1 00:00:07,480 --> 00:00:10,320 WELCOME TO TODAY'S COVID 2 00:00:10,320 --> 00:00:10,720 LECTURE. 3 00:00:10,720 --> 00:00:12,800 IT REALLY IS A PLEASURE FOR ME 4 00:00:12,800 --> 00:00:16,160 TO INTRODUCE MY GOOD FRIEND AND 5 00:00:16,160 --> 00:00:19,000 FELLOW NEUROLOGIST DR. CLINTON 6 00:00:19,000 --> 00:00:19,200 WRIGHT. 7 00:00:19,200 --> 00:00:20,800 DR. WRIGHT IS A VASCULAR 8 00:00:20,800 --> 00:00:25,480 NEUROLOGIST AND A SPECIALIST IN 9 00:00:25,480 --> 00:00:26,320 COGNITIVE DISORDERS. 10 00:00:26,320 --> 00:00:27,840 HE'S ASSOCIATE DIRECTOR OF THE 11 00:00:27,840 --> 00:00:29,840 NATIONAL INSTITUTE OF 12 00:00:29,840 --> 00:00:30,400 NEUROLOGICAL DISORDERS AND 13 00:00:30,400 --> 00:00:32,080 STROKE AND THE DIRECTOR OF THE 14 00:00:32,080 --> 00:00:33,680 DIVISION OF CLINICAL RESEARCH. 15 00:00:33,680 --> 00:00:35,480 HE'S A MEMBER OF THE STROKE 16 00:00:35,480 --> 00:00:39,360 BRANCH WITHIN THE DIVISION OF 17 00:00:39,360 --> 00:00:40,400 INTRAMURAL RESEARCH. 18 00:00:40,400 --> 00:00:42,880 DR. WRIGHT RECEIVED HIS MD FROM 19 00:00:42,880 --> 00:00:45,680 THE COLLEGE OF PHYSICIANS AND 20 00:00:45,680 --> 00:00:46,760 SURGEONS AT COLUMBIA UNIVERSITY 21 00:00:46,760 --> 00:00:50,920 AND HIS MASTERS DEGREE IN 22 00:00:50,920 --> 00:00:53,000 EPIDEMIOLOGY FROM THE MAILMAN 23 00:00:53,000 --> 00:00:55,000 SCHOOL OF PUBLIC HEALTH ALSO AT 24 00:00:55,000 --> 00:00:55,600 COLUMBIA. 25 00:00:55,600 --> 00:01:00,440 HE COMPLETED A NEUROLOGY 26 00:01:00,440 --> 00:01:02,040 RESIDENCY AT COLUMBIA'S 27 00:01:02,040 --> 00:01:02,720 UNIVERSITY NEUROLOGICAL 28 00:01:02,720 --> 00:01:05,440 INSTITUTE OF NEW YORK AND THEN 29 00:01:05,440 --> 00:01:08,240 DID A VASCULAR NEUROLOGY 30 00:01:08,240 --> 00:01:09,960 FELLOWSHIP. 31 00:01:09,960 --> 00:01:11,320 BEFORE JOINING NINDS, DR. WRIGHT 32 00:01:11,320 --> 00:01:13,560 SERVED AS THE EVELYN F. 33 00:01:13,560 --> 00:01:14,760 Mc KNIGHT CHAIR FOR LEARNING 34 00:01:14,760 --> 00:01:18,160 AND MEMORY IN THE AGING AND WAS 35 00:01:18,160 --> 00:01:20,800 A TENURED PROFESSOR OF 36 00:01:20,800 --> 00:01:22,120 NEUROLOGY, PUBLIC HEALTH 37 00:01:22,120 --> 00:01:23,320 SCIENCES AND NEUROSCIENCE AS 38 00:01:23,320 --> 00:01:26,840 WELL AS CHIEF OF THE DIVISION OF 39 00:01:26,840 --> 00:01:29,240 COGNITIVE DISORDERS AT THE 40 00:01:29,240 --> 00:01:31,640 LEONARD M. MILLER SCHOOL OF 41 00:01:31,640 --> 00:01:35,040 MEDICINE AT THE UNIVERSITY OF 42 00:01:35,040 --> 00:01:35,560 MIAMI. 43 00:01:35,560 --> 00:01:37,640 HE SERVED AS SCIENTIFIC DIRECTOR 44 00:01:37,640 --> 00:01:40,240 OF THE Mc KNIGHT BRAIN 45 00:01:40,240 --> 00:01:43,520 INSTITUTE AT THE UNIVERSITY OF 46 00:01:43,520 --> 00:01:47,640 MIAMI UNTIL HE JOINED THE NIH IN 47 00:01:47,640 --> 00:01:47,840 2008. 48 00:01:47,840 --> 00:01:49,360 SO TODAY DR. WRIGHT IS GOING TO 49 00:01:49,360 --> 00:01:52,920 TALK WITH US ABOUT THE RECOVER 50 00:01:52,920 --> 00:01:55,640 INITIATIVE EARLY FINDINGS AND 51 00:01:55,640 --> 00:01:58,720 OTHER EMERGING LONG COVID 52 00:01:58,720 --> 00:01:59,400 SCIENCE. 53 00:01:59,400 --> 00:02:03,000 CLINT, THE VIRTUAL PODIUM IS 54 00:02:03,000 --> 00:02:03,200 YOURS. 55 00:02:03,200 --> 00:02:04,960 >>THANK YOU VERY MUCH, NINA. 56 00:02:04,960 --> 00:02:08,280 IT'S A PLEASURE TO BE HERE 57 00:02:08,280 --> 00:02:08,480 TODAY. 58 00:02:08,480 --> 00:02:11,240 THANK YOU SO MUCH FOR THAT KIND 59 00:02:11,240 --> 00:02:13,120 INTRODUCTION AND THANKS TO 60 00:02:13,120 --> 00:02:14,320 EVERYONE FOR INVITING ME. 61 00:02:14,320 --> 00:02:17,160 IT'S A REAL PLEASURE TO TALK TO 62 00:02:17,160 --> 00:02:20,960 YOU TODAY ABOUT RECOVER, BUT 63 00:02:20,960 --> 00:02:30,280 ALSO ABOUT THIS EMERGING AREA OF 64 00:02:30,280 --> 00:02:30,680 EXCITING RESEARCH. 65 00:02:30,680 --> 00:02:32,840 SO OVERALL THE ESTIMATES OF 66 00:02:32,840 --> 00:02:34,320 INDIVIDUALS EXPERIENCING LONG 67 00:02:34,320 --> 00:02:37,440 COVID HAVE BEEN DECREASING OVER 68 00:02:37,440 --> 00:02:37,680 TIME. 69 00:02:37,680 --> 00:02:40,760 SURVEY RESULTS FROM THE NATIONAL 70 00:02:40,760 --> 00:02:42,040 CENTER FOR L-STATISTICS OF 71 00:02:42,040 --> 00:02:44,760 ADULTS WHO HAD COVID-19 AS OF 72 00:02:44,760 --> 00:02:50,880 AUGUST SHOWED THAT ABOUT 28% 73 00:02:50,880 --> 00:02:52,160 REPORTED EVERY EXPERIENCING LONG 74 00:02:52,160 --> 00:02:54,200 COVID AND 10% EXPERIENCING LONG 75 00:02:54,200 --> 00:02:54,760 COVID. 76 00:02:54,760 --> 00:02:57,600 AND THEN OF COURSE CURRENTLY 77 00:02:57,600 --> 00:02:59,400 EXPERIENCING LONG COVID ABOUT 78 00:02:59,400 --> 00:03:02,440 80% REPORT ACTIVITY LIMITATIONS 79 00:03:02,440 --> 00:03:06,080 AND 25% REPORT SIGNIFICANT 80 00:03:06,080 --> 00:03:06,560 ACTIVITY LIMITATIONS. 81 00:03:06,560 --> 00:03:10,520 SO THIS IS A VERY SIGNIFICANT 82 00:03:10,520 --> 00:03:12,120 AND SERIOUS PROBLEM THAT 83 00:03:12,120 --> 00:03:13,760 OBVIOUSLY AFFECTS A VERY LARGE 84 00:03:13,760 --> 00:03:15,480 NUMBER OF PEOPLE GIVEN THE 85 00:03:15,480 --> 00:03:20,040 NUMBER OF PEOPLE THAT HAVE BEEN 86 00:03:20,040 --> 00:03:21,360 AFFECTED BY COVID. 87 00:03:21,360 --> 00:03:23,360 BUT HERE'S THE PROBLEM. 88 00:03:23,360 --> 00:03:26,560 THE PROBLEM IS THAT IT IS A VERY 89 00:03:26,560 --> 00:03:30,360 COMPLEX SET OF DISORDERS THAT WE 90 00:03:30,360 --> 00:03:31,760 DON'T COMPLETELY UNDERSTAND EVEN 91 00:03:31,760 --> 00:03:31,960 NOW. 92 00:03:31,960 --> 00:03:34,960 AND I THINK THIS SLIDE IS VERY 93 00:03:34,960 --> 00:03:36,000 ILLUSTRATIVE OF IT BECAUSE YOU 94 00:03:36,000 --> 00:03:40,040 SEE THAT THERE ARE SO MANY 95 00:03:40,040 --> 00:03:41,360 SYSTEMS THAT ARE INVOLVED AND 96 00:03:41,360 --> 00:03:43,160 THEN YOU SEE SOME OF THE 97 00:03:43,160 --> 00:03:45,480 SYMPTOMS AND SOME OF THE 98 00:03:45,480 --> 00:03:47,560 PATHOLOGIES THAT ARE ASSOCIATED 99 00:03:47,560 --> 00:03:51,520 WITH EACH 1 OF THOSE ORGAN 100 00:03:51,520 --> 00:03:52,320 SYSTEMS. 101 00:03:52,320 --> 00:03:59,160 SO WHEN NIH SET ABOUT TO 102 00:03:59,160 --> 00:04:01,800 UNDERSTAND THE POST ACUTE SEQUEL 103 00:04:01,800 --> 00:04:04,680 I OF COVID AND NOW WE'RE 104 00:04:04,680 --> 00:04:08,360 REFERRING TO LONG COVID, IT WAS 105 00:04:08,360 --> 00:04:12,000 REALLY IMPORTANT TO REALLY DIG 106 00:04:12,000 --> 00:04:16,240 INTO WHAT--SO WE NEEDED TO 107 00:04:16,240 --> 00:04:18,280 UNDERSTAND IT AND YOU SEE HOW 108 00:04:18,280 --> 00:04:19,480 COMPLEX IT WAS, YOU NEED TO BE 109 00:04:19,480 --> 00:04:21,800 ABLE TO PREDICT IT, TREAT IT AND 110 00:04:21,800 --> 00:04:24,720 PREVENT IT SO THE KEY AIMS OF 111 00:04:24,720 --> 00:04:26,160 THE RECOVER INITIATIVE WHEN IT 112 00:04:26,160 --> 00:04:29,840 WAS SET UP TO DO THAT WERE TO 113 00:04:29,840 --> 00:04:31,560 UNDERSTAND FIRST THE CLINICAL 114 00:04:31,560 --> 00:04:34,160 SPECTRUM AND THE BIOLOGY 115 00:04:34,160 --> 00:04:35,960 UNDERLYING RECOVERY FROM COVID 116 00:04:35,960 --> 00:04:38,320 INFECTION OVER TIME TO DEFINE 117 00:04:38,320 --> 00:04:40,560 RISK FACTORS, TO UNDERSTAND THE 118 00:04:40,560 --> 00:04:42,560 EPIDEMIOLOGY, THE INCIDENCE, THE 119 00:04:42,560 --> 00:04:44,640 PREVALENCE, TO UNDERSTAND THE 120 00:04:44,640 --> 00:04:46,040 PHENOTYPES THEMSELVES, YOU KNOW 121 00:04:46,040 --> 00:04:49,440 WHAT ARE THE DIFFERENT 122 00:04:49,440 --> 00:04:49,880 PHENOTYPES. 123 00:04:49,880 --> 00:04:51,680 STUDY PATHOGENESIS OVER TIME AND 124 00:04:51,680 --> 00:04:53,640 THE RELATION TO OTHER ORGAN 125 00:04:53,640 --> 00:04:56,200 SYSTEMS AND DISORDERS AND THEN 126 00:04:56,200 --> 00:04:58,320 IDENTIFY INTERVENTIONS, YOU KNOW 127 00:04:58,320 --> 00:05:00,080 OBVIOUSLY TO HOPEFULLY PREVENT 128 00:05:00,080 --> 00:05:00,640 AND TREAT IT. 129 00:05:00,640 --> 00:05:04,600 BUT 1 OF THE THINGS THAT WAS 130 00:05:04,600 --> 00:05:05,960 RECOGNIZED WAS GIVEN THAT THERE 131 00:05:05,960 --> 00:05:10,040 WAS SO MUCH AT STAKE, IT WAS 132 00:05:10,040 --> 00:05:11,560 ABSOLUTELY CRITICAL TO DO A 133 00:05:11,560 --> 00:05:13,120 NUMBER OF THINGS AND THE GUIDING 134 00:05:13,120 --> 00:05:16,360 PRINCIPLES ON THIS SLIDE, I 135 00:05:16,360 --> 00:05:17,640 THINK ARE EXTREMELY IMPORTANT. 136 00:05:17,640 --> 00:05:20,600 FIRST OF ALL, IT HAD TO BE AND 137 00:05:20,600 --> 00:05:22,200 I'M GOING TO SKIP THE 138 00:05:22,200 --> 00:05:22,840 PATIENT-CENTERED PIECE BECAUSE I 139 00:05:22,840 --> 00:05:24,080 WILL TALK ABOUT IT MORE BUT THE 140 00:05:24,080 --> 00:05:25,480 FIRST THING WAS JUST TO 141 00:05:25,480 --> 00:05:29,080 RECOGNIZE THAT IN ORDER TO GET 142 00:05:29,080 --> 00:05:34,160 DATA THAT WAS OF VALUE OUT OF 143 00:05:34,160 --> 00:05:35,640 THIS, YOU KNOW MORAS OF 144 00:05:35,640 --> 00:05:37,000 INFORMATION THAT WAS COMING OUT 145 00:05:37,000 --> 00:05:38,440 OF SO MANY DIFFERENT AREAS, WE 146 00:05:38,440 --> 00:05:39,760 NEEDED TO HAVE A STUDY OF 147 00:05:39,760 --> 00:05:43,640 NATIONAL SCALE THAT WAS ALSO 148 00:05:43,640 --> 00:05:44,920 VERY ENCLUESIVE OF DIVERSE 149 00:05:44,920 --> 00:05:49,480 POPULATIONS THAT MAY BE MORE 150 00:05:49,480 --> 00:05:50,680 AFFECTED, NOT KNOWING WHICH 151 00:05:50,680 --> 00:05:51,800 SUBGRUPS MY BE MORE AFFECTED AND 152 00:05:51,800 --> 00:05:53,680 THEN ALSO TO BE ABLE TO 153 00:05:53,680 --> 00:05:57,080 HARMONIZE THAT DATA SO THAT IT 154 00:05:57,080 --> 00:05:58,640 COULD BE LOOKED AT ACROSS THE 155 00:05:58,640 --> 00:06:00,920 DIFFERENT STUDIES AND THEN THE 156 00:06:00,920 --> 00:06:01,520 OTHER RECOGNITION WAS THAT 157 00:06:01,520 --> 00:06:05,560 BECAUSE OF THE NUMBER OF 158 00:06:05,560 --> 00:06:07,520 DIFFERENT WAVES OF THE VIRUS 159 00:06:07,520 --> 00:06:08,720 THAT HAD HAPPENED, IT WAS 160 00:06:08,720 --> 00:06:10,720 RECOGNIZED IT WOULD HAVE TO BE 161 00:06:10,720 --> 00:06:12,680 ADAPTIVE AS THESE DIFFERENT 162 00:06:12,680 --> 00:06:14,200 WAVES HAPPEN, THERE MIGHT BE 163 00:06:14,200 --> 00:06:16,320 DIFFERENT EFFECTS BASED ON THE 164 00:06:16,320 --> 00:06:17,040 DIFFERENT VARIANTS. 165 00:06:17,040 --> 00:06:22,600 SO ALL THOSE THINGS WERE DRIVING 166 00:06:22,600 --> 00:06:22,880 FACTORS. 167 00:06:22,880 --> 00:06:25,440 THE PATIENT ENGAGEMENT AND 168 00:06:25,440 --> 00:06:27,320 COMMUNITY ENGAGEMENT PIECE WAS 169 00:06:27,320 --> 00:06:29,040 ALSO RECOGNIZED TO BE EXTREMELY 170 00:06:29,040 --> 00:06:30,120 IMPORTANT FROM THE VERY, VERY 171 00:06:30,120 --> 00:06:33,800 BEGINNING AND I THINK 1 OF THE 172 00:06:33,800 --> 00:06:35,800 ININIVATIVE THINGS ABOUT RECOVER 173 00:06:35,800 --> 00:06:38,920 WAS INCLUDING PATIENTS AT ALL 174 00:06:38,920 --> 00:06:40,920 LEVELS OF THE STRUCTURE OF THE 175 00:06:40,920 --> 00:06:41,840 RECOVER PROGRAM. 176 00:06:41,840 --> 00:06:44,280 SO HAVING THE PATIENT 177 00:06:44,280 --> 00:06:45,640 PERSPECTIVE INVOLVED NOT ONLY AT 178 00:06:45,640 --> 00:06:47,360 THE BEGINNING SORT OF 179 00:06:47,360 --> 00:06:49,880 IDENTIFYING, YOU KNOW WHAT ARE 180 00:06:49,880 --> 00:06:52,800 THE SYMPTOMS AND PROBLEMS THAT 181 00:06:52,800 --> 00:06:54,240 WERE OF MOST IMPORTANCE TO THE 182 00:06:54,240 --> 00:06:56,880 PATIENTS, BUT ALSO GETTING THEM 183 00:06:56,880 --> 00:06:58,760 INVOLVED IN THE STEERING 184 00:06:58,760 --> 00:07:00,040 COMMITTEES AND THE SCIENTIFIC 185 00:07:00,040 --> 00:07:02,160 WORKING GROUPS, THE EXECUTIVE 186 00:07:02,160 --> 00:07:02,640 COMMITTEE, THE OVERSIGHT 187 00:07:02,640 --> 00:07:04,520 COMMITTEES TO MAKE SURE THAT 188 00:07:04,520 --> 00:07:06,000 THEIR INPUT WAS CARRIED ALL THE 189 00:07:06,000 --> 00:07:07,520 WAY THROUGH THE PROGRAM AND MAKE 190 00:07:07,520 --> 00:07:12,560 SURE THAT THOSE VOICES WERE 191 00:07:12,560 --> 00:07:12,760 HEARD. 