1 00:00:05,760 --> 00:00:09,360 IT'S A TERRIFIC HONOR TO BE ABLE 2 00:00:09,360 --> 00:00:13,640 TO INTRODUCE 2 OF NIAIDs MOST 3 00:00:13,640 --> 00:00:21,360 BRILLIANT STARTS D 4 00:00:21,360 --> 00:00:23,040 R. VERONIQUE NUSSENBLATT AND 5 00:00:23,040 --> 00:00:25,000 DR. ELODI GHEDIN WHO WILL TALK 6 00:00:25,000 --> 00:00:25,720 ABOUT WHAT, ELSE? 7 00:00:25,720 --> 00:00:29,320 SO I WILL GIVE A BRIEF 8 00:00:29,320 --> 00:00:33,120 INTRODUCTION AND ELODIIS OUR 9 00:00:33,120 --> 00:00:34,320 CHIEF OF CONSULTATION SERVICES 10 00:00:34,320 --> 00:00:35,120 SO YOU SLEEP APNEA AND OBESITYY 11 00:00:35,120 --> 00:00:36,880 HER ALL OVER AND OUR PROGRAM 12 00:00:36,880 --> 00:00:38,640 DIRECTOR FOR TRAINING AND 13 00:00:38,640 --> 00:00:39,680 INFECTIOUS DISEASE, SHE GREW UP 14 00:00:39,680 --> 00:00:40,640 IN THE REGION, WENT TO 15 00:00:40,640 --> 00:00:41,760 UNIVERSITY OF MARYLAND AND JOHNS 16 00:00:41,760 --> 00:00:44,640 LOP KINS WHERE SHE GOT HER MHS 17 00:00:44,640 --> 00:00:46,000 IN EPIDEMIOLOGY AND INFECTIOUS 18 00:00:46,000 --> 00:00:48,440 DISEASE, YOU SEE THE LINK HERE 19 00:00:48,440 --> 00:00:51,440 AND THEN HER M. D. AT MARYLAND, 20 00:00:51,440 --> 00:00:55,120 HER RESIDENCY ON THE ESTEEMED 21 00:00:55,120 --> 00:00:58,920 [INDISCERNIBLE] SERVICE, I HAVE 22 00:00:58,920 --> 00:01:01,880 A STAKE HERE AND THEN DID 23 00:01:01,880 --> 00:01:03,440 INFECTIOUS DISEASE TRAINING AT 24 00:01:03,440 --> 00:01:04,760 JOHNS HOPKINS FOLLOWED BY 25 00:01:04,760 --> 00:01:06,360 FURTHER TRAINING IN EPIDEMIOLOGY 26 00:01:06,360 --> 00:01:07,760 AND PUBLIC HEALTH. 27 00:01:07,760 --> 00:01:09,520 A SHORT STINT IN [INDISCERNIBLE] 28 00:01:09,520 --> 00:01:10,560 BEFORE COMING BACK TO HOPKINS 29 00:01:10,560 --> 00:01:12,280 WHERE SHE WAS RUNNING PART OF 30 00:01:12,280 --> 00:01:14,440 THE PROGRAM OUT AT THE BAYVIEW 31 00:01:14,440 --> 00:01:16,720 MEDICAL CENTER AND THEN WE WERE 32 00:01:16,720 --> 00:01:18,440 FANTASTICALLY LUCKY TO GET HER 33 00:01:18,440 --> 00:01:26,960 TO COME BACK HERE AND TO RUN OUR 34 00:01:26,960 --> 00:01:27,960 TRAINING PROGRAM. 35 00:01:27,960 --> 00:01:32,080 AND SHE IS A 2021 NIH RECIPIENT 36 00:01:32,080 --> 00:01:34,080 OF THE COVID-19 AWARD FOR THE 37 00:01:34,080 --> 00:01:34,840 OUTBREAK RESPONSE TEAM. 38 00:01:34,840 --> 00:01:41,560 FOLLOWING HER WILL BE 39 00:01:41,560 --> 00:01:42,480 DR. ELODIE GHEDIN, YOU YOU MIGHT 40 00:01:42,480 --> 00:01:45,040 BE SAYING WAIT A MINUTE 41 00:01:45,040 --> 00:01:46,000 COVID-19'S A FASCINATING PROGRAM 42 00:01:46,000 --> 00:01:48,480 BUT IT'S NOT TYPICALLY 43 00:01:48,480 --> 00:01:49,240 CONSIDERED A PARASITIC DISEASE. 44 00:01:49,240 --> 00:01:51,040 THIS WAS AN ERROR, I DON'T KNOW 45 00:01:51,040 --> 00:01:52,520 HOW THIS HAPPENED HERE BUT THE 46 00:01:52,520 --> 00:01:55,360 FACT IS THAT MICROBIAL GENOMICS 47 00:01:55,360 --> 00:01:56,760 IS ALWAYS IMPORTANT. 48 00:01:56,760 --> 00:01:58,280 SO ELODIE COMES TO US FROM 49 00:01:58,280 --> 00:01:58,520 CANADA. 50 00:01:58,520 --> 00:01:59,480 YOU WOULDN'T KNOW IT LOOKING 51 00:01:59,480 --> 00:02:01,120 OUTSIDE RIGHT NOW BUT GOT HER B. 52 00:02:01,120 --> 00:02:03,680 S. AT Mc GILL AND HER MASTERS 53 00:02:03,680 --> 00:02:07,160 AT UNIVERSITY OF QUEBEC AND 54 00:02:07,160 --> 00:02:08,760 Ph.D. AT Mc GILL. 55 00:02:08,760 --> 00:02:11,080 SHE DID HER POST DOC HERE AT THE 56 00:02:11,080 --> 00:02:13,400 LPD DISP WENT FROM LEER TO THE 57 00:02:13,400 --> 00:02:14,640 INSTITUTE FOR IME NATIONAL 58 00:02:14,640 --> 00:02:16,160 LIBRARY OF MEDICINIC RESEARCH 59 00:02:16,160 --> 00:02:18,360 TIGER IN THE YEAR OF ROCKVILLE 60 00:02:18,360 --> 00:02:20,040 AND THEN WENT TO PITTSBURGH 61 00:02:20,040 --> 00:02:23,000 WHERE SHE ROSE THROUGH THE RANKS 62 00:02:23,000 --> 00:02:26,040 TO AN ASSOCIATE PROFESSOR WITH 63 00:02:26,040 --> 00:02:27,320 TENURE BEFORE DECAMPING TO 64 00:02:27,320 --> 00:02:45,840 NEW YORK WHERE SHE WAS THE-- 65 00:02:45,840 --> 00:02:49,320 WE WERE FORTUNATE TO THIS AND 66 00:02:49,320 --> 00:02:51,840 SHE'S ALSO THE RECIPIENT TO THE 67 00:02:51,840 --> 00:02:52,520 FOUNDATION FELLOWSHIP. 68 00:02:52,520 --> 00:02:54,280 SO WITH THAT I WILL STOP AND 69 00:02:54,280 --> 00:02:55,640 TURN IT OVER TO 70 00:02:55,640 --> 00:02:58,160 DRS. NUSSENBLATT AND GHEDIN. 71 00:02:58,160 --> 00:03:00,640 >> THANK YOU SO MUCH FOR JUST A 72 00:03:00,640 --> 00:03:01,240 KIND INTRODUCTION. 73 00:03:01,240 --> 00:03:02,800 AND ON BEHALF OF BOTH OF US AS 74 00:03:02,800 --> 00:03:05,960 WELL, THANK THE COVID-19 SIG 75 00:03:05,960 --> 00:03:07,120 LECTURE COMMITTEE FOR THE 76 00:03:07,120 --> 00:03:14,120 INVITATION TO SPEAK TODAY ABOUT 77 00:03:14,120 --> 00:03:16,520 A TOPIC THAT'S OF GREAT INTEREST 78 00:03:16,520 --> 00:03:18,800 TO BOTH OF US WHICH IS WHETHER 79 00:03:18,800 --> 00:03:21,160 THE INABILITY OF SOME IMMUNE O 80 00:03:21,160 --> 00:03:22,960 COMPROMISED INDIVIDUALS TO 81 00:03:22,960 --> 00:03:25,600 EFFECTIVELY CONTROL AND CLEAR 82 00:03:25,600 --> 00:03:26,640 SARS-COV-2 AFTER INFECTION COULD 83 00:03:26,640 --> 00:03:29,360 BE CONTRIBUTING TO A POTENTIAL 84 00:03:29,360 --> 00:03:31,440 VARIANT EMERGENCE. 85 00:03:31,440 --> 00:03:32,880 SO THIS ILLUSTRATION SHOWS US 86 00:03:32,880 --> 00:03:34,760 THE TIMELINE OF THE INNATE AND 87 00:03:34,760 --> 00:03:37,200 THE ADAPTIVE IMMUNE RESPONSES 88 00:03:37,200 --> 00:03:37,920 DURING SARS-COV-2 INFECTION, SO 89 00:03:37,920 --> 00:03:42,040 WE SEE THE INNATE RESPONSE 90 00:03:42,040 --> 00:03:43,480 PRETTY IMMEDIATELY SIMULATING 91 00:03:43,480 --> 00:03:44,520 INTERFERON TO COMBAT THE VIRUS 92 00:03:44,520 --> 00:03:46,480 AND AS THE VIRAL LOAD INCREASES, 93 00:03:46,480 --> 00:03:49,680 WE THEN SEE THE ADAPTIVE IMMUNE 94 00:03:49,680 --> 00:03:52,280 RESPONSE WITH THE B-CELL AND 95 00:03:52,280 --> 00:03:53,280 T-CELL PROLIFERATION, ANTIBODY 96 00:03:53,280 --> 00:03:54,600 PRODUCTION LEADING TO DECREASE 97 00:03:54,600 --> 00:03:56,280 IN VIRAL LOAD, RESOLUTION OF 98 00:03:56,280 --> 00:03:57,120 SYMPTOMS AND ULTIMATELY, THE 99 00:03:57,120 --> 00:04:01,280 CLEARANCE OF THE VIRUS. 100 00:04:01,280 --> 00:04:02,080 NEXT SLIDE, PLEASE. 101 00:04:02,080 --> 00:04:04,360 SO IN THIS ILLUSTRATION THAT YOU 102 00:04:04,360 --> 00:04:06,680 SEE ON THE RIGHT, WE ARE SHOWING 103 00:04:06,680 --> 00:04:08,840 WHAT WE OFTEN SEE IN MANY IMMUNE 104 00:04:08,840 --> 00:04:09,880 O COMPROMISED HOSTS WHICH IS 105 00:04:09,880 --> 00:04:11,960 THAT YOU STILL SEE THIS INNATE 106 00:04:11,960 --> 00:04:15,920 RESPONSE BUT YOU DON'T HAVE THAT 107 00:04:15,920 --> 00:04:18,000 ROBUST ADAPTIVE IMMUNE RESPONSE 108 00:04:18,000 --> 00:04:20,080 LEADING TO PROLONGED VIRAL 109 00:04:20,080 --> 00:04:20,920 PROLIFERATION, PROLONGED 110 00:04:20,920 --> 00:04:22,280 INFECTION AND IN COMBINATION 111 00:04:22,280 --> 00:04:24,440 WITH INFLAMMATION FROM THE 112 00:04:24,440 --> 00:04:26,680 INNATE IMMUNE SYSTEM, WE ALSO 113 00:04:26,680 --> 00:04:30,240 SEE PROLONGED SYMPTOMS AS WELL. 114 00:04:30,240 --> 00:04:30,760 NEXT SLIDE, PLEASE. 115 00:04:30,760 --> 00:04:32,080 SO WHY DOES THAT MATTER, WELL IN 116 00:04:32,080 --> 00:04:34,680 THE UNITED STATES ALONE, WE HAVE 117 00:04:34,680 --> 00:04:35,920 APPROXIMATELY 7 MILLION 118 00:04:35,920 --> 00:04:37,560 INDIVIDUALS WITH SOME TYPE OF 119 00:04:37,560 --> 00:04:38,520 IMMUNE O COMPROMISE, AND WHILE 120 00:04:38,520 --> 00:04:40,920 ALL OF THE CONDITIONS YOU SEE ON 121 00:04:40,920 --> 00:04:43,480 THIS SLIDE TODAY ARE ASSOCIATED 122 00:04:43,480 --> 00:04:47,280 TO SOME DEGREE WITH PROLONGED 123 00:04:47,280 --> 00:04:48,000 INFECTION WITH SARS-COV-2, THE 124 00:04:48,000 --> 00:04:52,440 PATIENTS IN WHICH WE REALLY SEE 125 00:04:52,440 --> 00:04:53,640 THE VERY PROLONGED REPRUITT 126 00:04:53,640 --> 00:04:55,360 DESSENT TYPES OF INFECTIONS ARE 127 00:04:55,360 --> 00:04:57,480 THOSE WHO HAVE SEVERE B-CELL 128 00:04:57,480 --> 00:04:59,920 DEPLETION, USUALLY WITH SOME 129 00:04:59,920 --> 00:05:02,200 T-CELL COMPROMISE AS WELL. 130 00:05:02,200 --> 00:05:04,320 SO THAT CAN BE BECAUSE OF 131 00:05:04,320 --> 00:05:07,160 UNDERLYING HEMEAT O LOGIC 132 00:05:07,160 --> 00:05:13,520 MALIGNANCIES OR FROM 133 00:05:13,520 --> 00:05:15,280 LYMPHO-DEPLETION, SO TODAY WE 134 00:05:15,280 --> 00:05:17,440 WILL FOCUS ON DURATION OF 135 00:05:17,440 --> 00:05:18,280 INFECTION, IT'S IMPORTANT TO 136 00:05:18,280 --> 00:05:19,320 POINT OUT THAT THE ISSUES WE ARE 137 00:05:19,320 --> 00:05:21,120 GOING TO BRING UP TODAY AND THE 138 00:05:21,120 --> 00:05:23,080 CONCERNS ABOUT VIRAL EVOLUTION 139 00:05:23,080 --> 00:05:27,960 CAN BE APPLIED TO ANY INDIVIDUAL 140 00:05:27,960 --> 00:05:29,800 WITH IMPAIRED IMMUNITY. 141 00:05:29,800 --> 00:05:30,640 NEXT SLIDE, PLEASE. 142 00:05:30,640 --> 00:05:34,240 SO WHILE THIS COMES WITH MEDICAL 143 00:05:34,240 --> 00:05:37,280 CONCERNS, IT ALSO BRINGS PUBLIC 144 00:05:37,280 --> 00:05:37,880 HEALTH CONCERNS. 145 00:05:37,880 --> 00:05:40,240 BECAUSE IT RAISES THE QUESTION 146 00:05:40,240 --> 00:05:42,480 COULD PATIENTS WITH IMMUNE O 147 00:05:42,480 --> 00:05:45,040 SUPPRESSION WHO HAVE PERSISTENT 148 00:05:45,040 --> 00:05:48,120 OR PROLONGED INFECTION BE 149 00:05:48,120 --> 00:05:50,080 SERVING A RESERVOIR FOR 150 00:05:50,080 --> 00:05:51,960 MULTIMUTATIONAL VIRUSES THAT MAY 151 00:05:51,960 --> 00:05:53,320 BE ACCUMULATING MORE MUTATIONS 152 00:05:53,320 --> 00:05:55,080 AT A FREQUENCY THAT'S HIGHER 153 00:05:55,080 --> 00:05:57,160 THAN EXPECTED AND COULD THOSE BE 154 00:05:57,160 --> 00:05:58,240 SPILLING OUT INTO THE COMMUNITY. 155 00:05:58,240 --> 00:05:59,960 WE KNOW THAT SOME VARIANTS OF 156 00:05:59,960 --> 00:06:04,680 CONCERN HAVE THESE MUTATIONAL 157 00:06:04,680 --> 00:06:07,120 LEAKS SO THESE SUGGEST AN 158 00:06:07,120 --> 00:06:10,480 EXTENDED OF PERIOD OF HOST 159 00:06:10,480 --> 00:06:12,120 WITHIN WHICH EVOLUTION HAS 160 00:06:12,120 --> 00:06:12,560 OCCURRED. 