>> GOOD AFTERNOON. I'M JIM GILMAN, CHIEF EXECUTIVE OFFICER OF THE NIH CLINICAL CENTER, I'M HERE TO INTRODUCE TODAY'S SPEAKER. I WANT TO START WITH HAVING -- WITH TWO BITS OF GOOD NEWS TO SHARE, YOU CAN NOW OBTAIN CME FOR THIS LECTURE SERIES. THE CODE FOR TODAY IS 24874. 24874 AND WE WILL REPEAT THAT NUMBER AT THE END OF THE LECTURE. THE SECOND PIECE OF GOOD NEWS IS DR. DEWITT, CHIEF OF THE NIAID MOLECULAR PATHOGENESIS UNIT HAS AGREED TO DELIVER THE NEXT LECTURE IN THE COVID-19 SERIES ON WEDNESDAY, MAY 6 AT 3 O'CLOCK P.M. THE LECTURE TITLE IS ANIMAL MODELS FOR COVID-19, A CRITICAL COMPONENT OF THEIR RESPONSE TO THE PANDEMIC. ONE MORE QUICK HOUSEKEEPING MESSAGE. IF YOU HAVE QUESTIONS DURING THE TALK YOU CAN USE THE QUESTION FORM ON THE VIDEO CAST WEB PAGE TO SUBMIT THEM. THIS IS AT THE BOTTOM OF THE VERY WEB PAGE YOU ARE ON WATCHING THIS LECTURE. LOOK FOR AND CLICK ON THE WORDS LIVE FEEDBACK FORM WHICH WILL TAKE YOU TO A NEW WEB PAGE AND A FORM TO SUBMIT YOUR QUESTIONS. YOUR QUESTIONS WILL GO DIRECTLY TO THE HOST WHO WILL RELAY THEM TO THE SPEAKER AT THE END OF THE LECTURE. PLEASE USE THIS FORM ONLY TO SUBMIT QUESTIONS TO THE HOST. PLEASE DO NOT USE FORM TO NOTIFY US THAT YOU ARE HAVING DIFFICULTY VIEWING THE WEBCAST. OR THE VIDEO CAST. THE HOST CAN'T HELP YOU WITH THAT. REST ASSURED THE VIDEO CAST IS BEING RECORDED AND WILL BE AVAILABLE AS AN ARCHIVE TOMORROW. NOW ON TO TODAY'S SPEAKER. IT'S THE CLINICAL CENTER IS VERY PROUD TO INTRODUCE DR. KAREN FRANK, CHIEF OF LABORATORY MEDICINE AT THE CLINICAL CENTER, SHE WAS APPOINTED TO THIS ROLE IN 2018 HAVING SERVED AS ACTING CHIEF FOR MOST OF THE YEAR BEFORE THAT. AND DEPARTMENT OF LABORATORY MEDICINE KAREN OVERSEE IT IS STAFF OF APPROXIMATELY 180 PEOPLE CONDUCTING 2,000,000 DIAGNOSTIC TESTS PER YEAR AND MOST TESTS ARE NOT ROUTINE TESTS BUT ARE AS COMPLEX AND DIVERSE AS OUR CLINICAL CENTER PROTOCOLS ARE. EVERY NEW PROTOCOL BRINGS NEW CHALLENGES WHICH KAREN AND HER TEAM RISE TO. THE COVID-19 PANDEMIC IS BUT ONE NEW CHALLENGE AND AS YOU WILL HEAR TODAY THE DEPARTMENT OF LABORATORY MEDICINE IS CONDUCTING TESTING THAT WILL HAVE GLOBAL CONSEQUENCES. KAREN RECEIVED HER M.D. AND Ph.D.s AT THE UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE AND RECEIVED POST-DOCTORAL TRAINING OF BRIGHAM AND WOMEN'S HOSPITAL AND CHILDREN'S HOSPITAL IN BOSTON. SHE WAS A CLINICAL FELLOW IN PATHOLOGY AT HARVARD MEDICAL SCHOOL. FROM 2000 TO 2012 KAREN HAD RESEARCH POSITIONS AT THE UNIVERSITY OF CHICAGO, RISING TO THE RANK OF ASSOCIATE PROFESSOR AND DIRECTOR OF THE CLINICAL MICROBIOLOGY AND CLINICAL IMMUNOLOGY LABORATORIES. IN 2012 KAREN CAME TO THE NIH TO BE CHIEF OF THE DEPARTMENT OF LABORATORY MEDICINE, MICROBIOLOGY SERVICE. KAREN MAINTAINS AN ACTIVE RESEARCH PORTFOLIO, HER RESEARCH INTERESTS INCLUDE STAFF FLOW COCUSS ARROYOS AND THE BIOLOGICAL FACTORS CAUSING RESISTANT GRAM NEGATIVE BACTERIA. SHE'S A BOARD CERTIFIED CLINICAL PATHOLOGIST, ALSO A TRIATHLETE. A FEW THINGS THAT ARE NOT IN THE WRITE UP THAT I WANT TO ALSO EMPHASIZE ABOUT KAREN, SHE'S A RECENT GRADUATE OF THE EXECUTIVE LEADERSHIP AND ACADEMIC MEDICINE AT DREXEL UNIVERSITY SO SHE'S AN ELUM, SECONDLY, I WANT TO SAY THAT IN KAREN'S INTERVIEW TO BECOME CHIEF OF THE DEPARTMENT OF LABORATORY MEDICINE THE THING THAT IMPRESSED US THE MOST WAS WHEN KAREN DESCRIBED HER VISION OF GETTING THE PATIENT INTHE THE LABORATORY. THAT IS, HAVING THE PATHOLOGISTS AND HAVING THE TECHNICIANS AND TECHNOLOGISTS IN THE LABORATORY TAKE OWNERSHIP FOR WHETHER THE PATIENTS IMPROVED OR DID NOT. THAT VISION IF WE HAD EVER HAD ANY DOUBTS BEFORE ABOUT KAREN'S ABILITY, HER ARTICULATION OF THAT VISION TOOK CARE OF ALL OF IT. WITH REGARD TO TODAY'S TOPIC KAREN HAS BEEN -- SHE HAS BEEN INCESSANT IN HER EFFORTS TO MAKE SURE SHE COULD OFFER THE BEST POSSIBLE DIAGNOSTIC CAPABILITIES WITH REGARD TO COVID-19. SHE WILL DESCRIBE SOME OF THAT -- THOSE ACTIVITIES FOR YOU. NOW THROUGH THE MAGIC OF WEBEX, I WILL HAND OVER THE MICROPHONE TO KAREN FRANK, EVEN WITHOUT BEING THERE TO TOUCH IT. KAREN, PLEASE TAKE IT. >> GOOD AFTERNOON. I WOULD LIKE TO THANK THE ORGANIZERS FOR THE INVITATION TO SPEAK WITH YOU. I WILL BE SHARING OUR EXPERIENCE FROM THE HOSPITAL LABORATORY OBTAINED DURING OUR IMPLEMENTATION OF TESTS FOR COVID-19. I HAVE NO DISCLOSEURES. TO START I WOULD LIKE TO THANK THE TEAMS WHO ARE INVOLVED TO GET THE TESTS UP AND RUNNING. THE LEADERS IN DLM WHO DESIGNED THE VALIDATIONS AND ASSAYS AND GOT THEM UP AND RUNNING AN OPERATING SEVEN DAYS A WEEK ARE ADRIENNE (INDISCERNIBLE). THE NEXT GROUP YOU SEE UNDER THEM ARE ALL THE TECHNOLOGISTS AND STAFF THAT HAVE BEEN KEEPING THESE ASSAYS GOING. THERE HAVE BEEN SOME VERY LONG DAYS AND I APPRECIATE ALL OF THEIR EFFORTS. THERE'S NUMBER OF STAFF BELOW THAT IN DLM WHO CONTRIBUTED IN A NUMBER OF WAYS BUT IN PARTICULAR I WANT TO POINT OUT HEATHER CRUMB AND REBECCA WHO IN ADDITION TO RUNNING THE DEPARTMENTS, HELPED MAKE SOME OF THESE SLIDES TODAY. AND CHIEF TECHNOLOGIST IN MICROBIOLOGY WHO OVERSEES THE PEOPLE MANY THE MIDDLE RUNNING THE TESTS. WE HAVE TO THANK CLINICAL LEADERSHIP DR. GILMAN PALMER AND HENDERSON WHO HAVE BEEN GREAT AT LEADING THE EFFORT TO BATTLE THIS PANDEMIC IN THIS SITE AND AT ROCKY MOUNTAIN LABS SENT US RNA VERY EARLIER ON WHICH WAS CRITICAL, MIKE LEONARDO WHO VOLUNTEERED TO LET US USE LAB SPACE AND HIS INSTRUMENT DAN WHO HELPED WITH QUANTITATIVE ANALYSES. BERNARD HARPER IS INSTRUMENTAL GETTING US EVERYTHING WE NEED TO KEEP OURSELVES RUNNING AND ORS AND OMS, THE CAR LINE COLLECTK ALL THESE SPECIMENS, IT'S BEEN A BIG TEAM EFFORT. SO I WILL START NOW WITH A PHONE CALL I RECEIVED RECENTLY. I GOT A PHONE CALL AND IT WAS DR. FRANK, WHAT WENT WRONG WITH MY TEST? WHY WAS THERE AN ERROR? HOW DID THIS OCCUR? THIS IS A CASE OF AN INDIVIDUAL WHO EXPERIENCED SUDDEN FEVER AND SEVERE HEADACHE OF SEVERAL DAYS DURATION LEADING TO HOME QUARANTINE FOR POSSIBLE COVID-19. ON DAY 3 OF THE ILLNESS THE SARS COV 2 TEST WAS POSITIVE. THE INDIVIDUAL SYMPTOMS RESOLVED RELATIVELY QUICKLY AND AFTER THREE WEEKS CELEBRATED HE HAD A NEGATIVE TEST RESULT. BUT AT FOUR WEEKS THE TEST WAS POSITIVE AGAIN AND THE INDIVIDUAL INTERPRETED THIS AS SOME KIND OF ERROR THEY HAD BEEN NEGATIVE ORIGINALLY AND I WILLMENT COME BACK TO THIS LATER IN THE TALK AND EXPLAIN HOW THIS CAN HAPPEN. HERE IS AN OUTLINE OF THE TALK. I WILL DESCRIBE THE TEST, COVER TESTING REGULATIONS, A LITTLE BIT ABOUT BIOSAFETY, AND THEN OUR NIH EXPERIENCE WITH VALIDATIONS. REAGENT LIMITATIONS WHICH HAVE BEEN VERY CRITICAL, STUDIES OF ALTERNATIVES THAT RESULTED, AND FINALLY WITH SERO LOGIC TESTING AND POINTS OF FUTURE STEPS. I WILL BE FOLLOWING A TIME LINE THROUGHOUT MY TALK TO HELP