192 00:07:12,760 --> 00:07:16,680 SO RECOVER WAS SET UP AND IT HAS 193 00:07:16,680 --> 00:07:18,320 A NUMBER OF COMPONENTS AND I 194 00:07:18,320 --> 00:07:20,800 WILL WALK YOU THROUGH THAT 195 00:07:20,800 --> 00:07:24,560 QUICKLY SO YOU SEE THE KEY 196 00:07:24,560 --> 00:07:25,240 SCIENTIFIC AIMS AND THEN ALONG 197 00:07:25,240 --> 00:07:27,760 THE TOP IN THE YELLOW BEND, YOU 198 00:07:27,760 --> 00:07:30,440 SEE THE THINGS I ALREADY TALKED 199 00:07:30,440 --> 00:07:32,520 ABOUT AND THEN, IN TERMS OF THE 200 00:07:32,520 --> 00:07:36,240 AIMS, WHICH WE ALREADY TALKED 201 00:07:36,240 --> 00:07:37,440 ABOUT, IDENTIFYING THE DIFFERENT 202 00:07:37,440 --> 00:07:40,240 ASPECT OF LONG COVID, WE NEEDED 203 00:07:40,240 --> 00:07:45,520 TO SET UP A NUMBER OF DIFFERENT 204 00:07:45,520 --> 00:07:47,920 TYPES OF DATA COLLECTION 205 00:07:47,920 --> 00:07:48,320 EFFORTS. 206 00:07:48,320 --> 00:07:52,640 SO AN ELECTRONIC HEALTH RECORD 207 00:07:52,640 --> 00:07:55,960 PROGRAM, COHORT STUDY PROGRAM 208 00:07:55,960 --> 00:07:58,360 THAT WOULD INCLUDE NOT ONLY DE 209 00:07:58,360 --> 00:08:00,840 NOVO COHORT THAT WOULD COLLECT 210 00:08:00,840 --> 00:08:03,960 DATA ON PATIENT SUFFERING FROM 211 00:08:03,960 --> 00:08:06,760 ACUTE INFECTION TO SEE WHO 212 00:08:06,760 --> 00:08:08,720 DEVELOPED A LONG COVID BUT ALSO 213 00:08:08,720 --> 00:08:10,120 PEOPLE HA ALREADY HAD LONG COVID 214 00:08:10,120 --> 00:08:11,240 THAT WANTED TO PARTICIPATE IN 215 00:08:11,240 --> 00:08:12,880 RESEARCH BUT ALSO TAKING 216 00:08:12,880 --> 00:08:15,720 ADVANTAGE OF SOME LONG STANDING 217 00:08:15,720 --> 00:08:17,920 COHORT STUDIES, FAMOUS COHORT 218 00:08:17,920 --> 00:08:19,640 STUDIES THAT HAD BEEN FUNDED BY 219 00:08:19,640 --> 00:08:21,880 NIH FOR A LONG TIME SIMILAR TO 220 00:08:21,880 --> 00:08:23,360 LIKE THE FRAMINGHAM STUDY AND 221 00:08:23,360 --> 00:08:26,880 OTHER STUDIES THAT HAVE BEEN 222 00:08:26,880 --> 00:08:27,560 DEEPLY PHENOTYPING PARTICIPANTS 223 00:08:27,560 --> 00:08:30,360 FOR MANY, MANY YEARS AND NOW 224 00:08:30,360 --> 00:08:32,480 MANY OF THEM WERE HAVING ACUTE 225 00:08:32,480 --> 00:08:33,320 COVID INFECTIONS AND SOME OF 226 00:08:33,320 --> 00:08:37,000 THEM GO ON TO DEVELOP LONG 227 00:08:37,000 --> 00:08:37,320 COVID. 228 00:08:37,320 --> 00:08:39,200 AND THEN, TISSUE AND PATHOLOGY 229 00:08:39,200 --> 00:08:40,800 STUDIES AND PATHOBIOLOGY STUDIES 230 00:08:40,800 --> 00:08:42,080 TO UNDERSTAND THE PATHOGENESIS 231 00:08:42,080 --> 00:08:43,920 AS I MENTIONED, YOU KNOW VERY, 232 00:08:43,920 --> 00:08:47,160 VERY CRITICAL AND THEN, MOVING 233 00:08:47,160 --> 00:08:49,760 ON A COHORT OF CLINICAL TRIALS, 234 00:08:49,760 --> 00:08:51,160 THAT WOULD THEN HAVE DATA COMING 235 00:08:51,160 --> 00:08:53,080 OUT OF THESE OTHER 4 FEEDING 236 00:08:53,080 --> 00:08:54,040 INTO THE INFORMATION THAT WENT 237 00:08:54,040 --> 00:08:56,480 INTO SETTING UP THE CLINICAL 238 00:08:56,480 --> 00:08:56,920 TRIALS. 239 00:08:56,920 --> 00:08:57,920 AND SO ASSOCIATED WITH THAT, 240 00:08:57,920 --> 00:08:59,560 THERE ARE MANY DIFFERENT TYPES 241 00:08:59,560 --> 00:09:00,960 OF DATA THAT NEEDED TO BE 242 00:09:00,960 --> 00:09:02,760 COLLECTED AND YOU SEE THOSE, YOU 243 00:09:02,760 --> 00:09:07,400 KNOW ALONG THE BOTTOM INCLUDING 244 00:09:07,400 --> 00:09:08,000 MOBILE HEALTH, IMAGING, 245 00:09:08,000 --> 00:09:08,720 PATHOLOGY AND SO ON. 246 00:09:08,720 --> 00:09:10,640 SO I WILL TALK A LITTLE BIT 247 00:09:10,640 --> 00:09:15,840 ABOUT THE ELECTRONIC HEALTH 248 00:09:15,840 --> 00:09:16,520 RECORD DATA. 249 00:09:16,520 --> 00:09:21,120 THIS WAS A PROGRAM THAT ANALYZED 250 00:09:21,120 --> 00:09:25,320 60 MILLION RECORDS WITH 251 00:09:25,320 --> 00:09:28,280 11 MILLION COVID CASES ACROSS 252 00:09:28,280 --> 00:09:29,520 DIVERSE POPULATIONS, TO 253 00:09:29,520 --> 00:09:32,360 UNDERSTAND, YOU KNOW 254 00:09:32,360 --> 00:09:33,560 EPIDEMIOLOGY, PARTICIPANT BURDEN 255 00:09:33,560 --> 00:09:35,600 AND SOME PHENOTYPES. 256 00:09:35,600 --> 00:09:36,680 1 OF THE STUDIES I WANT TO 257 00:09:36,680 --> 00:09:40,320 TALK ABOUT WAS THE RECOVER, FROM 258 00:09:40,320 --> 00:09:42,520 THE RECOVER EHR FINDINGS WAS 259 00:09:42,520 --> 00:09:46,800 JUST THE ABILITY TO UNDERSTAND 260 00:09:46,800 --> 00:09:48,920 THE INCREASED RISK OF NEW ONSET 261 00:09:48,920 --> 00:09:51,040 CONDITIONS IN PAST PATIENTS. 262 00:09:51,040 --> 00:09:52,600 SO, YOU KNOW THAT WAS 1 OF THE 263 00:09:52,600 --> 00:09:54,880 BIG QUESTIONS, JUST STARTING 264 00:09:54,880 --> 00:09:55,800 OUT. 265 00:09:55,800 --> 00:10:00,880 DO PEOPLE WHO SUFFER FROM P A SC 266 00:10:00,880 --> 00:10:02,760 HAVE A HIGHER INCIDENCE OF NEW 267 00:10:02,760 --> 00:10:04,240 ONSET CONDITIONS AND YOU CAN SEE 268 00:10:04,240 --> 00:10:07,080 A WHOLE LIST OF CONTICKSES THAT 269 00:10:07,080 --> 00:10:09,760 WERE GENERATED BY EHR DATA. 270 00:10:09,760 --> 00:10:12,360 SO 1 OF THE BENEFITS OF RECOVER 271 00:10:12,360 --> 00:10:15,880 IS YOU KNOW HAVING THOSE 272 00:10:15,880 --> 00:10:17,480 DIFFERENT DATA TYPES WE CAN TAKE 273 00:10:17,480 --> 00:10:19,240 FOR EXAMPLE, THE EHR DATA AND 274 00:10:19,240 --> 00:10:21,360 RELATE IT TO THE DATA COMING OUT 275 00:10:21,360 --> 00:10:22,960 OF THE COHORT STUDY AND 276 00:10:22,960 --> 00:10:24,600 VALENTINED DIADIC AND CROSS 277 00:10:24,600 --> 00:10:27,440 VALIDATE THE DATA COMES OUT OF 278 00:10:27,440 --> 00:10:29,720 THOSE SO THE MESSAGE I WILL GIVE 279 00:10:29,720 --> 00:10:31,800 YOU ACROSS THESE DIFFERENT TYPES 280 00:10:31,800 --> 00:10:34,480 OF DATA ARE SORT OF A--IT'S A 281 00:10:34,480 --> 00:10:35,280 SYNERGY OF DATA FINDINGS THAT 282 00:10:35,280 --> 00:10:37,320 ARE COMING OUT TO LEAD US YOU 283 00:10:37,320 --> 00:10:42,960 KNOW TO THE NEXT STEP. 284 00:10:42,960 --> 00:10:44,720 THIS PARTICULAR SLIDE, ALTHOUGH 285 00:10:44,720 --> 00:10:45,800 SLIGHTLY COMPLICATED IS REALLY 286 00:10:45,800 --> 00:10:48,480 JUST MEANT TO ILLUSTRATE THAT 287 00:10:48,480 --> 00:10:51,520 THE EHR STUDIES WERE USED TO MAP 288 00:10:51,520 --> 00:10:54,240 SUBPHENOTYPES OF P A SC USING 289 00:10:54,240 --> 00:10:57,400 MACHINE LEARNING TECHNIQUES JUST 290 00:10:57,400 --> 00:10:59,240 TO UNDERSTAND IN THE MEDICAL 291 00:10:59,240 --> 00:11:00,640 RECORD WHAT ARE THE 292 00:11:00,640 --> 00:11:01,680 SUBPHENOTYPES THAT ARE BEING 293 00:11:01,680 --> 00:11:04,280 SEEN IN THESE HEALTH SYSTEMS. 294 00:11:04,280 --> 00:11:06,520 SO THIS INVOLVED PATIENTS WHO 295 00:11:06,520 --> 00:11:12,240 HAD A POSITIVE PC R TEST, IN THE 296 00:11:12,240 --> 00:11:15,480 EHR BETWEEN 2020-2021, ABOUT 297 00:11:15,480 --> 00:11:16,880 24,000 PEOPLE, AND SOME 298 00:11:16,880 --> 00:11:17,840 PHENOTYPES WERE BASED ON NEW 299 00:11:17,840 --> 00:11:20,160 CONDITIONS IN THE POST ACUTE 300 00:11:20,160 --> 00:11:21,360 INFECTION PERIOD ABOUT A MONTH 301 00:11:21,360 --> 00:11:23,440 TO 6 MONTHS AFTER THE DATE OF 302 00:11:23,440 --> 00:11:26,280 THE CONFIRMED INFECTION AND SO, 303 00:11:26,280 --> 00:11:28,560 THE RESEARCHERS IDENTIFIED 4 304 00:11:28,560 --> 00:11:30,640 SUBPHENOTYPES THROUGH THE 305 00:11:30,640 --> 00:11:37,240 ELECTRONIC HEALTH RECORD AND 306 00:11:37,240 --> 00:11:44,720 THERE WERE 137 PRESPECIFIED P A 307 00:11:44,720 --> 00:11:47,400 SC SEQUELLAI STUDIED TO BE 308 00:11:47,400 --> 00:11:47,680 IMPORTANT. 309 00:11:47,680 --> 00:11:48,560 HERE ARE THE TOP 2. 310 00:11:48,560 --> 00:11:52,600 SO 1 OF THEM INVOLVED CARDIAC 311 00:11:52,600 --> 00:11:54,360 AND RENAL SYMPTOMS WHICH 312 00:11:54,360 --> 00:11:56,120 AFFECTED 33% OF PATIENTS AND 313 00:11:56,120 --> 00:11:59,560 THEN ANOTHER PHENOTYPE INVOLVING 314 00:11:59,560 --> 00:12:01,560 RESPIRATORY SYMPTOMS, SLISM 315 00:12:01,560 --> 00:12:02,920 DISORDERS AND ANXIETY WHICH ALSO 316 00:12:02,920 --> 00:12:05,400 INVOLVED ABOUT 30% OF THE 317 00:12:05,400 --> 00:12:05,880 PATIENTS. 318 00:12:05,880 --> 00:12:09,480 SO THIS WAS JUST A LOOK AT THE 319 00:12:09,480 --> 00:12:11,560 PHENOTYPES THAT WERE POPPING OUT 320 00:12:11,560 --> 00:12:14,320 OF THE ELECTRONIC HEALTH RECORD 321 00:12:14,320 --> 00:12:16,720 TO HELP TELL US WHETHER WE MIGHT 322 00:12:16,720 --> 00:12:22,560 SEE IN THIS THE COHORT STUDIES 323 00:12:22,560 --> 00:12:23,040 AS WELL. 324 00:12:23,040 --> 00:12:25,160 THE OTHER THING THAT THE HR DAT 325 00:12:25,160 --> 00:12:29,040 WAS VERY HELPFUL IN DOING WAS 326 00:12:29,040 --> 00:12:31,320 LOOKING AT P A SCAND LONG COVID 327 00:12:31,320 --> 00:12:32,160 IN CHILDREN. 328 00:12:32,160 --> 00:12:33,800 SO THE RESEARCHERS IN THIS CASE, 329 00:12:33,800 --> 00:12:36,280 USE THE EHR TO IDENTIFY THE 330 00:12:36,280 --> 00:12:37,720 INCIDENCE AND PREVALENCE OF P A 331 00:12:37,720 --> 00:12:38,920 SC IN CHILDREN, AS WELL AS THE 332 00:12:38,920 --> 00:12:43,000 RISK FACTORS THAT WERE ASSOCIAE 333 00:12:43,000 --> 00:12:43,800 WIDE IT. 334 00:12:43,800 --> 00:12:48,240 SO THESE WERE CHILDREN, SAME 335 00:12:48,240 --> 00:12:49,600 TIME FRAME, ABOUT 660,000 TOTAL 336 00:12:49,600 --> 00:12:52,120 PATIENTS AND BASICALLY WHAT DID 337 00:12:52,120 --> 00:12:53,520 THEY--WHAT DISCIPLINARY THEY 338 00:12:53,520 --> 00:12:54,960 PRESENT WITH AND YOU COULD SEE 339 00:12:54,960 --> 00:13:02,680 HERE THAT IT E --IDENTIFIED A 340 00:13:02,680 --> 00:13:05,360 ABOUT A 4% PREVALENCE OF 341 00:13:05,360 --> 00:13:06,440 DEVELOPING LONG COVID IN THIS 342 00:13:06,440 --> 00:13:08,640 GROUP, AND THEN RISK FACTORS, 343 00:13:08,640 --> 00:13:10,400 VERY YOUNG AGE, ICU ADMISSION 344 00:13:10,400 --> 00:13:12,320 AND PRESENCE OF OTHER COMPLEX 345 00:13:12,320 --> 00:13:12,840 CONDITIONS. 346 00:13:12,840 --> 00:13:16,720 AND YOU CAN SEE SOME OF THE 347 00:13:16,720 --> 00:13:18,520 HIGHER RATES OF DIFFERENT 348 00:13:18,520 --> 00:13:21,000 SYMPTOMS THAT WERE SHOWING UP IN 349 00:13:21,000 --> 00:13:23,840 THOSE WHO WERE INFECTED VERSUS 350 00:13:23,840 --> 00:13:26,800 NOT IN THE OTHER FOREST PLOT. 351 00:13:26,800 --> 00:13:29,120 AND THEN ANOTHER THING, THAT THE 352 00:13:29,120 --> 00:13:34,400 EHR DATA WAS EXTREMELY HELPFUL 353 00:13:34,400 --> 00:13:36,800 WITH BECAUSE WE KNOW FROM THE 354 00:13:36,800 --> 00:13:40,880 PANDEMIC ITSELF THAT RACIAL AND 355 00:13:40,880 --> 00:13:42,160 ETHNIC DISPARITIES OCCURRED AND 356 00:13:42,160 --> 00:13:44,520 THAT THOSE WHO WERE TYPICALLY 357 00:13:44,520 --> 00:13:46,840 UNDERREPRESENTED IN RESEARCH 358 00:13:46,840 --> 00:13:48,160 WERE MORE AFFECTED BY COVID, SO 359 00:13:48,160 --> 00:13:51,200 THE QUESTION WAS, YOU KNOW IS 360 00:13:51,200 --> 00:13:54,200 THIS HAPPENING ALSO IN LONG 361 00:13:54,200 --> 00:13:54,680 COVID? 362 00:13:54,680 --> 00:13:57,920 SO THE EHR DATA WAS HELPFUL FOR 363 00:13:57,920 --> 00:13:58,200 THAT. 364 00:13:58,200 --> 00:14:02,480 THIS IS A STUDY OF COVID 365 00:14:02,480 --> 00:14:03,320 POSITIVE PATIENTS EITHER BASED 366 00:14:03,320 --> 00:14:05,920 ON A TEST OR ICD CODE IN THE 367 00:14:05,920 --> 00:14:07,360 SAME SORT OF TIME PERIOD THEY 368 00:14:07,360 --> 00:14:11,520 WAS TALKING ABOUT AND THIS 369 00:14:11,520 --> 00:14:14,800 LOOKED AT 137 PRESPECIFIED PAST 370 00:14:14,800 --> 00:14:16,160 CONDITIONS OR LONG COVID 371 00:14:16,160 --> 00:14:17,640 CONDITIONS AND THEN NEW 372 00:14:17,640 --> 00:14:19,880 CONDITIONS A MONTH TO 6 MONTHS 373 00:14:19,880 --> 00:14:22,640 AFTER THE POSITIVE COVID-19 TEST 374 00:14:22,640 --> 00:14:24,400 AND BASICALLY WHAT IT SHOWED WAS 375 00:14:24,400 --> 00:14:26,240 THAT COMPARED TO WHITE PATIENTS, 376 00:14:26,240 --> 00:14:29,200 HISPANIC AND BLACK PATIENTS WERE 377 00:14:29,200 --> 00:14:35,400 MORE LIKELY TO DEVELOP A P A 378 00:14:35,400 --> 00:14:36,640 SC SEQUELLAI, AND THAT WORSE 379 00:14:36,640 --> 00:14:39,600 COVID WERE OBSERVED IN 380 00:14:39,600 --> 00:14:40,320 HOSPITALIZED PATIENTS. 