161 00:06:12,560 --> 00:06:13,400 NEXT SLIDE, PLEASE. 162 00:06:13,400 --> 00:06:15,120 SO THIS TABLE HERE SHOW US US 163 00:06:15,120 --> 00:06:18,640 STUDIES THAT HAVE BEEN PUBLISHED 164 00:06:18,640 --> 00:06:20,640 OF PATIENTS WITH--WHO ARE IMMUNE 165 00:06:20,640 --> 00:06:22,520 O SUPPRESSED WITH A LONG 166 00:06:22,520 --> 00:06:24,640 DURATION OF LONG DURATION OF 167 00:06:24,640 --> 00:06:25,360 ACTIVE SARS-COV-2 INFECTION AND 168 00:06:25,360 --> 00:06:27,560 YOU CAN SEE THAT MOST OF THEM 169 00:06:27,560 --> 00:06:31,760 WHAT THEY HAVE IN COMMON IS 170 00:06:31,760 --> 00:06:33,720 SEVERE B-CELL IMPAIRMENT EITHER 171 00:06:33,720 --> 00:06:43,320 FROM A MEDICATION LIKE 172 00:06:43,320 --> 00:06:45,080 RETUXIMAB, OR A SETTING THR 173 00:06:45,080 --> 00:06:47,320 THERAPY FOR A HEMEAT O LOGIC 174 00:06:47,320 --> 00:06:49,760 MALIGNANCY, ALTHOUGH WE ARE 175 00:06:49,760 --> 00:06:50,720 SEEING REPORTS NOW COME NOTHING 176 00:06:50,720 --> 00:06:52,480 THE LITERATURE OF PATIENTS WITH 177 00:06:52,480 --> 00:06:55,080 UNCONTROLLED HIV FOR EXAMPLE, 178 00:06:55,080 --> 00:07:07,160 HAVING PROLONGED INFECTION AS 179 00:07:07,160 --> 00:07:07,480 WELL. 180 00:07:07,480 --> 00:07:08,560 SOMETIMES THEY'RE IN THE 181 00:07:08,560 --> 00:07:10,000 HOSPITAL THE ENTIRE TIME, 182 00:07:10,000 --> 00:07:11,360 SOMETIMES THEY GET BETTER WITH 183 00:07:11,360 --> 00:07:16,920 THE THERAPIES WE GIVE THEM ONLY 184 00:07:16,920 --> 00:07:17,880 TO REPRUITT DESAND REPRESENT. 185 00:07:17,880 --> 00:07:19,960 SO SOME OF THESE REQUIRE SOME 186 00:07:19,960 --> 00:07:22,360 KIND OF FREQUENT INTERVENTION TO 187 00:07:22,360 --> 00:07:22,880 GET THEM BETTER. 188 00:07:22,880 --> 00:07:26,080 AND SO YOU CAN IMAGINE THAT AN 189 00:07:26,080 --> 00:07:28,480 INFECTION THAT GOES ON FOR THAT 190 00:07:28,480 --> 00:07:31,200 LONG GIVES THE VIRUS AMPLE 191 00:07:31,200 --> 00:07:32,080 OPPORTUNITY TO MUTATE AND IN 192 00:07:32,080 --> 00:07:36,960 FACT, ALL OF THESE CASES REPORT 193 00:07:36,960 --> 00:07:39,600 MUTATIONS IN THE RECEPTOR 194 00:07:39,600 --> 00:07:41,840 BINDING DOMAIN, THE PRIME TARGET 195 00:07:41,840 --> 00:07:43,080 OF THE PROTECTIVE ANTIBODY 196 00:07:43,080 --> 00:07:45,720 RESPONSE AND IMPORTANT FOR VIRAL 197 00:07:45,720 --> 00:07:45,960 ENTRY. 198 00:07:45,960 --> 00:07:50,640 IN ADDITION MANY PATIENTS ARE 199 00:07:50,640 --> 00:07:52,720 ALSO TREATED WITH CONVALESCENT 200 00:07:52,720 --> 00:07:55,200 PLASMA OR ANTIBODIES AND 201 00:07:55,200 --> 00:07:56,360 CONVALESCENT PLASMA IS 202 00:07:56,360 --> 00:07:58,280 RECOMMENDEDDER ON USED ROUTINELY 203 00:07:58,280 --> 00:08:00,440 IN NONIMMUNE O SUPPRESSED 204 00:08:00,440 --> 00:08:01,000 PATIENTS. 205 00:08:01,000 --> 00:08:02,920 BUT, WE DO HAVE EVIDENCE THAT IN 206 00:08:02,920 --> 00:08:04,120 PATIENTS WHO ARE IMMUNE O 207 00:08:04,120 --> 00:08:05,080 SUPPRESSED SPECIFICALLY THOSE 208 00:08:05,080 --> 00:08:09,480 WITH HEMEAT O LOGIC MALIGNANCIES 209 00:08:09,480 --> 00:08:10,920 CONVALESCENT PLASMA CAN LEAD TO 210 00:08:10,920 --> 00:08:11,880 BETTER OUTCOMES AND SO EVENT 211 00:08:11,880 --> 00:08:13,480 THOUGH IT'S NOT USED ROUTINELY 212 00:08:13,480 --> 00:08:18,800 IN THE COMMUNITY, MANY CENTERS 213 00:08:18,800 --> 00:08:20,680 ARE STILL USING THESE TO TREAT 214 00:08:20,680 --> 00:08:22,120 THESE VERY DIFFICULT CASES. 215 00:08:22,120 --> 00:08:22,640 NEXT SLIDE, PLEASE. 216 00:08:22,640 --> 00:08:25,360 SO THIS FIGURE SHOWS US SEQUENCE 217 00:08:25,360 --> 00:08:26,200 POLYMORPHISMS OVER TIME IN A 218 00:08:26,200 --> 00:08:28,560 PATIENT WITH A VERY PROLONGED 219 00:08:28,560 --> 00:08:29,480 INFECTION OF 152 DAYS. 220 00:08:29,480 --> 00:08:36,480 SO THIS IS A PEASHT WHO'S HAD A 221 00:08:36,480 --> 00:08:43,160 SEVERE ANTILIPID 222 00:08:43,160 --> 00:08:44,840 PHOSPHO-INFECTION, THIS PATIENT 223 00:08:44,840 --> 00:08:47,280 REQUIRED MANY ROUNDS OF 224 00:08:47,280 --> 00:08:49,120 REMDESIVIR AND EVENTUALLY AROUND 225 00:08:49,120 --> 00:08:50,880 DAY 140 WAS GIVEN MONOCLONAL 226 00:08:50,880 --> 00:08:52,400 ANTIBODY AS WELL TO HELP HIM TRY 227 00:08:52,400 --> 00:08:56,600 TO CLEAR THE VIRUS AND WHAT YOU 228 00:08:56,600 --> 00:08:59,480 CAN SEE IS THAT AT THE LAST TIME 229 00:08:59,480 --> 00:09:01,800 POINT AT DAY 152 WE SEE THE 230 00:09:01,800 --> 00:09:02,880 EMERNLG ENSEL OF MUTATIONS THAT 231 00:09:02,880 --> 00:09:04,280 YOU CAN SEE HERE IN RED THAT 232 00:09:04,280 --> 00:09:05,960 HAVE BEEN REPORT INDEED A 233 00:09:05,960 --> 00:09:14,480 VARIANCE OF CONCERN PREVIOUSLY. 234 00:09:14,480 --> 00:09:14,960 NEXT SLIDE, PLEASE. 235 00:09:14,960 --> 00:09:16,640 THIS FIGURE ALSO SHOWS US 236 00:09:16,640 --> 00:09:18,360 MUTATIONS THAT OCCUR IN THE 237 00:09:18,360 --> 00:09:19,880 VIRUS IN A PATIENT INFECTED OVER 238 00:09:19,880 --> 00:09:20,680 TIME. 239 00:09:20,680 --> 00:09:22,240 THIS PATIENT HAD SARS-COV-2 240 00:09:22,240 --> 00:09:23,200 INFECTION FOR OVER A YEAR. 241 00:09:23,200 --> 00:09:27,200 THIS WAS A PATIENT WHO HAD 242 00:09:27,200 --> 00:09:29,400 UNDERGONE HEMATOPOIETIC STEM 243 00:09:29,400 --> 00:09:30,080 CELL TRANSPLANTATION 6 MONTHS 244 00:09:30,080 --> 00:09:32,960 PRIOR TO INFECTION AND HE 245 00:09:32,960 --> 00:09:35,960 RECEIVED RETUX MAB AT THE SAME 246 00:09:35,960 --> 00:09:38,640 TIME FOR ACTIVATION SO THIS 247 00:09:38,640 --> 00:09:40,800 PATIENT PROLONGED COURSE 248 00:09:40,800 --> 00:09:42,640 RECEIVED CONVALESCENT PLASMA 249 00:09:42,640 --> 00:09:44,600 MULTIPLE TIMES THROUGHOUT HIS 250 00:09:44,600 --> 00:09:46,520 INFECTION WITH THE SECOND 1 251 00:09:46,520 --> 00:09:48,040 OCCURRING HERE AROUND DAY 200 252 00:09:48,040 --> 00:09:49,360 AND THEN BECAUSE HE DIDN'T 253 00:09:49,360 --> 00:09:51,000 IMPROVE, HE WAS ALSO GIVEN 254 00:09:51,000 --> 00:09:53,680 MONOCLONAL ANTIBODY AT THE END 255 00:09:53,680 --> 00:09:55,120 OF HIS INFECTION. 256 00:09:55,120 --> 00:09:56,200 AND WHAT YOU ARE SUPPOSED TO BE 257 00:09:56,200 --> 00:09:57,400 SEEING ON THE SLIDE, I'M NOT 258 00:09:57,400 --> 00:09:59,440 SURE IF YOU CAN SEE IT, I'M NOT 259 00:09:59,440 --> 00:10:00,200 SEEING IT ON MINE BUT WHAT YOU 260 00:10:00,200 --> 00:10:03,040 SLEEP APNEA AND OBESITYY IN 261 00:10:03,040 --> 00:10:06,760 THE--WITH THE BLUE LINE HERE IS 262 00:10:06,760 --> 00:10:08,600 THAT THE EMERGENCE OF A MUTATION 263 00:10:08,600 --> 00:10:10,240 AGAIN THAT'S BEEN ASSOCIATE WIDE 264 00:10:10,240 --> 00:10:11,400 VARIANTS OF CONCERN IN THE PAST 265 00:10:11,400 --> 00:10:17,680 AND BY THE END OF HIS INFECTION, 266 00:10:17,680 --> 00:10:20,720 A HUNDRED PERCENT OF HIS VIRAL 267 00:10:20,720 --> 00:10:21,280 MUTATION SAW THIS HAPPEN. 268 00:10:21,280 --> 00:10:22,800 SO AGAIN SEEING THIS HAPPEN OVER 269 00:10:22,800 --> 00:10:24,560 A LONG PERIOD OF TIME IN A 270 00:10:24,560 --> 00:10:25,360 PATIENT WITH INFECTION. 271 00:10:25,360 --> 00:10:25,880 NEXT SLIDE, PLEASE. 272 00:10:25,880 --> 00:10:28,400 SO WHAT I WOULD LIKE TO SHARE 273 00:10:28,400 --> 00:10:32,640 WITH YOU NOW IS A CASE THAT I 274 00:10:32,640 --> 00:10:35,800 CAN AND ALLISON RODER, A 275 00:10:35,800 --> 00:10:37,960 COMPUTATION BIOLOGIST IN 276 00:10:37,960 --> 00:10:40,680 ELODIE'S LAB PUBLISH INDEED THE 277 00:10:40,680 --> 00:10:41,360 JOURNAL OF INFECTIOUS DISEASES 278 00:10:41,360 --> 00:10:44,320 AND THIS IS THE CASE OF A NEARLY 279 00:10:44,320 --> 00:10:45,080 YEAR LONG COVID-19 INFECTION IN 280 00:10:45,080 --> 00:10:46,880 A PATIENT WHO WAS TREATED HERE 281 00:10:46,880 --> 00:10:48,400 AT THE NIH CLINICAL CENTER. 282 00:10:48,400 --> 00:10:53,840 AND IN WHOM WE ALSO FOUND 283 00:10:53,840 --> 00:10:56,320 IN-HOST EVOLUTION OF SARS-COV-2. 284 00:10:56,320 --> 00:10:56,880 NEXT SLIDE, PLEASE. 285 00:10:56,880 --> 00:10:58,640 SO THIS IS A 48 YEAR-OLD WOMAN 286 00:10:58,640 --> 00:11:01,280 WITH A HISTORY OF DIFFUSE LARGE 287 00:11:01,280 --> 00:11:05,120 B-CELL EMILY POEM FOAMA AND SHE 288 00:11:05,120 --> 00:11:06,120 WAS--B-CELL LYMPHOMA AND SHE WAS 289 00:11:06,120 --> 00:11:08,600 TREATED WITH THE CAR-T CELL 290 00:11:08,600 --> 00:11:12,360 THERAPY AND AS A RESULT SHE HAD 291 00:11:12,360 --> 00:11:15,720 ONGOING DISPLACIA, CD4 T-CELL 292 00:11:15,720 --> 00:11:16,760 LYMPHPENIA AND INCREASED 293 00:11:16,760 --> 00:11:17,400 RESPIRATORY INFECTIONS BECAUSE 294 00:11:17,400 --> 00:11:17,800 OF THAT. 295 00:11:17,800 --> 00:11:20,280 THIS WAS 1 OF THE FIRST PATIENTS 296 00:11:20,280 --> 00:11:21,960 THAT ADMITTED HERE AT THE 297 00:11:21,960 --> 00:11:23,200 CLINICAL CENTER WITH COVID-19. 298 00:11:23,200 --> 00:11:24,720 SHE WAS 1 OF OUR FIRST PATIENTS 299 00:11:24,720 --> 00:11:27,160 THAT WE TOOK CARE OF AND SHE 300 00:11:27,160 --> 00:11:29,120 REPRESENTED TO UTION ON 301 00:11:29,120 --> 00:11:30,240 APRIL 27th, 2020 WITH AN 11 302 00:11:30,240 --> 00:11:32,440 DAY HISTORY OF FEVER, HEADACHE, 303 00:11:32,440 --> 00:11:34,480 CONGESTION, COUGH AND RIGHT 304 00:11:34,480 --> 00:11:39,960 AWAY, SARS-KICKOFF 2 WAS 305 00:11:39,960 --> 00:11:40,680 SUSPECTED. 306 00:11:40,680 --> 00:11:45,120 HOWEVER, SHE TESTED NEGATIVE ON 307 00:11:45,120 --> 00:11:46,400 NAIS O-PHARYNGIAL SWAB PRIOR TO 308 00:11:46,400 --> 00:11:49,480 ADMISSION AND THEN TWICE AFTER 309 00:11:49,480 --> 00:11:49,720 ADMISSION. 310 00:11:49,720 --> 00:11:51,480 ON ADMISSION SHE REQUIRED 311 00:11:51,480 --> 00:11:52,880 SUPPLEMENTAL OXYGEN AND DESPITE 312 00:11:52,880 --> 00:11:55,240 TREATMENT WITH BROAD SPECTRUM 313 00:11:55,240 --> 00:11:57,520 ANTIBIOTICS, HER SYMPTOMS 314 00:11:57,520 --> 00:11:59,800 CONTINUED TO WORSEN AND SHE 315 00:11:59,800 --> 00:12:01,440 WIRED MORE OXYGEN. 316 00:12:01,440 --> 00:12:05,160 SO ON MAY FIRST A BRANCHIAL 317 00:12:05,160 --> 00:12:06,720 LAVAGE WAS PERFORMED MEANING 318 00:12:06,720 --> 00:12:17,680 DEEP LUNG SPECIMENS WERE 319 00:12:17,680 --> 00:12:17,920 OBTAINED. 