdis/158.6.1220.

7. Mellors JW, Grifﬁth BP, Ortiz MA, Landry ML, Ryan JL. 1991. Tumor necrosis factor-alpha/cachectin enhances human immunodeﬁciency vi-rus type 1 replication in primary macrophages. J Infect Dis 163:78 – 82. https://doi.org/10.1093/infdis/163.1.78.

8. Landry ML, Stanat S, Biron K, Brambilla D, Britt W, Jokela J, Chou S, Drew WL, Erice A, Gilliam B, Lurain N, Manischewitz J, Miner R, Nokta M, Reichelderfer P, Spector S, Weinberg A, Yen-Lieberman B, Crumpacker C. 2000. A standardized plaque reduction assay for determination of drug susceptibilities of cytomegalovirus clinical isolates. Antimicrob Agents Chemother 44:688 – 692.https://doi.org/10.1128/aac.44.3.688-692.2000. 9. Landry ML, Zibello TA, Hsiung GD. 1986. Comparison of in situ hybrid-ization and immunologic staining with cytopathology for detection and identiﬁcation of herpes simplex virus infection in cultured cells. J Clin Microbiol 24:968 –971.

10. Zhao LS, Landry ML, Balkovic ES, Hsiung GD. 1987. Impact of cell culture sensitivity and virus concentration on rapid detection of herpes simplex virus by cytopathic effects and immunoperoxidase staining. J Clin Mi-crobiol 25:1401–1405.

11. Persing DH, Landry ML. 1989. In vitro ampliﬁcation techniques for the detection of nucleic acids: new tools for the diagnostic laboratory. Yale J Biol Med 62:159 –171.

12. Landry ML, Ferguson D. 1993. Comparison of quantitative cytomegalo-virus antigenemia assay with culture methods and correlation with clinical disease. J Clin Microbiol 31:2851–2856.

13. Landry ML, Ferguson D, Stevens-Ayers T, de Jonge MW, Boeckh M. 1996. Evaluation of CMV Brite kit for detection of cytomegalovirus pp65 antigenemia in peripheral blood leukocytes by immunoﬂuorescence. J Clin Microbiol 34:1337–1339.

14. Landry ML, Cohen S, Huber K. 1997. Comparison of EDTA and acid-citrate-dextrose collection tubes for detection of cytomegalovirus anti-genemia and infectivity in leukocytes before and after storage. J Clin Microbiol 35:305–306.

15. Landry ML, Ferguson D. 2000. 2-hour cytomegalovirus pp65 antigen-emia assay for rapid quantitation of cytomegalovirus in blood samples. J Clin Microbiol 38:427– 428.

16. Landry ML, Ferguson D, Wlochowski J. 1997. Detection of herpes simplex virus in clinical specimens by cytospin-enhanced direct immunoﬂuores-cence. J Clin Microbiol 35:302–304.

17. Landry ML, Ferguson D. 2000. SimulFluor respiratory screen for rapid detection of multiple respiratory viruses in clinical specimens by immu-noﬂuorescence staining. J Clin Microbiol 38:708 –711.

18. Campbell S, Landry ML. 2018. Rapid micriobial antigen tests, p 99 –126.

InTang Y-W, Stratton CW (ed), Advanced techniques in diagnostic microbiology, 3rd ed, vol 2. Springer-Nature Publishing, New York, NY. 19. Landry ML, Ferguson D, Cohen S, Peret TC, Erdman DD. 2005. Detection of human metapneumovirus in clinical samples by immunoﬂuorescence staining of shell vial centrifugation cultures prepared from three differ-ent cell lines. J Clin Microbiol 43:1950 –1952.https://doi.org/10.1128/ JCM.43.4.1950-1952.2005.

20. Landry ML, Garner R, Ferguson D. 2003. Comparison of the NucliSens Basic kit (nucleic acid sequence-based ampliﬁcation) and the Argene Biosoft Enterovirus Consensus reverse transcription-PCR assays for rapid detection of enterovirus RNA in clinical specimens. J Clin Microbiol 41:5006 –5010.https://doi.org/10.1128/jcm.41.11.5006-5010.2003.

21. Landry ML, Garner R, Ferguson D. 2003. Rapid enterovirus RNA detection in clinical specimens by using nucleic acid sequence-based ampliﬁca-tion. J Clin Microbiol 41:346 –350.https://doi.org/10.1128/jcm.41.1.346 -350.2003.