YOU FOLLOW ALONG. SO IN THE EVERYONE KNOWS IN THE END OF DECEMBER THERE WERE CASES OF PNEUMONIA IN CHINA THAT WERE REPORTEDTO THE CHINESE CKC AND -- CDC AND TO THE WORLD HEALTH ORGANIZATION. ON JANUARY 1 SEAFOOD MARKET WAS CLOSED IN CHINA IN WUHAN AND SHORTLY AFTER THAT THE VIRUS WAS ISOLATED. SO VERY QUICKLY. IT WAS THEN SEQUENCED WITHIN THREE DAYS AND THEN WHEN THREE DAYS OF THAT THE PCR ASSAY WAS PUBLISHED BY THE WORLD HEALTH ORGANIZATION SO THAT WAS A VERY RAPID SERIES OF EVENTS FROM TIME OF ISOLATION TO HAVING ASSAY AVAILABLE. SO I WILL TELL YOU A LITTLE BIT ABOUT THE TEST. HERE IS A DIAGRAM OF THE SARS COV 2 VIRUS, ANN RNA VIRUS THAT YOU CAN SEE A DIAGRAM OF THE SPIKE PROTEIN, THE ENVELOPE PROTEIN, NUCLEAR CAPSID MEMBRANE AND SOME OF THESE ARE IMPORTANT WHEN TALKING ABOUT THE ASSAY. THE SPIKE PROTEIN IS CRITICAL FOR NEUTRALIZING ANTIBODIES. THIS IS A DIAGRAM OF THE RNA GENOME OF THE VIRUS. AND ON THE LEFT-HAND SIDE YOU SEE DIFFERENT COUNTRIES IN THE -- THAT ARE LISTED THAT HAVE DEVELOPED ASSAYS OR USING ASSAYS. THEN YOU CAN SEE WITH ARROWS THE DIFFERENT PRIMER SETS USED AND FOR THE WHO THEY USING THE RDRP, THE E AND THE N GENE. THE CDC DOWN TOWARD THE BOTTOM IS USING THREE DIFFERENT PARTS OF THE NUCLEAR CAPSID FOR THEIR ASSAY. BUT ALMOST EVERYONE USES THE N FOR SPECIFICITY. THEN TO BLOW IT UP A LITTLE BIT BIGGER THERE'S THREE PRIMER SETS FOR THE INITIAL CDC ASSAY LISTED AS N 1 N 2 AND N 3. SO HOW DO WE DO THIS ASSAY? IT'S AN RNA VIRUS SO WE HAVE TO EXTRACT RNA FROM THE VIRUS AND THEN REVERSE TRANSCRIBE INTO CDNA. WE THEN AMPLIFY THE CDNA THROUGH A STANDARD PCR REACTION. THEN THERE NEEDS TO BE SOME KIND OF PROBE THAT DETECTS THE AMPLIFIED DNA RECENT -- RELEASING A FLUORESCENT SIGNAL THAT WE CAN THEN FOLLOW IN REAL TIME WITH OUR CYCLES. THAT WAS SHOWN AS A TWO STEP PROCEDURE BUT YOU SEE HERE ON THIS THEY HAVE ONE STEP RT PCR REACTION KITS. SO ON THE LEFT-HAND SIDE YOU SEE EVERYTHING DONE IN ONE TUBE INSTEAD OF RIGHT HAND SIDE WHERE YOU SEE TWO DIFFERENT STEPS. THIS IS A DIAGRAM SHOWING YOU WHAT WE SEE COMING OFF AT THE PCR MACHINE THAT YOU CAN SEE THESE DIFFERENT CYCLE NUMBERS ON THE BOTTOM, EACH CYCLE OF AMPLIFICATION OF THE DNA GETS A NUMBER. AND IN THE RED YOU SEE A HIGH VIRAL LOAD SO COMING UP VERY QUICKLY. THERE WAS A LOT OF VIRUS SO WE CAN DETECT IT QUICKLY. ON THE RIGHT WHEN YOU SEE GREENS AND YELLOW COLOR THERE'S LITTLE VIRUS THERE, IT TOOK A LOT OF CYCLES OF AMPLIFICATION TO DETECT THE VIRUS. THE ASSAYS ARE QUITE GOOD, THIS IS ONE FIGURE FROM ONE PAPER TO DEMONSTRATE SPECIFICITY OF THE ASSAY. SO YOU SEE ON THE LEFT SERIES OF DIFFERENT VIRUSES, AND THEN A WHOLE BUNCH OF NEGATIVES FOR THE -- IN THE MIDDLE OF THE SLIDE SHOWING THAT NONE ARE BEING DETECTED FOR THE DIFFERENT GENE COMPONENTS FOR ANY OF THESE VIRUSES SO IT'S A GOOD SPECIFIC ASSAY. THIS DIAGRAM SHOWS A BUNCH OF PICTURES OF DIFFERENT PLATFORMS OR DIFFERENT INSTRUMENTS AVAILABLE COMMERCIALLY TO RUN THESE ASSAYS. ON THE BOTTOM LEFT YOU SEE A MANUAL KIT, YOU SEE AUTOMATED AS A RESULTS YOU SEE POINT OF CARE INSTRUMENTS, THE POINT BEING THAT YOU CAN TO THESE PCR ASSAYS OR RT PCR ASSAYS ON A NUMBER OF KINDS OF INSTRUMENTS. YOU MIGHT ASK HOW EXPENSIVE IS THIS TEST YOU ARE RUNNING? HERE IS A CHART SHOWK YOU A NUMBER OF DIFFERENT VENDORS OFFERING A TESTS AND COST RANGE TO WALK YOU THROUGH IT A LITTLE BIT. SO THE BIOFIRE IS THE MOST EXPENSIVE. ON THIS PARTICULAR LIST IT'S RELATIVELY LOW CAPACITY. BUT IT HAS A FULL RESPIRATORY PANEL. SO IT SHOWS US A PANEL OF VIRUSES OR MICROORGANISMS CAUSING A RESPIRATORY INFECTION. THE ASSAY IS NOT YET AVAILABLE FOR COVID-19 BUT IT WILL BE LATER IN THE SUMMER LIKELY. IT'S A RAPID ASSAY IN AN HOUR. SOME OTHER INSTRUMENTS YOU SEE WHICH RANGE FROM 16 TO $30 MIGHT BE AUTOMATED PLATFORMS WITH VERY HIGH CAPACITY, A THOUSAND PER DAY, THE INSTRUMENTS THEMSELVES ARE EXPENSIVE BUT BEING AUTOMATED TAKES LESS MAN POWER. WE ARE USING THE ABI 7500 CURRENTLY WHICH IS A MEDIUM WORKLOAD IF YOU WILL BUT MORE LABOR INTENSIVE. HOWEVER, WE WERE ABLE TO USE IT IMMEDIATELY. WE HAD THE INSTRUMENTS AS DID MANY PEOPLE WE CAN GET THE ASSAY UP AND RUNNING BEFORE THE COMMERCIAL COMPANIES HAD TIME TO DEVELOP A NEW ASSAY AND PUT IT ON MARKET. SO IT'S ABOUT $100 REIMBURSEMENT FROM CMS FOR THIS ASSAY IF YOU INCLUDE LABOR IN ADDITION TO REAGENT COSTS WHICH ISN'T MUCH BUT IF YOU WANT TO TEST EVERYONE IN NEW YORK CITY THAT'S $800,000,000 FOR ONE TIME TEST. THEN YOU HAVE TO WEIGH COST OF TESTING VERSUS PROTECTIVE EQUIPMENT FOR ALL THE PEOPLE, ICU CARE WHICH IS EXTREMELY EXPENSIVE AND OBVIOUSLY YOU CAN'T PUT A NUMBER ON COST OF SOMEONE'S HEALTH OR WELL BEING. SO YOU HAVE TO TAKE IT IN CONTEXT BUT THE TESTS ARE ESSENTIAL AND I BELIEVE THE COSTS WORTHWHILE. SO ANOTHER ASPECT TO THIS WHOLE TESTING IS HAVING GOOD CONTROLS. SO ONE THING THAT WAS CHALLENGING IS WE WERE DEVELOPING THESE ASSAYS AND IMPLEMENTING THEM BEFORE WE HAD ANY PATIENT SAMPLES OR ANY VIRUS BECAUSE WE WERE NOT CULTURING THE VIRUS. DUE TO SAFETY PRECAUTIONSES. SO YOU NEED TO PROVE YOUR ASSAY IS GOOD ENOUGH TO DETECT PATIENT BUT YOU DON'T HAVE A WAY TO PROVE THAT. SO THERE'S DIFFERENT CONTROLS, SOME OF THE CONTROLS ARE HUMAN CONTROLS, SO RNA P GENE OR HOUSEKEEPING GENE IN THE MATERIAL THAT YOU GET FROM THE PERSON'S NASO PHARENGEAL AREA, RNA WHICH SAY THE SAMPLE COLLECTION WAS GOOD, EXTRACTION WAS GOOD AND BECAUSE YOU AMPLIFY A GENE YOU GO THROUGH STEPS OF PCR BUT IT DOESN'T TELL YOU THAT YOU CAN DETECT THE VIRUS. YOU CAN PUT IN PALACE MID DNA, -- PLASMID DNA WHICH IS EASY TO GET AND SHOW YOU HAD THE TARGET CORRECT, THE PCR CORRECT BUT YOU CAN'T SAY SAMPLE COLLECTION IS GOOD OR EXTRACTION IS GOOD OR REVERSE TRANSCRIPTION IS GOOD. IF YOU IN VITRO TRANSCRIBE OLIGOS, YOU HAVE THE REVERSE TRANSCRIPTION STEP AND YOU CAN SPIKE IT IN TO GET SOME EXTRACTION CONTROL BUT IT'S STILL NOT GOOD FOR THE SAMPLE COLLECTION. SO YOU HAVE TO USE A NUMBER OF DIFFERENT CONTROLS TO BALANCE OUT THIS ISSUE OF TRYING TO ADDRESS A PANDEMIC RAPIDLY. THIS IS A PAPER WHERE THEY ASK THE LABORATORIES WHAT WERE THEIR LIMITATIONS OR OBSTACLES TO OVERCOME. AT THE TOP YOU SEE MOST COMMON FREQUENT OBSTACLE WAS LACK OF POSITIVE CONTROL, NEEDING PEOPLE, SOME DIDN'T HAVE PRIMERS AND PROBES OR SPECIFICITY PANEL, THE PANEL OF OTHER VIRUSES SAMPLES TO SAY I'M NOT PICKING UP THE WRONG THING. FUNDING TRAINING AND EQUIPMENT WERE ALSO MENTIONED. SO SUMMARY INITIALLY, THE VIRUS WAS ISOLATED IN SEQUENCED EXTREMELY RAPIDLY, THINK OF THE AMAZING DIFFERENCE FROM TODAY COMPARED TO THE 1918 PANDEMIC. AND THE INITIAL PCRs WERE DEVELOPED WITHIN A FEW DAYS. MULTIPLE VERSIONS OF THE MOLECULAR ASSAYS HAVE BEEN DEVELOPED BY ACADEMIC LAB