320 00:12:17,920 --> 00:12:19,440 AND AGAIN THIS WAS WAY AT THE 321 00:12:19,440 --> 00:12:21,240 BEGINNING OF THE PANDEMIC AND WE 322 00:12:21,240 --> 00:12:22,280 DID NOT HAVE REMDESIVIR 323 00:12:22,280 --> 00:12:24,680 AVAILABLE TO US TO TREAT HER. 324 00:12:24,680 --> 00:12:27,480 WE ALSO DID NOT HAVE ROBUST 325 00:12:27,480 --> 00:12:29,000 CLINICAL TRIAL DATA SURROUNDING 326 00:12:29,000 --> 00:12:34,400 THE USE OF CORTICOSTEROIDS FOR 327 00:12:34,400 --> 00:12:35,440 ACUTE COVID-19 INFECTIONS SO 328 00:12:35,440 --> 00:12:38,120 NEITHER OF THOSE AGENTS WERE 329 00:12:38,120 --> 00:12:39,240 ADMINISTEREDDA THE TIME. 330 00:12:39,240 --> 00:12:41,080 SO SHE WAS HOSPITALIZED HERE FOR 331 00:12:41,080 --> 00:12:44,720 1 MONTH ANDURE DIDDING THAT 332 00:12:44,720 --> 00:12:46,080 MONTH WE OBTAINED ORAL SWAP 333 00:12:46,080 --> 00:12:48,480 SWABS TO TEST FOR SARS-COV-2, 334 00:12:48,480 --> 00:12:49,880 YOU CAN SEE WITH VIRAL LOADS 335 00:12:49,880 --> 00:12:52,280 HERE WITH THE PURPLE CIRCLE, SHE 336 00:12:52,280 --> 00:12:53,840 WAS POSITIVE THE ENTIRE TIME. 337 00:12:53,840 --> 00:12:55,880 SO AFTER A MONTH, BECAUSE WE 338 00:12:55,880 --> 00:12:57,360 RECOGNIZE THAT JUST LIKE WITH 339 00:12:57,360 --> 00:12:59,560 OTHER INFECT YOWZ DECEASES, THAT 340 00:12:59,560 --> 00:13:01,680 AS AN IMMUNE O COMPROMISED 341 00:13:01,680 --> 00:13:03,920 PATIENT, SHE MAY NOT RECOVER AS 342 00:13:03,920 --> 00:13:04,440 QUICKLY AS RECALLINGS. 343 00:13:04,440 --> 00:13:07,320 WE SENT HER HOME WITH A PLAN FOR 344 00:13:07,320 --> 00:13:09,080 HER TO CONVALESCE AT HOME AND TO 345 00:13:09,080 --> 00:13:13,840 GET BETTER. 346 00:13:13,840 --> 00:13:14,280 NEXT SLIDE, PLEASE. 347 00:13:14,280 --> 00:13:17,080 SO FROM THE PERIOD OF TIME WHEN 348 00:13:17,080 --> 00:13:19,680 SHE WENT HOME UNTIL 349 00:13:19,680 --> 00:13:20,560 DECEMBER 2020, SO FOR SEVERAL 350 00:13:20,560 --> 00:13:22,280 MONTHS SHE CONTINUED TO HAVE 351 00:13:22,280 --> 00:13:23,640 WAXING AND WANING SYMPTOMS. 352 00:13:23,640 --> 00:13:26,240 SHE HAD A PERSISTENT COUGH, 353 00:13:26,240 --> 00:13:28,120 STILL SHORT OF BREATH BUT SHE 354 00:13:28,120 --> 00:13:30,480 WOULD TELL US THIS WOULD GET 355 00:13:30,480 --> 00:13:32,080 MUCH, MUCH, BETTER ONLY TO GET 356 00:13:32,080 --> 00:13:33,840 WORSE A FEW WEEKS LATER. 357 00:13:33,840 --> 00:13:36,840 SHE ALSO HAD WAXING AND--SHE HAD 358 00:13:36,840 --> 00:13:37,760 INTERMITTENT LOW GRADE FEVERS AS 359 00:13:37,760 --> 00:13:38,400 WELL. 360 00:13:38,400 --> 00:13:40,600 SO ALL OF THOSE SYMPTOMS WERE 361 00:13:40,600 --> 00:13:43,280 STILL PRESENT BUT WAXING AND 362 00:13:43,280 --> 00:13:45,560 WANING AND SHE ALSO HAD A 363 00:13:45,560 --> 00:13:46,480 PERSISTENT OXYGEN REQUIREMENT SO 364 00:13:46,480 --> 00:13:48,080 CLEARLY SOMETHING WAS GOING ON 365 00:13:48,080 --> 00:13:48,640 IN HER LUNGS. 366 00:13:48,640 --> 00:13:53,600 DURING THAT PERIOD OF TIME, WE 367 00:13:53,600 --> 00:13:56,800 ALSO OBTAINED NAIS O PHARYNGIAL 368 00:13:56,800 --> 00:13:59,680 SWABS THAT WERE EITHER NEGATIVE 369 00:13:59,680 --> 00:14:01,960 PC Rs FOR SARS-COV-2 OR HAD 370 00:14:01,960 --> 00:14:03,880 VERY LOW VIRAL LOADS. 371 00:14:03,880 --> 00:14:06,880 AND SO AT THAT POINT BECAUSE OF 372 00:14:06,880 --> 00:14:10,480 HER OVERALL MILD SYMPTOMATOLOGY 373 00:14:10,480 --> 00:14:12,840 AND LOW VIRAL LOADS, THESE 374 00:14:12,840 --> 00:14:14,280 POSITIVE PC Rs WERE THOUGHT TO 375 00:14:14,280 --> 00:14:18,040 BE MOST LIKELY DUE TO SHUTTING 376 00:14:18,040 --> 00:14:22,960 OF NONVIABLE VIRAL PARTICLES 377 00:14:22,960 --> 00:14:25,160 WHICH WAS ALREADY RECOGNIZED TO 378 00:14:25,160 --> 00:14:26,800 HAPPEN IN BOTH IMMUNE O 379 00:14:26,800 --> 00:14:28,320 COMPROMISED AND NONIMMUNE O 380 00:14:28,320 --> 00:14:31,240 COMPROMISED INDIVIDUALS. 381 00:14:31,240 --> 00:14:31,760 NEXT SLIDE, PLEASE. 382 00:14:31,760 --> 00:14:34,440 SO WHAT YOU CAN SEE HERE ARE THE 383 00:14:34,440 --> 00:14:36,080 PATIENT CT SCANS. 384 00:14:36,080 --> 00:14:40,640 SO, ON YOUR LEFT THIS IS THE CT 385 00:14:40,640 --> 00:14:42,360 SCAN FROM APRIL 2020 SO THIS IS 386 00:14:42,360 --> 00:14:44,240 WHEN SHE RESENTED TO US. 387 00:14:44,240 --> 00:14:45,520 SO IMAGINE THE PATIENT IS LYING 388 00:14:45,520 --> 00:14:47,720 ON A TABLE WITH HER HEAD BEHIND 389 00:14:47,720 --> 00:14:49,080 THIS IMAGE, SHE'S LYING ON HER 390 00:14:49,080 --> 00:14:50,680 BACK WITH THE HEAD BEHIND THIS 391 00:14:50,680 --> 00:14:52,840 IMAGE AND WE ARE STANDING AT HER 392 00:14:52,840 --> 00:14:54,600 FEET AND THIS IS A CROSS SECTION 393 00:14:54,600 --> 00:14:55,160 OF HER CHEST. 394 00:14:55,160 --> 00:14:56,480 SO IN THE MIDDLE IS HER HEART 395 00:14:56,480 --> 00:14:58,440 AND ON BOTH SIDES ARE HER LUNGS 396 00:14:58,440 --> 00:15:00,680 AND WHAT THE BLUE ARROWS ARE 397 00:15:00,680 --> 00:15:04,280 SHOWING YOU ARE THESE KIND OF 398 00:15:04,280 --> 00:15:06,480 ROUND IRREGULAR KIND OF WHAT WE 399 00:15:06,480 --> 00:15:08,680 WOULD CALL FLUFFY INFILTRATES 400 00:15:08,680 --> 00:15:11,280 THAT REPRESENT COVID-19 401 00:15:11,280 --> 00:15:11,680 PNEUMONIA. 402 00:15:11,680 --> 00:15:14,960 ON THE RIGHT IS HER CT SCAN FROM 403 00:15:14,960 --> 00:15:15,280 DECEMBER 2020. 404 00:15:15,280 --> 00:15:19,520 AND I'M NOT SHOWING YOU THE SAME 405 00:15:19,520 --> 00:15:21,360 CUT IN HER CHEST BUT YOU CAN 406 00:15:21,360 --> 00:15:23,120 PROBABLY APPRECIATE THAT THE 407 00:15:23,120 --> 00:15:25,840 INFILTRATE NOW THAT'S IN THE 408 00:15:25,840 --> 00:15:28,240 CIRCLE LOOKING DIFFERENT THAN 409 00:15:28,240 --> 00:15:30,000 THE 1 FROM 2020. 410 00:15:30,000 --> 00:15:31,360 SO THESE CHANGES HERE ARE 411 00:15:31,360 --> 00:15:33,640 CONSIST WENT SOMETHING CALLED 412 00:15:33,640 --> 00:15:35,360 ORGANIZING PNEUMONIA, AND 413 00:15:35,360 --> 00:15:36,680 ORGANIZING PNEUMONIA IS AN 414 00:15:36,680 --> 00:15:38,680 INTERSTITIAL LUNG DISEASE THAT 415 00:15:38,680 --> 00:15:39,920 ESSENTIALLY REPRESENTS THE LUNG 416 00:15:39,920 --> 00:15:42,240 TRYING TO HEAL ITSELF, SO IT'S 417 00:15:42,240 --> 00:15:43,680 AN IMMUNE DRIVEN PROCESS AND WE 418 00:15:43,680 --> 00:15:46,680 SEE THIS IN DIFFERENT CLINICAL 419 00:15:46,680 --> 00:15:48,560 SCENARIOS, INCLUDING AFTER 420 00:15:48,560 --> 00:15:50,480 SARS-COV-2 INFECTION. 421 00:15:50,480 --> 00:15:53,280 AND THIS TYPE OF--SO ORGANIZING 422 00:15:53,280 --> 00:15:56,080 PNEUMONIA IS TREATED WITH 423 00:15:56,080 --> 00:15:56,360 STEROIDS. 424 00:15:56,360 --> 00:15:57,680 SO THIS WAS BROUGHT UP AS 425 00:15:57,680 --> 00:16:01,440 PERHAPS A CAUSE OF OUR PATIENTS 426 00:16:01,440 --> 00:16:01,920 ONGOING SYMPTOMS. 427 00:16:01,920 --> 00:16:03,320 NOW BEFORE TREATING HER WITH 428 00:16:03,320 --> 00:16:06,880 STEROIDS, WE DID WANT TO MAKE 429 00:16:06,880 --> 00:16:09,120 SURE THAT SHE ESPECIALLY AS AN 430 00:16:09,120 --> 00:16:10,760 IMMUNE O COMPROMISE TD HOST DID 431 00:16:10,760 --> 00:16:12,080 NOT HAVE ANY OTHER INFECTIONS WE 432 00:16:12,080 --> 00:16:14,080 HAD TO WORRY ABOUT BEFORE GIVING 433 00:16:14,080 --> 00:16:15,040 HER STEROIDS. 434 00:16:15,040 --> 00:16:19,480 NOW THE PATIENT DECLINED ANOTHER 435 00:16:19,480 --> 00:16:20,400 BRANCHIAL ALVEOLAR LAVAGE BUT WE 436 00:16:20,400 --> 00:16:22,880 WERE ABLE TO GET INDUCED SPUTUM 437 00:16:22,880 --> 00:16:25,200 AND THAT WAS NEGATIVE FOR 438 00:16:25,200 --> 00:16:28,680 BACTERIAL OR FUNGAL PATHOGENS. 439 00:16:28,680 --> 00:16:29,200 NEXT SLIDE, PLEASE. 440 00:16:29,200 --> 00:16:33,960 SO THE DECISION WAS MADE TO 441 00:16:33,960 --> 00:16:34,680 TREAT WITH PREDNISONE, BECAUSE 442 00:16:34,680 --> 00:16:36,280 WE THOUGHT WE WOULD IMPROVE HER 443 00:16:36,280 --> 00:16:40,880 SYMPTOMS AND GET BETTER AND SO 444 00:16:40,880 --> 00:16:43,680 ON DECEMBER DAY 242 PREDNISONE 445 00:16:43,680 --> 00:16:45,560 WAS STARTED AND THAT WAS WITH A 446 00:16:45,560 --> 00:16:47,800 MILD IMPROVEMENT IN SYMPTOMS, 447 00:16:47,800 --> 00:16:49,800 VERY MILD IMPROVEMENT IN HER CT 448 00:16:49,800 --> 00:16:51,000 SCAN. 449 00:16:51,000 --> 00:16:53,200 NEXT SLIDE, PLEASE. 450 00:16:53,200 --> 00:16:54,480 BUT ON DAY 284, WE WERE TIPPED 451 00:16:54,480 --> 00:16:57,360 OFF THAT SOMETHING WAS NOT RIGHT 452 00:16:57,360 --> 00:17:02,640 BECAUSE WE OBTAINED ANOTHER 453 00:17:02,640 --> 00:17:04,320 NASO-PHARYNGIAL SWAB AND THAT 1 454 00:17:04,320 --> 00:17:06,520 HAD A VIRAL LOAD THAT WAS MUCH 455 00:17:06,520 --> 00:17:07,880 HIGHER THAN THE 1S SHE HAD 456 00:17:07,880 --> 00:17:08,880 PREVIOUSLY AND THAT TIPPED US 457 00:17:08,880 --> 00:17:10,160 OFF THAT SOMETHING WAS NOT RIGHT 458 00:17:10,160 --> 00:17:11,760 ESPECIALLY IN THE SETTING OF 459 00:17:11,760 --> 00:17:13,880 HAVING STARTED THE STEROIDS. 460 00:17:13,880 --> 00:17:26,960 SO THEN WE STARTED ASKING 461 00:17:26,960 --> 00:17:28,920 OURSELVES THE QUESTION:--AND SHE 462 00:17:28,920 --> 00:17:30,920 REQUIRED A LOT MORE OXYGEN SO WE 463 00:17:30,920 --> 00:17:32,680 BROUGHT HER INTO THE HOSPITAL. 464 00:17:32,680 --> 00:17:34,800 WE TREATED HER WITH CONVALESCENT 465 00:17:34,800 --> 00:17:38,560 PLASMA, THIS TIME WE DID GIVE 466 00:17:38,560 --> 00:17:41,280 HER REMDESIVIR FOR 10 DAYS, AND 467 00:17:41,280 --> 00:17:44,000 WE STARTED WEANING HER STEROIDS. 468 00:17:44,000 --> 00:17:45,920 AND HER SYMPTOMS GOT BETTER, SO 469 00:17:45,920 --> 00:17:48,480 HER COUGH GOT BETTER HER 470 00:17:48,480 --> 00:17:50,000 SHORTNESS OF BREATH GOT BETTER 471 00:17:50,000 --> 00:17:53,760 AND ABOUT 3 WEEKS LATER, ON DAY 472 00:17:53,760 --> 00:17:57,080 334 SHE CLEARED THE VIRUS. 473 00:17:57,080 --> 00:17:59,160 AND AND IN ADDITION, YOU KNOW WE 474 00:17:59,160 --> 00:18:01,000 SAW THAT HER INFLAMMATORY 475 00:18:01,000 --> 00:18:02,400 MARKERS HAD GOTTEN BETTER AND 476 00:18:02,400 --> 00:18:06,320 THAT HER CT SCAN WAS IMPROVING. 