381 00:14:40,320 --> 00:14:43,400 AND IT ALSO VARIED BY 382 00:14:43,400 --> 00:14:44,320 RACE/ETHNICITY SO SOME OF 383 00:14:44,320 --> 00:14:46,160 SYMPTOMS LIKE DIABETES THAT WAS 384 00:14:46,160 --> 00:14:48,560 PRESENT MORE IN BLACKS, 385 00:14:48,560 --> 00:14:49,640 HEADACHES, CHEST PAIN, JOINT 386 00:14:49,640 --> 00:14:52,400 PAIN, AND SOME OF THOSE THINGS 387 00:14:52,400 --> 00:14:54,360 WERE PRESENT IN BLACKS AND 388 00:14:54,360 --> 00:14:55,920 HISPANICS MORE THAN WHITES AND 389 00:14:55,920 --> 00:14:57,880 THEN WHITES HAVE MORE SYMPTOMS 390 00:14:57,880 --> 00:14:59,080 OF COGNITIVE IMPAIRMENT AND 391 00:14:59,080 --> 00:15:00,480 FATIGUE THAN BLACKS OR 392 00:15:00,480 --> 00:15:00,760 HISPANICS. 393 00:15:00,760 --> 00:15:03,000 SO THIS WAS A HELPFUL TO HAVE 394 00:15:03,000 --> 00:15:05,080 THIS INFORMATION COMING OUT FROM 395 00:15:05,080 --> 00:15:06,880 RELATIVELY EARLY IN THE PANDEMIC 396 00:15:06,880 --> 00:15:11,400 ABOUT LONG ASHING TO HELP INFORM 397 00:15:11,400 --> 00:15:11,880 FUTURE RESEARCH. 398 00:15:11,880 --> 00:15:15,400 I'M GOING TO TALK NOW ABOUT THE 399 00:15:15,400 --> 00:15:18,400 LONGITUDINAL COHORT STUDIES AND 400 00:15:18,400 --> 00:15:20,000 I ALREADY MENTIONED THAT THERE 401 00:15:20,000 --> 00:15:23,520 WERE 2 DIFFERENT AREAS THAT, YOU 402 00:15:23,520 --> 00:15:27,600 KNOW THE DE NOVO STUDY AND THEN 403 00:15:27,600 --> 00:15:29,520 EXISTING STUDIES, THE STRATEGY 404 00:15:29,520 --> 00:15:32,920 HERE WAS TO DEEPLY PHENOTYPE 405 00:15:32,920 --> 00:15:34,920 DIVERSE PARTICIPANTS ACROSS THE 406 00:15:34,920 --> 00:15:38,640 LIFE SPAN AND CLINICAL 407 00:15:38,640 --> 00:15:39,120 CONTINUUM. 408 00:15:39,120 --> 00:15:42,680 THE IDEA WAS TO HAVE DIFFERENT 409 00:15:42,680 --> 00:15:44,360 TIERS OF TESTING, SO HAVE A TIER 410 00:15:44,360 --> 00:15:46,120 OF SCREENING TESTS THAT WOULD BE 411 00:15:46,120 --> 00:15:48,400 DONE WITH A VERY LARGE GROUP AND 412 00:15:48,400 --> 00:15:50,200 THEN, BASED ON TRIGGERS, DO 413 00:15:50,200 --> 00:15:53,240 DEEPER AND DEEPER DIVES INTO 414 00:15:53,240 --> 00:15:55,720 WHAT WAS HAPPENING WITH THESE 415 00:15:55,720 --> 00:15:56,040 PARTICIPANTS. 416 00:15:56,040 --> 00:15:58,480 AND SO THE IDEA WAS TO ENROLL 417 00:15:58,480 --> 00:16:00,360 NOT ONLY ACUTE FOLKS THAT WERE 418 00:16:00,360 --> 00:16:02,920 ACUTELY INFECTED TO SEE WHO 419 00:16:02,920 --> 00:16:04,040 DEVELOPED IT LONG COVID BUT ALSO 420 00:16:04,040 --> 00:16:07,080 TO LOOK AT POST ACUTE FOLKS AND 421 00:16:07,080 --> 00:16:09,920 SEE WHAT SYMPTOMS THEY WERE 422 00:16:09,920 --> 00:16:11,320 REPORTING AND THEN DEFINE THE 423 00:16:11,320 --> 00:16:12,280 TRAJECTORY AND OTHER THINGS AND 424 00:16:12,280 --> 00:16:14,840 ALSO TO HAVE AN OPPORTUNITY TO 425 00:16:14,840 --> 00:16:21,760 LOOK AT BIOMARKERS IN THE MORE 426 00:16:21,760 --> 00:16:22,880 DEEPLY PHENOTYPE LEVELS. 427 00:16:22,880 --> 00:16:24,840 IT'S ENROLLED AT THIS POINT AND 428 00:16:24,840 --> 00:16:27,640 THERE'S DATA COMING OUT OF 429 00:16:27,640 --> 00:16:28,000 THESE. 430 00:16:28,000 --> 00:16:29,880 BUT IT--IT HAS SO FAR BEEN ABLE 431 00:16:29,880 --> 00:16:33,400 TO CHARACTERIZE THE IMPACTS OF 432 00:16:33,400 --> 00:16:34,280 DIFFERENT VARIANTS AND 433 00:16:34,280 --> 00:16:35,360 VACCINATIONS AND THAT'S AN 434 00:16:35,360 --> 00:16:36,560 INTERESTING PIECE THAT'S COME 435 00:16:36,560 --> 00:16:39,560 OUT OF IT IS JUST THE SENSE THAT 436 00:16:39,560 --> 00:16:42,160 YOU KNOW SYMPTOMS ARE CONSISTENT 437 00:16:42,160 --> 00:16:43,880 ACROSS THE DIFFERENT INFECTION 438 00:16:43,880 --> 00:16:48,760 WAVES, SO IT HASN'T BORNE OUT 439 00:16:48,760 --> 00:16:49,840 THAT IT'S CHANGED DRAMATICALLY 440 00:16:49,840 --> 00:16:51,160 BETWEEN THE EARLY WAVES WHEN 441 00:16:51,160 --> 00:16:54,480 PEOPLE WERE OBVIOUSLY MUCH MORE 442 00:16:54,480 --> 00:16:54,960 ACUTELY ILL ALTHOUGH 443 00:16:54,960 --> 00:16:55,960 HOSPITALIZATION STATUS DOES HAVE 444 00:16:55,960 --> 00:16:58,440 AN EFFECT BUT A LOT OF THE 445 00:16:58,440 --> 00:17:00,680 SYMPTOMS REMAIN STABLE. 446 00:17:00,680 --> 00:17:02,720 IT ALSO SHOWED HELPFULLY THAT 447 00:17:02,720 --> 00:17:03,800 VACCINATION APPEARED TO BE SAFE 448 00:17:03,800 --> 00:17:06,280 IN CHILDREN WHO HAD MIS-C. 449 00:17:06,280 --> 00:17:08,120 AND THEN THERE'S A LOT OF 450 00:17:08,120 --> 00:17:12,520 BIOMARKER TESTING THAT'S 451 00:17:12,520 --> 00:17:12,760 ONGOING. 452 00:17:12,760 --> 00:17:14,720 SO THE FIRST SORT OF LARGE PIECE 453 00:17:14,720 --> 00:17:19,520 OF DATA TO COME OUT OF THE 454 00:17:19,520 --> 00:17:23,840 COHORT STUDY WAS THIS PAPER IN 455 00:17:23,840 --> 00:17:26,240 JAMA THAT INCLUDED ABOUT 10,000 456 00:17:26,240 --> 00:17:27,400 PARTICIPANTS THAT ALL HAD 6 457 00:17:27,400 --> 00:17:30,200 MONTHS OF FOLLOW UP AND THE 458 00:17:30,200 --> 00:17:34,680 PURPOSE OF THIS STUDY WAS TO TRY 459 00:17:34,680 --> 00:17:40,120 TO DEVELOP A DEFINITION OF POST 460 00:17:40,120 --> 00:17:40,920 ACUTE SEQUELLACE INFECTION WITH 461 00:17:40,920 --> 00:17:42,920 THE IDEA THAT THIS WOULD BE 462 00:17:42,920 --> 00:17:46,640 EVOLVING OVER TIME BUT JUST A 463 00:17:46,640 --> 00:17:48,360 FIRST LOOK. 464 00:17:48,360 --> 00:17:50,040 THE PROSPECTIVE OBSERVATIONAL 465 00:17:50,040 --> 00:17:53,160 COHORT STUDY OF PEOPLE WITH AND 466 00:17:53,160 --> 00:17:55,240 WITHOUT COVID-19 INFECTION AT 85 467 00:17:55,240 --> 00:17:57,600 SITES ACROSS THE U.S. LOOKED AT 468 00:17:57,600 --> 00:18:02,280 KNOWN HISTORY OF INFECTION OR 469 00:18:02,280 --> 00:18:04,560 PAST COVID-19 STATUS ENROLLMENT 470 00:18:04,560 --> 00:18:06,640 PRIOR TO APRIL IN 2023 AND THEY 471 00:18:06,640 --> 00:18:09,640 HAD TO HAVE LIKE I SAID, A STUDY 472 00:18:09,640 --> 00:18:11,560 VISIT WITHIN 6 MONTHS OR MORE 473 00:18:11,560 --> 00:18:13,320 AFTER THE INDEX CASE. 474 00:18:13,320 --> 00:18:15,800 SO, EACH SYMPTOM WAS ASSIGNED A 475 00:18:15,800 --> 00:18:17,320 SCORE, BASED ON THE CO 476 00:18:17,320 --> 00:18:19,560 EFFICIENTS AND YOU KNOW THERE 477 00:18:19,560 --> 00:18:21,480 WAS COMPLEX MODELING AND AS I 478 00:18:21,480 --> 00:18:22,720 SAID, THERE WERE 10,000 479 00:18:22,720 --> 00:18:26,840 PARTICIPANTS THAT ENDED UP IN 480 00:18:26,840 --> 00:18:28,840 THE STUDY AND BASICALLY PEOPLE 481 00:18:28,840 --> 00:18:29,760 WERE GIVEN A SCORE. 482 00:18:29,760 --> 00:18:32,200 THEY WERE ABLE TO CREATE A 483 00:18:32,200 --> 00:18:33,680 SYMPTOM-BASED TOOL THAT COULD BE 484 00:18:33,680 --> 00:18:37,160 USED TO IDENTIFY PEOPLE WITH P A 485 00:18:37,160 --> 00:18:38,400 SC, FOR RESEARCH STUDY 486 00:18:38,400 --> 00:18:39,680 INCLUSION, THAT'S SORT OF THE 487 00:18:39,680 --> 00:18:41,600 IDEA BEHIND THE STUDY AND AGAIN 488 00:18:41,600 --> 00:18:43,440 IT WOULD EVOLVE OVER TIME. 489 00:18:43,440 --> 00:18:45,640 AND SO, THIS IS NOT IF YOU READ 490 00:18:45,640 --> 00:18:47,560 THE PAPER, A FIXED DEFINITION OF 491 00:18:47,560 --> 00:18:53,640 P A SC, BUT MORE WHAT THE 492 00:18:53,640 --> 00:18:58,480 SPOTLIGHT LOOKED AT AT THAT 493 00:18:58,480 --> 00:18:59,080 PARTICULAR MOMENT. 494 00:18:59,080 --> 00:19:02,440 SO IT BASICALLY SHOWED THAT P A 495 00:19:02,440 --> 00:19:04,560 SC POSITIVITY WAS MORE COMMON 496 00:19:04,560 --> 00:19:08,560 AND ASSOCIATED WITH MORE SEVERE 497 00:19:08,560 --> 00:19:09,880 COVID-19 INFECTIONS PREOMICRON. 498 00:19:09,880 --> 00:19:11,640 SO THE SYMPTOMS REMAIN SOMEWHAT 499 00:19:11,640 --> 00:19:14,560 THE SAME, BUT MORE SEVERE. 500 00:19:14,560 --> 00:19:16,640 AND THEN IT CAME UP WITH A SCORE 501 00:19:16,640 --> 00:19:20,760 THAT COULD BE USED HOPEFULLY IN 502 00:19:20,760 --> 00:19:21,880 FUTURE RESEARCH TO DEFINE WHAT 503 00:19:21,880 --> 00:19:25,800 IS LONG COVID AS WELL AS SOME 504 00:19:25,800 --> 00:19:26,600 DIFFERENT SUBPHENOTYPES OF LONG 505 00:19:26,600 --> 00:19:28,920 COVID THAT COULD BE THEN USED IN 506 00:19:28,920 --> 00:19:30,120 THE FUTURE. 507 00:19:30,120 --> 00:19:31,440 SO THERE'S MORE DAILY BASIS THEA 508 00:19:31,440 --> 00:19:32,600 THAT WILL INCREASINGLY BE COMING 509 00:19:32,600 --> 00:19:35,800 OUT OF THIS VERY LARGE STUDY. 510 00:19:35,800 --> 00:19:40,280 NOW RHYME --I'M GOING TO SHIFT O 511 00:19:40,280 --> 00:19:41,080 2 OTHER PILLARS OF THE PROGRAM 512 00:19:41,080 --> 00:19:43,360 TO TALK ABOUT SOME OF THE 513 00:19:43,360 --> 00:19:45,000 EMERGING DATA TO GIVE US AN IDEA 514 00:19:45,000 --> 00:19:45,800 OF THE DIRECTIONS THAT WE SHOULD 515 00:19:45,800 --> 00:19:52,040 GO IN THE FUTURE. 516 00:19:52,040 --> 00:19:54,880 SO THE NIH FUNDED A SUITE OF 517 00:19:54,880 --> 00:19:57,080 MORE THAN 42 MULTIDISCIPLINARY 518 00:19:57,080 --> 00:20:01,240 PATHOBIOLOGY STUDIES THAT ARE 519 00:20:01,240 --> 00:20:03,320 NOW UNDERWAY. 520 00:20:03,320 --> 00:20:04,800 THIS IS A COMPLEX SLIDE BUT THE 521 00:20:04,800 --> 00:20:08,360 WHYED IS THAT COVID-19 PATIENTS 522 00:20:08,360 --> 00:20:09,800 WITHIN AND WITHOUT LONG COVID 523 00:20:09,800 --> 00:20:11,760 ARE STUDIED IN THESE LARGE 524 00:20:11,760 --> 00:20:12,560 COHORTS. 525 00:20:12,560 --> 00:20:14,160 THERE ARE MECHANISTING ASSAYS 526 00:20:14,160 --> 00:20:17,360 THAT ARE RUN ON ALL OF THESE 527 00:20:17,360 --> 00:20:18,800 PARTICIPANTS AND THEN DATA FROM 528 00:20:18,800 --> 00:20:20,440 THE MECHANISTIC ASSAYS WILL BE 529 00:20:20,440 --> 00:20:22,320 INTEGRATED WITH THE CLINICAL 530 00:20:22,320 --> 00:20:26,360 DATA AND THEN WE CAN STUDY THE 531 00:20:26,360 --> 00:20:28,440 THINGS IN THE HEXAGONS BELOW 532 00:20:28,440 --> 00:20:31,480 SUCH AS THE CONSEQUENCES, THE 533 00:20:31,480 --> 00:20:34,000 QUESTION ABOUT WHAT IS GOING ON 534 00:20:34,000 --> 00:20:39,880 IN THE PATHOBIOLOGY, IS THERE 535 00:20:39,880 --> 00:20:41,720 VIRAL PERSISTENCE, IS THERE VIAL 536 00:20:41,720 --> 00:20:42,520 RESERVOIRS, IS THERE SECONDARY 537 00:20:42,520 --> 00:20:43,280 DAMAGE AND SO ON. 538 00:20:43,280 --> 00:20:45,960 I WILL SHOW YOU EXAMPLES, THIS 539 00:20:45,960 --> 00:20:53,560 IS NOT A RECOVER STUDY BUT IT'S 540 00:20:53,560 --> 00:20:54,720 AN IMPORTANT STUDY BECAUSE IT'S 541 00:20:54,720 --> 00:20:56,640 GETTING AT 1 OF THE MAIN 542 00:20:56,640 --> 00:20:57,720 HYPOTHESIS IN LONG COVID WHICH 543 00:20:57,720 --> 00:21:01,800 IS THAT THERE IS IMMUNE 544 00:21:01,800 --> 00:21:05,000 DISREGULATION, SO ACUTE SEVERE 545 00:21:05,000 --> 00:21:06,840 COVID-19 OFTEN DEMONSTRATED IN 546 00:21:06,840 --> 00:21:09,400 INNATE IMMUNE CELL ACTIVATION 547 00:21:09,400 --> 00:21:11,320 AND DELAYED ADAPTIVE IMMUNE AND 548 00:21:11,320 --> 00:21:12,080 INTERFERON RESPONSES BUT REALLY 549 00:21:12,080 --> 00:21:13,120 UNKNOWN LAWEDDER DALE THE 550 00:21:13,120 --> 00:21:15,480 LONG-TERM EFFECTS ARE IN THE 551 00:21:15,480 --> 00:21:19,520 IMMUNE SYSTEM AND IF ANY OF THEM 552 00:21:19,520 --> 00:21:22,360 ARE PERSISTENT AND IMPORTANTLY, 553 00:21:22,360 --> 00:21:24,200 INNATE IMMUNE CELLS AND 554 00:21:24,200 --> 00:21:26,040 PROGENITOR TO THOSE CELLS CAN 555 00:21:26,040 --> 00:21:28,600 MAINTAIN A MEMORY OF PRIOR 556 00:21:28,600 --> 00:21:29,440 INFECTION AND INFLAMMATION WHICH 557 00:21:29,440 --> 00:21:30,240 THEN MIGHT AFFAIRS TEAM 558 00:21:30,240 --> 00:21:32,360 LEADERRER THE RESPONSE TO LATER 559 00:21:32,360 --> 00:21:35,000 IMMUNE CHALLENGES, SO THIS STUDY 560 00:21:35,000 --> 00:21:38,760 LOOKED AT HEMATOPOIETIC STEM AND 561 00:21:38,760 --> 00:21:39,960 PROGENITOR CELLS AND HPCs THAT 562 00:21:39,960 --> 00:21:42,920 ARE LONG LIVED SELF-RENEWING 563 00:21:42,920 --> 00:21:44,920 PRECURSORS TO DIFFERENT IMMUNE 564 00:21:44,920 --> 00:21:48,520 CELLS, AND THEY'RE ABLE TO STORE 565 00:21:48,520 --> 00:21:49,800 INFLAMMATION INDUCED EPIGENETIC 566 00:21:49,800 --> 00:21:52,240 MEMORIES AND SO THEY CAN LOOK AT 567 00:21:52,240 --> 00:21:53,520 THE DURABILITY OF EPIGENETIC 568 00:21:53,520 --> 00:21:55,200 MEMORY, SO THIS STUDY LOOKED AT 569 00:21:55,200 --> 00:21:59,240 4 GROUPS OF PARTICIPANTS THAT 570 00:21:59,240 --> 00:22:01,480 WERE EITHER HEALTHY, THEY WERE 571 00:22:01,480 --> 00:22:02,800 EITHER COVID-19 NEGATIVE BUT 572 00:22:02,800 --> 00:22:04,480 RECOVERING FROM A CRITICAL 573 00:22:04,480 --> 00:22:06,640 ILLNESS THAT WAS NOT COVID 574 00:22:06,640 --> 00:22:09,480 RELATED OR THEY WERE EITHER 575 00:22:09,480 --> 00:22:11,720 EARLY 2-4 MONTHS AFTER COVID-19 576 00:22:11,720 --> 00:22:14,000 OR LATE 4-12 MONTHS AFTER 577 00:22:14,000 --> 00:22:14,560 COVID-19 INFECTION. 