AND COMMERCIAL MANUFACTURERS. BUT IMPLEMENTING IN A LARGE SCALE IS VERY CHALLENGING. MOST OF THE ASSAYS HAVE EXCELLENT SENSITIVITY AND SPECIFICITY WITH FEW EXCEPTIONS THAT ARE LOWER AND THE COMMERCIAL ASSAYS TEND TO BE LESS LABOR INTENSIVE WITH MORE RAPID TURNAROUND TIME AND-OR HIGHER CAPACITY BUT COULDN'T BE AVAILABLE IMMEDIATELY AND SUPPLIES HAVE BEEN AN ISSUE AS YOU WILL SEE LATER. THE RETURNING BACK TO THE TIME LINE. LET'S MOVE TO JANUARY 20TH. THE FIRST REPORTED CASE IN THE UNITED STATES WAS A TRAVEL FROM WUHAN. SO AT THIS POINT WE WEREN'T SURE IF WE WERE GOING TO BE HAVING A LOT OF TESTING IN THE UNITED STATES OR IF THIS MIGHT BE LIKE MERS AND SARS WHERE OUTBREAK HAPPEN, IT WAS CONTAINED, FOR THE MOST PART IN OTHER COUNTRIES AND WE NEVER DEVELOPED IT AS ROUTINE ASSAY WE DO MERS AND SARS IN OUR LABORATORY. NEEDLESS TO SAY ON JANUARY 21ST, THEY BEGAN WORKING ON A CORONA VIRUS ASSAY WITH A PAN CORONA VIRUS ASSAY. JANUARY 23 WUHAN CITY IS SHUT DOWN, JANUARY 24 THE FIRST CASE IS SEEN IN EUROPE. JANUARY 30TH THE WORLD HEALTH ORGANIZATION SAYS WE HAVE AN EMERGENCY OF INTERNATIONAL CONCERN. ON FEBRUARY 4TH, THE CDC RECEIVES AN FDA EMERGENY USE AUTHORIZATION, I WILL EXPLAIN WHAT THAT MEANS, THEY HAD THE KIT AN COULD USE IT BUT WITHIN A VERY SHORT PERIOD OF TIME THERE WAS A PROBLEM WITH THE KITSH WAS ANNOUNCED AN ONLY 12 LABS IN THE COUNTRY COULD DO TESTING. A FEW DAYS LATER ON THE 15TH OF FEBRUARY, WE RECEIVED NOTIFICATION THAT WE MIGHT BE RECEIVING SOME COVID-19 PATIENTS. SO THERE WAS A DISCUSSION WHETHER THIS MIGHT HAPPEN SO WE WERE SCRAMBLING WHAT WILL WE DO IF WE RECEIVE PATIENTS BUT NO TESTS AVAILABLE TO TRACK WHAT WAS GOING ON? FEW DAYS AFTER THAT WE RECEIVED A POSITIVE CONTROL RNA FROM THE ROCKY MOUNTAIN LAB WHICH WAS GREAT SO WE COULD AT LEAST START DOING SOME OF THE ASSAYS THAT WE WERE ABLE TO DEVELOP OURSELVES. SO LET'S TALK ABOUT THE TESTING REGULATIONS. WHY TO WE HAVE THESE FDA REGULATIONS? THIS IS ONE EXAMPLE. THIS IS AN EXAMPLE OF THE THERNOS COMPANY WHICH AVOID THESE REGULATIONS, PRODUCED BAD TESTS AND GAVE INCORRECT PATIENT RESULTS FOR A PERIOD OF TIME. SO THE FDA EXISTS TO AVOID THESE ABUSES TO HAVE REGULATION SO WE CAN WE CAN HAVE A GOOD HEALTHCARE SYSTEM WITH GOOD TESTING. THE EMERGENCY USE AUTHORIZATION WAS A LEGAL MEANS FOR THE FDA TO PROVE -- APPROVE TESTING QUICKLY BY DECLARING IT AN EMERGENCY THAT REQUIRES -- OR THAT ALLOWED THEM TO MOVE MORE QUICKLY. THESE TESTS WERE MODERATE TO HIGH COMPLEXITY, MEANING YOU NEEDED A CLEAR OR CERTIFIED LAB THAT HAD THE ABILITY TO RUN THESE KINDS OF TESTS THEY COULDN'T BE DONE POINT OF CARE IN THE EMERGENCY ROOM. THIS IS ALL VERY IMPORTANT BECAUSE DIAGNOSTIC ERRORS ARE KNOWN TO CAUSE CONTRIBUTE TO A LOT OF PATIENT DEATH AND BY REDUCING DIAGNOSTIC ERRORS IT IS SAFER FOR THE PATIENTS. SO BACK TO THIS DIAGRAM OF THE CDC ASSAY THERE WAS A PROBLEM WITH THE MANUFACTURING OF THE N 3 COMPONENT AS CONTAMINATION SO WHAT THEY DID MOVING FORWARD IS ONLY USED THE N 1 AND N 2 COMPONENTS, AND THE ASSAY WAS FINE WITH THOSE TWO COMPONENTS, SO THAT'S HOW THEY PROCEEDED AFTER THAT. JUST TO GIVE YOU SOME CONTEXT I'M SURE MANY OF YOU AS I WAS WERE LOOKING AT THIS JOHNS HOPKINS WEBSITE MULTIPLE TIMES PER DAY. ABOUT THIS TIME THE END OF FEBRUARY 26, THERE WERE 56 -- 57 PEOPLE IN THE UNITED STATES WITH CONFIRMED COVID DISEASE. SO BACK TO OUR TIME LINE. AT THIS POINT WE WERE EXPLORING HOW WE WOULD HANDLE BIOSAFETY. SO WE HAVE THE ABILITY HERE AT NIH TO HANDLE THINGS SUCH AS EBOLA CASE AND WE HAVE THE LABORATORY FACILITIES. AND WE STARTED PREPARING TO HAVE EXTRA PRECAUTIONSES IN CASE IT WAS NEEDED. SO FOR A TWO WEEK PERIOD THERE WAS A LOT OF VALIDATIONS DONE BY ANNA AND HEATHER CRUMB TO MAKE OUR CAPABILITIES VERY HIGH IF WE WERE BRINGING COVID PATIENTS INTO THE SPECIAL STUDIES CARE UNIT BUT TURNS OUT THAT WAS ABOVE AND BEYOND WHAT THE CDC REQUIRED AND FOR NUMBER OF REASONS WE THEN PROCEEDED TO WORK IN THE LABORATORY AND I WILL SHOW YOU PICTURES HOW WE DO OUR BIOSAFETY. SO THE ISSUE HERE IS WE HAVE A RESPIRATORY SPECIMEN WITH A HIGH VIRAL LOAD. IF YOU HAVE AEROSOLIZATION COMBINED WITH RESPIRATORY SPECIMEN THAT IS WHAT IS THE SAFETY RISK. SO AEROSOLS CAN BE PRODUCED BY CENTRIFUGATION, PIPETTING AND SON KATEING MAKING SMEARS OR IF YOU HAD A BIG SPILL THAT WOULD BE CAUSING AEROSOLIZATION. SO HERE ARE PICTURES OF THE PEOPLE IN LABORATORY. ON THE LEFT YOU SEE A TECHNOLOGIST WORKING IN A BIOSAFETY CABINET. AS LONG AS SPECIMENS ARE IN THE BIOSAFETY CABINET SHE IS PROTECTED AND CAN CONTINUE TO WORK THOUGH LABORATORY -- IN THE MAIN LABORATORY. THE TWO PEOPLE IN THE RIGHT ARE GOING IN TO A ROOM WHERE IT'S NOT IN A BIOSAFETY CABINET. THERE'S SOME INSTRUMENT THAT'S OUT IN THE OPEN AND IS A RESPIRATORY SPECIMEN SO THEY ARE USING THESE FACE SHIELDS TO PROTECT THEMSELVES. WHAT ABOUT THE REST OF THE LAB? ON THE LEFT YOU CAN SEE HUMANTOLOGY, ON THE RIGHT YOU SEE CHEMISTRY, THEY ARE HANDLING BLOOD AND URINE SAMPLES. THESE HAVE LITTLE IF ANY VIRUS. SO THEY ARE USING CDC STANDARD PRECAUTIONSES, BY HAVING A WORKING UNDER A PORTABLE SHIELD SO THEY DECAP OR WHATEVER THEY NEED TO DO BEHIND THE SHIELD TO PROTECT THEMSELVES. SO MOVING BACK TO OUR TIME LINE, ON FEBRUARY 28 THE NIH CLINICAL CENTER LAB HAD THE WORLD HEALTH ORGANIZATION UP AND RUNK, WE WERE ABLE TO QUICKLY ORDER PRIMERS GET THIS GOING AND AT LEAST DO IT IF WE HAD TO DO IT BUT WE WEREN'T FDA APPROVED. NEXT DAY THE FDA MODIFIES ITS EUA CRITERIA THAT YOU CAN NOW START TESTING AND SUBMIT WITHIN 15 DAYS SO YOU CAN START TESTING BEFORE YOU GOT THE APPROVAL BUT YOU HAVE TO SUBMIT ALL YOUR PAPERWORK AND GET APPROVAL FROM THE FDA OR THEY COULD HAVE YOU STOP YOUR TESTING. THAT SAME DAY WE RECEIVED A KIT FROM THE CDC WE HAVE BEEN TRYING VERY HARD TO GET A KIT SO THAT WE CAN USE THE FDA APPROVE KIT AND WE RECEIVED ON THE SAME DAY WHICH HAS THE -- WE DID NOT HAVE TO SUBMIT THAT TO THE FDA. THEN WITHIN SHORT PERIOD OF TIME WE ORDERED THE KIT FROM A COMPANY IDT SO THAT BECAME NOT LIMIT FACTOR. YOU CAN GET PRIMERS AND PROBES QUICKLY. ON MARCH 5 WE HAD THE FIST PATIENT -- FIRST COVID PATIENT IN MARYLAND, MARCH 14 WE HAD THE FIRST NIH EMPLOYEE. THEN THE FIRST NIH PATIENT IN THE CLINICAL CENTER WAS MARCH 24. ON MARCH 16 YOU SEE THE FDA AGAIN CHANGES REGULATIONS. WHAT THEY DID ON MARCH 16 WAS SEE IF STATES COULD HAVE AUTHORITY SO INSTEAD OF SUBMITTING TO THE FDA YOU COULD SUBMIT TO YOUR STATE, IF THEY WOULD TAKE OVER THE PAPERWORK. HOWEVER BEING A FEDERAL FACILITY WE STILL SUBMIT TO THE FDA. SO A LITTLE BIT ABOUT THE NIH EXPERIENCE. THIS IS JUST ONE CHART OF ONE OF OUR VALIDATIONS TO DEMONSTRATE IF YOU LOOK DOWN ON THE BOTTOM ROW YOU CAN SEE WE ARE DETECTING LESS THAN 1 RNA COPY MER MICROLITER PER CALCULATIONS USING TWO EXTRACTION SYSTEMS, N 1, N 2 AND RP, CONTROL GENE. SO AN EXCELLENT SIGNAL. THIS IS SIMILAR DATA SHOWN IN GRAPHIC FORMAT THAT YOU CAN SEE THE N 2 SIGNAL IN ORANGE WHICH IS A LITTLE LESS SENSITIVE THAN THE N 1 SIGNAL BUT MANY REPLICATES THAT LIMIT OF DETECTION WE ARE ABLE TO GET TWO GENOME COPIES PER MICROLITER WHAT IS STATED TO BE NEEDED FOR THE CDC LIMIT OF DETECTION. SO MOVEING A LITTLE BIT INTO HOW WE CAN USE THESE DIFFERENT TESTS THAT WE HAVE AND WHAT IS IT TELLING US ABOUT THE PATIENTS AND THEIR ILLNESS? SO THIS IS A LITTLE DIAGRAM WHICH SHOWS YOU THE TYPICAL DESCRIPTION OF THE LAYTANT PERIOD AN INFECTIOUS PERIOD, INCUBATION OCCURS AND THE PATIENT HAD SYMPTOMS THEN THERE IS A RESOLUTION OF SYMPTOMS. THEY SHOW IT ON A MAP OF TWO WEEK PERIOD. BUT IF YOU READ THE LITERATURE AND TALK TO SOME PHYSICIANS YOU WILL SEE A NUMBER OF CASES WHERE THE VIRUS IS DETECTED MANY DAYS LATER. 