477 00:18:06,320 --> 00:18:10,000 SO THANKFULLY A HAPPY ENDING 478 00:18:10,000 --> 00:18:11,200 HERE. 479 00:18:11,200 --> 00:18:12,920 NEXT SLIDE PLEASE. 480 00:18:12,920 --> 00:18:14,000 BUT AGAIN, THIS CASE REALLY 481 00:18:14,000 --> 00:18:16,000 BROUGHT UP A LOT OF QUESTIONS IN 482 00:18:16,000 --> 00:18:17,200 OUR MINDS ABOUT, YOU KNOW WHAT 483 00:18:17,200 --> 00:18:20,840 HAD GONE ON THIS ENTIRE TIME IS 484 00:18:20,840 --> 00:18:22,400 QUITE A LEARNING CASE AND YOU 485 00:18:22,400 --> 00:18:24,800 KNOW THE MAIN QUESTION THAT WE 486 00:18:24,800 --> 00:18:32,600 REALLY HAD WAS HAD WE 487 00:18:32,600 --> 00:18:34,680 RECRUDESCED, THIS UNDER LYING 488 00:18:34,680 --> 00:18:36,480 YEAR LONG SARS-COV-2 INFECTION 489 00:18:36,480 --> 00:18:42,080 OR MAYBE THAL PATIENT BEEN 490 00:18:42,080 --> 00:18:43,880 EXPOSED TO COVID-19, AND COULD 491 00:18:43,880 --> 00:18:47,000 SHE BEEN EXPOSED ABOUT, SHE LIVE 492 00:18:47,000 --> 00:18:47,920 INDEED A MULTIGENERATIONAL 493 00:18:47,920 --> 00:18:49,280 HOUSE, AND WOE SOPHISTICATEDY WE 494 00:18:49,280 --> 00:18:51,480 APPROACHED HER AND WE TOOK VIRAL 495 00:18:51,480 --> 00:18:53,080 ISOLATES FROM THE BEGINNING OF 496 00:18:53,080 --> 00:18:54,640 THE INFECTION AND THE END OF HER 497 00:18:54,640 --> 00:18:55,480 INFECTION AND THEY WERE 498 00:18:55,480 --> 00:18:57,120 SEQUENCED AND WITH THAT I WILL 499 00:18:57,120 --> 00:19:04,920 PASS THE MIC TO ELODIE. 500 00:19:04,920 --> 00:19:05,480 >> THANK YOU, VERONIQUE. 501 00:19:05,480 --> 00:19:07,360 SO THAT WAS THE MAIN QUESTION 502 00:19:07,360 --> 00:19:09,120 SHE HAD WHEN THIS CASE HAPPENED. 503 00:19:09,120 --> 00:19:11,840 WAS IT THE SAME VIRUS OR WAS IT 504 00:19:11,840 --> 00:19:12,280 A REINFECTION? 505 00:19:12,280 --> 00:19:16,680 AND SO WHAT YOU SEE HERE IS A 506 00:19:16,680 --> 00:19:18,640 PHILOGENETIC TREE, A CIRCULAR N 507 00:19:18,640 --> 00:19:23,360 TREE AND WE SEQUENCED THE WHOLE 508 00:19:23,360 --> 00:19:24,320 GENOME FROM THESE SAMPLES FROM 509 00:19:24,320 --> 00:19:29,760 EARLY MAY AND THEN FROM 510 00:19:29,760 --> 00:19:31,080 MARCH 2021 AND WHAT WE SAW WAS 511 00:19:31,080 --> 00:19:32,880 THAT ACTUALLY ALL THE SAMPLES 512 00:19:32,880 --> 00:19:33,800 CLUSTERED TOGETHER IN THE TREE 513 00:19:33,800 --> 00:19:37,000 SHOWING THAT THEY'RE ALL RELATED 514 00:19:37,000 --> 00:19:37,480 IN SOME WAY. 515 00:19:37,480 --> 00:19:39,600 WHAT YOU SEE HERE, THIS VERY 516 00:19:39,600 --> 00:19:41,480 LONG BRANCH INDICATES THAT THE 517 00:19:41,480 --> 00:19:42,640 VIRUS HAS EVOLVED OVER THAT 518 00:19:42,640 --> 00:19:46,400 PERIOD OF TIME, BUT IT'S STILL 519 00:19:46,400 --> 00:19:50,640 ALL--THEY ALL BELONG TOGETHER. 520 00:19:50,640 --> 00:19:53,040 THIS LINEAGE WAS BASICALLY AN 521 00:19:53,040 --> 00:19:54,480 OLD LINEAGE WE SAW CIRCULATING 522 00:19:54,480 --> 00:19:59,160 IN 2020 BUT THAT WAS NO LONGER 523 00:19:59,160 --> 00:19:59,880 CIRCULATING IN 2021. 524 00:19:59,880 --> 00:20:03,680 SO THAT FURTHER JUSTIFIED AGAIN 525 00:20:03,680 --> 00:20:04,880 THAT THIS WAS ONCE INFECTION 526 00:20:04,880 --> 00:20:09,000 THAT WAS JUST A LONG, LONG 527 00:20:09,000 --> 00:20:09,280 INFECTION. 528 00:20:09,280 --> 00:20:10,080 THE BUT WHAT WAS MORE 529 00:20:10,080 --> 00:20:12,800 INTERESTING WHEN YOU LOOK AT THE 530 00:20:12,800 --> 00:20:14,680 VIRUS AND THE VIRUS GENOME 531 00:20:14,680 --> 00:20:16,320 INFORMATION IS REALLY WHERE THE 532 00:20:16,320 --> 00:20:18,160 VIRUS EVOLVES AND HOW IT 533 00:20:18,160 --> 00:20:18,480 EVOLVES. 534 00:20:18,480 --> 00:20:22,080 SO THIS IS A REPRESENTATION 535 00:20:22,080 --> 00:20:23,120 ESCHEMA OF THE DIFFERENT GENES 536 00:20:23,120 --> 00:20:25,920 OF THE WHOLE GENOME OF 537 00:20:25,920 --> 00:20:26,240 SARS-COV-2. 538 00:20:26,240 --> 00:20:29,760 THE SPIKE IS RIGHT HERE. 539 00:20:29,760 --> 00:20:33,800 AND BELOW IS JUST A BLOCK WITH 540 00:20:33,800 --> 00:20:35,560 LITTLE COLORED BOXES THAT 541 00:20:35,560 --> 00:20:37,080 INDICATE POSITIONS ALONG THE 542 00:20:37,080 --> 00:20:39,680 GENOME WHERE YOU DO SEE A 543 00:20:39,680 --> 00:20:41,520 MUTATION OCCURRING OVER TIME. 544 00:20:41,520 --> 00:20:43,640 SO EACH ROW REPRESENTS A 545 00:20:43,640 --> 00:20:44,520 DIFFERENT SAMPLE. 546 00:20:44,520 --> 00:20:46,680 AND EACH OF THESE SAMPLES ARE 547 00:20:46,680 --> 00:20:52,680 COMPARED TO THE FIRST 1 TAKEN IN 548 00:20:52,680 --> 00:20:53,760 MAY FIRST 2020. 549 00:20:53,760 --> 00:20:58,320 THAT WAS THE BALL SAMPLE THAT 550 00:20:58,320 --> 00:20:58,960 VERONIQUE MENTIONED. 551 00:20:58,960 --> 00:21:01,840 YOU CAN CAN SEE ACCUMULATIONS 552 00:21:01,840 --> 00:21:02,280 OCCURRING OVER TIME. 553 00:21:02,280 --> 00:21:04,200 NOW IF THIS WAS JUST A VIRUS 554 00:21:04,200 --> 00:21:06,080 CIRCULATING IN THE POPULATION, 555 00:21:06,080 --> 00:21:08,200 YOU WOULD EXPECT TO SEE 556 00:21:08,200 --> 00:21:10,240 MUTATIONS OVER THIS 335 DAYS AND 557 00:21:10,240 --> 00:21:12,560 YOU WOULD EXPECT AN EVOLUTIONARY 558 00:21:12,560 --> 00:21:14,560 RATE OF ABOUT, YOU KNOW 1 559 00:21:14,560 --> 00:21:17,480 MUTATION OCCURRING EVERY 2 WEEKS 560 00:21:17,480 --> 00:21:19,400 WHICH IS A LITTLE WHAT WE WERE 561 00:21:19,400 --> 00:21:21,800 SEEING IN THIS PATIENT BUT THESE 562 00:21:21,800 --> 00:21:22,360 MUTATIONS WERE ACCUMULATING 563 00:21:22,360 --> 00:21:23,760 WITHIN THE HOST BUT WE DID SEE A 564 00:21:23,760 --> 00:21:26,280 LITTLE BIT MORE THAN WE WOULD 565 00:21:26,280 --> 00:21:29,000 HAVE EXPECTED SIMPLY WITH THE 566 00:21:29,000 --> 00:21:29,400 EVOLUTIONARY RATE. 567 00:21:29,400 --> 00:21:31,080 WHAT'S MORE INTERESTING IS WHEN 568 00:21:31,080 --> 00:21:33,680 YOU FOCUS SPECIFICALLY ON THE 569 00:21:33,680 --> 00:21:36,200 TYPES OF MUTATIONS YOU IDENTIFY 570 00:21:36,200 --> 00:21:38,840 AND SO FOR EXAMPLE, IF YOU LOOK 571 00:21:38,840 --> 00:21:40,480 AT THE SPIKE IN ANOTHER REGION 572 00:21:40,480 --> 00:21:45,160 OF THE GENOME, WE SAW 2 573 00:21:45,160 --> 00:21:45,440 DELETIONS. 574 00:21:45,440 --> 00:21:48,280 NOW 1 OF THESE DELETIONS IS WELL 575 00:21:48,280 --> 00:21:49,600 REPORTED AND I'LL GO INTO THAT 576 00:21:49,600 --> 00:21:51,120 IN A MINUTE AND IT'S IN THE 577 00:21:51,120 --> 00:21:54,480 SPIKE PROTEIN BUT ANOTHER 1 THAT 578 00:21:54,480 --> 00:21:55,880 IS QUITE INTERESTING AND THERE 579 00:21:55,880 --> 00:22:00,440 HAVE BEEN OTHER STUDIES PUT IN 580 00:22:00,440 --> 00:22:01,880 IMMUNE O COMPETENT MUTATIONS 581 00:22:01,880 --> 00:22:03,680 WHERE YOU SEE DELETION OF 582 00:22:03,680 --> 00:22:08,880 PORTIONS OF CERTAIN GENES, 67 B 583 00:22:08,880 --> 00:22:11,760 AND ORF8, IN OUR CASE WE SAW 584 00:22:11,760 --> 00:22:18,320 FULL DELETION OF THESE 2 GENES 585 00:22:18,320 --> 00:22:23,680 AND DELETION IS PARTICULARLY 586 00:22:23,680 --> 00:22:25,400 INTERESTING BEFORE AND IMMUNE O 587 00:22:25,400 --> 00:22:26,480 COMPROMISED PATIENTS, THESE 588 00:22:26,480 --> 00:22:42,520 KINDS OF DELETIONS AND I 589 00:22:42,520 --> 00:22:44,400 WILL--DESPITE THIS IN THE REGION 590 00:22:44,400 --> 00:22:45,920 AND DESPITE THE TERMINAL DOMAIN 591 00:22:45,920 --> 00:23:05,480 THAT BINDS TO THE RECEPTOR,--TRY 592 00:23:05,480 --> 00:23:08,600 TO CONTROL THE VIRUS, SO WE 593 00:23:08,600 --> 00:23:13,280 OBSERVE THIS DELETION IN THE 594 00:23:13,280 --> 00:23:13,480 GENOME. 595 00:23:13,480 --> 00:23:16,120 WHAT WAS MORE INTERESTING IS 596 00:23:16,120 --> 00:23:17,760 ACTUALLY THE DYNAMICS OF THIS 597 00:23:17,760 --> 00:23:20,800 MUTATION SO WE ONLY OBSERVE THIS 598 00:23:20,800 --> 00:23:25,480 DELETION WITHIN THE 2 LAST 599 00:23:25,480 --> 00:23:26,720 SAMPLES THIS NUCLEOTIDES GENOME 600 00:23:26,720 --> 00:23:30,840 RECEIVE THE DELETION AND 601 00:23:30,840 --> 00:23:33,760 REPRESENTED HERE BASICALLY A 602 00:23:33,760 --> 00:23:37,320 CLIFF SO WHAT I NOTED HERE IS 603 00:23:37,320 --> 00:23:38,760 ACTUALLY THE READ COVERAGE, AND 604 00:23:38,760 --> 00:23:40,520 IF YOU DON'T KNOW WHAT READ 605 00:23:40,520 --> 00:23:41,840 COVERAGE IS, THIS IS WHAT IT 606 00:23:41,840 --> 00:23:43,680 MEANS SO WHEN YOU SAMPLE 607 00:23:43,680 --> 00:23:45,240 SOMEBODY, THEY DON'T JUST HAVE 1 608 00:23:45,240 --> 00:23:46,760 VIRUS, THEY HAVE A POPULATION OF 609 00:23:46,760 --> 00:23:47,960 VIRUSES AND EACH OF THESE 610 00:23:47,960 --> 00:23:49,120 VIRUSES HAVE A GENOME. 611 00:23:49,120 --> 00:23:52,000 SO WHEN WE BASICALLY BREAK UP 612 00:23:52,000 --> 00:23:54,000 THESE GENOMES, SO THAT WE CAN 613 00:23:54,000 --> 00:23:55,280 DECODE THEM AND SEQUENCE THEM, 614 00:23:55,280 --> 00:23:58,560 WE HAVE THE SEQUENCE READS THAT 615 00:23:58,560 --> 00:23:59,440 WE THEN READ BACK. 616 00:23:59,440 --> 00:24:01,480 SO WHEN YOU HEAR A GENOMICS 617 00:24:01,480 --> 00:24:02,480 PERSON TALKING ABOUT HIGH 618 00:24:02,480 --> 00:24:03,520 COVERAGE OR LOW COVERAGE, THIS 619 00:24:03,520 --> 00:24:05,000 IS WHAT WE MEAN, IT MEANS A 620 00:24:05,000 --> 00:24:07,880 REGION OF THE GENOME THAT IS 621 00:24:07,880 --> 00:24:09,400 VERY WELL REPRESENTED BY A LOT 622 00:24:09,400 --> 00:24:13,120 OF SEQUENCE READS OR A REGION 623 00:24:13,120 --> 00:24:14,520 THAT IS UNDERREPRESENTED BY 624 00:24:14,520 --> 00:24:15,880 SEQUENCE READS, BUT THEN WE 625 00:24:15,880 --> 00:24:17,680 GENERATE WHAT'S CALLED A CONE 626 00:24:17,680 --> 00:24:19,440 CENSUS SEQUENCE, SO GOING OVER 627 00:24:19,440 --> 00:24:22,960 THE WHOLE GENOME, AND EVERY 628 00:24:22,960 --> 00:24:24,560 POSITION, WE TAKE WHAT SEEMS TO 629 00:24:24,560 --> 00:24:26,360 BE THE MOST DOMINANT NUCLEOTIDE 630 00:24:26,360 --> 00:24:29,440 AND YOU GENERATE THIS VIRUS 631 00:24:29,440 --> 00:24:31,200 GENOME, SO WHEN YOU'RE HEAR 632 00:24:31,200 --> 00:24:32,640 ABOUT VIRUS GENOMES THAT ARE 633 00:24:32,640 --> 00:24:34,640 BEING DECODED AND RIGHT NOW IF 634 00:24:34,640 --> 00:24:38,080 PUBLIC DATABASES CLOSE TO 635 00:24:38,080 --> 00:24:39,560 9 MILLION SARS-COV-2 VIRUS 636 00:24:39,560 --> 00:24:42,080 GENOMES, IT'S ALWAYS TALKING 637 00:24:42,080 --> 00:24:43,720 ABOUT A CONSENSUS SEQUENCE BUT 638 00:24:43,720 --> 00:24:47,800 THERE'S INFORMATION IN THESE 639 00:24:47,800 --> 00:24:48,280 UNDERLYING READS. 