578 00:22:14,560 --> 00:22:17,120 AND BASIC LE WHAT THE RESULTS 579 00:22:17,120 --> 00:22:19,600 SHOWED WAS THAT THERE WERE 580 00:22:19,600 --> 00:22:22,080 LASTING EPIGENETIC AND 581 00:22:22,080 --> 00:22:24,160 TRANSCRIPTION CHANGES IN THESE 582 00:22:24,160 --> 00:22:26,040 PRECURSOR CELLS AND MONOCYTES 583 00:22:26,040 --> 00:22:28,120 THAT INDICATED AN ALTERED IMMUNE 584 00:22:28,120 --> 00:22:31,040 RESPONSE THAT WAS SEEN UP TO A 585 00:22:31,040 --> 00:22:33,360 YEAR POST INFECTION. 586 00:22:33,360 --> 00:22:35,160 SO THESE CHANGES APPEARED TO BE 587 00:22:35,160 --> 00:22:38,480 CONTROLLED IN PART BY THE 588 00:22:38,480 --> 00:22:40,800 ACTIVITY OF IL6 WHICH AS MANY 589 00:22:40,800 --> 00:22:42,680 PEOPLE KNOW WAS VERY IMPORTANT 590 00:22:42,680 --> 00:22:46,320 IN THE INFLAMMATORY CASCADE 591 00:22:46,320 --> 00:22:48,880 STIMULATED BY COVID INFECTION. 592 00:22:48,880 --> 00:22:51,560 SO THESE EPIGENETIC AND 593 00:22:51,560 --> 00:22:52,880 TRANSCRIPTION CHANGES CAN 594 00:22:52,880 --> 00:22:54,480 CONTRIBUTE TO ONGOING PATHOLOGY 595 00:22:54,480 --> 00:22:56,840 IN TISSUES WITH INFLAMMATION, 596 00:22:56,840 --> 00:22:58,560 AND ACTIVATION, POTENTICALLY OF 597 00:22:58,560 --> 00:23:00,280 THE VASCULATURE, SO THAT'S 598 00:23:00,280 --> 00:23:02,400 SOMETHING THAT NEEDS TO BE 599 00:23:02,400 --> 00:23:08,360 FOLLOWED UP FURTHER. 600 00:23:08,360 --> 00:23:10,440 ANOTHER STUDY THAT I THINK 601 00:23:10,440 --> 00:23:12,000 SOUNDED VERY IMPORTANT TO THE 602 00:23:12,000 --> 00:23:14,160 DIRECTION THAT RESEARCH IS GOING 603 00:23:14,160 --> 00:23:16,040 WAS THIS STUDY THAT WAS ALSO NOT 604 00:23:16,040 --> 00:23:22,480 A PART OF THE RECOVER STUDY, BUT 605 00:23:22,480 --> 00:23:24,840 IT WAS AN AUTOPSIES STUDY OF 44 606 00:23:24,840 --> 00:23:26,960 PATIENT WHO IS DIED OF COVID-19 607 00:23:26,960 --> 00:23:30,200 AND 11 OF THEM THAT INCLUDED 608 00:23:30,200 --> 00:23:32,200 BRAIN AUTOPSIES AND THE IDEA WAS 609 00:23:32,200 --> 00:23:34,160 TO MAP AND QUANTIFY THE 610 00:23:34,160 --> 00:23:36,440 DISTRIBUTION, REPLICATION AND 611 00:23:36,440 --> 00:23:38,000 CELL SPECIFICITY OF SARS-COV-2 612 00:23:38,000 --> 00:23:40,760 ACROSS THE HUMAN BODY AND THEY 613 00:23:40,760 --> 00:23:44,240 USED DINLITTAL DROPLET PC R TO 614 00:23:44,240 --> 00:23:49,480 QUANTIFY SARS-COV-2 AND THEY 615 00:23:49,480 --> 00:23:50,640 USED INSITU HYBRIDIZATION TO GET 616 00:23:50,640 --> 00:23:54,200 THE PC R FINDINGS AND BRAIN 617 00:23:54,200 --> 00:23:56,520 TISSUE THEY USED IMMUNO 618 00:23:56,520 --> 00:23:57,120 FLUORESCENCE AND HISTOCHEMIST 619 00:23:57,120 --> 00:23:59,000 RADIOY AND THE FINDINGS FOUND 620 00:23:59,000 --> 00:24:01,720 THAT SARS-COV-2 WAS WIDELY 621 00:24:01,720 --> 00:24:02,520 DISTRIBUTED INCLUDING IN EARLY 622 00:24:02,520 --> 00:24:03,440 DISEASE AND IN THE BRAIN. 623 00:24:03,440 --> 00:24:06,760 SO YOU COULD SEE THIS SORT OF 624 00:24:06,760 --> 00:24:08,240 COMPLEX HEAT MAP BASICALLY 625 00:24:08,240 --> 00:24:09,840 WHEREVER YOU'RE SEEING COLOR, 626 00:24:09,840 --> 00:24:11,520 YOU ARE SEEING THAT THERE WAS 627 00:24:11,520 --> 00:24:14,360 RNA THAT WAS MEASURED IN A 628 00:24:14,360 --> 00:24:15,840 NUMBER OF DIFFERENT BODY TYPES 629 00:24:15,840 --> 00:24:18,920 AND YOU COULD SEE THAT OUR BODY 630 00:24:18,920 --> 00:24:21,160 PARTS AND YOU COULD SEE THAT 631 00:24:21,160 --> 00:24:22,720 THAT INCLUDED THE CNS AND THAT'S 632 00:24:22,720 --> 00:24:24,120 ALONG THE BOTTOM AND YOU COULD 633 00:24:24,120 --> 00:24:25,960 SEE IT WAS PRESENT NOT ONLY IN 634 00:24:25,960 --> 00:24:27,400 LESS THAN 2 WEEKS AFTER THE 635 00:24:27,400 --> 00:24:29,000 INFECTION BUT ALSO UP A MONTH 636 00:24:29,000 --> 00:24:32,640 AND ALSO EVEN GREATER THAN A 637 00:24:32,640 --> 00:24:33,200 MONTH. 638 00:24:33,200 --> 00:24:34,600 SO THIS WAS PRESENT PRETTY MUCH 639 00:24:34,600 --> 00:24:37,040 ACROSS THE BOARD IN THESE 640 00:24:37,040 --> 00:24:37,480 DIFFERENT PATIENTS. 641 00:24:37,480 --> 00:24:41,480 SO THERE'S 6 PATIENTS IN THE 642 00:24:41,480 --> 00:24:45,160 ACUTE AND THOSE ARE THE COLUMNS. 643 00:24:45,160 --> 00:24:47,000 AND THEN THE DIFFERENT COLORS 644 00:24:47,000 --> 00:24:48,360 JUST REPRESENT THE DIFFERENT 645 00:24:48,360 --> 00:24:49,880 AMOUNT OF RNA THAT WAS MEASURED 646 00:24:49,880 --> 00:24:51,240 SO THIS STUDY WAS A VERY 647 00:24:51,240 --> 00:24:52,240 IMPORTANT STUDY TO UNDERSTAND 648 00:24:52,240 --> 00:24:54,400 THE TISSUES WHERE WE WERE 649 00:24:54,400 --> 00:24:55,880 SEEING--WHERE WE WERE SEEING THE 650 00:24:55,880 --> 00:24:57,880 VIRUS BECAUSE 1 OF THE MAIN 651 00:24:57,880 --> 00:25:00,760 QUESTIONS IS CAN WE GO AFTER, 652 00:25:00,760 --> 00:25:02,080 YOU KNOW IN LONG COVID, CAN WE 653 00:25:02,080 --> 00:25:03,280 GO AFTER THAT AND I WILL TALK 654 00:25:03,280 --> 00:25:06,280 MORE ABOUT THAT LATER. 655 00:25:06,280 --> 00:25:08,880 THIS IS ALSO NOT A RECOVER STUDY 656 00:25:08,880 --> 00:25:12,240 BUT COMES OUT OF 657 00:25:12,240 --> 00:25:14,560 DR. [INDISCERNIBLE]'S GROUP AT 658 00:25:14,560 --> 00:25:16,320 THE INTRAMURAL AT NINDS, IT WAS 659 00:25:16,320 --> 00:25:19,920 A STUDY OF 12 PATIENTS WHO 660 00:25:19,920 --> 00:25:24,360 REPORTED ONGOING NEUROLOGICAL 661 00:25:24,360 --> 00:25:26,640 ABNORMALITIES AFTER THEIR COVID 662 00:25:26,640 --> 00:25:28,800 ILLNESS, BY PC R AND THE 663 00:25:28,800 --> 00:25:30,720 SYMPTOMS LASTING 9 MONTHS AFTER 664 00:25:30,720 --> 00:25:32,280 THE INFECTION WITH A HEALTHY 665 00:25:32,280 --> 00:25:34,520 CONTROL GROUP. 666 00:25:34,520 --> 00:25:35,920 AND SOME OF THE COMMON SYMPTOMS 667 00:25:35,920 --> 00:25:38,120 THAT WERE REPORTED BY FOLKS WERE 668 00:25:38,120 --> 00:25:39,800 COGNITIVE DIFFICULTYINGS WHICH 669 00:25:39,800 --> 00:25:41,680 WE KNOW TO BE VERY COMMON AND 670 00:25:41,680 --> 00:25:44,560 FATIGUE AND THE MAJORITY HAD A 671 00:25:44,560 --> 00:25:47,400 DISABLING DISEASE, YOU KNOW THEY 672 00:25:47,400 --> 00:25:48,640 FELT DISABLED BY THE SYMPTOMS. 673 00:25:48,640 --> 00:25:53,000 AND MANY OF THEM HAD NORMAL 674 00:25:53,000 --> 00:25:54,400 BRAIN IMAGING. 675 00:25:54,400 --> 00:25:55,800 SO THE DEEP PHENOTYPING HERE 676 00:25:55,800 --> 00:25:58,840 INCLUDED A LOT OF CLINICAL WORK 677 00:25:58,840 --> 00:26:01,440 UP AND IMAGING, BUT ALSO BRAIN 678 00:26:01,440 --> 00:26:03,120 AND SORRY, BLOOD AND SPINAL 679 00:26:03,120 --> 00:26:06,160 FLUID AS WELL AS AUTONOMIC 680 00:26:06,160 --> 00:26:06,400 TESTING. 681 00:26:06,400 --> 00:26:08,880 SO, AND YOU COULD SEE THE CHARTS 682 00:26:08,880 --> 00:26:11,280 HERE, SO ON THE LEFT, THE 683 00:26:11,280 --> 00:26:13,080 RESULTS SHOWED THAT PEOPLE WITH 684 00:26:13,080 --> 00:26:15,520 LONG COVID HAD LOWER LEVELS OF 685 00:26:15,520 --> 00:26:17,560 CD4 AND CD8 T-CELLS COMPARED TO 686 00:26:17,560 --> 00:26:19,160 HEALTHY CONTROLS AND IT ALSO 687 00:26:19,160 --> 00:26:20,560 SHOWED INCREASES IN THE NUMBER 688 00:26:20,560 --> 00:26:22,400 OF B-CELLS, AND OTHER TYPES OF 689 00:26:22,400 --> 00:26:25,080 IMMUNE CELLS, SO AGAIN, 690 00:26:25,080 --> 00:26:28,760 SUGGESTING THERE MAY BE 691 00:26:28,760 --> 00:26:30,480 VASCULAR--SORRY IMMUNOLOGICAL 692 00:26:30,480 --> 00:26:31,440 PROBLEMS GOING ON HERE. 693 00:26:31,440 --> 00:26:34,080 AND ON THE RIGHT SIDE SHOWS 694 00:26:34,080 --> 00:26:36,040 ABNORMALITIES AND VASCULAR TONE, 695 00:26:36,040 --> 00:26:37,200 HEART RATE, AND BLOOD PRESSURE 696 00:26:37,200 --> 00:26:38,600 WITH A CHANGE IN POSTURE IN ALL 697 00:26:38,600 --> 00:26:40,640 OF THESE PATIENTS AND THAT'S 1 698 00:26:40,640 --> 00:26:41,680 OF THE MOST IMPORTANT THINGS 699 00:26:41,680 --> 00:26:43,160 THAT WE'VE BEEN TRYING TO 700 00:26:43,160 --> 00:26:45,960 UNDERSTAND IS WHAT IS THE 701 00:26:45,960 --> 00:26:47,480 RELATIONSHIP BETWEEN COVID AND 702 00:26:47,480 --> 00:26:49,080 THE VASCULAR SYSTEM, ANDENTIOUS 703 00:26:49,080 --> 00:26:52,400 SPECIALLY WITH LONG ASHING. 704 00:26:52,400 --> 00:26:54,040 --LONG COVID. 705 00:26:54,040 --> 00:26:57,400 THIS STUDY HERE IS ALSO NOT A 706 00:26:57,400 --> 00:27:02,480 RECOVER STUDY BUT IT'S A LARGE 707 00:27:02,480 --> 00:27:03,600 PERSPECTIVE LONGITUDINAL COHORT 708 00:27:03,600 --> 00:27:04,480 STUDY OF ABOUT 2000 PEOPLE IN 709 00:27:04,480 --> 00:27:06,480 THE UK THAT WERE HOSPITALIZED 710 00:27:06,480 --> 00:27:09,080 WITH COVID-19 PRETTY EARLY ON 711 00:27:09,080 --> 00:27:10,360 FROM 2020 TO 2021. 712 00:27:10,360 --> 00:27:14,680 AND IT EXAMINED A LARGE GROUP OF 713 00:27:14,680 --> 00:27:16,520 BLOOD BIOMARKER PROFILES IN 714 00:27:16,520 --> 00:27:18,720 ASSOCIATION WITH COGNITIVE 715 00:27:18,720 --> 00:27:19,680 DYSFUNCTION ISSUES THE 716 00:27:19,680 --> 00:27:21,000 BIOMARKERS WERE TAKEN DURING A 717 00:27:21,000 --> 00:27:24,080 HOSPITAL VISIT BUT THE POST 718 00:27:24,080 --> 00:27:26,080 ACUTE COGNITIVE DYSFUNCTION WAS 719 00:27:26,080 --> 00:27:29,480 MEASURED 6 MONTHS LATER AND IT 720 00:27:29,480 --> 00:27:34,440 WAS MEASURED BY NOT ONLY A LOCA 721 00:27:34,440 --> 00:27:36,440 SCORE, WHICH IS A MEASURE OF 722 00:27:36,440 --> 00:27:39,360 COGNITIVE FUNCTION BUT IT ALSO 723 00:27:39,360 --> 00:27:40,200 ASKED ABOUT COGNITIVE FUNCTION. 724 00:27:40,200 --> 00:27:45,080 AND WHAT YOU SEE HERE IS ON THE 725 00:27:45,080 --> 00:27:46,000 LEFT, THE ASSOCIATION BETWEEN 726 00:27:46,000 --> 00:27:48,920 HIGH FIEB RIN O GENERATED WITH 727 00:27:48,920 --> 00:27:51,240 RELATIVELY LOW CRP AND WORSE 728 00:27:51,240 --> 00:27:54,320 REPORTED SYMPTOMS AT 6 AND 12 729 00:27:54,320 --> 00:27:57,160 MONTHS AS WELL AS LOWER SCORES, 730 00:27:57,160 --> 00:27:59,200 ASSESSMENT SCORES IN THE SAME 731 00:27:59,200 --> 00:27:59,840 TIME PERIOD. 732 00:27:59,840 --> 00:28:04,240 SO IT MAY BE THAT THESE SYMPTOMS 733 00:28:04,240 --> 00:28:06,800 ARE CAUSED BY IMMUNO THROMBOTIC 734 00:28:06,800 --> 00:28:07,000 EVENTS. 735 00:28:07,000 --> 00:28:09,840 AND THEN ON THE RIGHT SIDE, IT 736 00:28:09,840 --> 00:28:12,960 LOOKS AT D-DIMER, AGAIN WITH 737 00:28:12,960 --> 00:28:14,920 RELATIVELY LOW CRP, AND IT 738 00:28:14,920 --> 00:28:17,760 SHOWED AN ASSOCIATION WITH THE 739 00:28:17,760 --> 00:28:20,960 SYMPTOMS AND IT DOESN'T SHOW AN 740 00:28:20,960 --> 00:28:21,480 ASSOCIATION WITH OBJECTIVE 741 00:28:21,480 --> 00:28:22,560 COGNITIVE FUNCTION BUT IT DID 742 00:28:22,560 --> 00:28:24,960 SHOW AN ASSOCIATION WITH 743 00:28:24,960 --> 00:28:25,680 OCCUPATIONAL CHANGES AT 6 744 00:28:25,680 --> 00:28:26,080 MONTHS. 745 00:28:26,080 --> 00:28:31,680 SO IT MAY BE AGAIN, THAT THE 746 00:28:31,680 --> 00:28:33,760 D-DIMER FINDINGS SUGGEST A 747 00:28:33,760 --> 00:28:36,000 RELATIONSHIP WITH THE THROMBOTIC 748 00:28:36,000 --> 00:28:38,560 SYSTEM AND NEITHER OF THESE 749 00:28:38,560 --> 00:28:40,280 PROFILES WAS MEDIATED BY 750 00:28:40,280 --> 00:28:44,880 DEPRESSION OR ANXIETY WHICH IS 751 00:28:44,880 --> 00:28:45,600 IMPORTANT TO UNDERSTAND. 752 00:28:45,600 --> 00:28:48,480 AND THENIME GOING TO SHOW 753 00:28:48,480 --> 00:28:49,320 ANOTHER NONRECOVER STUDY. 