45 DAYS LATER OR MORE SO IF THE PATIENT HAD INFECTION STARTING MAY 1, ON JUNE 14 THEY MIGHT STILL HAVE A POSITIVE SIGNAL. WE NEED TO TAKE THAT INTO CONTEXT AND SEE WHAT THAT MEANS AS WE MANAGE THIS GOING FORWARD. ANOTHER POINT ABOUT DETECTION OF VIRAL SIGNAL WITH THESE DIFFERENT ASSAYS WHICH ARE SENSITIVE. WHAT YOU ARE LOOKING AT IS A PAPER WHERE THEY ARE TALKING ABOUT FECAL SHEDDING OF THE VIRUS, FROM JANUARY, FEBRUARY, MARCH AND ON THE LEFT YOU SEE ALL THESE PINKISH LINES WHICH ARE THE RESPIRATORY SPECIMENS POSITIVE. THEN THE ORANGE LINES ARE SHOWING YOU ADDITIONAL FECAL DETECTION OF THE VIRUS IN FECES EVEN AFTER PATIENTS ARE DISCHARGED SO WE CAN DETECT SIGNAL, THIS IS TRUE WE SEE THIS IN OTHER INFECTIOUS DISEASES IN THE CLINICAL LABORATORY WHERE WE GET A SIGNAL WHEN WE MIGHT NOT HAVE A CULTURE POSITIVE AND CLINICIANS DECIDE WHAT DO THEY DO WITH THAT AND HOSPITAL EPIDEMIOLOGY ALSO DECIDES WHAT THE GOOD NEWS FROM THE CDC WEBSITE IS THIS IS NOT KNOWN A FECAL ORAL TRANSMISSION, IT'S NOT REPORTED AND THE RISK IS EXPECTED TO BE LOW FROM THAT BASED ON MERS AND SARS STUDIES. I THOUGHT YOU WOULD WANT TO SEE THE SIGNAL FOR WHAT WE HAVE SEEN AT THE NIH TESTING LAB. WE HAVE TESTED ABOUT 2000 SAMPLES WITH 250 POSITIVES, FROM -- SINCE MARCH ON UNTIL NOW, THIS INCLUDES DUPLICATES. SO I WILL SHOW YOU THE SIGNAL IN A MINUTE FROM OMS. I'M COMPARING IT TO THIS SLIDE WHICH SHOWS YOU THE STATE OF MARYLAND UP TO A FEW DAYS AGO COMPARED TO THE STATE OF WASHINGTON. YOU CAN SEE THAT THE SIGNAL IN MARYLAND IS NOT EXPONENTIAL, STILL GOING UP SOME LEVEL BUT IT HASN'T PEAKED AND GONE DOWN AS WE SEE IN STATE OF WASHINGTON. THIS IS IN CONTRAST TO OUR OMS SIGNAL WHERE WE HAD 82 UNIQUE POSITIVES. THERE'S ADDITIONAL PEOPLE MAY HAVE BEEN DETECTED OUTSIDE OUR TESTING SITE SO THE NUMBER ON THE WEBSITE MIGHT BE DIFFERENT BUT YOU SEE THIS IS NOT EXPONENTIALLY GOING UP AND NOT ACTUALLY EVEN GOING UP, IT'S PRETTY STEADY. THIS IS A GOOD THING. THERE ARE A NUMBER OF REASONS WHY OUR SIGNAL MIGHT BE A BIT DIFFERENT THAN WHAT YOU SEE IN THE COMMUNITY AND HOW TESTS COME IN AND IF THEY HAVE AN OUTBREAK IN THE COMMUNITY AREA FOR EXAMPLE. ONE QUESTION THAT I OFTEN GET FROM NURSES PHYSICIANS OR EVEN YOU MIGHT IF YOU WERE TESTED HAVE GOTTEN AN INDETERMINANT RESULT. YOU SEE WHAT IS THIS INDETERMINANT RESULT? WHAT DOES IT MEAN? THIS IS BACK TO THIS N 1, N 2 SIGNAL. IF ONE OF THE TWO TARGETS IS POSITIVE BUT NOT THE OTHER, IT'S CALL INDETERMINATE, AND IT IS A LOW POSITIVE SIGNAL. SO BACK TO THE ORIGINAL CASE I HAD IN THAT PHONE CALL. WHAT WAS GOING ON? SO AT THE BEGINNING OF THE ILLNESS, THE VIRAL LOAD WAS FAIRLY HIGH. THEN THEY PROCEEDED AND GOT BETTER AND THEIR VIRAL LOAD WENT DOWN THEN THEY HAD A NEGATIVE TEST BUT THEN NUMBER OF DAYS LATER AT WEEK FOUR THEIR TEST IS POSITIVE AGAIN. THEN NEGATIVE AGAIN SO THEY ARE BOUNCING BACK AND FORTH OVER AND ABOVE LIMIT OF DETECTION OF THE ASSAY. SO IT'S NOT THAT AN ERROR WAS MADE BUT IT'S A COMBINATION OF THE PATIENTS IMMUNE RESPONSE, THE VIRAL LEVEL ON THAT DAY OF THE COLLECTION, HOW GOOD THE COLLECTION WAS, AND WHETHER WE CAN DETECT IT OR NOT. WHAT ABOUT TESTING IN PRE-SYMPTOMATIC OR ASYMPTOMATIC INDIVIDUAL? THERE'S BEEN A LOT OF DISCUSSION ON THAT. THIS IS A PAPER IN THE NEW ENGLAND JOURNAL OF MEDICINE TESTING PRE-SYMPTOMATIC INDIVIDUALS AND FOLLOWING THEM SO ANYTHING TO THE LEFT OF THE SLIDE ON THE OTHER SIDE OF ZERO IS BEFORE THEY HAVE ANY SYMPTOMS. YOU CAN SEE THEY HAVE A HIGH VIRAL LOAD. THEN ON THE NEXT SLIDE WHAT YOU WILL SEE IS THEY ARE SHOWING YOU THE SAME PATIENTS AGAIN TYPICAL SYMPTOMS, ATYPICAL SYMPTOMS, PRE-SYMPTOMATIC. WHAT I WANT TO POINT OUT IS THE BLACK DIAMONDS. SO THE BLACK DIAMONDS ARE SHOWING YOU NEGATIVE CULTURES. AGAIN WE CAN SEE THIS IN OTHER CASES WHERE WE CAN DETECT THE VIRAL SIGNAL WITH OUR PCR ASSAYS BUT IT MIGHT NOT BE POSITIVE IN CULTURE. ONE QUESTION WE NEED TO THINK ABOUT GOING FORWARD IS HOW INFECTIOUS ARE THESE INDIVIDUALS AND WHAT ARE OUR ROLES GOING TO BE TO BRING PEOPLE BACK TO WORK, ISOLATE THEM, ET CETERA WHEN WE GET IN THESE TAIL END PERIODS? WHAT DO WE NEED TO DO PRACTICALLY? REAGENT LIMITATIONS WHICH I'M SURE YOU HAVE SEEN IN THE NEWS. THERE'S BEEN LOTS OF REPORTS OF WHY THERE'S A PROBLEM GETTING THE TESTING, MANY DIFFERENT TYPES OF REPORTS. AND THIS -- YOU CAN RELATE TO HAVE THE EMPTY TOILET PAPER SHELVES YOU CAN UNDERSTAND SUPPLY AND DEMAND. SO LET ME EXPLAIN SOMETHING ABOUT THE TEST. SO WHEN PEOPLE SAY THE TEST THEY CAN MEAN DIFFERENT THINGS. SOFT TO COMPLETE A FULL TEST YOU NEED FIVE DIFFERENT COMPONENTS. YOU IMMEDIATE THE SWAB, THE NASO PHARENGEAL SWAB, A THIN FLEXIBLE SWAB USED COLLECTED THROUGH THE PATIENT'S NOSE, VIRAL TRANSPORT MEDIA. YOU IMMEDIATE EXTRACTION REAGENT, A SMALL KIT OR BUFFERS INTO AUTOMATED MACHINE. YOU NEED PRIMERS AND PROBES AND THE LITTLE BOX YOU SEE IN THE PICTURE THAT'S WHAT YOU GET FROM THE CDC. ALL IT IS IS PRIMERS AND PROBES AND A CONTROL. AND THE PROBE IS WHAT GIVES YOU THAT FLUORESCENT SIGNAL. THEN YOU NEED A SEPARATE ORDER OF ENZYMES TO MAKE THE REACTION WORK. EACH ONE OF THESE DIFFERENT COMPONENTS HAS BEEN IN SHORT SUPPLY DURING THE COURSE OF THIS OUTBREAK. I WANT TO NOTE WHEN YOU ARE THINKING ABOUT REAGENTS BEING LIMITING, THE CDC ASSAY IS THREE PCR RUNS. N 1, N 2 AND RP. IF YOU MULTIPLEX THE AA SAY YOU ONLY DO ONE PCR RUN INSTEAD OF THREE BUT MANY YOU MULTIPLEX THE ASSAY YOU MUTT SUBMIT TO FDA FOR NEW ASSAY. WE HAVEN'T DONE THAT BUT A LOT OF HOSPITAL LABS HAVE DONE THAT AND USE ONE REACTION. WHAT ABOUT THE VALIDATION THAT'S REQUIRED? SO THERE'S MULTIPLE VALIDATIONS THROUGH THE COURSE OFFER THIS PARTLY MOVELY DUE TO THE REAGENT ISSUE. AT THE NIH WE VALIDATED THREE PLATFORMS TWO ENZYME SOLUTIONS