640 00:24:48,280 --> 00:24:51,200 SO IF WE GO BACK TO OUR REGION 641 00:24:51,200 --> 00:24:54,120 OF THE VIRUS AND HOW IT MUTATED 642 00:24:54,120 --> 00:24:59,200 OVER TIME, WE SEE THAT THAT ORF7 643 00:24:59,200 --> 00:25:01,240 B OR 8 REGION HAS A FEW VIRUSES 644 00:25:01,240 --> 00:25:03,360 STILL IN THE POPULATION OF 645 00:25:03,360 --> 00:25:05,480 VIRUSES THAT HAVE THAT REGION 646 00:25:05,480 --> 00:25:07,360 THAT IS INTACT AND THAT'S WHY 647 00:25:07,360 --> 00:25:09,080 YOU SEE 24 X OR 24 READS THAT 648 00:25:09,080 --> 00:25:11,480 WILL COVER THAT REGION, BUT VERY 649 00:25:11,480 --> 00:25:15,880 QUICKLY WITHIN 1 DAY, THIS 650 00:25:15,880 --> 00:25:17,960 PATIENT LOST ALL THE REGIONS SO 651 00:25:17,960 --> 00:25:20,480 7 B AND ORF8 ARE COMPLETELY 652 00:25:20,480 --> 00:25:22,200 DELETED IN THAT GENOME. 653 00:25:22,200 --> 00:25:26,200 NOW THAT DELETION IS PRETTY 654 00:25:26,200 --> 00:25:28,440 LARGE, CLOSE TO 500 NUCLEOTIDES 655 00:25:28,440 --> 00:25:30,120 AND IT'S IN FACT THE LARGEST 656 00:25:30,120 --> 00:25:32,160 REGION THAT HAS BEEN REPORTED TO 657 00:25:32,160 --> 00:25:32,480 DATE. 658 00:25:32,480 --> 00:25:36,080 NOW WHAT DOES ORF8 OR 7 B DO? 659 00:25:36,080 --> 00:25:37,880 SO ORF8 EXPRESSION IS THOUGHT TO 660 00:25:37,880 --> 00:25:39,960 NOT BE ESSENTIAL FOR 661 00:25:39,960 --> 00:25:41,440 REPLICATIONS AND SAME THING FOR 662 00:25:41,440 --> 00:25:44,040 ORF 7 B BUT THEY ARE THOUGHT TO 663 00:25:44,040 --> 00:25:45,200 BE INVOLVED IN IMMUNE RESPONSE 664 00:25:45,200 --> 00:25:49,160 SO IT COULD BE THAT IN PATIENT, 665 00:25:49,160 --> 00:25:51,800 THERE IS NO USE FOR THIS VIRUS 666 00:25:51,800 --> 00:25:55,880 TO CARRY THESE GENES BECAUSE THE 667 00:25:55,880 --> 00:25:58,080 IMMUNE RESPONSE IS PRETTY LOW. 668 00:25:58,080 --> 00:26:00,360 NOW THERE HAVE BEEN OTHER 669 00:26:00,360 --> 00:26:02,000 STUDIES SHOWING OTHER LARGE 670 00:26:02,000 --> 00:26:05,280 DELETIONS IN THAT REGION SUCH AS 671 00:26:05,280 --> 00:26:06,680 THIS 382 NUCLEOTIDE DELETION AND 672 00:26:06,680 --> 00:26:10,320 THEY FOUND THAT IT DID CORRELATE 673 00:26:10,320 --> 00:26:13,760 WITH MILDER DISEASE IN 1 STUDY 674 00:26:13,760 --> 00:26:15,720 LOWER INCIDENCE OF HYPOXIA. 675 00:26:15,720 --> 00:26:17,240 SO THESE ARE DIFFERENT STUDIES 676 00:26:17,240 --> 00:26:18,320 AND DIFFERENT PARTS OF THE WORLD 677 00:26:18,320 --> 00:26:19,840 WHERE THEY HAVE OBSERVED 678 00:26:19,840 --> 00:26:20,920 DELETIONS IN THAT REGION. 679 00:26:20,920 --> 00:26:25,680 SO IT SEEMS THAT THE ORF 8 680 00:26:25,680 --> 00:26:27,480 REGION IS A PRETTY MALLEABLE 681 00:26:27,480 --> 00:26:29,760 REGION OF THE GENOME, SO THERE'S 682 00:26:29,760 --> 00:26:32,880 A LOT OF DIVERSITY IN THAT 683 00:26:32,880 --> 00:26:33,240 REGION. 684 00:26:33,240 --> 00:26:36,080 SO THIS TAKES ME TO THE 685 00:26:36,080 --> 00:26:38,800 DIVERSITY OF THE POPULATION THAT 686 00:26:38,800 --> 00:26:42,600 EXISTS IN A PATIENT BE IT AN 687 00:26:42,600 --> 00:26:44,240 IMMUNE O COMPETENT PATIENT OR 688 00:26:44,240 --> 00:26:45,160 IMMUNE O COMPROMISED PATIENT SO 689 00:26:45,160 --> 00:26:47,160 IF YOU GO BACK TO MY SCHEMA OF 690 00:26:47,160 --> 00:26:49,600 LOOKING AT THE SEQUENCE READS, 691 00:26:49,600 --> 00:26:51,240 THE OTHER INFORMATION WE CAN 692 00:26:51,240 --> 00:26:53,280 CAPTURE IS YOU SEE AN ORANGE 693 00:26:53,280 --> 00:26:55,600 HERE, WHAT WOULD BE MUTATIONS. 694 00:26:55,600 --> 00:26:57,240 BUT THEY'RE NOT IN THE MAJORITY 695 00:26:57,240 --> 00:26:59,440 OF THE SEQUENCE READS, MEANING 696 00:26:59,440 --> 00:27:03,080 THAT SOME OF THE VIRUSES WITHIN 697 00:27:03,080 --> 00:27:05,240 THE POPULATION, WITHIN THAT 698 00:27:05,240 --> 00:27:07,880 PATIENT OR CARRYING DIFFERENT 699 00:27:07,880 --> 00:27:09,240 MUTATIONS BUT THEY'VE 700 00:27:09,240 --> 00:27:10,280 ACCUMULATED AT ENOUGH HIGH LEVEL 701 00:27:10,280 --> 00:27:15,280 THAT WE CAN CAPTURE THEM AS 702 00:27:15,280 --> 00:27:16,880 PRETTY IMPORTANT MINOR VARIANTS. 703 00:27:16,880 --> 00:27:18,720 SO FROM THIS SEQUENCE DATA, YOU 704 00:27:18,720 --> 00:27:21,040 CAN ACTUALLY PULL OUT THE 705 00:27:21,040 --> 00:27:23,000 CONSENSUS SEQUENCE BUT ALSO SOME 706 00:27:23,000 --> 00:27:25,920 INFORMATION OF MINOR VARIANTS. 707 00:27:25,920 --> 00:27:28,080 SO ON THE LEFT HERE, HOW YOU CAN 708 00:27:28,080 --> 00:27:29,680 SHOW THIS ALSO, SO IN THIS 709 00:27:29,680 --> 00:27:31,480 PATIENT, WE HAVE THE DIFFERENT 710 00:27:31,480 --> 00:27:33,960 COLLECTION DATES, WE HAVE 711 00:27:33,960 --> 00:27:40,960 DIFFERENT GENES AND THESE ARE 712 00:27:40,960 --> 00:28:04,080 IMMUNE O ACID ACID POSITIONS WHERE 713 00:28:04,080 --> 00:28:05,720 THE--SO THERE IS CHATTER IN THE 714 00:28:05,720 --> 00:28:07,560 VIRAL POPULATION THAT CAN LEAD 715 00:28:07,560 --> 00:28:10,800 TO NEW VIRUS GENOMES THAT HAVE 716 00:28:10,800 --> 00:28:12,000 NEW MUTATIONS INSERT REGIONS OF 717 00:28:12,000 --> 00:28:12,920 THE GENOME. 718 00:28:12,920 --> 00:28:14,000 NOW I'M MENTIONING THIS BECAUSE 719 00:28:14,000 --> 00:28:17,840 IF YOU GO BACK TO SOME OF THESE 720 00:28:17,840 --> 00:28:18,520 IMMUNO COMPROMISED PATIENTS AND 721 00:28:18,520 --> 00:28:21,440 SOME OF THESE STUDIES, THERE'S 1 722 00:28:21,440 --> 00:28:23,680 STUDY BY HENSLY WHERE THEY'VE 723 00:28:23,680 --> 00:28:25,600 LOOKED OVER TIME AT DIFFERENT 724 00:28:25,600 --> 00:28:27,880 MINOR VARIANTS AND YOU CAN SEE 725 00:28:27,880 --> 00:28:29,520 HOW THERE ARE DELETIONS THAT CAN 726 00:28:29,520 --> 00:28:31,640 OCCUR, THAT CAN APPEAR IN SOME 727 00:28:31,640 --> 00:28:34,720 OF THESE MINOR VARIANTS AND 728 00:28:34,720 --> 00:28:37,320 POSITIONS ALSO IN THE RECEPTOR 729 00:28:37,320 --> 00:28:39,240 BINDING DOMAIN THAT SEEM TO 730 00:28:39,240 --> 00:28:40,640 OCCUR ALSO OVER TIME AND THAT 731 00:28:40,640 --> 00:28:45,000 YOU CAN CAPTURE IN THE MINOR 732 00:28:45,000 --> 00:28:45,280 VARIANTS. 733 00:28:45,280 --> 00:28:46,400 NOW ANYTHING THAT CIRCULATING IN 734 00:28:46,400 --> 00:28:50,120 THE WORLD THAT BECOMES YOU KNOW 735 00:28:50,120 --> 00:28:52,960 A VIRUS THAT'S CIRCULATING 736 00:28:52,960 --> 00:28:56,680 GLOBALLY, YOU CAN SEE EVOLUTION 737 00:28:56,680 --> 00:28:58,640 HAPPENING BETWEEN HOSTS SO AS WE 738 00:28:58,640 --> 00:29:00,480 TRANSMIT VIRUSES, THEY CAN ADAPT 739 00:29:00,480 --> 00:29:02,240 DIFFERENTLY IN DIFFERENT HOSTS 740 00:29:02,240 --> 00:29:05,160 BUT EVOLUTION ALSO HAPPENS OF 741 00:29:05,160 --> 00:29:06,360 COURSE WITHIN THE HOST AND 742 00:29:06,360 --> 00:29:08,760 THAT'S THE INFORMATION WE'RE 743 00:29:08,760 --> 00:29:10,520 TRYING TO CAPTURE ESPECIALLY IN 744 00:29:10,520 --> 00:29:13,960 THE CONTEXT OF IDENTIFYING 745 00:29:13,960 --> 00:29:14,920 POTENTIALLY EMERGING VARIANTS 746 00:29:14,920 --> 00:29:16,240 AND VARIANTS OF CONCERN. 747 00:29:16,240 --> 00:29:27,880 AND SO, WHEN YOU LOOK AT THIS 748 00:29:27,880 --> 00:29:29,480 POPULATION AND EMERGENCE OF A 749 00:29:29,480 --> 00:29:30,320 NEW VARIANTS. 750 00:29:30,320 --> 00:29:32,640 SO THERE'S THIS 1 STUDY THAT 751 00:29:32,640 --> 00:29:34,880 POST DOC IN MY LAB 752 00:29:34,880 --> 00:29:36,640 [INDISCERNIBLE] IS DOING WHERE 753 00:29:36,640 --> 00:29:40,160 SHE'S TRYING TO LEVERAGE VERY 754 00:29:40,160 --> 00:29:42,880 LARGE DATA SETS OF NEXT 755 00:29:42,880 --> 00:29:44,200 GENERATION SEQUENCING DATA TO BE 756 00:29:44,200 --> 00:29:45,280 ABLE TO ANSWER SOME OF THESE 757 00:29:45,280 --> 00:29:48,440 QUESTIONS ON WHAT IS THE 758 00:29:48,440 --> 00:29:50,480 DIVERSITY WITHIN A HOST. 759 00:29:50,480 --> 00:29:52,520 SO ACTUALLY SASHA IS GIVING A 760 00:29:52,520 --> 00:29:55,680 TALK AT THE LPD SEMINARS AT 761 00:29:55,680 --> 00:29:56,840 1:00 O'CLOCK WHERE SHE WILL GO 762 00:29:56,840 --> 00:29:59,840 IN DETAIL SO I WON'T BE SHOWING 763 00:29:59,840 --> 00:30:02,120 TO 764 00:30:02,120 --> 00:30:02,680 SHOWING--TOO MUCH ABOUT HER 765 00:30:02,680 --> 00:30:04,320 STUDY BUT I WANT TO MAKE A POINT 766 00:30:04,320 --> 00:30:06,400 IN THE CONTEXT OF WHAT WE'RE 767 00:30:06,400 --> 00:30:09,800 TALKING ABOUT WITH EVOLUTION 768 00:30:09,800 --> 00:30:11,960 WITH AN IMMUNO COMPETENT AND 769 00:30:11,960 --> 00:30:12,520 IMMUNO COMPROMISED PATIENTS. 770 00:30:12,520 --> 00:30:14,520 SO THERE HAVE BEEN A FEW STUDIES 771 00:30:14,520 --> 00:30:15,080 LOOKING AT MINOR VALID AND 772 00:30:15,080 --> 00:30:18,240 RELIABLE YABT AND COUNTING MINOR 773 00:30:18,240 --> 00:30:18,840 VARIANTS WITHIN INDIVIDUALS. 774 00:30:18,840 --> 00:30:20,200 AND THIS IS JUST A 775 00:30:20,200 --> 00:30:22,120 REPRESENTATION OF 2 OF THESE 776 00:30:22,120 --> 00:30:22,640 STUDIES. 777 00:30:22,640 --> 00:30:25,360 NOW MINOR VARIANTS HAPPEN, BUT 778 00:30:25,360 --> 00:30:26,680 THEY'RE NOT PRESENT AT A HUGE 779 00:30:26,680 --> 00:30:29,480 NUMBER SO IT'S NOT AS IF YOU 780 00:30:29,480 --> 00:30:31,120 HAVE A LOT OF DIVERSITY 781 00:30:31,120 --> 00:30:33,320 OCCURRING WITHIN THIS VIRUS 782 00:30:33,320 --> 00:30:35,040 POPULATION BECAUSE ALTHOUGH THE 783 00:30:35,040 --> 00:30:37,280 VIRUS MAKES MISTAKES, EVERY TIME 784 00:30:37,280 --> 00:30:39,480 IT REPLICATES, A LOT OF THESE 785 00:30:39,480 --> 00:30:41,880 MISTAKES WILL JUST BE PUDGIERED 786 00:30:41,880 --> 00:30:44,040 AND YOU WILL GET REALLY JUST 787 00:30:44,040 --> 00:30:46,680 VIRUSES THAT ARE COMPETENT AND 788 00:30:46,680 --> 00:30:47,120 THAT CAN REPLICATE. 789 00:30:47,120 --> 00:30:50,880 SO WHAT YOU'RE SEEING IN THE 790 00:30:50,880 --> 00:30:52,480 MINOR VARIANTS ARE VIRUSES THAT 791 00:30:52,480 --> 00:30:54,480 HAVE MUTATIONS OR THESE 792 00:30:54,480 --> 00:30:55,480 DELETIONS OR MISTAKES BUT THAT 793 00:30:55,480 --> 00:30:56,560 ARE ABLE TO REPLICATE. 