754 00:28:49,320 --> 00:28:51,600 SO STUDIES HAVE DESCRIBED THAT 755 00:28:51,600 --> 00:28:53,920 COVID-19 YOU KNOW IS 756 00:28:53,920 --> 00:28:57,160 MULTISYSTEMIC AND THAT IT MAY BE 757 00:28:57,160 --> 00:29:00,000 A VASCULAR DISEASE ASSOCIATED 758 00:29:00,000 --> 00:29:02,160 WITH SEVERE MICROVASCULAR 759 00:29:02,160 --> 00:29:02,920 IMPAIRMENT AND ENDOTHELIAL 760 00:29:02,920 --> 00:29:04,960 INJURY BUT THERE HASN'T BEEN 761 00:29:04,960 --> 00:29:06,280 MUCH DATA IN THIS AREA. 762 00:29:06,280 --> 00:29:09,640 SO THIS STUDY CHARACTERIZED 763 00:29:09,640 --> 00:29:10,520 MICROVASCULAR CHANGES IN LONG 764 00:29:10,520 --> 00:29:13,760 COVID PATIENTS AND IT DID IT IN 765 00:29:13,760 --> 00:29:20,040 AN INNOVATIVE WAY LOOKING AT 766 00:29:20,040 --> 00:29:20,960 SUBLINGUAL MICROVESSELS LOOKING 767 00:29:20,960 --> 00:29:22,760 AT THE DIAMETER OF THE VESSELS 768 00:29:22,760 --> 00:29:24,400 AS WELL AS COMPLEXITY OF NETWORK 769 00:29:24,400 --> 00:29:28,840 AS WELL AS THE SPEED OF BLOOD 770 00:29:28,840 --> 00:29:31,160 FLOW RBC FLOW THROUGH THESE 771 00:29:31,160 --> 00:29:34,560 VESSELS. 772 00:29:34,560 --> 00:29:36,040 SO IT INCLUDED 27 PARTICIPANTS 773 00:29:36,040 --> 00:29:38,560 WITH LONG COVID WHO HAD SYMPTOMS 774 00:29:38,560 --> 00:29:40,600 MORE THAN 12 WEEKS AFTER THE 775 00:29:40,600 --> 00:29:41,840 INITIAL SYMPTOMS THAT WERE 776 00:29:41,840 --> 00:29:43,040 REFERRED TO LONG COVID CLINIC 777 00:29:43,040 --> 00:29:44,800 AND THEN A BUNCH OF CONTROLS 778 00:29:44,800 --> 00:29:48,040 THAT WERE EITHER HEALTHY OR 779 00:29:48,040 --> 00:29:50,080 CRITICALLY ILL SO IMPORTANT TO 780 00:29:50,080 --> 00:29:51,400 SEPARATE OUT YOU KNOW PEOPLE 781 00:29:51,400 --> 00:29:52,440 THAT HAD LONG ASHING FROM THOSE 782 00:29:52,440 --> 00:29:56,880 WHO MIGHT HAVE HAD A PRIOR 783 00:29:56,880 --> 00:29:57,280 CRITICAL ILLNESS. 784 00:29:57,280 --> 00:29:59,520 AND SO, THE MEASUREMENTS WERE 785 00:29:59,520 --> 00:30:01,200 TAKEN WHEN THEY WERE FIRST 786 00:30:01,200 --> 00:30:01,880 EXAMINED AND THEN THEY WERE 787 00:30:01,880 --> 00:30:02,360 FOLLOWED UP. 788 00:30:02,360 --> 00:30:08,920 SO WHAT IT SHOWED WAS THAT 789 00:30:08,920 --> 00:30:10,480 COMPARED TO CONTROLS, THERE WERE 790 00:30:10,480 --> 00:30:11,960 DIFFERENCES IN DENNITY, SO ON 791 00:30:11,960 --> 00:30:15,840 THE LEFT, YOU SEE THE DENSITY 792 00:30:15,840 --> 00:30:17,480 AND VASCULAR DIAMETER, SO THE 793 00:30:17,480 --> 00:30:19,640 VASCULAR DENSITY WAS DECREASED 794 00:30:19,640 --> 00:30:24,960 COMPARED TO HEALTHY CONTROLS AND 795 00:30:24,960 --> 00:30:27,800 ALSO THE COMPLEX SCORING THAT 796 00:30:27,800 --> 00:30:29,560 THEY CALLED MICROVASCULAR 797 00:30:29,560 --> 00:30:30,760 HEALTHCARE. 798 00:30:30,760 --> 00:30:31,960 THERE WAS WORSE MICROVASCULAR 799 00:30:31,960 --> 00:30:32,920 HEALTH COMPARED TO HEALTHY 800 00:30:32,920 --> 00:30:35,280 CONTROLS AFTER THEY ADJUSTED FOR 801 00:30:35,280 --> 00:30:35,880 OTHER CO-MORBIDITIES. 802 00:30:35,880 --> 00:30:37,840 AND THEN ON THE RIGHT SIDE, IT 803 00:30:37,840 --> 00:30:43,840 SHOWED THAT THE RED BLOOD CELL, 804 00:30:43,840 --> 00:30:45,720 VELOCITY WAS SIGNIFICANTLY 805 00:30:45,720 --> 00:30:46,960 HIGHER IN CAPILLARIES AND FEED 806 00:30:46,960 --> 00:30:48,800 VESSELS IN THE LONG COVID 807 00:30:48,800 --> 00:30:50,600 PATIENTS COMPARED TO HEALTHY 808 00:30:50,600 --> 00:30:54,000 CONTROLS AND SO, BOTH OF THESE 809 00:30:54,000 --> 00:30:55,360 EXAM NATIONS AND TYPES OF 810 00:30:55,360 --> 00:30:57,920 LOOKING AT THE DATA, SHOW THAT 811 00:30:57,920 --> 00:30:59,520 THERE MAY BE A RELATIONSHIP WITH 812 00:30:59,520 --> 00:31:01,320 THESE MICROVESSEL WHICH IS IS 813 00:31:01,320 --> 00:31:02,840 EXTREMELY IMPORTANT AS A 814 00:31:02,840 --> 00:31:03,640 POTENTIAL TARGET TO UNDERSTAND 815 00:31:03,640 --> 00:31:07,480 HOW TO MOVE FORWARD. 816 00:31:07,480 --> 00:31:09,480 THEN I'M GOING TO TALK ABOUT 817 00:31:09,480 --> 00:31:11,080 THIS BEFORE I MOVE ON TO TALK 818 00:31:11,080 --> 00:31:14,720 ABOUT THE CLINICAL TRIALS, SO 819 00:31:14,720 --> 00:31:18,240 THIS IS ALSO NOT A RECOVER STUY 820 00:31:18,240 --> 00:31:20,960 BUT IT'S A STUDY THAT MEASURED A 821 00:31:20,960 --> 00:31:22,760 LOT OF VASCULAR BLOOD BIOMARKERS 822 00:31:22,760 --> 00:31:25,120 FROM LONG COVID PATIENTS VERSUS 823 00:31:25,120 --> 00:31:28,200 ACUTELY ILL COVID PATIENTS OR 824 00:31:28,200 --> 00:31:29,320 VERSUS HEALTHY CONTROLS. 825 00:31:29,320 --> 00:31:31,600 SO AGAIN, REALLY IMPORTANT TO 826 00:31:31,600 --> 00:31:34,000 SEPARATE OUT THE LONG COVID FROM 827 00:31:34,000 --> 00:31:36,040 PEOPLE WHO MIGHT HAVE BEEN 828 00:31:36,040 --> 00:31:39,400 ACUTELY VERY ILL WITH COVID-19 829 00:31:39,400 --> 00:31:41,720 AND ALL TO SEPARATE THAT OUT 830 00:31:41,720 --> 00:31:43,240 FROM HEALTHY CONTROLS. 831 00:31:43,240 --> 00:31:46,320 AND SO, THE PURPOSE WAS TO 832 00:31:46,320 --> 00:31:47,840 DETERMINE THE IMPORTANCE OF 833 00:31:47,840 --> 00:31:49,120 THESE DIFFERENT VASCULAR 834 00:31:49,120 --> 00:31:51,160 BIOMARKERS TO PREDICT LONG COVID 835 00:31:51,160 --> 00:31:53,000 AND TO DETERMINE WHETHER 836 00:31:53,000 --> 00:31:55,040 RELATIONSHIPS BETWEEN SOME OF 837 00:31:55,040 --> 00:31:57,440 THESE BIOMARKERS AND DEMOGRAPHIC 838 00:31:57,440 --> 00:31:59,200 OR CLINICAL FACTORS. 839 00:31:59,200 --> 00:32:02,040 SO, THE VASCULAR BIOMARKERS THAT 840 00:32:02,040 --> 00:32:04,320 WERE LOOKED AT INVOLVED 841 00:32:04,320 --> 00:32:08,640 ANGIOGENESIS AND ENDOTHELIAL AND 842 00:32:08,640 --> 00:32:10,320 PLATELET ACTIVATION AND 843 00:32:10,320 --> 00:32:12,080 COAGULATION AND VASCULAR 844 00:32:12,080 --> 00:32:13,760 JUNCTIONAL INTEGRITY AND 845 00:32:13,760 --> 00:32:15,560 PERMIABILITY AND IN PARTICULAR, 846 00:32:15,560 --> 00:32:19,600 I WILL JUST POINT OUT THE LEFT 847 00:32:19,600 --> 00:32:22,760 SIDE OF THE FIGURE SHOWS 2 BOX 848 00:32:22,760 --> 00:32:26,080 PLOTS FOR 2 VASCULAR BIOMARKERS 849 00:32:26,080 --> 00:32:29,480 WHICH ARE P-SELECTIN AND ANCHLIO 850 00:32:29,480 --> 00:32:30,880 POETIN 1 THAT SHOWED 851 00:32:30,880 --> 00:32:31,800 CONCENTRATIONS COMPARED TO 852 00:32:31,800 --> 00:32:32,040 CONTROLS. 853 00:32:32,040 --> 00:32:35,000 YOU CAN SEE THAT THEY'RE QUITE 854 00:32:35,000 --> 00:32:37,960 DIFFERENT, QUITE ELEVATED, THE 855 00:32:37,960 --> 00:32:41,560 SAME WAY THAT THE RIGHT SIDE 856 00:32:41,560 --> 00:32:43,760 WHERE THE ROC CURVES THAT 857 00:32:43,760 --> 00:32:45,280 DEPRIVATIONON STRAIGHT EXCELLENT 858 00:32:45,280 --> 00:32:48,880 DIAGNOSTIC POTENTIAL FOR BOTH 859 00:32:48,880 --> 00:32:51,960 THE ANG IOPOETIN, AND THE 860 00:32:51,960 --> 00:32:53,720 P-SELECTIN BIOMARKERS IN THE 861 00:32:53,720 --> 00:32:54,920 VALIDATION ANALYSIS. 862 00:32:54,920 --> 00:32:58,440 SO AGAIN, ANOTHER POTENTIAL AREA 863 00:32:58,440 --> 00:33:03,680 AND TARGET TO GO AFTER IN THE 864 00:33:03,680 --> 00:33:04,200 CLINICAL TRIALS. 865 00:33:04,200 --> 00:33:05,680 SO NOW I'M GOING TO SHIFT GEARS 866 00:33:05,680 --> 00:33:06,920 AND TALK A LITTLE BIT ABOUT THE 867 00:33:06,920 --> 00:33:10,120 CLINICAL TRIALS AND YOU KNOW AS 868 00:33:10,120 --> 00:33:12,440 I MENTIONED YOU KNOW AT THE 869 00:33:12,440 --> 00:33:14,840 BEGINNING, IT'S VERY HARD TO--I 870 00:33:14,840 --> 00:33:17,440 MEAN, YOU CAN--YOU CAN DO 871 00:33:17,440 --> 00:33:19,240 CLINICAL TRIALS TO EXAMINE 872 00:33:19,240 --> 00:33:21,680 SYMPTOMS, YOU KNOW THE LOW 873 00:33:21,680 --> 00:33:23,440 HANGING FRUIT IS CERTAINLY, YOU 874 00:33:23,440 --> 00:33:24,960 KNOW YOU HAVE CERTAIN SYMPTOMS, 875 00:33:24,960 --> 00:33:27,240 YOU HAVE KNOWN DRUGS THAT CAN 876 00:33:27,240 --> 00:33:28,640 TREAT THOSE SYMPTOMS, YOU CAN GO 877 00:33:28,640 --> 00:33:31,720 AFTER THAT, BUT IT'S VERY 878 00:33:31,720 --> 00:33:34,360 IMPORTANT TO UNDERSTAND WHAT THE 879 00:33:34,360 --> 00:33:37,560 MECHANISMS ARE AND REALLY TRY TO 880 00:33:37,560 --> 00:33:39,800 ATTACK THE MECHANISMS AT THEIR 881 00:33:39,800 --> 00:33:42,680 SEED AND IF YOU'RE REALLY GOING 882 00:33:42,680 --> 00:33:44,120 TO PREVENT LONG COVID, OR YOU'RE 883 00:33:44,120 --> 00:33:48,640 REALLY GOING TO BE ABLE TO MAKE 884 00:33:48,640 --> 00:33:50,520 A DIFFERENCE. 885 00:33:50,520 --> 00:33:53,360 AND SO THAT IS THE REASON THAT 886 00:33:53,360 --> 00:33:55,680 RECOVER WAS BUILT ALONG THOSE 887 00:33:55,680 --> 00:33:57,720 OTHER 4 PILLARS TO GENERATE DATA 888 00:33:57,720 --> 00:34:00,560 THAT COULD THEN FEED INTO 889 00:34:00,560 --> 00:34:02,320 CLINICAL TRIALS AND THEN ANOTHER 890 00:34:02,320 --> 00:34:03,960 PIECE OF IT, I WILL EXPLAIN A 891 00:34:03,960 --> 00:34:06,640 BIT LATER IS JUST, THE NEED TO 892 00:34:06,640 --> 00:34:08,160 DO THIS IN AN EFFICIENT MANNER 893 00:34:08,160 --> 00:34:12,080 AND SO TO SET UP AN ADAPTIVE 894 00:34:12,080 --> 00:34:14,360 PLATFORM WITH MULTIPLE 895 00:34:14,360 --> 00:34:15,680 THERAPEUTIC DOMAINS SO WE CAN 896 00:34:15,680 --> 00:34:17,480 HAVE MANY SHOTS ON GOAL INSTEAD 897 00:34:17,480 --> 00:34:19,200 OF DOING MANY SEQUENTIAL TRIALS 898 00:34:19,200 --> 00:34:24,880 THAT WOULD TAKE A LONG TIME. 899 00:34:24,880 --> 00:34:28,080 SO THIS FIRST SLIDE IS NOT A 900 00:34:28,080 --> 00:34:31,360 RECOVER SLIDE, BUT IT'S 2 RECENT 901 00:34:31,360 --> 00:34:34,800 STUDIES THAT HELPED TO GENERATE 902 00:34:34,800 --> 00:34:36,360 DATA THAT LED TO SOME OF THE 903 00:34:36,360 --> 00:34:39,640 TRIALS THAT ARE BEING INITIATED 904 00:34:39,640 --> 00:34:41,040 IN RECOVER. 905 00:34:41,040 --> 00:34:43,120 SO LOOKING AT ANTIVIRAL 906 00:34:43,120 --> 00:34:44,880 MEDICATION TO SEE IF IT HAD AN 907 00:34:44,880 --> 00:34:48,160 IMPACT ON P A SC, WITH THE IDEA 908 00:34:48,160 --> 00:34:51,440 THAT LONG COVID MAY HAVE 909 00:34:51,440 --> 00:34:53,840 PERSISTENT VIRUS AND THAT THAT 910 00:34:53,840 --> 00:34:55,800 PERSISTENT VIRUS IS WREAKING 911 00:34:55,800 --> 00:34:56,800 HAVOC AND YOU COULD TREAT THAT. 912 00:34:56,800 --> 00:35:00,880 SO THE STUDY ON THE LEFT LOOKED 913 00:35:00,880 --> 00:35:04,480 AT WHETHER P A XLOVID DURING THE 914 00:35:04,480 --> 00:35:06,360 ACUTE CASE OF COVID WOULD REDUCE 915 00:35:06,360 --> 00:35:08,440 THE RISK OF P A SC. 916 00:35:08,440 --> 00:35:09,920 AND THEN THE STUDY ON THE RIGHT 917 00:35:09,920 --> 00:35:12,520 IS A MORE RECENT STUDY THAT 918 00:35:12,520 --> 00:35:13,320 ACTUALLY EXAMINED TREATING 919 00:35:13,320 --> 00:35:14,560 INDIVIDUALS WITH P A SC. 920 00:35:14,560 --> 00:35:16,960 SO THE LEFT 1 WAS A 921 00:35:16,960 --> 00:35:19,400 RETROSPECTIVE OF THE A-COHORT 922 00:35:19,400 --> 00:35:20,720 STUDY USING ELECTRONIC HEALTH 923 00:35:20,720 --> 00:35:22,760 RECORD DATA OF PARTICIPANTS THAT 924 00:35:22,760 --> 00:35:24,920 HAD A POSITIVE COVID-19 TEST 925 00:35:24,920 --> 00:35:27,400 BETWEEN JANUARY OF 22 AND 926 00:35:27,400 --> 00:35:28,040 DECEMBER OF 22. 927 00:35:28,040 --> 00:35:30,920 AND THEY HAD AT LEAST 1 RISK 928 00:35:30,920 --> 00:35:32,920 FACTOR FOR PROGRESSION TO SEVERE 929 00:35:32,920 --> 00:35:33,320 DISEASE. 930 00:35:33,320 --> 00:35:37,160 AND THEN THEY WERE COMPARED, 931 00:35:37,160 --> 00:35:40,080 COMPARED THOSE WHO WERE TREATED 932 00:35:40,080 --> 00:35:43,920 WITH P A XLOVID WITH 5 DAYS TO 933 00:35:43,920 --> 00:35:45,200 THEIR TEST AND THEN NOT, AND 934 00:35:45,200 --> 00:35:46,600 LOOK AT ANY POST ACUTE 935 00:35:46,600 --> 00:35:47,600 COMPLICATIONS THAT WOULD HAVE 936 00:35:47,600 --> 00:35:49,760 ARISED FROM THAT AND THE 937 00:35:49,760 --> 00:35:52,600 FINDINGS FROM THAT EHR STUDY 938 00:35:52,600 --> 00:35:54,600 INDICATE THAD P A SC WAS 939 00:35:54,600 --> 00:35:56,600 TREATMENT WITH REDUCED RISK OF P 940 00:35:56,600 --> 00:35:59,760 A SC SYMPTOMS ABOUT 10 OUT OF 13 941 00:35:59,760 --> 00:36:03,320 AND INCLUDING A WIDER RANGE OF 942 00:36:03,320 --> 00:36:06,240 SYMPTOMS THAT INCLUDED PULMONARY 943 00:36:06,240 --> 00:36:09,360 SYMPTOMS, THROMBOTIC SYMPTOMS, 944 00:36:09,360 --> 00:36:11,080 RENAL SYMPTOMS, MUSCLE COGNITIVE 945 00:36:11,080 --> 00:36:14,960 SYMPTOMS AND OTHER NERVOUS 946 00:36:14,960 --> 00:36:15,880 SYSTEM SYMPTOMS. 