22. Landry ML, Garner R, Ferguson D. 2005. Real-time nucleic acid sequence-based ampliﬁcation using molecular beacons for detection of enterovi-rus RNA in clinical specimens. J Clin Microbiol 43:3136 –3139.https://doi .org/10.1128/JCM.43.7.3136-3139.2005.

23. Habib-Bein NF, Beckwith WH, III, Mayo D, Landry ML. 2003. Comparison of SmartCycler real-time reverse transcription-PCR assay in a public health laboratory with direct immunoﬂuorescence and cell culture assays in a medical center for detection of inﬂuenza A virus. J Clin Microbiol 41: 3597–3601.https://doi.org/10.1128/JCM.41.8.3597-3601.2003.

24. Landry ML, Cohen S, Ferguson D. 2008. Real-time PCR compared to Binax NOW and cytospin-immunoﬂuorescence for detection of inﬂuenza in hospitalized patients. J Clin Virol 43:148 –151.https://doi.org/10.1016/ j.jcv.2008.06.006.

25. Landry ML, Cohen S, Ferguson D. 2008. Prospective study of human metapneumovirus detection in clinical samples by use of light diagnos-tics direct immunoﬂuorescence reagent and real-time PCR. J Clin Micro-biol 46:1098 –1100.https://doi.org/10.1128/JCM.01926-07.

26. Landry ML, Ferguson D. 2009. Polymerase chain reaction and the diag-nosis of viral gastrointestinal disease due to cytomegalovirus, herpes simplex virus and adenovirus. J Clin Virol 45:83– 84.https://doi.org/10 .1016/j.jcv.2009.02.007.

27. Landry ML, Ferguson D. 2010. Cytospin-enhanced immunoﬂuorescence and impact of sample quality on detection of novel swine origin (H1N1) inﬂuenza virus. J Clin Microbiol 48:957–959.https://doi.org/10.1128/JCM .01678-09.

28. Landry ML, Ferguson D. 2014. Comparison of Simplexa Flu A/B & RSV PCR with cytospin-immunoﬂuorescence and laboratory-developed Taq-Man PCR in predominantly adult hospitalized patients. J Clin Microbiol 52:3057–3059.https://doi.org/10.1128/JCM.00738-14.

29. Landry ML, Tang Y-W. 2016. Immunologic and molecular assays for viral diagnosis, p 538 –549.InDetrick B, Schmitz JL, Hamilton RG (ed), Manual of molecular and clinical laboratory immunology, 8th ed. ASM Press, Washington, DC.

30. Esper F, Weibel C, Ferguson D, Landry ML, Kahn JS. 2005. Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children. J Infect Dis 191:492– 498.https://doi.org/ 10.1086/428138.

31. Zhu Z, Tang W, Ray A, Wu Y, Einarsson O, Landry ML, Gwaltney J, Jr, Elias JA. 1996. Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor kappa B-dependent transcriptional activa-tion. J Clin Invest 97:421– 430.https://doi.org/10.1172/JCI118431. 32. Zhao J, Liu J, Vemula SV, Lin C, Tan J, Ragupathy V, Wang X,

Mbondji-Wonje C, Ye Z, Landry ML, Hewlett I. 2016. Sensitive detection and simultaneous discrimination of inﬂuenza A and B viruses in nasopharyn-geal swabs in a single assay using next-generation sequencing-based diagnostics. PLoS One 11:e0163175.https://doi.org/10.1371/journal .pone.0163175.

33. Landry ML, Foxman EF. 2018. Antiviral response in the nasopharynx identiﬁes patients with respiratory virus infection. J Infect Dis 217: 897–905.https://doi.org/10.1093/infdis/jix648.

34. Azar MM, Landry ML. 2018. Detection of inﬂuenza A and B viruses and respiratory syncytial virus by use of Clinical Laboratory Improvement Amendments of 1988 (CLIA)-waived point-of-care assays: a paradigm shift to molecular tests. J Clin Microbiol 56.https://doi.org/10.1128/JCM .00367-18.

35. Pfaller MA, Carroll KC, Funke G, Landry ML, Richter SS, Warnock D (ed). 2019. Manual of clinical microbiology, 12th ed. ASM Press, Washington, DC.