794 00:30:56,560 --> 00:30:58,440 SO IN GENERAL, IF YOU LOOK AT 795 00:30:58,440 --> 00:31:00,440 THE NUMBER OF SPECIMENS SO THIS 796 00:31:00,440 --> 00:31:02,280 IS A STUDY WHERE THEY HAD YOU 797 00:31:02,280 --> 00:31:03,880 KNOW ABOUT A HUNDRED SPECIMENS 798 00:31:03,880 --> 00:31:08,840 HERE, THEY HAD MANY MORE AND YOU 799 00:31:08,840 --> 00:31:11,440 LOOK AT THE NUMBER OF MINOR 800 00:31:11,440 --> 00:31:13,200 VARIANTS PER SAMPLE, THE NUMBER 801 00:31:13,200 --> 00:31:16,120 SEEMS TO BE AROUND 2-3, SO IN 802 00:31:16,120 --> 00:31:18,600 GENERAL THERE ARE VERY FEW MINOR 803 00:31:18,600 --> 00:31:19,840 VARIANTS IN A POPULATION OF 804 00:31:19,840 --> 00:31:23,000 VIRUSES BUT YOU DO HAVE 805 00:31:23,000 --> 00:31:24,200 EXCEPTIONINGS WHERE THERE ARE 806 00:31:24,200 --> 00:31:28,080 SOME SAMPLES THAT HAVE A LOT OF 807 00:31:28,080 --> 00:31:29,040 MINOR VARIANTS SO WE'RE TRYING 808 00:31:29,040 --> 00:31:31,760 TO UNDERSTAND WHAT LEADS TO 809 00:31:31,760 --> 00:31:32,680 THIS. 810 00:31:32,680 --> 00:31:34,200 ARE THESE PATIENTS DO THEY HAVE 811 00:31:34,200 --> 00:31:37,240 SOMETHING DIFFERENT ABOUT THEIR 812 00:31:37,240 --> 00:31:37,960 IMMUNE SYSTEM, IS THERE 813 00:31:37,960 --> 00:31:41,960 SOMETHING THAT WE CAN CAPTURE IN 814 00:31:41,960 --> 00:31:44,080 THIS DIVERSITY IN THEIR VIRUS 815 00:31:44,080 --> 00:31:44,800 POPULATION. 816 00:31:44,800 --> 00:31:50,280 SO WITH SASHA HAS BEEN DOING IS 817 00:31:50,280 --> 00:31:51,560 SHE'S BEEN GETTING ALL THE RAW 818 00:31:51,560 --> 00:31:54,680 DATA FROM A STUDY THAT IS GOING 819 00:31:54,680 --> 00:31:57,800 ON IN HOUSTON METHODIST AND LED 820 00:31:57,800 --> 00:32:04,320 BY JIM MUSSER WHERE THEY'VE BEEN 821 00:32:04,320 --> 00:32:05,480 SEQUENCING OR SEQUENCING FOR 822 00:32:05,480 --> 00:32:09,400 EVERY SINGLE PATIENT THAT TESTS 823 00:32:09,400 --> 00:32:11,000 POSITIVE FOR SARS-COV-2 AS PART 824 00:32:11,000 --> 00:32:12,080 OF THE HOUSTON METHOD SESSION. 825 00:32:12,080 --> 00:32:14,600 SO WE OBLIGATIONS STAINED ABOUT 826 00:32:14,600 --> 00:32:16,920 40 NOVA SEEK RUNS, IT'S A 827 00:32:16,920 --> 00:32:18,760 SEQUENCING TRIEWMENT THAT 828 00:32:18,760 --> 00:32:21,160 PROVIDES A VERY LARGE MEMBER OF 829 00:32:21,160 --> 00:32:24,040 SAMPLES AND VERY HIGH DEPTH OF 830 00:32:24,040 --> 00:32:24,480 COVERAGE. 831 00:32:24,480 --> 00:32:28,040 AND WE'VE LOOKED AT ABOUT 21,000 832 00:32:28,040 --> 00:32:32,080 WHOLE GENOMES THAT WERE 833 00:32:32,080 --> 00:32:33,600 SEQUENCED BETWEEN DECEMBER 2020 834 00:32:33,600 --> 00:32:35,560 AND JULY 2021 TO LOOK AT MINOR 835 00:32:35,560 --> 00:32:36,880 VARIANTS AND SEE IF WE CAN 836 00:32:36,880 --> 00:32:39,160 CAPTURE SOME OF THIS INFORMATION 837 00:32:39,160 --> 00:32:43,680 NOW I'M CUTTING OUT A LOT OF 838 00:32:43,680 --> 00:32:45,040 STEPS BUT 1 THING THAT SASHA 839 00:32:45,040 --> 00:32:46,320 OBSERVED IS THAT IF YOU LOOK AT 840 00:32:46,320 --> 00:33:00,680 THE NUMBER OF SAMPLES WITH--ARE 841 00:33:00,680 --> 00:33:01,360 THERE MUSEUM TAIPGZ AFFAIRS TEAM 842 00:33:01,360 --> 00:33:02,880 LEADER HOT SPOTS IN THE GENOME 843 00:33:02,880 --> 00:33:06,160 WHERE WE WOULD SEE CERTAIN 844 00:33:06,160 --> 00:33:07,120 VARIANTS EMERGING. 845 00:33:07,120 --> 00:33:08,280 I'VE HIGHLIGHTED THE SPIKED 846 00:33:08,280 --> 00:33:10,680 PROTEIN HERE IN RED TO SHOW YOU 847 00:33:10,680 --> 00:33:12,360 THAT IT'S NOT NECESSARILY IN THE 848 00:33:12,360 --> 00:33:14,800 SPIKE WHERE YOU WOULD HAVE THE 849 00:33:14,800 --> 00:33:16,560 MOST MINOR VARIANTS THAT WOULD 850 00:33:16,560 --> 00:33:18,680 BE OBSERVED. 851 00:33:18,680 --> 00:33:20,800 WE ACTUALLY SEE THEM A LOT IN 852 00:33:20,800 --> 00:33:24,440 THE NUCLEOCAP SID PROTEIN AND 853 00:33:24,440 --> 00:33:25,760 ALSO IN ORF 8. 854 00:33:25,760 --> 00:33:28,600 IN ORF 8 AS YOU HEARD EARLIER, 855 00:33:28,600 --> 00:33:30,280 SEEMS TO BE PRETTY MALLEABLE 856 00:33:30,280 --> 00:33:32,200 REGION OF THE GENOME. 857 00:33:32,200 --> 00:33:35,280 SO YOU SEE DELETIONS, BUT YOU 858 00:33:35,280 --> 00:33:38,520 ALSO SEE A FEW MUTATIONS. 859 00:33:38,520 --> 00:33:40,640 SO, WHAT YOU SEE IN SOME OF 860 00:33:40,640 --> 00:33:47,920 THESE GENES IS THAT YOU HAVE YOU 861 00:33:47,920 --> 00:33:49,840 TEND TO SEE MANY SAMPLES THAT 862 00:33:49,840 --> 00:33:50,920 HAVE MULTIPLE VARIANTS SO FOR 863 00:33:50,920 --> 00:33:52,000 EXAMPLE, YOU SEE HERE THAT YOU 864 00:33:52,000 --> 00:33:55,280 CAN COULD GO CAP SID THAT YOU 865 00:33:55,280 --> 00:33:56,600 CAN HAVE DIFFERENT NUCLEOTIDES 866 00:33:56,600 --> 00:34:01,000 THAT OCCUR IN THAT SAME 867 00:34:01,000 --> 00:34:01,480 POSITION. 868 00:34:01,480 --> 00:34:03,600 SO AGAIN IT'S THIS CHATTER. 869 00:34:03,600 --> 00:34:05,280 THERE ARE SPOTS OR REGIONS IN 870 00:34:05,280 --> 00:34:06,960 THE GENOME WHERE YOU HAVE A LOT 871 00:34:06,960 --> 00:34:09,720 OF DIVERSITY, A LOT OF 872 00:34:09,720 --> 00:34:10,600 FLEXIBILITY AND CHATTER. 873 00:34:10,600 --> 00:34:12,280 AND IF I TAKE THE EXAMPLE HERE 874 00:34:12,280 --> 00:34:14,120 FROM THE SPIKE, THERE'S ACTUALLY 875 00:34:14,120 --> 00:34:19,200 AN IMPORTANT POSITION WHICH IS 876 00:34:19,200 --> 00:34:21,680 THE FEWER AND CLEAVAGE SITE AND 877 00:34:21,680 --> 00:34:23,800 WE SEE THIS IS A SITE THAT HAS A 878 00:34:23,800 --> 00:34:27,280 LOT OF MUTATIONS OFTEN IN THESE 879 00:34:27,280 --> 00:34:27,800 SAMPLES. 880 00:34:27,800 --> 00:34:31,520 SO, LET'S GO BACK TO OUR IDEA OF 881 00:34:31,520 --> 00:34:32,120 VARIANTS OF CONCERN. 882 00:34:32,120 --> 00:34:37,040 SO IF YOU LOOK GLOBALLY AT 883 00:34:37,040 --> 00:34:39,480 SOMETHING LIKE ALFOBBS THAT'S 884 00:34:39,480 --> 00:34:41,480 THE B117 AND THE DELTA WE'RE 885 00:34:41,480 --> 00:34:44,160 MORE FAMILIAR WITH, THE 681 886 00:34:44,160 --> 00:34:46,080 POSITION TENDS TO TWITCH BETWEEN 887 00:34:46,080 --> 00:34:48,720 THIS H AND THE R AND WE SEE 888 00:34:48,720 --> 00:34:50,000 SUBSTITUTIONS IN THIS MINORITY 889 00:34:50,000 --> 00:34:53,280 FRACTION OF THE GENOME. 890 00:34:53,280 --> 00:34:56,480 SO THE REASON I MENTION THIS IS 891 00:34:56,480 --> 00:34:58,680 THAT VARIANTS OF CONCERN DO TEND 892 00:34:58,680 --> 00:35:00,440 TO MERGE WITH A LARGE NUMBER OF 893 00:35:00,440 --> 00:35:03,040 NEW MUTATIONS AND CAN WE CAPTURE 894 00:35:03,040 --> 00:35:05,200 THESE MUTATIONS IN THE SEQUENCE 895 00:35:05,200 --> 00:35:08,760 DATA IN THE MINOR VARIANT DATA? 896 00:35:08,760 --> 00:35:12,080 NOW, HAVING A LOT OF DIVERSITY 897 00:35:12,080 --> 00:35:14,920 WITHIN AN INDIVIDUAL ACCOUNTED 898 00:35:14,920 --> 00:35:15,800 FACILITATE EMERGES ENSEL OF 899 00:35:15,800 --> 00:35:37,320 DIFFERENT VERSIONS OF THE VIRUS, 900 00:35:37,320 --> 00:35:38,280 INCLUDING AND SHE'S ACTUALLY 901 00:35:38,280 --> 00:35:45,760 DETERMINED THAT THERE IS AN 902 00:35:45,760 --> 00:35:47,280 ASSOCIATION BETWEEN HIGH VARIANT 903 00:35:47,280 --> 00:35:48,680 NUMBERS AND DISEASE ASSOCIATION 904 00:35:48,680 --> 00:35:48,960 VARIABILITY. 905 00:35:48,960 --> 00:35:50,560 AND 1 QUESTION WE HAVE IS 906 00:35:50,560 --> 00:35:52,720 WHETHER DIVERSE IS SEEN IN 907 00:35:52,720 --> 00:35:55,280 IMMUNO SUPPRESSED PATIENTS AND 908 00:35:55,280 --> 00:35:57,040 SO THIS IS THE TYPE OF ANALYSIS 909 00:35:57,040 --> 00:36:00,720 THAT IS ONGOING RIGHT NOW, WHERE 910 00:36:00,720 --> 00:36:03,840 WE WOULD NEED TO LOOK AT LARGER 911 00:36:03,840 --> 00:36:05,080 POPULATIONS OF IMMUNO SUPPRESSED 912 00:36:05,080 --> 00:36:06,360 INDIVIDUALS TO ANSWER THAT 913 00:36:06,360 --> 00:36:07,600 QUESTION. 914 00:36:07,600 --> 00:36:10,920 BECAUSE IF WE GO TO OMICRON AND 915 00:36:10,920 --> 00:36:14,040 WE KNOW THAT OMICRON HAS SEEMED 916 00:36:14,040 --> 00:36:17,840 TO ACCUMULATE A LOT OF MUTATIONS 917 00:36:17,840 --> 00:36:20,240 OVER OVER ITS GENOME AND HERE'S 918 00:36:20,240 --> 00:36:22,600 A REPRESENTATION OF A 919 00:36:22,600 --> 00:36:24,480 PHILOGENETIC TREE THAT WAS MADE 920 00:36:24,480 --> 00:36:27,640 BY NEXT STRAIN AND HERE CAN YOU 921 00:36:27,640 --> 00:36:28,960 SEE OMICRON HAS THIS VERY LONG 922 00:36:28,960 --> 00:36:31,280 BRANCH LENGTH AND THAT INDICATES 923 00:36:31,280 --> 00:36:32,480 THAT GENETICALLY IT'S QUITE 924 00:36:32,480 --> 00:36:40,680 DIFFERENT FROM THE REST OF THESE 925 00:36:40,680 --> 00:36:42,600 VARIANTS OF CONCERN AND IN FACT 926 00:36:42,600 --> 00:36:44,640 IF THERE'S THIS NICE PAPER THAT 927 00:36:44,640 --> 00:36:46,280 IS A PERSPECTIVE TYPE PAPER IN 928 00:36:46,280 --> 00:36:48,080 NATURE THAT WAS PUBLISHED I 929 00:36:48,080 --> 00:36:49,840 THINK IN THE LAST WEEK OR 930 00:36:49,840 --> 00:36:53,800 EARLIER THIS WEEK WHERE THEY 931 00:36:53,800 --> 00:36:55,120 SHOW HERE OVER TIME THE NUMBER 932 00:36:55,120 --> 00:36:58,160 OF MUTATIONS IN THE SPIKE 933 00:36:58,160 --> 00:36:59,240 PROTEIN FOR OMICRON, COMPARED TO 934 00:36:59,240 --> 00:37:00,680 OTHER VARIANTS OF CONCERN, CAN 935 00:37:00,680 --> 00:37:02,840 YOU SEE THAT OMIKRON HAS MANY 936 00:37:02,840 --> 00:37:06,040 MORE BUT ALSO IT SEEMS THAT IT'S 937 00:37:06,040 --> 00:37:08,560 CLOSEST KNOWN ANCESTOR PROBABLY 938 00:37:08,560 --> 00:37:13,480 DATES BACK PRETTY FAR BACK. 939 00:37:13,480 --> 00:37:15,800 NOW THIS PARTICULAR PIECE IS 940 00:37:15,800 --> 00:37:19,960 ABOUT WHAT WOULD BE THE SOURCE 941 00:37:19,960 --> 00:37:24,320 OF OMICRON, IS IT FROM AN ANIMAL 942 00:37:24,320 --> 00:37:25,280 RESERVOIR WHERE THIS IVLIEWGZ 943 00:37:25,280 --> 00:37:27,600 WOULD OCCUR OR IN IMMUNO 944 00:37:27,600 --> 00:37:30,360 COMPROMISED PATIENT WHERE IS THE 945 00:37:30,360 --> 00:37:32,680 VIRUS COULD HAVE EVOLVED OVER 946 00:37:32,680 --> 00:37:34,000 TIME AND HADN'T BEEN PICKED UP 947 00:37:34,000 --> 00:37:34,960 BEFORE AND THAT'S SORT OF WHAT 948 00:37:34,960 --> 00:37:36,040 WE'RE TRYING TO ANSWER. 