947 00:36:15,880 --> 00:36:20,000 IT DID NOT FIND A DECREASE IN 948 00:36:20,000 --> 00:36:22,560 DIABETES OR LIVER DISEASE OR 949 00:36:22,560 --> 00:36:23,440 COUGH. 950 00:36:23,440 --> 00:36:26,760 SO BASICALLY THE TREATMENT WAS 951 00:36:26,760 --> 00:36:28,560 FOUND THAT IN ACUTE INFECTION IT 952 00:36:28,560 --> 00:36:33,040 COULD REDUCE THE RISK FOR P A SC 953 00:36:33,040 --> 00:36:34,800 SEQUELLACE, SO ON THE RIGHT SIDE 954 00:36:34,800 --> 00:36:36,800 IS THE STOP P A SC TRIAL THAT 955 00:36:36,800 --> 00:36:39,040 WAS A STOP COLLABORATION BETWEEN 956 00:36:39,040 --> 00:36:41,160 PFIZER AND STANFORD THAT HAS 957 00:36:41,160 --> 00:36:44,280 BEEN STOPPED AND THIS INCLUDED 958 00:36:44,280 --> 00:36:45,560 PATIENTS THAT WERE ADULT AND HAD 959 00:36:45,560 --> 00:36:49,120 A HISTORY OF CONFIRMED COVID-19 960 00:36:49,120 --> 00:36:51,280 INFECTION, HAD P A SC SYMPTOMS 961 00:36:51,280 --> 00:36:52,920 MORE THAN 3 MONTHS AND HAD 2OR 962 00:36:52,920 --> 00:36:55,960 MORE P A SC SYMPTOMS THAT ARE 963 00:36:55,960 --> 00:36:57,200 EITHER MODERATE OR SEVERE IN 964 00:36:57,200 --> 00:36:59,840 SEVERITY AND THE DATA ARE NOT 965 00:36:59,840 --> 00:37:06,480 YET PUBLISHED BUT IT'S LOOKING 966 00:37:06,480 --> 00:37:12,400 AT THAT TREATMENT AND THE STUDY 967 00:37:12,400 --> 00:37:13,920 WAS HALTED EARLY WITH INTERIM 968 00:37:13,920 --> 00:37:18,240 ANALYSIS EXPECTED VERY SOON. 969 00:37:18,240 --> 00:37:20,600 SO THAT LED SORT OF IN PARALLEL 970 00:37:20,600 --> 00:37:25,120 TO SETTING UP SOME OF THE 971 00:37:25,120 --> 00:37:25,680 RECOVER TRIALS. 972 00:37:25,680 --> 00:37:28,280 SO THE CLINICAL TRIALS IN 973 00:37:28,280 --> 00:37:30,560 RECOVER FOLLOWED AN OVERALL 974 00:37:30,560 --> 00:37:35,120 STRATEGY OF BEING VERY RIGOROUS, 975 00:37:35,120 --> 00:37:37,720 BEING INTEGRATED, HAVING 976 00:37:37,720 --> 00:37:38,400 ADAPTIVE PLATFORM PROTOCOLS TO 977 00:37:38,400 --> 00:37:41,840 LOOK AT SAFETY AND EFFICACY AND 978 00:37:41,840 --> 00:37:43,560 TO HAVE INTEGRATED MECHANISTIC 979 00:37:43,560 --> 00:37:45,840 STUDIES SO THAT IT COULD ALSO 980 00:37:45,840 --> 00:37:49,880 YIELD DATA THAT WOULD HELP 981 00:37:49,880 --> 00:37:51,840 UNDERSTAND THE CAUSE AND THEN TO 982 00:37:51,840 --> 00:37:53,520 TEST KNOWN AND NOVEL 983 00:37:53,520 --> 00:37:54,520 INTERVENTIONS ACROSS DIFFERENT 984 00:37:54,520 --> 00:37:57,920 DOMAINS LIKE DRUGS AND DEVICES 985 00:37:57,920 --> 00:37:59,560 AND REHABILITATION TO TREAT LONG 986 00:37:59,560 --> 00:38:01,960 COVID SYMPTOMS AND ADDRESS THE 987 00:38:01,960 --> 00:38:05,040 UNDERLYING CAUSES AND AND SO, IT 988 00:38:05,040 --> 00:38:06,760 STARTED BY ENGAGING THE 989 00:38:06,760 --> 00:38:08,400 COMMUNITY IN PATIENT ADVOCACY 990 00:38:08,400 --> 00:38:11,240 GROUPS THROUGHOUT THE 991 00:38:11,240 --> 00:38:16,280 DEVELOPMENT TO UNDERSTAND THE 992 00:38:16,280 --> 00:38:17,360 INTERVENTION PRIORITIZATION, TO 993 00:38:17,360 --> 00:38:19,080 USE THE CROSS CONSORTIUM 994 00:38:19,080 --> 00:38:20,440 CLINICAL DATA AND LITERATURE TO 995 00:38:20,440 --> 00:38:21,640 INFORM THE DEVELOPMENT OF THE 996 00:38:21,640 --> 00:38:23,760 TRIALS AS I ALREADY REFERRED TO, 997 00:38:23,760 --> 00:38:32,440 AND THEN TO ESTABLISH 998 00:38:32,440 --> 00:38:33,440 SYNERGISTIC COLLABORATIONS AS A 999 00:38:33,440 --> 00:38:34,600 WAY OF MULTIPLE INTERVENTIONS 1000 00:38:34,600 --> 00:38:38,280 AND AS A RESULT TWEP PLATFORM 1001 00:38:38,280 --> 00:38:39,560 PROTOCOLS AND THIS SLIDE GIVES 1002 00:38:39,560 --> 00:38:42,040 YOU AN OVERVIEW OF THE INPUTS, 1003 00:38:42,040 --> 00:38:44,960 THE SOURCES AND INPUTS TO THAT 1004 00:38:44,960 --> 00:38:46,040 PROCESS WHICH INCLUDED THE 1005 00:38:46,040 --> 00:38:48,040 THINGS THAT I'VE ALREADY 1006 00:38:48,040 --> 00:38:49,760 MENTIONED, REALLY BUT THERE WAS 1007 00:38:49,760 --> 00:38:51,160 A LANDSCAPE ANALYSIS OF WHAT WAS 1008 00:38:51,160 --> 00:38:53,720 OUT THERE, THE EHR DATA, WE 1009 00:38:53,720 --> 00:38:57,280 BROUGHT IN CONCEPT PROPOSALS. 1010 00:38:57,280 --> 00:38:59,320 THERE WAS CLIN ITIONZ INPUT, 1011 00:38:59,320 --> 00:39:01,040 PATIENT INPUT, FEDERAL AGENCIES 1012 00:39:01,040 --> 00:39:02,000 PARTNERS WERE INVOLVED, INDUSTRY 1013 00:39:02,000 --> 00:39:05,960 WAS INVOLVED AND SO ON. 1014 00:39:05,960 --> 00:39:08,400 AND THEN THESE WERE DESIGNED AS 1015 00:39:08,400 --> 00:39:09,360 MASTER PROTOCOLS TO RUN 1016 00:39:09,360 --> 00:39:10,760 PLATFORMS WHERE YOU CAN TAKE 1017 00:39:10,760 --> 00:39:12,800 PATIENTS IN, YOU CAN HAVE 1018 00:39:12,800 --> 00:39:13,680 DIFFERENT INTERVENTIONS BEING 1019 00:39:13,680 --> 00:39:18,160 TESTED AT THE SAME TIME. 1020 00:39:18,160 --> 00:39:19,840 YOU CAN COMPLETE ENROLLMENT IN 1 1021 00:39:19,840 --> 00:39:21,240 STUDY AND HAVE THAT STOP AND 1022 00:39:21,240 --> 00:39:25,520 GENERATE DATA FROM THAT 1 ARM. 1023 00:39:25,520 --> 00:39:28,000 YOU CAN ALSO HAVE INTERVENTIONS 1024 00:39:28,000 --> 00:39:30,800 THAT ARE ADDED LATER ON LIKE 1025 00:39:30,800 --> 00:39:34,000 NUMBER 3 AND 4 THAT ARE 1026 00:39:34,000 --> 00:39:36,160 INTRODUCED YOU COULD EVEN 1027 00:39:36,160 --> 00:39:36,760 POTENTIALLY COMBINE 1028 00:39:36,760 --> 00:39:41,200 INTERVENTIONS LATER ON AND 1029 00:39:41,200 --> 00:39:42,120 THAT'S THE IDEA. 1030 00:39:42,120 --> 00:39:43,640 AND SOME OF THE INTEGRATED 1031 00:39:43,640 --> 00:39:46,360 INFRASTRUCTURE THAT WAS USED 1032 00:39:46,360 --> 00:39:48,840 INCLUDE THINGS LIKE SINGLE IRB, 1033 00:39:48,840 --> 00:39:50,320 SINGLE DSMB, TRIAL OVERSIGHT, 1034 00:39:50,320 --> 00:39:51,560 TRIAL MANAGEMENT, ALL THOSE 1035 00:39:51,560 --> 00:39:55,680 THINGS AND THEN FUNCTIONAL 1036 00:39:55,680 --> 00:40:02,360 INTEGRATION WHICH SHARED END 1037 00:40:02,360 --> 00:40:04,920 POINTS, APPROACH TO PATIENT 1038 00:40:04,920 --> 00:40:05,520 PARTICIPATION, CLINICAL GROUPS 1039 00:40:05,520 --> 00:40:06,840 WORKING ON THE PROBLEM, COMMON 1040 00:40:06,840 --> 00:40:08,600 DATA ELEMENTS AND THEN 1041 00:40:08,600 --> 00:40:09,880 MECHANISTIC STUDIES THAT ARE 1042 00:40:09,880 --> 00:40:11,680 CROSS CUTTING ACROSS THE 1043 00:40:11,680 --> 00:40:17,640 DIFFERENT AREAS AND SO, THE 1044 00:40:17,640 --> 00:40:19,960 INITIAL PROGRAM OF 5 MASTER 1045 00:40:19,960 --> 00:40:22,160 PROTOCOLS INCLUDE A VIRAL 1046 00:40:22,160 --> 00:40:24,960 PERSISTENCE AND IMMUNE 1047 00:40:24,960 --> 00:40:26,440 DISREGULATION, 1 INCLUDING 1048 00:40:26,440 --> 00:40:28,200 NEUROQUESTIONS, 1 INCLUDING 1049 00:40:28,200 --> 00:40:31,360 AUTONOMIC, 1 INCLUDING SLEEP AND 1050 00:40:31,360 --> 00:40:36,360 1 INCLUDING CARDIO PULMONARY 1051 00:40:36,360 --> 00:40:37,440 EXERCISING TOLERANCE AND 1052 00:40:37,440 --> 00:40:37,680 FATIGUE. 1053 00:40:37,680 --> 00:40:39,800 AND SO THERE ARE 2 TRIALS THAT 1054 00:40:39,800 --> 00:40:42,160 ARE ALREADY OPEN FOR ENROLLMENT, 1055 00:40:42,160 --> 00:40:45,840 THE FIRST IS THE VITAL TRIAL 1056 00:40:45,840 --> 00:40:48,560 WHICH IS FOCUSED ON TREATING 1057 00:40:48,560 --> 00:40:50,000 SARS-COV-2 PERSISTENCE AND THEN 1058 00:40:50,000 --> 00:40:52,200 THE NEUROTRIAL WHICH IS FOCUSED 1059 00:40:52,200 --> 00:40:53,280 ON BRAIN FOG. 1060 00:40:53,280 --> 00:40:59,040 I WILL TALK A BIT ABOUT THOSE 1061 00:40:59,040 --> 00:41:01,960 ANDEN THIS WE WILL FOCUS ON THE 1062 00:41:01,960 --> 00:41:04,080 OTHERS SLEEP DISREGULATION, 1063 00:41:04,080 --> 00:41:07,000 AUTONOMIC DYSFUNCTION AND THE 1064 00:41:07,000 --> 00:41:07,840 THEN THE ENERGIZE PIECE. 1065 00:41:07,840 --> 00:41:11,000 SO I WILL TALK BRIEFLY ABOUT THE 1066 00:41:11,000 --> 00:41:12,480 VITAL STUDY, THE OBJECTIVE OF 1067 00:41:12,480 --> 00:41:17,360 WHICH IS TO EVALUATE THE EFFECT 1068 00:41:17,360 --> 00:41:21,760 OF THE SARS-COV-2 TREATMENT ON 1069 00:41:21,760 --> 00:41:23,320 SYMPTOM SPECIFIC AND PATIENT 1070 00:41:23,320 --> 00:41:25,200 REPORTED MEASURES WITHIN EACH P 1071 00:41:25,200 --> 00:41:27,000 A SC SYMPTOM CLUSTER AT 1072 00:41:27,000 --> 00:41:28,600 DISCIPLINARY 90 AND THIS FIRST 1073 00:41:28,600 --> 00:41:32,240 SET OF STUDY ARMS INCLUDES P A 1074 00:41:32,240 --> 00:41:37,040 XLOVID, AND IT ALSO INCLUDES 1075 00:41:37,040 --> 00:41:37,840 RITONAVIR AND PLACEBO AND THERE 1076 00:41:37,840 --> 00:41:40,680 WILL BE UP TO A HUNDRED SITES 1077 00:41:40,680 --> 00:41:43,520 WITH 900 PARTICIPANTS AND TELL 1078 00:41:43,520 --> 00:41:46,440 LOOK AT THESE COMBINATIONS AND 1079 00:41:46,440 --> 00:41:48,520 IT LENGTHENS THE TREATMENT OF P 1080 00:41:48,520 --> 00:41:50,720 A XLOVID COMPARED TO THE 1081 00:41:50,720 --> 00:41:52,960 IMPROVED TREATMENT TO UNDERSTAND 1082 00:41:52,960 --> 00:41:54,360 IN 1 ARM WHETHER LONGER 1083 00:41:54,360 --> 00:41:57,800 TREATMENT IS NECESSARY. 1084 00:41:57,800 --> 00:42:00,880 AND THEN THE RECOVER 1085 00:42:00,880 --> 00:42:02,760 NEUROPLATFORM FOR THE EVALUATION 1086 00:42:02,760 --> 00:42:05,640 OF INTERVENTIONS FOR COGNITIVE 1087 00:42:05,640 --> 00:42:07,920 DYSFUNCTION IN LONG COVID, SO 1088 00:42:07,920 --> 00:42:11,440 THE HYPOTHESIS HERE IS THAT P A 1089 00:42:11,440 --> 00:42:13,080 SC ASSOCIATED DECLINES IN 1090 00:42:13,080 --> 00:42:14,880 COGNITIVE DOMAINS SUCH AS 1091 00:42:14,880 --> 00:42:16,400 EXECUTIVE FUNCTION AND RETENTION 1092 00:42:16,400 --> 00:42:18,600 MAY BE IMPROVED BY INTERVENTIONS 1093 00:42:18,600 --> 00:42:20,160 THAT SELECTIVELY FOCUS ON 1094 00:42:20,160 --> 00:42:22,120 ENHANCING THOSE DOMAINS AND SO 1095 00:42:22,120 --> 00:42:27,000 THE STUDY ARMS HERE INCLUDE AN 1096 00:42:27,000 --> 00:42:28,280 ACTIVE COMPARRITIOR ARM OR 1097 00:42:28,280 --> 00:42:31,240 CONTROL ARM WHERE PARTICIPANTS 1098 00:42:31,240 --> 00:42:34,120 WILL USE VIDEO GAMES THEN BRAIN 1099 00:42:34,120 --> 00:42:36,760 HQ WHICH DOES COGNITIVE TRAINING 1100 00:42:36,760 --> 00:42:39,480 OR BRAIN HQ BECAUSE ANOTHER 1101 00:42:39,480 --> 00:42:42,360 INTERVENTION THAT IS KIND OF A 1102 00:42:42,360 --> 00:42:43,320 BEHAVIORIAL INTERVENTION AND 1103 00:42:43,320 --> 00:42:47,240 THEN 1 THAT LOOKS AT DIRECT 1104 00:42:47,240 --> 00:42:48,680 CURRENT STIMULATION WHICH IS 1105 00:42:48,680 --> 00:42:49,720 EITHER ACTIVE OR SHAM. 1106 00:42:49,720 --> 00:42:52,400 AND THIS WILL INCLUDE UP TO 45 1107 00:42:52,400 --> 00:42:53,880 SITES AND 300 PARTICIPANTS. 1108 00:42:53,880 --> 00:42:57,520 SO THESE ARE THE INITIAL STUDIES 1109 00:42:57,520 --> 00:43:00,600 AND AGAIN INFORMED BY THE DATA. 1110 00:43:00,600 --> 00:43:02,920 AND THEN THE LAST THING THAT I 1111 00:43:02,920 --> 00:43:04,480 WANTED TO MENTION WAS JUST THAT 1112 00:43:04,480 --> 00:43:06,520 ALL OF THE DATA THAT ARE COMING 1113 00:43:06,520 --> 00:43:07,560 OUT OF THE ELECTRONIC HEALTH 1114 00:43:07,560 --> 00:43:09,360 RECORD, OUT OF ALL THESE 1115 00:43:09,360 --> 00:43:11,000 MECHANISTIC STUDIES, OUT OF THE 1116 00:43:11,000 --> 00:43:15,120 COHORT STUDIES ARE GOING INTO 1117 00:43:15,120 --> 00:43:18,240 BIODATA CATALYST, SO THAT WE CAN 1118 00:43:18,240 --> 00:43:20,280 REALLY HAVE AN OPEN SCIENCE 1119 00:43:20,280 --> 00:43:23,080 WHERE THERE'S CROSS LINKING OF 1120 00:43:23,080 --> 00:43:25,080 THE DATA, THERE'S COLLABORATION 1121 00:43:25,080 --> 00:43:27,640 OPPORTUNITIES FOR THE SCIENTIFIC 1122 00:43:27,640 --> 00:43:30,640 COMMUNITY AT LARGE AND IT'S 1123 00:43:30,640 --> 00:43:31,560 INTEROPERABLE AND SHAREABLE. 