TWO PRIMER PROBE SETS, TWO RAPID PLATFORMS ONE ALTERNATIVE SWAB COLLECTION METHOD AND WE ARE ABOUT TO VALIDATE TWO NEW AUTOMATED PLATFORMS. MANY, THAT'S MORE THAN 12 VALIDATIONS WHEN WE ARE ALL DONE, FOR ONE TARGET, ONE VIRUS. MANY LABORATORIES ARE RUNNING FIVE INDEPENDENT PLATFORMS IN PARALLEL FOR ONE VIRAL TARGET WHICH IS NOT HOW YOU WOULD DESIGN FROM SCRATCH IF YOU HAD A CHOICE. LET'Ss PAUSE AND TAKE A MOMENT TO THANK EVERYONE WHO HELPED FROM THE RESEARCH COMMUNITY. MICHAEL GOTTESMAN SENT OUT AN EMAIL TO THE INTRAMURAL COMMUNITY LISTING SPECIFIC AGENTS THAT COULD BE USED DOS COLLECTED ALL THOSE REPLIES, MADE A HUGE EXCEL SPREAD SHEET, SHARED WITH ME WHEN I CIRCLED ITEM THEY WENT AND GOT THEM AND BROUGHT THEM TO US. ANKER RANT EMAIL WENT OUT CALLING FOR VOLUNTEERS TO WORK IN THE BENCH AND I GOT HUNDREDS OF EMAIL REPLIES PEOPLE OFFERING TO COME HELP BUT WE ACTUALLY NEED CERTIFIED MEDICAL TECHNOLOGIST WHOSE ARE FAMILIAR WITH THE COMPUTER SYSTEM AND ACTUALLY THE TRAINING IS NOT TRIVIAL, NOT SO SMALL BEYOND DOING RT PCR REACTION. MIKE VOLUNTEERED LAB SPACE AND INSTRUMENT, I WANT TO GIVE A SPECIFIC EXAMPLE OF AMAZING THINGS THAT HAPPENED DURING THE COURSE OF THIS OUTBREAK. WE DETERMINED TO USE THE INSTRUMENT AND WE NEEDED A PIECE OF HARDWARE TO MAKE IT WORK FOR US. SO WE ORDERED HARDWARE ON A SUNDAY AND IT WAS APPROVE IMMEDIATELY. I'M SPEAKING WITH A VENDOR ON A SUNDAY. IT WAS DELIVERED AND INSTALLED BY VENDOR ON WEDNESDAY AND WE HAVE VALIDATION COMPLETE BY FRIDAY BECAUSE WE HAD ALL COMPONENTS LINED UP FROM OUR PREVIOUS VALIDATIONS. SO THAT WOULD NEVER HAPPEN NORMALLY AND IT WAS A HUGE AMOUNT OF WORK SO I WANT TO THANK EVERYONE WHO CONTRIBUTED TO THAT. SO TO SUMMARIZE ABOUT THE REAGENTS. THE SUPPLY OF TESTS OR REAGENTS FOR THE TESTS COULDN'T MEET DEMAND AND WE STILL HAVE THAT ISSUE. BUT THIS ISSUE IS VERY COMPLEX. IT'S NOT AS IF ONE SINGLE PERSON OR GROUP MADE A MISTAKE TO CAUSE THIS ISSUE. IT'S AN UNPRECEDENTED CHALLENGE AND WE MUST ALL DEBRIS WHEN TIME TO DO THAT GOING FORWARD, DEBRIEF AND CONSIDER HOW TO ADDRESS THE SIMILAR CHALLENGE IN THE FUTURE MEANING EITHER THE FALL AND WINTER OF THIS YEAR OR A FUTURE YEAR WHEN WE MIGHT HAVE A NEW OUTBREAK. ONE GOOD THING IS CREATIVITY THAT RESULTED FROM NEEDING THESE ALTERNATIVES. ONE QUESTION WAS RAISED, ARE THERE GOOD ALTERNATIVES TO GETTING A NASO PHARENGEAL SWAB IN A CAR LINE, STICKING THIS TINY SWAB ALL THE WAY BACK REACHING IN TO SOMEBODY'S CAR WITH ALL THE PPE ON TO DO THAT. SO IT'S BEEN PROPOSED THAT YOU MIGHT USE SALIVA. THERE'S BEEN DIFFERENT ASSAYS SOME ARE POSITIVE -- SOME MORE POSITIVE THAN OTHERS. THIS IS ONE STUDY WHERE I SHOW WITH THE RED ARROW COMPARING SALIVA TO NAY SEW PHARENGEAL COLLECTION AND DEPENDING ON THE LINE THE SLIDE IS NOT AS SENSITIVE AS THE NP FOR THAT PAPER. THIS IS ANOTHER PAPER WHERE IT'S VERY SIMILAR BUT THE BLUE DOTS ARE SHOWING YOU SALIVA AND SIGNAL SHOWING LESS VIRUS THAN THE NP BUT A PRETTY GOOD SIGNAL. THE SAMPLING SIZE FOR THESE STUDIES TENDS TO BE RELATIVELY SMALL BECAUSE WE ARE VERY NEW IN THE COURSE OF IT SO THEY HAVE 39 POSITIVES IN THE STUDY THOUGH THEY HAD A BIG COLLECTION. THEN ADDITIONAL STUDIES, ONE FROM RUTGERS WHETHER USING A SPECIAL COLLECTION DICE -- DEVICE, FOR BIOSPECTRUM WHERE PEOPLE SPIT INTO THE TUBE AND THEN SHAKEN AND PROTECTS THE RNA SO THAT YOU CAN MAINTAIN THE SIGNAL. ON THE RIGHT FOR THE YALE STUDY THEY USED UNDILUTED SALIVA. THEY DIDN'T HAVE A SPECIAL DEVICE, THEY DIDN'T DILUTE IN BTM AND USED A LARGER AMOUNT AND GOT A VERY GOOD SIGNAL SAYING THEIR SALIVA SIGNAL WAS COMPARABLE TO THE NP SIGNAL BUT NOTE THE LAST THREE STUDIES I MENTIONED ALL THREE USE DIFFERENT METHODS SO WE DON'T HAVE ONE SINGLE METHOD SAYING THIS IS THE WAY THE GO FOR THIS TYPE OF COLLECTION. HERE AT THE NIH WE HAD TO USE AN ALTERNATIVE TO THE FLOCK SWAB, ARE WE PREPARED TO DO THAT, WE USE A DACRON SWAB WITH PBS YOU CAN SEE THE DOTS ARE SIMILAR IN HORIZONTALLY TO THE BLUE SQUARES SO WE WERE ABLE TO SWAB OUT THE SWAB -- SWAP OUT THE SWABS AND THE PBS. NOW, A NUMBER OF CREATIVE PEOPLE AT DIFFERENT INSTITUTIONS DECIDED TO DO 3-D PRINTING TO MAKE THE SWABS THAT WE ARE LIMITING. THE FIGURES ON THE LEFT ARE FROM BETH ISRAEL DEACONESS MAKING OVER A HUNDRED PROTOTYPES SO A LOT OF VOLUNTEERS TO TRY THESE DIFFERENT SWABS, 3-D PRINTENING THEIR NOSE AND SOME WOULD BREAK, WOULD BE TOO BRITTLE BUT THEY DID COME UP WITH A GOOD SWAB THAT MET ALL THE CRITERIA FOR BEING USED. ON THE RIGHT YOU SEE A PICTURE OF 3-D PRINTED SWABS FROM FORM LABS THAT ARE PACKAGED AND SOLD. SO A SUMMARY FROM THE ALTERNATIVES. CREATIVITY HAS BEEN EVIDENT WHEN CHALLENGES AROSE, 3-D SWABS DEVELOPED, ALTERNATIVE TRANSPORT MEDIA US WITH TESTED, AND PEOPLE ARE LOOKING AT ALTERNATIVE SPECIMENS NOT REQUIRING SWABS TO BE PROPOSED. MANY LABS HAVE MULTIPLE TESTING PLATFORMS THEY ARE RUNNING IN PARALLEL. FINALLY I WILL MOVE ON TO SERO LOGIC TESTING. I READ THIS THIS MORNING IN THE NEW YORK TIMES THE HEADLINE, LET'S GET REAL ABOUT CORONA VIRUS TESTS. THERE AREN'T ENOUGH, MANY SHODDY, MOST NOT DESIGNED TO TELL US WHAT WE WANT TO KNOW. I'M NOT QUITE SO MEGTIVE AS THIS, I DON'T AGREE WITH THE TONE QUITE BUT THERE ARE SPECIFIC THINGS THEY DESCRIBE IN THE ARTICLE THAT I'M GOING TO SHOW YOU IN SOME OF THE UPCOMING SLIDES, ABOUT PREVALENCE. AS YOU KNOW LIKELY THERE ARE MANY SERO LOGIC ASSAYS BEING DEVELOPED. THIS IS A RAPID SEROLOGIC ASSAY IMMUNOCHROMATOGRAPHIC ASSAY WHERE YOU READ THE LINES WHEN THE SIGNAL COMES UP AND THAT TELLS YOU WHETHER POSITIVE OR NEGATIVE KIND OF LIKE A PREGNANCY TEST. I WANT TO GET BACK TO THE FDA REGULATION. SO SOMEONE EMAILED ME YESTERDAY AND SAID THERE'S ALL THESE IMMUNOASSAYS OUT THERE, ARE YOU GOING TO TALK ABOUT THIS AND WHAT WE DO ABOUT IT, HOW DO WE KNOW WHICH IS CORRECT? THIS IS A QUOTE FROM SOMEONE SAYING, BASICALLY THE FDA AUTHORIZATION SAYS YOU CAN START SELLING RIGHT AWAY SEND YOUR DATA AND IF WE DON'T LIKE IT WE'LL TAKE YOUR PRODUCT BACK. SO I THINK IT WAS VERY VALUABLE FOR THE FDA TO LOSEN REGULATIONS AND GET ALL RT PCR ASSAYS OUT, ACT DENIMMIC LABS, GOOD QUALITY ASSAYS AND WE NEEDED TO GET THEM OUT FAST. YOU ALSO KNOW ALL THESE IMMUNOASSAYS ARE COMING OUT, NOT ALL EQUAL. HOW DO WE ADDRESS AND WHICH SAY TO BRING IN TO USE AS A GOOD TEST. I WANT TO DISCUSS SPECIFICITY OF SOME OF THESE TESTS SO THIS IS AN EXAMPLE OF A REPORT WHERE THEY SAID THEIR SPECIFICITY WAS 91% FOR THEIR ASSAY. SO I'M GOING TO WALK YOU THROUGH THE RELEVANCE OF PREVALENCE. YOU DON'T NEED JUST HIGH SENSITIVITY AND SPECIFICITY BUT FOR POSITIVE AND NECKTIVE PREDICTIVE VALUE OF TEST AND TELL YOU WHAT TO DO WITH IT AND HOW TO USE IT DEPENDS PREVALENCE OF THE DISEASE IN THE POPULATION. TAKE