949 00:37:36,040 --> 00:37:39,040 SO LET'S GO BACK TO THAT TABLE 950 00:37:39,040 --> 00:37:40,720 THAT THEY SHOWED EARLIER WHERE 951 00:37:40,720 --> 00:37:43,480 SHE LISTED A LOT OF THESE 952 00:37:43,480 --> 00:37:45,080 STUDIES WITH IMIEWNL O 953 00:37:45,080 --> 00:37:47,520 COMPROMISED PATIENTS AND I HAD 954 00:37:47,520 --> 00:37:48,920 ADDED HERE OUR OWN STUDY AND 955 00:37:48,920 --> 00:37:51,280 THIS IS JUST THE SCHEMA OF THE 956 00:37:51,280 --> 00:37:53,480 WHOLE GENOME, SORRY OF THE SPIKE 957 00:37:53,480 --> 00:37:54,480 PROTEIN ONLY WITH DIFFERENT 958 00:37:54,480 --> 00:38:03,640 DOMAINS IN THE PROTEIN THAT ARE 959 00:38:03,640 --> 00:38:12,160 IMPORTANT. 960 00:38:12,160 --> 00:38:14,520 THIS IS--AND YOU CAN SEE IN OUR 961 00:38:14,520 --> 00:38:15,520 IMMUNO COMPROMISED PATIENTS, 962 00:38:15,520 --> 00:38:16,400 THESE PATIENTS HAVE ACCUMULATED 963 00:38:16,400 --> 00:38:17,880 OVER TIME SO MANY OF THESE 964 00:38:17,880 --> 00:38:19,600 STUDIES SHOW THE EARLIEST TIME 965 00:38:19,600 --> 00:38:22,120 POINT AND THE LATEST TIME POINT 966 00:38:22,120 --> 00:38:24,440 AND WHAT I'M SHOWING HERE IS 967 00:38:24,440 --> 00:38:26,320 REALLY THE LATEST TIME POINT, 968 00:38:26,320 --> 00:38:30,800 THE TYPES OF MUTATIONS THAT HAVE 969 00:38:30,800 --> 00:38:31,280 ACCUMULATED OVER TIME. 970 00:38:31,280 --> 00:38:33,120 AND YOU CAN SEE THAT THERE ARE 971 00:38:33,120 --> 00:38:35,120 CERTAIN SPOTS OF THE GENOME 972 00:38:35,120 --> 00:38:36,520 WHERE THE MUTATIONS TEND TO 973 00:38:36,520 --> 00:38:38,520 ACCUMULATE OVER TIME AND IF YOU 974 00:38:38,520 --> 00:38:41,360 COMPARE WITH THE VARIANCE OF 975 00:38:41,360 --> 00:38:42,760 CONCERN, THEY'RE VERY SIMILAR 976 00:38:42,760 --> 00:38:45,680 POSITIONS SO THERE ARE--SO YOU 977 00:38:45,680 --> 00:38:47,680 HAVE OMICRON HERE THAT OF COURSE 978 00:38:47,680 --> 00:38:50,720 HAS MANY MORE OF THESE MUTATIONS 979 00:38:50,720 --> 00:38:52,920 BUT THEY DO SEEM TO OCCUR WHERE 980 00:38:52,920 --> 00:38:56,000 WE HAVE SEEN THEM HAPPENING IN 981 00:38:56,000 --> 00:38:57,080 OUR IMMUNO COMPROMISED PATIENTS. 982 00:38:57,080 --> 00:39:00,680 NOW THAT DOESN'T MEAN THAT ALL 983 00:39:00,680 --> 00:39:05,080 VARIANTS OF CONCERN COME FROM 984 00:39:05,080 --> 00:39:06,320 IMMUNO COMPROMISED PATIENTS, 985 00:39:06,320 --> 00:39:09,080 INDICATING THAT THERE ARE YOU 986 00:39:09,080 --> 00:39:10,720 KNOW POSITIONS THAT APPEAR TO BE 987 00:39:10,720 --> 00:39:14,640 FROM THE MINOR VARIANT DATA, WE 988 00:39:14,640 --> 00:39:16,280 DO SEE THERE ARE POSITIONS THAT 989 00:39:16,280 --> 00:39:19,400 ARE MUTATIONAL HOT SPOTS, AND 990 00:39:19,400 --> 00:39:22,640 THAT THESE VIRUSES MAY BE 991 00:39:22,640 --> 00:39:25,000 FAVORED IN IMMUNO COMPROMISED 992 00:39:25,000 --> 00:39:25,320 HOSTS. 993 00:39:25,320 --> 00:39:29,040 AND I WILL LET VERONIQUE CLOSE 994 00:39:29,040 --> 00:39:31,520 THIS OFF FROM OUR TAKE AWAYS 995 00:39:31,520 --> 00:39:33,480 FROM THESE DIFFERENT STUDIES. 996 00:39:33,480 --> 00:39:34,000 >> THANK YOU ELODIE. 997 00:39:34,000 --> 00:39:35,680 SO JUST A FEW POINTS BEFORE WE 998 00:39:35,680 --> 00:39:39,280 CLOSE, CLEARLY YOU CAN SEE 999 00:39:39,280 --> 00:39:42,920 MUTATED VARIANTS EMERGING ON 1000 00:39:42,920 --> 00:39:44,560 INDIVIDUALS AND WE DON'T REALLY 1001 00:39:44,560 --> 00:39:46,800 UNDERSTAND TO WHAT EXTENT AND 1002 00:39:46,800 --> 00:39:50,040 ALL OF OUR IMMUNO COMPROMISED 1003 00:39:50,040 --> 00:39:52,200 PATIENTS IS, AND THE EMERGENCE 1004 00:39:52,200 --> 00:39:53,400 OF SUCH VARIANTS IN THE 1005 00:39:53,400 --> 00:39:56,280 COMMUNITY AND BEYOND, IT'S 1006 00:39:56,280 --> 00:39:58,560 REALLY IMPERATIVE THAT WE 1007 00:39:58,560 --> 00:39:59,480 INVESTIGATE WHAT THEIR ROLE IS 1008 00:39:59,480 --> 00:40:02,280 IN ALL OF THIS, AND AGAIN, WELL 1009 00:40:02,280 --> 00:40:04,440 WE'VE BEEN PRESENTING CASE 1010 00:40:04,440 --> 00:40:07,200 REPORTS HERE TODAY, I THINK THIS 1011 00:40:07,200 --> 00:40:10,800 IS ACTUALLY HAPPENING A LOT MORE 1012 00:40:10,800 --> 00:40:12,280 THAN WHAT WE'RE SEEING BEING 1013 00:40:12,280 --> 00:40:13,680 REPORTED IN THE LITERATURE SO 1014 00:40:13,680 --> 00:40:15,080 I'VE HEARD AND BEEN INVOLVED IN 1015 00:40:15,080 --> 00:40:16,960 SEVERAL CASES IN THE COMMUNITY 1016 00:40:16,960 --> 00:40:18,680 OF PATIENTS AGAIN, WITH VERY 1017 00:40:18,680 --> 00:40:19,880 PROLONGED INFECTIONS AND AFTER 1018 00:40:19,880 --> 00:40:23,920 OUR CASE WAS PUBLISHED, ELODIE 1019 00:40:23,920 --> 00:40:27,000 AND I RECEIVED E-MAILS FROM 1020 00:40:27,000 --> 00:40:30,480 INTERNATIONAL PHYSICIANS WHO ARE 1021 00:40:30,480 --> 00:40:34,040 TRYING TO MANAGE PATIENTS WITH 1022 00:40:34,040 --> 00:40:35,480 REPRUITT DESSENT INFECTIONS AND 1023 00:40:35,480 --> 00:40:36,200 PROLONGED INFECTIONS SO AGAIN, I 1024 00:40:36,200 --> 00:40:37,640 THINK THIS IS A MUCH GREATER 1025 00:40:37,640 --> 00:40:38,880 PROBLEM THAT WE'RE JUST SEEING 1026 00:40:38,880 --> 00:40:41,880 WITH THESE CASE REPORTS. 1027 00:40:41,880 --> 00:40:43,800 I THINK WE NEED TO BE THOUGHTFUL 1028 00:40:43,800 --> 00:40:47,880 ABOUT THE THERAPIES WE USE TO 1029 00:40:47,880 --> 00:40:48,960 TREAT OUR PATIENTS. 1030 00:40:48,960 --> 00:40:51,160 WE, RIGHT NOW, WE DON'T HAVE 1031 00:40:51,160 --> 00:40:52,080 REALLY VERY EFFECTIVE ANTIVIRALS 1032 00:40:52,080 --> 00:40:55,640 TO USE TO TREAT OUR PATIENTS AND 1033 00:40:55,640 --> 00:40:58,080 SO WE FOCUSED--WE FOCUS A LOT ON 1034 00:40:58,080 --> 00:41:01,080 MONOCLONAL ANTIBODIES AND ON 1035 00:41:01,080 --> 00:41:01,520 CONVALESCENT PLASMA. 1036 00:41:01,520 --> 00:41:03,480 NOW WE DO HAVE 2 NEW ORAL DRUGS 1037 00:41:03,480 --> 00:41:06,160 THAT HAVE JUST BEEN APPROVED 1038 00:41:06,160 --> 00:41:07,720 UNDER AN EUA RECENTLY BUT NONE 1039 00:41:07,720 --> 00:41:14,160 OF THESE THERAPIES HAVE BEEN 1040 00:41:14,160 --> 00:41:15,840 EXTENSIVELY INVESTIGATED IN 1041 00:41:15,840 --> 00:41:16,880 IMMUNO COMPROMISED PERSONS SO DO 1042 00:41:16,880 --> 00:41:19,520 WE KNOW WE'RE GIVING THEM THE 1043 00:41:19,520 --> 00:41:21,440 RIGHT DOSE, THE RIGHT TITERS, 1044 00:41:21,440 --> 00:41:22,480 ARE WE TREATING THEM LONG 1045 00:41:22,480 --> 00:41:22,720 ENOUGH? 1046 00:41:22,720 --> 00:41:24,480 ARE WE GOING TO GET THEM BETTER 1047 00:41:24,480 --> 00:41:27,600 ABOUT YOU NOT FAST ENOUGH TO 1048 00:41:27,600 --> 00:41:29,960 PREVENT NEW VARIANTS FROM 1049 00:41:29,960 --> 00:41:30,240 EMERGING? 1050 00:41:30,240 --> 00:41:36,200 SO I THINK THERE'S A LOT LEFT TO 1051 00:41:36,200 --> 00:41:37,280 BE INVESTIGATED THERE AND LASTLY 1052 00:41:37,280 --> 00:41:38,680 I THINK THERE ARE CONTROL 1053 00:41:38,680 --> 00:41:40,000 CONSIDERATIONS AND TO PUT THIS 1054 00:41:40,000 --> 00:41:42,480 INTO CONTEXT, I THINK WE'RE VERY 1055 00:41:42,480 --> 00:41:46,080 LUCKY TO HAVE A FANTASTIC 1056 00:41:46,080 --> 00:41:48,440 LABORATORY HERE AND ELODIE AS A 1057 00:41:48,440 --> 00:41:49,400 RESOURCE WHEN WE ARE TRYING TO 1058 00:41:49,400 --> 00:41:50,600 THINK ABOUT OUR PATIENTS AND 1059 00:41:50,600 --> 00:41:52,640 WHAT ON DO ABOUT OUR PATIENTS 1060 00:41:52,640 --> 00:41:54,080 BUT MOST LABORATORIES AND 1061 00:41:54,080 --> 00:41:55,160 HOSPITALS IN THE UNITED STATES 1062 00:41:55,160 --> 00:42:01,880 LET ALONE THE WORLD ARE NOT ABLE 1063 00:42:01,880 --> 00:42:03,680 TO SEQUENCE VIRUSES WITHIN A 1064 00:42:03,680 --> 00:42:05,920 COUPLE OF DAYS OR USE MOLECULAR 1065 00:42:05,920 --> 00:42:11,400 MEANS TO DETERMINE WHETHER OR 1066 00:42:11,400 --> 00:42:12,600 NOT THE VIRUS IS PRESENT AND 1067 00:42:12,600 --> 00:42:14,200 THIS IS SOMETHING WE DO 1068 00:42:14,200 --> 00:42:15,640 FREQUENTLY HERE AT THE CLINICAL 1069 00:42:15,640 --> 00:42:17,280 CENTER, MOST LABS DON'T REPORT 1070 00:42:17,280 --> 00:42:18,480 CT VALUES SO WE DON'T EVEN HAVE 1071 00:42:18,480 --> 00:42:21,920 THAT TO GO ON IN MANY PLACES IN 1072 00:42:21,920 --> 00:42:22,880 THE COMMUNITY. 1073 00:42:22,880 --> 00:42:26,840 AND SO WITH THE UC RECOMMENDING 1074 00:42:26,840 --> 00:42:27,920 THAT FOR IMMUNO COMPROMISE 1075 00:42:27,920 --> 00:42:30,080 PATIENTS THAT WE SHOULD BE USING 1076 00:42:30,080 --> 00:42:31,280 A TESTING STRATEGY TO DETERMINE 1077 00:42:31,280 --> 00:42:32,640 WHETHER OR NOT THEY NEED TO BE 1078 00:42:32,640 --> 00:42:34,960 IN ISOLATION OR NOT, THAT CAN 1079 00:42:34,960 --> 00:42:36,360 GET VERY COMPLICATED WITH MANY 1080 00:42:36,360 --> 00:42:38,200 OF THESE PATIENTS. 1081 00:42:38,200 --> 00:42:41,960 NOW OUR PATIENTS AS FAR AS WE 1082 00:42:41,960 --> 00:42:43,160 KNOW DID NOT TRANSMIT HER 1083 00:42:43,160 --> 00:42:44,440 INFECTION TO ANYBODY IN HER 1084 00:42:44,440 --> 00:42:44,840 FAMILY. 1085 00:42:44,840 --> 00:42:46,440 I KNOW WE DIDN'T TEST EVERYBODY 1086 00:42:46,440 --> 00:42:48,680 BUT WE WERE NOT TOLD OF ANY 1087 00:42:48,680 --> 00:42:49,840 INFECTIONS THERE, SO WHETHER OR 1088 00:42:49,840 --> 00:42:51,280 NOT THATEE EVEN OF A CONCERN, WE 1089 00:42:51,280 --> 00:42:53,880 DON'T KNOW BUT WE ASSUME THAT IT 1090 00:42:53,880 --> 00:42:55,600 IS BECAUSE AGAIN WE'RE SEEING 1091 00:42:55,600 --> 00:42:56,680 REPLICATING VIRUS FOR A LONG 1092 00:42:56,680 --> 00:42:59,160 TIME IN THESE INDIVIDUALS. 1093 00:42:59,160 --> 00:43:01,600 SO I THINK I'M LEAVING YOU WITH 1094 00:43:01,600 --> 00:43:04,440 MORE QUESTIONS THAN ANSWERS BUT 1095 00:43:04,440 --> 00:43:05,920 I HOPE WE'VE PIQUED YOUR 1096 00:43:05,920 --> 00:43:07,000 INTEREST IN THIS VERY IMPORTANT 1097 00:43:07,000 --> 00:43:08,080 TOPIC TODAY AND THANK YOU SO 1098 00:43:08,080 --> 00:43:19,200 MUCH FOR YOUR ATTENTION. 1099 00:43:19,200 --> 00:43:20,120 NEXT SLIDE. 