1124 00:43:31,560 --> 00:43:34,160 AND THIS WILL HOPEFULLY LEAD TO 1125 00:43:34,160 --> 00:43:36,560 MORE DIAGNOSTIC TOOLS AND MORE 1126 00:43:36,560 --> 00:43:38,920 THERAPEUTIC OPTIONS AND MORE 1127 00:43:38,920 --> 00:43:40,160 POTENTIAL PREVENTION STRATEGIES, 1128 00:43:40,160 --> 00:43:43,960 SO THE SUM AND MUCH GREATER THAN 1129 00:43:43,960 --> 00:43:45,200 THE PARTS WHEN THE SCIENTIFIC 1130 00:43:45,200 --> 00:43:47,960 METHOD CAN BE APPLIED AND IT'S 1131 00:43:47,960 --> 00:43:49,240 OPEN TO EVERYONE AND THEN THE 1132 00:43:49,240 --> 00:43:51,880 END RESULT IS THAT IT WILL 1133 00:43:51,880 --> 00:43:55,600 HOPEFULLY HELP LONG COVID 1134 00:43:55,600 --> 00:43:56,480 PATIENTS. 1135 00:43:56,480 --> 00:44:00,320 SO IN SUMMARY, THESE RESEARCH 1136 00:44:00,320 --> 00:44:01,000 FINDINGS HAVE IDENTIFIED 1137 00:44:01,000 --> 00:44:02,560 DIFFERENT HEALTH AND DEMOGRAPHIC 1138 00:44:02,560 --> 00:44:04,480 FACTORS THAT PUT INDIVIDUALS AT 1139 00:44:04,480 --> 00:44:08,960 A HIGHER RISK FOR LONG COVID. 1140 00:44:08,960 --> 00:44:12,400 DETERMINING THESE PHENOTYPES MAY 1141 00:44:12,400 --> 00:44:14,040 HELP TO TARGET TREATMENT AND 1142 00:44:14,040 --> 00:44:17,200 INCREASE RECRUITMENT FOR 1143 00:44:17,200 --> 00:44:17,960 RESEARCH STUDIES. 1144 00:44:17,960 --> 00:44:19,040 THE PATHOBIOLOGY AND POGHT O 1145 00:44:19,040 --> 00:44:21,680 PHYSIOLOGY OF P A, C IS COMPLEX 1146 00:44:21,680 --> 00:44:22,640 AND MULTIDISSEMESTERRIC BUT 1147 00:44:22,640 --> 00:44:24,480 APPEARS TO INVOLVE ALTERED 1148 00:44:24,480 --> 00:44:25,960 IMMUNE RESPONSES AND VASCULAR 1149 00:44:25,960 --> 00:44:27,640 RELATED CHANGES THAT WE NEED TO 1150 00:44:27,640 --> 00:44:28,720 LEARN MORE ABOUT, AND NO DOUBT 1151 00:44:28,720 --> 00:44:30,480 THERE ARE MANY OTHER MECHANISMS 1152 00:44:30,480 --> 00:44:32,240 THAT WILL NEED TO BE STUDIED AND 1153 00:44:32,240 --> 00:44:35,640 WILL COME OUT OF THESE DIFFERENT 1154 00:44:35,640 --> 00:44:36,840 PROGRAMS AND BOTH WITHIN RECOVER 1155 00:44:36,840 --> 00:44:37,320 AND WITHOUT. 1156 00:44:37,320 --> 00:44:39,920 SO THEREYA A LOT TO UNDERSTAND 1157 00:44:39,920 --> 00:44:41,360 ABOUT POTENTIAL TREATMENTS FOR P 1158 00:44:41,360 --> 00:44:43,840 A SC, BUT WE'RE HOPING THAT AT 1159 00:44:43,840 --> 00:44:46,320 LEAST THE FIRST SHOT ON GOAL, IF 1160 00:44:46,320 --> 00:44:50,240 THERE IS VIRAL PERSISTENCE, THAT 1161 00:44:50,240 --> 00:44:51,600 THIS TREATMENT WILL BE EFFECTIVE 1162 00:44:51,600 --> 00:44:54,440 BUT AGAIN, IT'S A MASTER 1163 00:44:54,440 --> 00:44:57,600 PROTOCOL AND OTHER AGENTS CAN BE 1164 00:44:57,600 --> 00:44:59,720 ADDED TO THIS PROTOCOL TO BE 1165 00:44:59,720 --> 00:45:06,040 TESTED AS MORE DATA ARE 1166 00:45:06,040 --> 00:45:07,120 GENERATED. 1167 00:45:07,120 --> 00:45:08,800 SO WHILE THE NUMBER OF 1168 00:45:08,800 --> 00:45:10,640 INDIVIDUALS EXPERIENCING P A SC 1169 00:45:10,640 --> 00:45:11,920 HAVE DECREASED OVER TIME, THERE 1170 00:45:11,920 --> 00:45:13,880 ARE STILL MEN PEOPLE SUFFERING 1171 00:45:13,880 --> 00:45:15,080 AND I THINK IT'S REALLY 1172 00:45:15,080 --> 00:45:17,600 IMPORTANT TO RECKIFIES THAT THE 1173 00:45:17,600 --> 00:45:21,520 IMPORTANCE OF THIS, THAT THERE 1174 00:45:21,520 --> 00:45:23,480 ARE MANY MULTISYSTEM SYMPTOMS 1175 00:45:23,480 --> 00:45:26,040 THAT ARE CAUSING A LOT OF 1176 00:45:26,040 --> 00:45:26,760 SUFFERING. 1177 00:45:26,760 --> 00:45:27,080 IT'S COMPLEX. 1178 00:45:27,080 --> 00:45:30,960 IT NEEDS TO BE STUDIED MORE AND 1179 00:45:30,960 --> 00:45:34,960 WE NEED ALL HANDS ON DECK BOTH 1180 00:45:34,960 --> 00:45:36,120 WITHIN THE RECOVER PROGRAM BUT 1181 00:45:36,120 --> 00:45:37,200 OUTSIDE OF THE RECOVER PROGRAM 1182 00:45:37,200 --> 00:45:42,920 AND IN THE WHOLE ECOSYSTEM THAT 1183 00:45:42,920 --> 00:45:44,400 IS SERVED BY FEDERAL AGENCIES 1184 00:45:44,400 --> 00:45:46,960 FUNDING RESEARCH IN THIS AREA. 1185 00:45:46,960 --> 00:45:48,280 AND HOPEFULLY THIS WILL ALL LEAD 1186 00:45:48,280 --> 00:45:50,360 TO A BETTER UNDERSTANDING SO WE 1187 00:45:50,360 --> 00:45:52,200 CAN PREDICT, PREVENT AND TREAT 1188 00:45:52,200 --> 00:45:53,720 THE LONG-TERM EFFECTS OF 1189 00:45:53,720 --> 00:45:54,160 COVID-19. 1190 00:45:54,160 --> 00:46:02,680 AND I WILL STOP THERE. 1191 00:46:02,680 --> 00:46:04,480 >>THANK YOU SO MUCH CLINT, FOR 1192 00:46:04,480 --> 00:46:05,040 THIS FASCINATING TALK. 1193 00:46:05,040 --> 00:46:06,160 THERE ARE QUITE A FEW QUESTIONS 1194 00:46:06,160 --> 00:46:08,680 SO IF YOU DON'T MIND HANGING OUT 1195 00:46:08,680 --> 00:46:12,160 AND I WILL READ YOU SOME OF THE 1196 00:46:12,160 --> 00:46:12,440 QUESTIONS. 1197 00:46:12,440 --> 00:46:13,560 ONE GENERAL QUESTION THAT CAME 1198 00:46:13,560 --> 00:46:17,280 UP A COUPLE OF TIMES IS HOW TO 1199 00:46:17,280 --> 00:46:22,160 ENROLL IN THIS INITIATIVE. 1200 00:46:22,160 --> 00:46:23,880 ONE OF THE QUESTIONERS SAID THEY 1201 00:46:23,880 --> 00:46:25,400 CAN SEE THE ENROLLMENT BY 1202 00:46:25,400 --> 00:46:29,000 INVITATION AT THE TOP OF THE% 1203 00:46:29,000 --> 00:46:30,800 CLINICAL TRIALS .GOV WEBPAGES 1204 00:46:30,800 --> 00:46:33,240 FOR THE VIRAL AND NEUROTRIALS, 1205 00:46:33,240 --> 00:46:35,440 THEY'RE ASKING, WHAT ABOUT THAT 1206 00:46:35,440 --> 00:46:38,280 MEAN BY ENROLLING BY INVITATION? 1207 00:46:38,280 --> 00:46:41,280 >>IT IS NECESSARY WHEN RUNNING 1208 00:46:41,280 --> 00:46:44,120 CLINICAL TRIALS TO HAVE CERTAIN 1209 00:46:44,120 --> 00:46:46,280 INCLUSION AND EXCLUSION CRITERIA 1210 00:46:46,280 --> 00:46:51,120 SO IT'S IMPORTANT FOR PEOPLE TO 1211 00:46:51,120 --> 00:46:52,360 CONTACT THE STUDY AND THEN THERE 1212 00:46:52,360 --> 00:46:54,560 ARE QUESTIONNAIRES THAT PEOPLE 1213 00:46:54,560 --> 00:46:55,760 GO THROUGH TO UNDERSTAND WHETHER 1214 00:46:55,760 --> 00:46:57,440 THE PERSON IS ELIGIBLE OR NOT. 1215 00:46:57,440 --> 00:47:00,520 SO I THINK THAT'S WHAT IT'S 1216 00:47:00,520 --> 00:47:01,480 REFERRING TO. 1217 00:47:01,480 --> 00:47:03,120 THE RECOVER WEBSITE IS VERY 1218 00:47:03,120 --> 00:47:03,880 HELPFUL IN TERMS OF 1219 00:47:03,880 --> 00:47:07,520 UNDERSTANDING HOW TO GET 1220 00:47:07,520 --> 00:47:10,640 INTEREST THESE STUDIES. 1221 00:47:10,640 --> 00:47:13,520 SO RECOVERCOVID.ORG VERY 1222 00:47:13,520 --> 00:47:14,120 INFORMATIVE STUDY WEBSITE. 1223 00:47:14,120 --> 00:47:15,040 >>THANK YOU. 1224 00:47:15,040 --> 00:47:17,480 THE DURATION OF LONG COVID IN 1225 00:47:17,480 --> 00:47:18,440 CHILDREN VERSUS ADULTS, DO YOU 1226 00:47:18,440 --> 00:47:21,240 HAVE ANY COMMENT ON THAT? 1227 00:47:21,240 --> 00:47:26,360 >>NO, I THINK IT'S EARLY TO 1228 00:47:26,360 --> 00:47:28,560 REALLY UNDERSTAND THAT. 1229 00:47:28,560 --> 00:47:31,160 THE PEDIATRIC COHORT STUDY WILL 1230 00:47:31,160 --> 00:47:33,200 BE EXTREMELY HELPFUL AT 1231 00:47:33,200 --> 00:47:35,280 DISENTANGLING SOME OF THOSE 1232 00:47:35,280 --> 00:47:36,640 QUESTIONS AND WE'RE LOOKING 1233 00:47:36,640 --> 00:47:39,240 FORWARD TO THE, YOU KNOW LARGE 1234 00:47:39,240 --> 00:47:43,400 DATA THAT'S BEING GENERATED BY 1235 00:47:43,400 --> 00:47:44,000 THAT PEDIATRIC COHORT. 1236 00:47:44,000 --> 00:47:45,880 THE RATE OF LONG COVID SEEMS TO 1237 00:47:45,880 --> 00:47:48,000 BE SOMEWHAT LOWER IN THE 1238 00:47:48,000 --> 00:47:49,520 PEDIATRIC POPULATION BUT HOW 1239 00:47:49,520 --> 00:47:51,680 LONG IT LASTS IS A QUESTION THAT 1240 00:47:51,680 --> 00:47:55,280 I'M NOT ABLE TO ANSWER AT THIS 1241 00:47:55,280 --> 00:47:55,480 TIME. 1242 00:47:55,480 --> 00:47:56,920 >>QUESTION REGARDING THE 1243 00:47:56,920 --> 00:47:59,960 MANAGEMENT OF THESE P A SC 1244 00:47:59,960 --> 00:48:01,920 SYMPTOMS, AT LEAST ACROSS THE 1245 00:48:01,920 --> 00:48:05,560 U.S. ARE THEY COMMON, FIRST ARE 1246 00:48:05,560 --> 00:48:08,000 THEY BEING RECOGNIZED BY 1247 00:48:08,000 --> 00:48:11,520 PHYSICIANS AS A P A SC SYMPTOM? 1248 00:48:11,520 --> 00:48:12,840 HOW MUCH COHERENCE IS THERE IN 1249 00:48:12,840 --> 00:48:14,360 THE RECOGNITION OF THESE 1250 00:48:14,360 --> 00:48:17,600 SYMPTOMS BY DIFFERENT TYPES OF 1251 00:48:17,600 --> 00:48:18,320 PHYSICIANS? 1252 00:48:18,320 --> 00:48:19,640 ARE THERE COMMON TREATMENTS 1253 00:48:19,640 --> 00:48:20,120 BEING IMPLEMENTED? 1254 00:48:20,120 --> 00:48:24,600 AND HOW DO THOSE TREATMENTS THEN 1255 00:48:24,600 --> 00:48:30,080 AFFECT THE LONGER P A 1256 00:48:30,080 --> 00:48:30,560 SC SEQUELLACE. 1257 00:48:30,560 --> 00:48:32,760 >>I WOULD SAY IT'S BEEN A 1258 00:48:32,760 --> 00:48:35,160 CHALLENGE FOR COVID PATIENTS, 1259 00:48:35,160 --> 00:48:37,000 WHENEVER THERE'S A NEW DISEASE 1260 00:48:37,000 --> 00:48:43,680 OR SET OF DISORDERS, THERE IS A 1261 00:48:43,680 --> 00:48:45,240 TENDENCY NOT TO RECOGNIZE IT ON 1262 00:48:45,240 --> 00:48:46,320 THE PART OF THE MEDICAL 1263 00:48:46,320 --> 00:48:47,160 COMMUNITY THIS WILL THEY REALLY 1264 00:48:47,160 --> 00:48:52,120 KNOW WHAT IT IS AND A LOT OF 1265 00:48:52,120 --> 00:48:53,600 PATIENTS HAVE SHOWN UP AT THE 1266 00:48:53,600 --> 00:48:54,680 DESCR AND THE DOCTOR DOESN'T 1267 00:48:54,680 --> 00:48:55,680 KNOW WHAT'S GOING ON AND 1268 00:48:55,680 --> 00:48:57,680 ATTRIBUTES IT TO SOME OTHER 1269 00:48:57,680 --> 00:48:59,240 THING AND THERE HAVE BEEN 1270 00:48:59,240 --> 00:49:00,200 PATIENTS THAT HAVE BEEN 1271 00:49:00,200 --> 00:49:03,920 DISMISSED AND I THINK IT'S VERY 1272 00:49:03,920 --> 00:49:05,320 IMPORTANT FOR THE WORD TO GET 1273 00:49:05,320 --> 00:49:11,200 OUT THAT LONG COVID IS REAL AND 1274 00:49:11,200 --> 00:49:12,400 WE DON'T COMPLETELY UNDERSTAND 1275 00:49:12,400 --> 00:49:16,000 IT AND FOR PATIENTS TO REALLY 1276 00:49:16,000 --> 00:49:17,680 LOOK FOR CAREGIVERS THAT CAN 1277 00:49:17,680 --> 00:49:19,560 HEAR THEM AND THAT--VALIDATE, 1278 00:49:19,560 --> 00:49:22,520 YOU KNOW WHAT IS GOING ON WITH 1279 00:49:22,520 --> 00:49:26,640 THEM SO THAT WAS THE FIRST PART 1280 00:49:26,640 --> 00:49:27,160 OF YOUR QUESTION. 1281 00:49:27,160 --> 00:49:32,400 I THINK IN TERMS OF THE SECOND 1282 00:49:32,400 --> 00:49:34,320 PART THAT THERE ARE SYMPTOMATIC 1283 00:49:34,320 --> 00:49:35,880 TREATMENTS THAT PEOPLE CAN TRY 1284 00:49:35,880 --> 00:49:37,920 AND I THINK DOCTORS ARE WILLING 1285 00:49:37,920 --> 00:49:43,400 TO TRY, YOU KNOW DIFFERENT 1286 00:49:43,400 --> 00:49:45,440 MOR 1287 00:49:45,440 --> 00:49:47,480 MODALITIES THAT ARE OFF-LABEL 1288 00:49:47,480 --> 00:49:48,640 FOR THE SYMPTOMS TO SEE IF THEY 1289 00:49:48,640 --> 00:49:51,640 WORK BUT IN THE END WE NEED 1290 00:49:51,640 --> 00:49:52,000 RIGOROUS TRIALS. 1291 00:49:52,000 --> 00:49:53,840 UNFORTUNATELY THERE'S A LOT OF 1292 00:49:53,840 --> 00:49:58,040 MISINFORMATION OUT THERE ON THE 1293 00:49:58,040 --> 00:49:59,520 INTERNET, CLAIMING THAT CERTAIN 1294 00:49:59,520 --> 00:50:01,280 TREATMENTS ARE EFFECTIVE IN HAD 1295 00:50:01,280 --> 00:50:04,320 LONG COVID THAT HAVE REALLY NO 1296 00:50:04,320 --> 00:50:08,520 BASIS IN EVIDENCE AND IT'S 1297 00:50:08,520 --> 00:50:09,040 CRITICAL THAT PATIENTS 1298 00:50:09,040 --> 00:50:11,080 UNDERSTAND WHAT IS REQUIRED TO 1299 00:50:11,080 --> 00:50:13,000 REALLY PROVE THAT SOMETHING 1300 00:50:13,000 --> 00:50:15,280 WORKS IF IT'S NOT SOMETHING 1301 00:50:15,280 --> 00:50:17,480 THAT'S ALREADY BEEN USED FOR THE 1302 00:50:17,480 --> 00:50:18,800 SAME SYMPTOM IN ANOTHER DISEASE, 1303 00:50:18,800 --> 00:50:24,240 WHICH A DOCTOR MAY BE WILLING TO 1304 00:50:24,240 --> 00:50:24,640 PRESCRIBE. 1305 00:50:24,640 --> 00:50:27,240 >>THE VASCULAR BIOMARKERS THAT 1306 00:50:27,240 --> 00:50:30,680 YOU PRESENTED, THE HIGH LEVELS 1307 00:50:30,680 --> 00:50:33,680 OF PLASMA ANGIO TENSEIN 1 FOR 1308 00:50:33,680 --> 00:50:36,920 INSTANCE, CORRELATING WITH THE 1309 00:50:36,920 --> 00:50:37,880 LONGER--LONG COVID, HAS THAT 1310 00:50:37,880 --> 00:50:39,920 BEEN SEEN BEFORE WITH OTHER 1311 00:50:39,920 --> 00:50:40,640 VIRAL INFECTIONS? 