THE LEFT-HAND SIDE, AND SHOWN WITH MY ARROW, LEFT-HAND SIDE WITH LOWER LEFT BOX AND SAY ASSAY IS GOOD. 99% SENSITIVE AND SPECIFIC AND IT'S IN AN AREA OF NEW YORK THAT HAD HIGH NUMBER OF PATIENTS 20% PREVALENCE IN THE POPULATION. IF YOU TEST A THOUSAND PEOPLE, YOU WILL ONLY HAVE A FALSE POSITIVE RATE OF 8 SO 8 WHO GET A POSITIVE RESULT BUT REALLY NOT IMMUNE, THEY DON'T HAVE THE ANTIBODIES. AND I WANT TO CONTRAST THAT UP TO THE UPPER RIGHT BOX IS WHERE YOU HAVE H THE ASSAY WITH 90% SENSITIVITY AND SPECIFICITY IN A LOW PREVALENCE AREA, SAY MONTANA OR SOMEWHERE WITHOUT A BIG OUTBREAK AND NOT MANY WERE EXPOSED. SO OF A THOUSAND TESTED 99 HAVE A FALSE POSITIVE RESULT SO THEY THINK THEY'RE IMMUNE BUT NOT AND THAT MIGHT CHANGE BEHAVIOR OR CHANGE LIKELIHOOD OF TRANSMISSION. HOW DOES THIS COMPARE TO OTHER IMMUNOASSAYS WE USE ALL THE TIME IN THE LABORATORY? I PULLED OUT MANUFACTURING SHEETS AND LOOKED AT THEM, THESE ARE THE LIST OF SENSITIVITY AND SPECIFICITY OF VARY USE ASSAYS. SOME HIGH, SO HIV, 99, 99 BUT YOU SEE THE MUMPS HAS ONLY 83% SPECIFICITY BUT YOU HAVE TO TAKE THAT IN CONTEXT OF WE HAVE VACCINES FOR SOME OF THESE DISEASES AND WE ARE NOT IN THE MIDDLE OF AN OUTBREAK SO THAT AFFECTS WHAT WE NEED TO MOVE FORWARD. LET ME MAKE A COMMENT WHY WE CARE SO MUCH ABOUT SPECIFICITY. THIS IS A DIAGRAM SHOWING YOU CORONA VIRUS FAMILY TREES AND IN THE GREEN BOX YOU SEE THE SARS COV 2 VIRUS WITH THE RED STAR AND TWO OTHER VIRUSES WITH RED ARROWS. SO THESE ARE VIRUSES WHICH ARE SIMILAR THAT CAUSE COMMON COLD SYMPTOMS SO YOU DON'T WANT THE ASSAY THAT WE ARE LOOKING FOR THE PANDEMIC TO PICK UP A SIGNAL TO COMMON COLD VIRUSES BECAUSE WE WILL GET THE WRONG INFORMATION. THIS IS SOME POSITIVE NEWS OUT OF UCS STUDY BIOHUB, THEY LOOK AT A NUMBER OF IMMUNOASSAYS AND REPORT SOME TO HAVE 100% SPECIFICITY. THAT'S EXCELLENT IF THIS HOLDS UP. SO WE HAVE IN THIS CASE TEN LATERAL FLOW ASSAYSSH MOSTLY ASSAYS FROM OTHER COUNTRIES NOT ONES DEVELOPED HERE. 130 SAMPLES FROM 80 WHO HAD PROVEN SARGES COV 2 VIRUS FROM THE RTPCR ASSAYS, 108 CONTROLS PRE-COVID-19 SO THERE WAS NO EXPOSURE. AND THEN 50 PEOPLE WHO HAD RESPIRATORY ILLNESSES WITH SOME OTHER VIRUS OTHER THAN COVID-19 OR SARS. THIS IS A PICTURE OF THE ONE OF THE ASSAYS THAT THEY ARE TESTING. AND YOU ARE SEEING THESE LINES THEY VISUALLY LOOK AT AND THE RED ARROWS POINTING TO SOME WEAK BANDS, THEY MADE A PINT IN THE PAPER IF YOU -- POINT IN THE PAPER IF YOU CALL WEAK BANDS NEGATIVE SPECIFICITY GOES UP SO DEPENDENT ON A HUMAN READING IT AND DETERMINING WHETHER THAT BAND IS THERE OR NOT AND HAVING A CONSISTENT READING BY ALL THE OPERATORS FOR THAT ASSAY. THIS IS ONE SLIDE FROM THEIR PAPER LOOKING AT ASSAYS AND DOWN ON THE BOTTOM YOU LOOK AT IGG, THEY SHOW SOME THAT ARE VERY HIGH UP AT THE TOP WITH GOOD SPECIFICITY, BUT THE AGREEMENT ACROSS WITH 75 TO 95 SO NOT ALL ARE THE SAME, ALL CREATED EQUAL, AND THERE WAS NO CONSISTENT CROSS REACTIVITY SO THAT'S A GOOD THING, THERE WASN'T ALWAYS ONE CROSS REACTION THAT WAS SEEN WITH EVERY I SAY BECAUSE THAT ASSAY BECAUSE THAT'S WORRYSOME. SO WE GET THE QUESTION DO YOU HAVE ANTIBODY ASSAY IN NIH CLINICAL CENTER LAB? I CAN TELL YOU THERE ARE MULTIPLE RESEARCH GROUPS ON THE NIH CAMPUS WHO ARE DEVELOPING ASSAYS. AND THERE ARE VAGUES UNDERWAY TO -- INVESTIGATIONS UNDERWAY TO TEST I ASSAYS TO SEE HOW GOOD THEY ARE. ALSO STUDIES TO TEST IMMUNITY IN THE COVID-19 PATIENTS STUDYING THE BIOLOGY AND IMMUNITY IS DIFFERENT THAN JUST TESTING THE ASSAY. HAVE MULTIPLE AUTOMATEDENT WE- ANALYZERS SO THREE PICTURES THERE, WE HAVE ALL THOSE ANALYZERS THAT CAN RUN OVER A THOUSAND PER DAY. WE WILL BE VALIDATING ASSAYS COMING OUT FROM ALL THOSE THREE COMPANIES, WE WILL START AS SOON AS WE CAN. WE HOPE TO HAVE IT BY JUNE WITH VALIDATION DONE AND YOU MAY SEE WE ASK FOR VOLUNTEERS OF PEOPLE WHO HAVE BEEN -- HAD COVID-19 DISEASE AND RECOVERED. WHY DO WE WANT THESE ASSAYS? WE WANT TO UNDERSTAND THE ASYMPTOMATIC POPULATION, PEOPLE WHO HAD THE DISEAS BUT DIDN'T KNOW IT TO UNDERSTAND THIS PANDEMIC. WE WANT TO UNDERSTAND THE ANTIBODY RESPONSE TO THE VACCINE AFTER WE START TESTING THE VACCINE OR AS WE START TESTING VACCINE. WE WANT TO GET PEOPLE BACK TO WORK ESPECIALLY HEALTHCARE WORKERS WITHOUT FEAR OF INFECTION AND IT WOULD BE GOOD TO KNOW IF THEY WERE IMMUNE. WE MIGHT JUICE THESE TO MAKE DECISIONS ABOUT REOPENING SCHOOLS FOR EXAMPLE. A POSITIVE ANTIBODY ASSAY IS NOT THE SAME AS SAY A PERSON IS PROTECTED FROM FROM INFECTION. SO YOU NEED SOMETHING CALLED NEUTRALIZING ANTIBODIES. YOU ALSO WANT THE NEUTRALIZING ANTIBODIES TO LAST A LONG TIME AND PREVENT INFECTION OR REINFECTION DEPENDING WHETHER THEY GOT A VACCINE OR HAD THE INFECTION. THIS IS A DIAGRAM JUST ILLUSTRATING WHAT A NEUTRALIZING ANTIBODY IS, SHOWING YOU DIAGRAM FORMAT YOU ARE PREVENTING THE VIRUS FROM DOING WHAT IT IS DOING GETTING INTO CELLS OR DOING MORE SO THE ANTIBODIES EFFECTIVELY BLOCKING THAT. THE WORLD HEALTH ORGANIZATION MAKES CAUTIONARY NOTES ABOUT THIS IMMUNITY PASSPORT IDEA THAT WE DON'T HAVE ENOUGH EVIDENCE YET FOR IT. AND THAT A POSITIVE ASSAY MIGHT CAUSE SOMEONE TO CHANGE THEIR BEHAVIOR IN TERMS OF SOCIAL DISTANCING, INCREASING TRANSMISSION RISK AND HOPEFULLY THE -- WE WILL HAVE MORE DATA SOON. I WANTED TO END ON A BIT OF GOOD QUOTE, A QUOTE FROM DR. WANG WHO STUDY SARS OUTBREAK. QUOTE, 17 YEARS LATER A SARS SURVIVOR HAS NEUTRALIZING ANTIBODIES, SO NOT ONLY HAD THE VIRUS BUT STILL NEUTRALIZE. WE DON'T KNOW IF IT'S TRUE FOR SARS COV 2, IF IT IS WE DON'T KNOW THE PERCENTAGE OF PEOPLE HAVING NEUTRALIZING ANTIBODIES. ANOTHER FACTOR TO CONSIDER MOVING FORWARD IS WE'LL WATCH TO SEE IF THE VIRUS MUTATES AND CHANGES WHETHER OR NOT SOMEBODY IS IMMUNE BECAUSE IF IT'S MUTATED AND WHETHER THE MUTATION ALSO MAKE THE VIRUS MORE OR LESS INFECTIOUS. THAT'S ALL THINGS WE CAN ONLY SPECULATE ABOUT. SO FIND -- ENDING ON FUTURE STEPS. THIS IS JUST ONE SLIDE TALKING ABOUT MIXED INFECTION. SO WHEN SOMEONE HAS MORE THAN ONE INFECTION EITHER BACTERIA OR VIRUS ALONG WITH THE SARS COV 2 VIRUS. ON THE LEFT YOU SEE VARIOUS PATHOGENS INFLUENZA AB, ET CETERA AND LOOKING WHO HAD ONE OF THOSE OTHER VICES AT THE SAME TIME THEY HAD SARS COV 2. THIS IS A SMALL STUDY, WE NEED TO DO MORE AND THEN WE WILL NEED TO SAY WHETHER OR NOT IT HAD IMPACT ON HOW THE COURSE OF THE ILLNESS WENT. THE LAST SLIDE ON FUTURE STUDIES, I WILL SUMMARIZE AT THE TOP BY SAYING THAT THE RTPCR TO ASSAYS ARE EXCELLENT ASSAYS FROM A QUALITY PERSPECTIVE. AND I THINK IT'S VERY LIKELY WE WILL HAVE AN EXCELLENT ZERHOUNI LOGIC -- SERO LOGIC ANTIBODY SOON TO BATTLE THE PANDEMIC. THERE IS A CALL TO ANSWER THE BETTER TEST ACCURATE FAST AN POINT CARE AND WE WANT TO UNDERSTAND