1312 00:50:40,640 --> 00:50:42,920 HAS IT BEEN LOOKED AT BEFORE FOR 1313 00:50:42,920 --> 00:50:46,000 INSTANCE IN FLU OR OTHER TYPES 1314 00:50:46,000 --> 00:50:49,720 OF RESPIRATORY VIRAL INFECTIONS? 1315 00:50:49,720 --> 00:50:50,520 >>WELL, I THINK--I DON'T KNOW 1316 00:50:50,520 --> 00:50:53,240 THE ANSWER TO THAT. 1317 00:50:53,240 --> 00:50:55,600 I DO KNOW THAT WE'RE MOTIVATED 1318 00:50:55,600 --> 00:50:57,720 WHEN I SAY WE, I MEAN THE 1319 00:50:57,720 --> 00:50:58,720 SCIENTIFIC COMMUNITY WAS 1320 00:50:58,720 --> 00:51:01,720 MOTIVATED TO LOOK AT THIS 1321 00:51:01,720 --> 00:51:04,760 BECAUSE OF THE EARLY THROMBOTIC 1322 00:51:04,760 --> 00:51:06,120 EFFECTS OF COVID ITSELF, THERE 1323 00:51:06,120 --> 00:51:10,480 WAS A LOT OF EVIDENCE OF 1324 00:51:10,480 --> 00:51:11,040 MICROTHROMBOSIS, PLATELET 1325 00:51:11,040 --> 00:51:13,760 ACTIVATION, AND THEN OF COURSE, 1326 00:51:13,760 --> 00:51:16,000 THERE WAS A CYTOKINE STORM, IN 1327 00:51:16,000 --> 00:51:18,400 SOME CASES THERE WERE A LOT OF 1328 00:51:18,400 --> 00:51:20,040 INFLAMMATORY MARKERS THAT WERE 1329 00:51:20,040 --> 00:51:20,880 ELEVATED INCLUDING IL6 FOR 1330 00:51:20,880 --> 00:51:24,760 EXAMPLE, AND THEN THAT 1331 00:51:24,760 --> 00:51:27,240 CONNECTION WITH THE THROMBOTIC 1332 00:51:27,240 --> 00:51:28,280 SYSTEM WAS OF GREAT INTEREST SO 1333 00:51:28,280 --> 00:51:31,640 I THAT WAS I THINK WAS THE 1334 00:51:31,640 --> 00:51:32,920 MOTIVATION FOR TRYING TO 1335 00:51:32,920 --> 00:51:35,400 UNDERSTAND, SOME OF THESE LONG 1336 00:51:35,400 --> 00:51:38,040 COVID SYMPTOMS DUE TO THROMBOTIC 1337 00:51:38,040 --> 00:51:39,800 PROBLEMS, THE WAY THEY WERE IN 1338 00:51:39,800 --> 00:51:40,520 THE ACUTE COVID. 1339 00:51:40,520 --> 00:51:43,880 SO THAT I THINK WAS THE 1340 00:51:43,880 --> 00:51:45,600 MOTIVATOR BUT--AND HOW THEY 1341 00:51:45,600 --> 00:51:47,160 DIFFERENTIATE FROM OTHER ILLNESS 1342 00:51:47,160 --> 00:51:48,560 AND OTHER SEVERE ILLNESSES, IT 1343 00:51:48,560 --> 00:51:54,320 MAY HAVE BEEN STUDIED, I DON'T 1344 00:51:54,320 --> 00:51:55,200 KNOW. 1345 00:51:55,200 --> 00:51:56,080 >>QUESTION REGARDING VIRAL 1346 00:51:56,080 --> 00:51:57,240 PERSISTENCE, HOW AND WHAT 1347 00:51:57,240 --> 00:51:58,320 TISSUES ARE BEING SAMPLED FOR 1348 00:51:58,320 --> 00:52:04,680 THAT IN THESE PATIENTS? 1349 00:52:04,680 --> 00:52:05,280 >>YEAH. 1350 00:52:05,280 --> 00:52:06,720 >>YEAH. 1351 00:52:06,720 --> 00:52:09,240 >>[INDISCERNIBLE]. 1352 00:52:09,240 --> 00:52:09,800 >>VERY TOUGH. 1353 00:52:09,800 --> 00:52:12,640 BECAUSE SOME OF THE VIRAL 1354 00:52:12,640 --> 00:52:13,360 RESERVOIRS MAY INVOLVE AREAS 1355 00:52:13,360 --> 00:52:17,000 THAT ARE VERY DIFFICULT TO HAVE 1356 00:52:17,000 --> 00:52:20,840 ACCESS TO SO IN ORDER TO LOOK IN 1357 00:52:20,840 --> 00:52:25,360 THE CENTRAL SERVOUS SYSTEM, YOU 1358 00:52:25,360 --> 00:52:27,240 NEED CEREBRAL SPINAL FLUID WHICH 1359 00:52:27,240 --> 00:52:29,960 REQUIRES A LUMBAR PUNCTURE AND A 1360 00:52:29,960 --> 00:52:31,520 LOT OF PATIENTS ARE NOT ALWAYS 1361 00:52:31,520 --> 00:52:33,440 WILLING TO UNDERGO THAT, ANOTHER 1362 00:52:33,440 --> 00:52:36,320 1 IS IN THE GASTROINTESTINAL 1363 00:52:36,320 --> 00:52:37,280 TRACT WHICH IS DIFFICULT ON IT 1364 00:52:37,280 --> 00:52:38,440 ACCESS, CAN YOU TRY TO ELECTRIC 1365 00:52:38,440 --> 00:52:40,160 AT IT WITH STOOL SAMPLES BUT 1366 00:52:40,160 --> 00:52:43,720 TIMES YOU MIGHT NEED TO LOOK BY 1367 00:52:43,720 --> 00:52:47,080 TAKING A SAMPLE IN THE 1368 00:52:47,080 --> 00:52:47,800 GASTROINTESTINAL TRACT ITSELF 1369 00:52:47,800 --> 00:52:49,960 AND SO AGAIN, THAT'S HARDER TO 1370 00:52:49,960 --> 00:52:50,680 GET ACCESS TO. 1371 00:52:50,680 --> 00:52:52,200 YOU OF COURSE CAN LOOK AT BLOOD, 1372 00:52:52,200 --> 00:52:55,200 AND SO, THESE ARE THE WAYS OF 1373 00:52:55,200 --> 00:52:57,480 LOOKING FOR THE VIRAL RESERVOIR 1374 00:52:57,480 --> 00:52:59,240 AND MANY OF THESE MECHANISTIC 1375 00:52:59,240 --> 00:53:01,960 STUDIES THAT ARE BEING DONE ARE 1376 00:53:01,960 --> 00:53:03,160 OFFERING THOSE TYPES OF TESTS SO 1377 00:53:03,160 --> 00:53:09,400 THAT WE CAN TRY TO GET TO THE 1378 00:53:09,400 --> 00:53:10,320 BOTTOM OF IT. 1379 00:53:10,320 --> 00:53:12,520 >>DOES THE DECREASE IN P A SC 1380 00:53:12,520 --> 00:53:15,480 USE A DIFFERENCE IN VARIANCE 1381 00:53:15,480 --> 00:53:17,680 LIKE IN OMICRON, ACTUAL LOWER 1382 00:53:17,680 --> 00:53:19,920 DISEASE SEVERITY, COMPARED TO 1383 00:53:19,920 --> 00:53:20,960 EARLIER STRAINS LIKE DELTA? 1384 00:53:20,960 --> 00:53:22,480 IS THERE ANY DATA ON THAT? 1385 00:53:22,480 --> 00:53:25,760 >>WHEN WE TALK ABOUT LONG COVID 1386 00:53:25,760 --> 00:53:28,800 SEVERITY, IT GETS A LITTLE BIT 1387 00:53:28,800 --> 00:53:29,200 MORE COMPLICATED. 1388 00:53:29,200 --> 00:53:31,280 YOU KNOW CERTAINLY THE EARLIER 1389 00:53:31,280 --> 00:53:33,560 COVID VARIANTS LED TO MORE 1390 00:53:33,560 --> 00:53:35,760 SEVERE ILLNESS IN THE ACUTE 1391 00:53:35,760 --> 00:53:39,600 INFECTION WHICH OF COURSE WAS 1392 00:53:39,600 --> 00:53:41,600 YOU KNOW WORSE FOR PATIENTS IN 1393 00:53:41,600 --> 00:53:44,320 TERMS OF THE AFTER EFFECTS AND 1394 00:53:44,320 --> 00:53:46,360 THAT'S BEEN 1 OF THE CHALLENGES 1395 00:53:46,360 --> 00:53:48,560 TRYING TO SEPARATE OUT ALL THE 1396 00:53:48,560 --> 00:53:53,360 ACUTE ILLNESS FROM THE LONG 1397 00:53:53,360 --> 00:53:54,440 COVID TO UNDERSTAND WHETHER THIS 1398 00:53:54,440 --> 00:53:56,880 IS SOMETHING THAT IS PERPETUATED 1399 00:53:56,880 --> 00:53:59,720 OR SOMETHING STARTING AT THE 1400 00:53:59,720 --> 00:54:00,920 BEGINNING AND STILL CONTINUING 1401 00:54:00,920 --> 00:54:02,240 WHICH IS ALSO IMPORTANT AS WELL 1402 00:54:02,240 --> 00:54:04,920 AND NEEDS TO BE ADDRESSED. 1403 00:54:04,920 --> 00:54:08,000 SO I THINK THAT IT'S IMPORTANT 1404 00:54:08,000 --> 00:54:11,760 TO GO AFTER BOTH OF THOSE ANGLES 1405 00:54:11,760 --> 00:54:14,120 BUT IN TERMS OF THE SEVERITY, I 1406 00:54:14,120 --> 00:54:16,480 THINK THAT MANY OF THE PEOPLE 1407 00:54:16,480 --> 00:54:18,160 THAT HAVE MILD ACUTE INFECTIONS 1408 00:54:18,160 --> 00:54:22,280 HAVE A LOT OF DISABILITY IN 1409 00:54:22,280 --> 00:54:23,920 THEIR LONG COVID ARE COMPLAINING 1410 00:54:23,920 --> 00:54:27,160 OF A LOT OF DISABILITY, UNABLE 1411 00:54:27,160 --> 00:54:28,320 TO WORK, UNABLE TO FUNCTION AND 1412 00:54:28,320 --> 00:54:30,160 SO I THINK THAT'S QUITE SEVERE. 1413 00:54:30,160 --> 00:54:34,120 SO YES, WE ARE SEEING, STILL 1414 00:54:34,120 --> 00:54:35,720 SEEING THAT SEVERITY EVEN THOUGH 1415 00:54:35,720 --> 00:54:41,720 THE INITIAL INFECTION MIGHT BE 1416 00:54:41,720 --> 00:54:42,720 MILD. 1417 00:54:42,720 --> 00:54:45,240 >>HOW DO YOU OPERATIONALIZE THE 1418 00:54:45,240 --> 00:54:47,200 SYMPTOM OF BRAIN FOG IN THE 1419 00:54:47,200 --> 00:54:49,680 SYMPTOM STUDY, WHY WAS THIS TERM 1420 00:54:49,680 --> 00:54:52,760 USED SUCH OTHER THAN ITS 1421 00:54:52,760 --> 00:54:54,560 COUNTERPART SUCH AS MEMORY OR 1422 00:54:54,560 --> 00:54:55,520 CONCENTRATION IMPAIRMENT. 1423 00:54:55,520 --> 00:54:59,880 >>I THINK THE LATTER 1S ARE THE 1424 00:54:59,880 --> 00:55:01,520 OBJECTIVE REFERENCES TO NEUROs 1425 00:55:01,520 --> 00:55:02,680 LIKE DOMAINS THAT WE THINK ABOUT 1426 00:55:02,680 --> 00:55:06,000 WHEN WE DO A FULL NEUROPSYCHE 1427 00:55:06,000 --> 00:55:07,600 BATTERY ON SOMEONE FOR EXAMPLE, 1428 00:55:07,600 --> 00:55:08,840 OR WE DO TESTING. 1429 00:55:08,840 --> 00:55:10,520 BRAIN FOG IS WHAT PEOPLE 1430 00:55:10,520 --> 00:55:11,040 COMPLAIN OF. 1431 00:55:11,040 --> 00:55:15,320 AND SO WE USE THE TERM SO THAT 1432 00:55:15,320 --> 00:55:16,040 PATIENTS AND PARTICIPANTS 1433 00:55:16,040 --> 00:55:18,920 UNDERSTAND WHAT WE'RE GOING 1434 00:55:18,920 --> 00:55:19,160 AFTER. 1435 00:55:19,160 --> 00:55:21,760 BUT CERTAINLY TO STUDY IT, YOU 1436 00:55:21,760 --> 00:55:24,600 NEED TO LOOK AT THINGS LIKE 1437 00:55:24,600 --> 00:55:26,600 ATTENTION AND EXECUTIVE FUNCTION 1438 00:55:26,600 --> 00:55:28,720 AND MEMORY AND ALL OF THE 1439 00:55:28,720 --> 00:55:29,440 DIFFERENT DOMAINS THAT ARE 1440 00:55:29,440 --> 00:55:31,200 IMPORTANT ON GIVE YOU AN 1441 00:55:31,200 --> 00:55:34,120 OBJECTIVE MEASURE OF WHAT'S 1442 00:55:34,120 --> 00:55:35,200 GOING ON AND AS YOU SAW FROM 1443 00:55:35,200 --> 00:55:37,920 THAT 1 STUDY THAT I SHOWED, 1444 00:55:37,920 --> 00:55:39,040 SOMETIMES THE OBJECTIVE MEASURE 1445 00:55:39,040 --> 00:55:41,080 EVEN THOUGH THAT MEASURE WAS A 1446 00:55:41,080 --> 00:55:43,720 VERY CRUDE SORT OF MEASURE, YOU 1447 00:55:43,720 --> 00:55:45,640 KNOW A GLOBAL MEASURE OF THE 1448 00:55:45,640 --> 00:55:46,440 [INDISCERNIBLE] DIDN'T SHOW 1449 00:55:46,440 --> 00:55:48,720 ANYTHING IN THE SYMPTOMS, DID 1450 00:55:48,720 --> 00:55:50,480 SHOW SOMETHING AND AT THE TIME 1451 00:55:50,480 --> 00:55:52,880 THAT THE SYMPTOMS SHOWED 1452 00:55:52,880 --> 00:55:54,200 SOMETHING, THE SUBJECTIVE 1453 00:55:54,200 --> 00:55:57,200 SYMPTOMS, THEY ALSO HAD 1454 00:55:57,200 --> 00:56:01,040 OCCUPATIONAL IMPAIRMENT. 1455 00:56:01,040 --> 00:56:02,840 SO THERE ISN'T A COMPLETE 1456 00:56:02,840 --> 00:56:03,920 OVERLAP BETWEEN THE SPECIFIC 1457 00:56:03,920 --> 00:56:07,280 DOMAINS BEING AFFECTED AND THE 1458 00:56:07,280 --> 00:56:08,680 SUFFERING THAT THE PATIENT IS 1459 00:56:08,680 --> 00:56:10,960 HAVING AND THE WAY THEY EXPLAIN 1460 00:56:10,960 --> 00:56:12,000 THE SYMPTOMS THAT THEY'RE HAVING 1461 00:56:12,000 --> 00:56:13,520 AND HOW IT'S AFFECTING THEIR 1462 00:56:13,520 --> 00:56:18,200 LIVES AND SO WE NEED TO GO AFTER 1463 00:56:18,200 --> 00:56:20,800 THE LARGER PICTURE, NOT JUST THE 1464 00:56:20,800 --> 00:56:22,360 OBJECTIVE STUFF. 1465 00:56:22,360 --> 00:56:24,600 >>AND THE FINAL QUESTION: DO 1466 00:56:24,600 --> 00:56:27,320 YOU HAVE ANY INSIGHT INTO THE 1467 00:56:27,320 --> 00:56:29,920 DIFFERENCES IN P A SC BETWEEN 1468 00:56:29,920 --> 00:56:31,280 MALES AND FEMALES? 1469 00:56:31,280 --> 00:56:36,240 >>THAT'S A REALLY GREAT 1470 00:56:36,240 --> 00:56:36,480 QUESTION. 1471 00:56:36,480 --> 00:56:37,240 THAT'S A VERY IMPORTANT QUESTION 1472 00:56:37,240 --> 00:56:38,960 THAT NEEDINGS TO BE LOOKED AT 1473 00:56:38,960 --> 00:56:39,560 FURTHER. 1474 00:56:39,560 --> 00:56:43,560 THEREYA --THERE'S A LOT OF 1475 00:56:43,560 --> 00:56:44,680 POTENTIAL DATA OUT THERE. 1476 00:56:44,680 --> 00:56:46,760 I REFER BACK TO 1 OF MY LAST 1477 00:56:46,760 --> 00:56:47,640 SLIDES ABOUT THE BIODATA 1478 00:56:47,640 --> 00:56:49,120 CATALYST AND ALL THE DATA 1479 00:56:49,120 --> 00:56:50,720 FEEDING INTO IT THAT WILL ALLOW 1480 00:56:50,720 --> 00:56:54,920 SCIENTISTS TO LOOK AT THAT I AM 1481 00:56:54,920 --> 00:56:59,240 NOT AWARE OFF THE TOP OF MY HEAD 1482 00:56:59,240 --> 00:56:59,960 OF MALE/FEMALE DIFFERENCES BUT 1483 00:56:59,960 --> 00:57:03,360 THAT COULD BE THAT I'M NOT ABLE 1484 00:57:03,360 --> 00:57:06,200 TO THINK OF IT AT THE MOMENT BUT 1485 00:57:06,200 --> 00:57:07,040 IT'S A VERY IMPORTANT SET OF 1486 00:57:07,040 --> 00:57:09,160 QUESTIONS AND I THINK IT COULD 1487 00:57:09,160 --> 00:57:10,520 ACTUALLY BE VERY HELPFUL IN 1488 00:57:10,520 --> 00:57:11,840 TERMS OF UNDERSTANDING 1489 00:57:11,840 --> 00:57:13,880 MECHANISMS IF WE COULD SEE SEX 1490 00:57:13,880 --> 00:57:15,080 DIFFERENCES, BECAUSE IT MIGHT 1491 00:57:15,080 --> 00:57:18,840 GIVE US SOME IDEA OF 1492 00:57:18,840 --> 00:57:19,440 DIFFERENT--DIFFERENT PATHWAYS 1493 00:57:19,440 --> 00:57:24,280 THAT ARE INVOLVED. 1494 00:57:24,280 --> 00:57:25,920 >>WELL, THANK YOU SO MUCH 1495 00:57:25,920 --> 00:57:28,240 DR. WRIGHT AND THIS CONCLUDES 1496 00:57:28,240 --> 00:57:29,120 TODAY'S SEMINAR. 1497 00:57:29,120 --> 00:57:30,240 THANK YOU. 1498 00:57:30,240 --> 00:57:38,960 >>MY PLEASURE, THANK YOU. 1499 00:57:38,960 --> 00:57:49,200 >>BYE-BYE.