LONG TERM PROTECTIVE IMMUNITY. WE ALSO WANT TO UNDERSTAND WHAT'S THE BEST SPECIMEN TYPE FOR COLLECTION AS WE MOVE FORWARD AND THEN WE WANT TO UNDERSTAND THE FULL COURSE OF THE COVID-19 DISEASE AND PATHOPHYSIOLOGY INVOLVED SO MUCH MORE RESEARCH WILL BE DONE FOR YEARS TO COME, I'M SURE. THANK YOU VERY MUCH FOR YOUR ATTENTION AND I WILL TAKE ANY QUESTIONS. >> THANK YOU SO MUCH, KAREN, FOR THIS SUMMARY OF COVID-19 DIAGNOSTICS. THERE ARE SEVERAL QUESTIONS, A LOT OF THOSE YOU COVERED IN YOUR MICE TALK BUT I'LL TRY TO SUMMARIZE SOME OF THOSE. SO YOU SHOW THAT VIGNETTE OF SOMEBODY WHO WAS POSITIVE, THEN BECAME NEGATIVE AND THEN WAS POSITIVE AND NEGATIVE AGAIN. AND I THINK YOU ALLUDED TOWARDS BEING CLOSE TO THRESHOLD OF DETECTION BEING THE PROBLEM. SO THERE ARE A FEW QUESTIONS REGARDING REINFECTION VERSUS REACTIVATION AND WHETHER THERE IS ANY EVIDENCE THAT REINFECTION COULD OCCUR ORTHOS CASES MIGHT MOSTLY REFLECT LOW LEVEL OF DETECTION THAT TEST BECOMES NEGATIVE THEN BECOMES POSITIVE AGAIN. COULD YOU COMMENT. >> I DON'T THINK WE HAVE ENOUGH DATA. IF I HAD TO SPECULATE BASED ON OTHER INFECTIOUS DISEASE, SO WHEN THERE'S TWO FACTORS TO CONSIDER. ONE IS THE ASSAY. SO I'M TALKING ABOUT THE TEST. THE OTHER FACTOR IS THE BIOLOGY AND PATIENT WITH THE DEE. IF WE TALK ABOUT WHAT WE HAVE SEEN IN OTHER CASES WHEN YOU HAVE SOMEONE WITH SOME LEVEL OF IMMUNOCOMPROMISED STATE, THEY MIGHT CARRY THE VIRUS FOR A LONG PERIOD OF TIME AND POTENTIALLY SHED THE VIRUS FOR A LONG PERIOD OF TIME. SO IN OTHER CASES SUCH AS NORO VIRUS, ET CETERA, THE PHYSICIANS HAVE BECOME FAMILIR WITH THOSE CASES WHAT DO THEY NEED TO DO, DO THEY NEED THE ACT, NOT ACT, AND HOSPITAL EPIDEMIOLOGY MADE DECISIONS ABOUT WHAT IT REQUIRES TO ISOLATE OR NOT, THOSE PATIENTS DEPENDING ON THE TESTING THEY DO. TO SAY HOW MANY NEGATIVES THEY NEED. SO IF YOU LOOK AT THE WHOLE POPULATION YOU WILL SEE A COMBINATION OF THESE THINGS. YOU WILL SEE PEOPLE WHOLE HAVE MORE SHEDDING OVER LONG PERIOD OF TIME AND IT'S REAL AND ASSAY IS GOOD AND JUST PICKING IT UP. YOU WILL SEE CASES WHERE LIMIT OF DETECTION, BOUNCING BACK AND FORTH NEAR INDETERMINANT AND THERE WILL BE SOME CASES BECAUSE NO TEST IS PERFECT, YOU HAVE A HUMAN ERROR OR TEST ERROR AND COUPLE OF CASES WHERE IT WAS AN INCORRECT RESULT. BUT OMS AND THE CLINICIANS AND HOSPITAL EPIDEMIOLOGY CAN SORT THAT OUT AS THEY ALWAYS DO WITH THESE CASES BUT IT WILL BE A MIXED PICTURE LOOKING AT ONE INDIVIDUAL. >> TO EXTEND YOUR ANSWER WITH SOME OTHERS THAT RELATE TO THAT, SO GIVEN THE LIMITATIONS AT LEAST AT THIS MOMENT OF CULTURE AND BSL 3 ASPECT WITH THAT, FIGURING OUT MOVING FORWARD SHEDDING VERSUS INFECTIVITY, HOW DO YOU SEE THAT COMING AROUND? >> THERE IS A GOOD POINT WITHIN THAT QUESTION. SO ONE THAT WILL DEFINITELY -- THERE ARE ALREADY LABS DOING CULTURING SO THAT'S DEFINITELY BSL 3 LABS UP AND RUNNING AND MORE THAT WILL DO GOOD QUALITY STUDIES ON THE HOW MUCH IS CULTURABLE BUT THE OTHER COMPONENT WE HAVE TO THINK ABOUT IS INFECTIOUSNESS AND CULTURIBILITY ARE NOT IDENTICAL. SO IT COULD BE YOU GET TO LOW LEVEL RT PCR SIGNAL AND JUST AT THRESHOLD THEY CAN CULTURE IN LABORATORY BUT THAT PERSON MIGHT NOT BE EXTREMELY INFECTIOUS SO IN TERMS OF OUR PRACTICAL ACTIONS THAT WE WANT TO TAKE, THAT WILL BE SLIGHTLY DIFFERENT. THOSE ARE HARD STUDIES TO DO BECAUSE YOU ARE NOT GOING TO LIKELY PURPOSEFULLY INFECT BUT YOU CAN DO CONTACT TRACING IN A VERY CONTROLLED STUDY IN A BIG ENOUGH POPULATION TO GET SOME OF THOSE ANSWERS. MORE STUDIES WILL BE DONE BUT IT WON'T BE AN IMMEDIATE ANSWER FOR SOME OF THOSE. >> A LOT OF PEOPLE ARE WONDERING GIVEN THE FIVE STEP GAPS THAT YOU MENTIONED. DO YOU SEE -- WHAT DO YOU SEE THE IMMEDIATE MAJOR GAP AND NEED IN ORDER TO ADDRESS IT? IS IT SCALING UP ONE OF THOSE FIVE ELEMENTS? IS IT INCREASING TESTING CAPACITY OR SOMETHING ELSE? IF YOU CAN PRIORITIZE SOMETHING, WHAT WOULD THAT BE? >> I CAN SAY I DON'T THINK THE SWABS ARE LIMITING BECAUSE PEOPLE MADE THE SWABS AND BECAUSE NUMBER OF YOU HAVE SHOWN SALIVA MIGHT WORK. PTM IS NOT A PROBLEM BECAUSE WE CAN USE PBS SO THOSE TWO ARE GONE. PRIMER PROBES ARE NOT REALLY LIMITING FACTOR BECAUSE WE CAN ORDER PRIMER PROBES. SO THE LIMITING REACTIONS ARE STILL COMPONENTS EXTRACTION AND ENZYMES. BUT THE OTHER PIECE TO KEEP IN MIND IS THIS IS WHEN YOU DO THE ASSAY AND PIECES AND YOU PUT IT TOGETHER IN A LABORATORY, WHAT IS BETTER IS WHEN IT'S ALL PUT TOGETHER IN COMMERCIALLY AVAILABLE AS ONE KIT AND RAPID KIT DONE QUICKLY IN 15 MINUTES OR ONE HOUR. AND THOSE ARE DEFINITELY LIMITING BECAUSE THE COMPANIES HAD TO DESIGN THEM SCALE THEM UP MANUFACTURE THEM AND GET FDA APPROVAL. SO WE ARE MAKING PROGRESS, IT WON'T BE FAST ENOUGH FOR US BECAUSE WE WANT TO MOVE FASTER. I'M HOPING THAT THE TASK FORCE THAT IS LOOKING AT THIS VERY SPECIFICALLY IS ADDRESSING THAT. THEY ARE ONES COLLECTING ALL THE -- WHAT IS CAPACITY OF EVERY LAB ACROSS THE COUNTRY, WHAT REAGENTS DO THEY HAVE IN STOCK AND WHAT DO THEY NEED AND THEY ARE COMMUNICATING WITH MANUFACTURERS AND I HOPE THEY MAKE THAT AN EVEN TIGHTER COLLABORATION TO GET THAT INFORMATION. THE OTHER OPTION IS IF THEY ARE ABLE TO WITH THIS NEW SHARK TANK OPTION OF ENOUGH CREATIVE IDEAS WILL SOMEBODY COME UP WITH AN IDEA WE HAVEN'T THOUGHT OF TO MAKE A BETTER ASSAY. NOT SURE THEY WILL COME UP WITH A TOTALLY NEW APPROACH BUT THEY CERTAINLY I THINK CAN WORK CLOSELY WITH THE MANUFACTURERS. IF WE GET THE RIGHT LEADERSHIP ON THE TASK FORCE TO ADDRESS THAT, WE AT LEAST WILL PREPARE EVEN IF IT TAKES A WHILE TO SCALE OVER THE NEXT SIX MONTHS THAT WE GET WHERE WE WANT TO BE. >> ANOTHER QUESTION THAT CAME THROUGH, IN REGARDS TO WE HAVE SEEN DIFFERENT COUNTRIES HAVING DIFFERENT CAPACITIES IN TO TESTING PER POPULATION. WHETHER THAT RELATES TO DIFFERENT PCR -- ASSAYS BEING USED, OTHER REGIONS THAT HAVE TO DO WITH TECHNICAL MOSTLY BUT COULD YOU EXPLAIN THAT? >> RIGHT. THERE'S ALL DIFFERENT REASONS. SO SOME OF THE COUNTRIES OBVIOUSLY JUST FUNDING IN HEALTHCARE INFRASTRUCTURE IN THE COUNTRY, IN SOME COUNTRIES THOUGH THAT WERE NOT LIMITED BY THAT, THEY DID HAVE A FASTER ASSAY. SOME HAD A MULTIPLEX ASSAY WITHOUT ONE OF THE CONTROLS, IT WAS A UNIFORM ASSAY SO THEY CAN DO A LOT OF THEM. SO THEY DIDN'T HAVE THE THREE ASSAYS WITH THE CONTROL, THEY HAD ONE. SO IT'S A MIXED ANSWER. AND ONE COULD -- THERE ARE SOME ASSAYS THAT ARE FASTER BUT NOT QUITE AS SENSITIVE. ONE COULD MAKE AN ARGUMENT FOR USING THEM IN SOME CASES. ONE MIGHT ALSO MAKE AN ARGUMENT FOR A MULTIPLEX ASSAY WITHOUT ONE CONTROL DEPENDING WHAT YOU ARE TRYING TO ACCOMPLISH. YOU HAVE TO BE CAREFUL SO ME AS LAB PERSON SAYING ANY NOTCH DOWN ON THE QUALITY I DON'T TEND THE DO THAT BUT ONE HAS TO THINK BROADLY BECAUSE THIS IS A PANDEMIC. >> DO YOU SEE A ROLE ON SELF TESTING FOR SALIVA OR SWABBING, WHAT LIMITATIONS DO YOU SEE IN THAT? >> I DEFINITELY SEE LIMITATIONS. THIS IS A -- WHEN THEY TALK ABOUT SELF TESTING, A LOT OF TIMES IT JUST MEANS SELF-COLLECTION. YOU SPIT IN THE TUBE AND MAIL IT IN SO IT WAS A SELF-COLLECTION WHICH AVOIDS CAR LINE AND AVOIDS SOMEONE IN PPE GOING IN WITH A NASO PHARENGEAL SWAB BUT THAT IS NOT A TEST. SO YOU DON'T HAVE RT PRCR AS HOME TEST. YOU MIGHT HAVE THE IMMUNOCHROMATOGRAPHIC ASSAYS, IT IS POSSIBLE THE THAT I WILL GET ONE GOOD ENOUGH. I CAN'T SAY SPECIFICALLY BUT BECAUSE WE CAN DO SOME KINDS OF ASSAYS VERY QUICKLY, THAT MIGHT BE DOWN THE ROAD AFTER THEY GET REALLY GOOD ASSESSMENT FOR NEUTRALIZING ANTIBODIES. THAT'S A CRITICAL STEP. >> DO WE KNOW IF WILL IS CORRELATION BETWEEN THE VIRAL BURDEN MEANING THE PATIENTS WHO MIGHT HAVE MORE VIRUS LOWER CT VALUES AND SEVERITY OF DISEASE? >> I DON'T HAVE THAT INFORMATION BUT I DEFINITELY THINK WE NEED TO LOOK. THERE SAW REPORT OUT THAT I AM NOT FAMILIAR WITH, BUT THE FORCE OF THE DISEASE AND THE -- COURSE OF THE DISEASE AND THE INFECTIOUSNESS. BUT I GUESS WHAT WE DO KNOW IS FROM PRESYMPTOMATIC, WE KNOW THERE ARE PEOPLE WHO HAD ALMOST NO SYMPTOMS OR WERE ASYMPTOMATIC WHO HAD A VERY HIGH VIRAL LOAD. WE DO KNOW THAT. SOME OF THE WORK DONE IN THE PRISON SYSTEM WHERE THEY HAVE MANY POSITIVE PEOPLE, THERE WERE MANY PEOPLE WHO WERE ASYMPTOMATIC WITH A HIGH VIRAL LOAD. SO WE DO KNOW THAT PIECE. I DON'T KNOW IF THERE'S ANY CORRELATION, IF YOU LOOK AT A THOUSAND OR 2,000 PEOPLE WE HAVE TO KEEP GATHERING DATA. >> COUPLE OF QUESTIONS THAT RELATE TO SPECIFIC TESTING. SO THERE'S A QUESTION THAT RESULTS TO THE RAPID TEST AND WHETHER WE KNOW HOW THAT COMPARES TO THE CDC TESTS FROM A SENSITIVITY SPECIFICITY -- >> THAT TEST IS EXCELLENT, VERY GOOD ASSAY. MULTIPLE PEOPLE TESTED THAT AND WE HAVE AS WELL. SO VERY GOOD ASSAY. >> DO WE HAVE EVIDENCE OF CROSS REACTIVITY AT THE PCR LEVEL OR THE SERO LOGICAL LEVEL WITH CORONA VIRUS, AT THE CONCERN LEVEL AT THE MOMENT. >> WE DO NOT HAVE CROSS REACTIVITY WITH THE RT PCR ASSAYS THAT ARE GOOD. THAT'S A VERY GOOD ASSAY. WE DEFINITELY HAVE SOME CROSS REACTIVITY WITH SOME OF THE SERO LOGIC ASSAYS. SO IT LOOKS LIKE WE HAVE HINTS SOME GOOD ASSAYS BUT NOT CREATED EQUAL AND IT IS A BIT OF A PROBLEM THEY ARE OUT THERE NOW USED AS THEY BECOME AVAILABLE AND NOT ALL EQUIVALENT. SO WE WILL HAVE TO DO A REGROUPING AND AS SOON AS WE HAVE GOOD ASSAYSES THAT ARE PROVEN, REPEAT SOME OF THESE SURVEILLANCE STUDIES. >> YOU MENTION IN YOUR INITIAL SCHEMATIC OF THE VIRUS A FEW PROTEINS OF THE VIRUS. AND THERE'S A QUESTION WITH REGARDS TO WHAT PROTEINS ARE SPECIFICALLY BEING USED FOR THESE ELISA SERO LOGICAL TESTING AND WHETHER THERE ARE DIFFERENCES IN PERFORMANCE THAT WE MIGHT KNOW SO FAR. >> I DON'T HAVE ALL THE ANSWERS TO THAT. I KNOW THE SPIKE PROTEIN HAS BEEN MENTIONED LIKELY BEING IMPORTANT FOR NEUTRALIZATION. I DON'T HAVE THE INFORMATION ON ALL THE DIFFERENT PROTEINS THAT ARE BEING EVALUATED. I KNOW IT'S MORE THAN ONE PROTEIN BUT I DON'T HAVE THOSE DATA. I'M NOT IN ONE OF THE GROUPS AT NIH WHO HAS BEEN DOING THE ACTUAL ANALYSES OF THOSE KITS. PROBABLY IN THE FUTURE WE SHOULD HAVE A FULL SERO LOGIC ASSAY WHEN THEY HAVE MORE DATA ON THOSE STUDIES. >> SOMEONE IS ASKING WHAT IS THE CURE AND TESTING CAPACITY OF DLM AND WHAT CAN YOU ESTIMATE THE FUTURE TESTING CAPACITY GO OVER THE SUMMER OVER THE NEXT FEW WEEKS? SO WE CAN CURRENTLY DO 100 TESTS PER DAY SOMEWHAT COMFORTABLY MEANING NOT WORKING 24/7. THE GOAL IS TO SCALE UP TO A THOUSAND TODAY IF WE CAN GET A THOUSAND PER DAY, IF WE CAN GET ONE OF THESE AUTOMATED INSTRUMENTS, THERE IS A LIMIT ON CAPACITY OR SUPPLY FOR BOTH REAGENTS AND THE INSTRUMENTS. SO WE ARE WORKING VERY HARD TO SCALE UP THE GOAL BEING A THOUSAND TESTS PER DAY IN THE COMING WEEKS IF WE CAN GET THE SUPPLIES AND THE EQUIPMENT. >> DO YOU SEE NON-PCR BASED DIAGNOSTIC TESTS FOR ACUTE INFECTION? >> DO I SEE THEM BEING USE -- >> IS THERE A ROLE FOR THEM AND IS THERE ANYTHING THAT IS DEVELOPED OR IN THE WORKS? >> NOT THAT I KNOW OF. I KNOW IT'S DISCUSSED IN SOME OF THE NEWS BRIEFINGS, ANTIGEN ASSAYS, AS OPPOSED TO MOLECULAR RT PCR ASSAYS WHICH IS DIFFERENT THAN ANTIBODY ASSAYS. I DON'T KNOW OF ANY REAL STUDIES OR ANY DATA YET ON IT. IT'S BEING TALKED ABOUT BUT IT WILL HAVE TO BE PROVEN TO BE MORE EFFECTIVE, SENTIVE OR SPECIFIC. SO AS OF RIGHT NOW I ONLY KNOW POTENTIAL DISCUSSIONS BUT NOT DATA. >> COMING CLOSE TO MAYBE COUPLE OF SHORT LAST QUESTIONS. IS THERE EVIDENCE OF PATIENTS BEING INFECTED WITH MORE THAN ONE SARS COVID 2 STRAINS? >> I HAVE NOT HEARD THAT YET. I DON'T KNOW THE ANSWER, IF THAT HAS BEEN REPORTED. I HAVEN'T SEEN IT REPORTED YET. >> ANOTHER QUESTION RELATES TO YOU COMMENTED ON THE SENSITIVITY AND IN THISTY OF NEUROLOGICAL TESTING. WOULD COMBINING DIFFERENT ASSAYS HELP WITH INCREASING SPECIFICITY >> YES. THAT IS AN OPTION PARTICULARLY WHEN THE PAPER REPORTED THAT THE CROSS REACTIVITY WAS NOT THE SAME. HOWEVER, I'M HOPING THAT IS NOT NECESSARY. I HOPE THAT THEY GET A REALLY GOOD ASSAY WITH 99 PLUS SENSITIVITY AND SPECIFICITY BECAUSE YOU ALSO THEN WILL HAVE A COST AND REAGENT ISSUE, YOU DON'T WANT TO DO THREE TESTS IF YOU CAN DO ONE SO I HOPE TO GET ONE GOOD OR SEVERAL GOOD IMMUNOLOGIC ASSAY, SERO LOGICAL ASSAYS. >> LET ME GO WITH A LAST QUESTION. SOMEONE IS ASKING, WOULD IT BE POSSIBLE TO DEVELOP IMMUNOASSAYS DESIGNED TO DETECT ANTIBODIES DIRECTED TO SPIKE PROTEINS THAT IS PRESUMABLY NEUTRALIZING ONLY TO BETTER INDICATE IMMUNITY OPPOSED TO HAVING A SEROLOGICAL TEST TO INDICATE WHETHER YOU MIGHT BE IMMUNE OR NEUTRALIZING OR NOT, TOW SEE THAT BECOMING A REALITY THE NEXT FEW WEEKS? IF I UNDERSTAND CORRECTLY, I THINK YOU ARE OUT OF MY EXPERIENCE LEVEL SO I'M NOT ONE OF THE PEOPLE DOING THESE STUDIES ON THE IMMUNOLOGIC ASSAYS BUT I BELIEVE THAT IS ONE OF THE GOALS THEY WILL BE ABLE TO DETECT NEUTRALIZING ANTIBODIES AND THEY WILL HAVE AN ASSAY TO DETECT IT. I DON'T KNOW IF IT WILL BE IN A COUPLE OF WEEKS OR NOT. AGAIN, I THINK WE NEED TO BRING& IN ONE OF THE VACCINE RESEARCH CENTER AS A SPEAKER COMING FORWARD AS THEY HAVE MORE DATA. >> KAREN, THANK YOU SO MUCH FOR THIS GREAT TALK. WE WENT THROUGH MOST OF THE QUESTIONS, UNFORTUNATELY DUE TO TIME WE COULDN'T GO THROUGH MAYBE A FEW MORE. THANK YOU FOR THIS GREAT TALK. THANKS TO EVERYBODY WHO IS ON THE VIDEO CAST, THOUSANDS OF PEOPLE LISTENING TO YOU. I'LL JUST END BY REMINDING EVERYBODY THAT THE CME CODE FOR TODAY'S TALK IS 24874. AGAIN 24874. THANK YOU AGAIN SO MUCH. WE'LL RESUME AGAIN NEXT WEDNESDAY WITH OUR NEXT SPEAKER IN THE SEMINAR SERIES. HAVE A GOOD AFTERNOON.