1100 00:43:20,120 --> 00:43:21,680 --OF THE WAY WITH OUR PATIENTS 1101 00:43:21,680 --> 00:43:22,560 WITH THE MOLECULAR TESTING AND 1102 00:43:22,560 --> 00:43:26,840 TRYING TO BED --UNDERSTAND WHAT 1103 00:43:26,840 --> 00:43:29,360 WAS GOING ON. 1104 00:43:29,360 --> 00:43:32,080 DR. TARA P A LMORE WHO WAS 1105 00:43:32,080 --> 00:43:32,880 INSTRUMENTAL IN EVERY STEP OF 1106 00:43:32,880 --> 00:43:34,480 THE WAY TRYING TO UNDERSTAND 1107 00:43:34,480 --> 00:43:35,760 THIS VERY COMPLEX CASE AND I'D 1108 00:43:35,760 --> 00:43:45,440 LIKE TO THANK OUR COLLEAGUES AT 1109 00:43:45,440 --> 00:43:47,200 NCI, DOCTOR'S BAROCHIA AND THEY 1110 00:43:47,200 --> 00:43:48,240 WERE INTIMATELY INVOLVED TO HELP 1111 00:43:48,240 --> 00:43:51,840 US UNDERSTAND AND MANAGE OUR 1112 00:43:51,840 --> 00:43:52,640 PATIENT'S LUNG PROBLEMS. 1113 00:43:52,640 --> 00:43:54,480 >> AND I WOULD LIKE TO THANK OUR 1114 00:43:54,480 --> 00:43:55,200 COLLABORATORS AT HOUSTON METHOD 1115 00:43:55,200 --> 00:43:58,920 AND --HOUSTON METHODIST AND WE 1116 00:43:58,920 --> 00:44:01,240 ARE WORKING WITH THEM CLOSELY 1117 00:44:01,240 --> 00:44:03,880 AND SPECIFIC STUDY ON OMICRON 1118 00:44:03,880 --> 00:44:06,560 AND ALL THEIR SEQUENCE DATA NOW 1119 00:44:06,560 --> 00:44:08,800 IS OMICRON AND SO WE WILL HAVE 1120 00:44:08,800 --> 00:44:09,880 MORE TO REPORT SOON AND I WOULD 1121 00:44:09,880 --> 00:44:11,200 LOAMACYIC TO THANK MY LAB WHO 1122 00:44:11,200 --> 00:44:13,960 HAS BEEN WORKING REALLY HARD ON 1123 00:44:13,960 --> 00:44:16,280 SIGNIFYQUENCING ALL THE NIH 1124 00:44:16,280 --> 00:44:20,680 SAMPLES OF POSITIVE CASES ON 1125 00:44:20,680 --> 00:44:22,680 CAMPUS AND SO, IT'S BEEN GREAT 1126 00:44:22,680 --> 00:44:23,480 WORKING WITH THEM ALL. 1127 00:44:23,480 --> 00:44:35,040 THANK YOU VERY MUCH. 1128 00:44:35,040 --> 00:44:38,200 >> GREAT, THANKS SO MUCH FOR A 1129 00:44:38,200 --> 00:44:38,680 REALLY EXCELLENT TALK. 1130 00:44:38,680 --> 00:44:39,880 WE HAVE A BUNCH OF QUESTIONS, 1131 00:44:39,880 --> 00:44:42,880 BUT FIRST I WANT TO REPEAT THE 1132 00:44:42,880 --> 00:44:46,680 CME CODE, WHICH IS 37963. 1133 00:44:46,680 --> 00:44:48,760 THAT'S 37963 AND I PRACTICE TOO 1134 00:44:48,760 --> 00:44:51,280 AND STEVE ALMOST MESSED ME UP 1135 00:44:51,280 --> 00:44:51,840 THERE SAYING IT EARLIER. 1136 00:44:51,840 --> 00:44:55,960 ALL RIGHT, SO WE HAVE A BUNCH OF 1137 00:44:55,960 --> 00:44:58,960 QUESTIONS THAT ARE RELATED TO 1138 00:44:58,960 --> 00:45:02,480 DIFFERENCES IN--SO HOW DO THESE 1139 00:45:02,480 --> 00:45:03,600 MUTATIONS CONTRIBUTE TO BOTH 1140 00:45:03,600 --> 00:45:06,400 INFECTION IN THE PATIENT BUT 1141 00:45:06,400 --> 00:45:09,280 MOSTLY INFECTIOUSNESS VERSUS 1142 00:45:09,280 --> 00:45:09,680 SHEDDING, VERSUS 1143 00:45:09,680 --> 00:45:11,520 TRANSMISSIBILITY, CAN YOU GO 1144 00:45:11,520 --> 00:45:13,280 INTO MORE DETAIL ABOUT WHAT SOME 1145 00:45:13,280 --> 00:45:14,560 OF THESE MUTATIONS SPECIFICALLY 1146 00:45:14,560 --> 00:45:17,040 IN THE S1 PROTEIN, HOW THOSE ARE 1147 00:45:17,040 --> 00:45:20,240 GOING TO AFFECT TRANSMISSIBILITY 1148 00:45:20,240 --> 00:45:21,480 AND INFECTIOUSNESS AND THEN TO 1149 00:45:21,480 --> 00:45:24,440 FOLLOW UP WITH THAT ALSO, TO 1150 00:45:24,440 --> 00:45:26,880 WHAT EXTENT DO YOU THINK THAT 1151 00:45:26,880 --> 00:45:30,440 THE PHENOMENON OF THIS VIRUS 1152 00:45:30,440 --> 00:45:32,560 SIMMERING AND MUTATING IN AN 1153 00:45:32,560 --> 00:45:33,720 IMMUNO COMPROMISED PERSON BEFORE 1154 00:45:33,720 --> 00:45:38,480 THEY EMERGE INTO THE HEALTHY 1155 00:45:38,480 --> 00:45:39,680 POPULATION, YOU KNOW HOW MUCH DO 1156 00:45:39,680 --> 00:45:41,880 YOU THINK THAT ACTUALLY WOULD 1157 00:45:41,880 --> 00:45:44,280 CONTRIBUTE TO VIRUS 1158 00:45:44,280 --> 00:45:44,600 TRANSMISSION? 1159 00:45:44,600 --> 00:45:46,360 >> ALL RIGHT, SO THE FIRST 1160 00:45:46,360 --> 00:45:48,880 QUESTION EMILY WAS WHAT ARE 1161 00:45:48,880 --> 00:45:52,080 THESE DIFFERENT MUTATIONS DOING 1162 00:45:52,080 --> 00:45:52,520 PHENOTYPICALLY, RIGHT? 1163 00:45:52,520 --> 00:45:54,280 IS THAT THE QUESTION? 1164 00:45:54,280 --> 00:45:56,800 >> YEAH, SO, WE'RE INTERESTED IN 1165 00:45:56,800 --> 00:45:58,960 YOU KNOW, OKAY, SO THESE IMMUNO 1166 00:45:58,960 --> 00:46:00,160 COMPROMISED PATIENTS THEY HAVE 1167 00:46:00,160 --> 00:46:01,280 THE VIRUS LONGER BUT WHAT DOES 1168 00:46:01,280 --> 00:46:05,840 THAT MEAN IN TERMS OF BOTH 1169 00:46:05,840 --> 00:46:07,760 WITHIN PATIENT, DURATION OF 1170 00:46:07,760 --> 00:46:09,440 DISEASE BUT ALSO 1171 00:46:09,440 --> 00:46:09,880 TRANSMISSIBILITY AND 1172 00:46:09,880 --> 00:46:11,040 INFECTIOUSNESS, BECAUSE IF 1173 00:46:11,040 --> 00:46:13,120 THEY'RE PC R POSITIVE THEY COULD 1174 00:46:13,120 --> 00:46:14,880 JUST BE SHEDDING VIRUS. 1175 00:46:14,880 --> 00:46:15,200 >> RIGHT. 1176 00:46:15,200 --> 00:46:17,280 SO THE REASON WE KNOW THEY'RE 1177 00:46:17,280 --> 00:46:19,400 NOT JUST SHEDDING SO WE KNOW 1178 00:46:19,400 --> 00:46:20,560 THEY'RE SHEDDING VIRUS BUT THAT 1179 00:46:20,560 --> 00:46:22,440 THE VIRUS IS ACTUALLY 1180 00:46:22,440 --> 00:46:23,120 REPLICATING SIMPLY BECAUSE THE 1181 00:46:23,120 --> 00:46:28,360 FACT THAT WE'RE ABLE TO SEQUENCE 1182 00:46:28,360 --> 00:46:31,440 THE SAMPLE THE SEQUENCE MEANS 1183 00:46:31,440 --> 00:46:34,680 THE VIRAL LOAD IS HIGH ENOUGH TO 1184 00:46:34,680 --> 00:46:35,720 SEQUENCE AND PHENOTYPICALLY WHAT 1185 00:46:35,720 --> 00:46:38,080 DOES THAT MEAN FOR TRANSMISSION, 1186 00:46:38,080 --> 00:46:40,680 YOU KNOW YOU KNOW A VIRUS CAN 1187 00:46:40,680 --> 00:46:41,680 HAVE MUTATIONS THAT DO DIFFERENT 1188 00:46:41,680 --> 00:46:43,080 THINGS, WE HAVE A MUTATION THAT 1189 00:46:43,080 --> 00:46:45,840 LEADS TO EITHER BETTER 1190 00:46:45,840 --> 00:46:48,880 TRANSMISSION AND THAT MAY BE 1191 00:46:48,880 --> 00:46:53,000 BECAUSE IT TENDS TO EITHER 1192 00:46:53,000 --> 00:46:56,280 ACCUMULATE EITHER LOAD SO THAT 1193 00:46:56,280 --> 00:46:57,680 TRANSMITTING IS EASIER BECAUSE 1194 00:46:57,680 --> 00:46:59,880 YOU HAVE MORE THAN YOU'RE 1195 00:46:59,880 --> 00:47:01,160 EXPELLING WHEN YOU SNEEZE FOR 1196 00:47:01,160 --> 00:47:03,280 EXAMPLE, BUT THERE ARE ALSO 1197 00:47:03,280 --> 00:47:05,360 MUTATIONS THAT EVEN IF YOU'RE 1198 00:47:05,360 --> 00:47:08,880 NOT TRANSMITTING BETTER BUT YOU 1199 00:47:08,880 --> 00:47:10,760 ACTUALLY CAN ENTER CELLS BETTER, 1200 00:47:10,760 --> 00:47:14,520 WHICH I GUESS IS A KIND OF 1201 00:47:14,520 --> 00:47:16,280 TRANSMISSION, SO THERE ARE 1202 00:47:16,280 --> 00:47:17,200 SPECIFIC MUTATIONS WITH 1203 00:47:17,200 --> 00:47:18,400 DIFFERENT PHENOTYPES LIKE THAT, 1204 00:47:18,400 --> 00:47:21,600 NOW THERE'S SOME THAT HAVE BEEN 1205 00:47:21,600 --> 00:47:22,520 WELL CHARACTERIZED AS WE 1206 00:47:22,520 --> 00:47:23,720 UNDERSTAND THIS VIRUS MORE AND 1207 00:47:23,720 --> 00:47:27,720 MORE AND THERE ARE TEAMS WORKING 1208 00:47:27,720 --> 00:47:29,560 ON INVITRO EXPERIMENTS AND 1209 00:47:29,560 --> 00:47:31,120 INVIVO EXPERIMENTS SO IN ANIMAL 1210 00:47:31,120 --> 00:47:32,080 MODELS WHERE THEY ARE TESTING 1211 00:47:32,080 --> 00:47:33,480 SOME OF THESE MUTATIONS. 1212 00:47:33,480 --> 00:47:36,360 SO MANY OF THE MUTATIONS WE'VE 1213 00:47:36,360 --> 00:47:37,680 SHOWN FROM THE VARIANTS OF 1214 00:47:37,680 --> 00:47:41,080 CONCERNS, SOME OF THEM ARE WELL 1215 00:47:41,080 --> 00:47:42,440 CHARACTERIZED LIKE THE 501 FOR 1216 00:47:42,440 --> 00:47:43,640 EXAMPLE, AND THERE ARE OTHERS 1217 00:47:43,640 --> 00:47:46,720 THAT ARE NOT SO WELL 1218 00:47:46,720 --> 00:47:50,560 CHARACTERIZED SO THE QUESTION TO 1219 00:47:50,560 --> 00:47:52,800 INFORM THE INVITRO 1220 00:47:52,800 --> 00:47:53,720 EXPERIMENTALIST OR INVIVO 1221 00:47:53,720 --> 00:47:54,440 EXPERIMENTALIST IS TO GIVE A 1222 00:47:54,440 --> 00:47:56,080 LIST OF SOME OF THESE MUTATIONS 1223 00:47:56,080 --> 00:47:59,240 THAT APPEAR TO BE RECURRING LIKE 1224 00:47:59,240 --> 00:48:02,280 THESE HOT SPOTS WE'VE SEEN AND 1225 00:48:02,280 --> 00:48:04,120 THEN TEST THEM TO SEE REALLY 1226 00:48:04,120 --> 00:48:07,880 WHAT IT MEANS, BUT TO TELL YOU 1227 00:48:07,880 --> 00:48:08,920 TODAY FOR THAT PATIENT WHAT IT 1228 00:48:08,920 --> 00:48:10,080 WOULD MEAN FOR THAT PATIENT, 1229 00:48:10,080 --> 00:48:11,640 UNLESS WE HAVE THAT EXPERIMENTAL 1230 00:48:11,640 --> 00:48:15,680 DATA WE DON'T REALLY KNOW WHAT 1231 00:48:15,680 --> 00:48:16,880 IS HAPPENING WITH THAT PATIENT. 1232 00:48:16,880 --> 00:48:35,840 I DON'T KNOW IF THAT ANSWERED 1233 00:48:35,840 --> 00:48:37,160 THE QUESTION. 1234 00:48:37,160 --> 00:48:38,200 >> --WE'VE SEEN REPORTS COMING 1235 00:48:38,200 --> 00:48:40,320 OUT RECENTLY ABOUT POTENTIAL 1236 00:48:40,320 --> 00:48:41,960 VARIANTS CROPPING UP IN HIV 1237 00:48:41,960 --> 00:48:42,880 POSITIVE PATIENTS OR SOMETHING 1238 00:48:42,880 --> 00:48:47,000 LIKE THAT, HOW MUCH DOES THIS 1239 00:48:47,000 --> 00:48:47,280 CONTRIBUTE? 1240 00:48:47,280 --> 00:48:48,960 YEAH SO THAT'S THE QUESTION, IT 1241 00:48:48,960 --> 00:48:51,000 WAS THOUGHT THAT ALPHA CAME FROM 1242 00:48:51,000 --> 00:48:52,480 AN IMMUNO COMPROMISED PATIENT 1243 00:48:52,480 --> 00:48:53,800 WITH THESE PATIENTS THAT 1244 00:48:53,800 --> 00:48:54,880 ACCUMULATED AND SOME POINT A 1245 00:48:54,880 --> 00:48:58,640 MUTATION THAT MADE THAT VIRUS 1246 00:48:58,640 --> 00:48:59,320 MORE TRANSMISSIBLE HAD OCCURRED 1247 00:48:59,320 --> 00:49:03,680 AND SO THE QUESTION, 1 OF THE 1248 00:49:03,680 --> 00:49:04,720 HYPOTHESIS WITH OMICRON IS 1249 00:49:04,720 --> 00:49:06,560 THAT'S WHAT HAPPENED ALSO, 1250 00:49:06,560 --> 00:49:09,080 PROBABLY AN UNCONTROLLED HIV, 1251 00:49:09,080 --> 00:49:10,680 YOU WOULD HAVE HAD THIS 1252 00:49:10,680 --> 00:49:12,000 ACCUMULATION OF MUTATIONS AND 1253 00:49:12,000 --> 00:49:13,400 THEN THIS VIRUS TOOK OFF. 1254 00:49:13,400 --> 00:49:17,400 NOW WE DON'T KNOW IF THAT IS THE 1255 00:49:17,400 --> 00:49:20,000 CASE, IT'S JUST A HYPOTHESIS AT 1256 00:49:20,000 --> 00:49:20,640 THIS POINT. 1257 00:49:20,640 --> 00:49:22,400 IT'S POSSIBLE, BUT WE--YOU KNOW 1258 00:49:22,400 --> 00:49:25,200 WE HAVE TO THINK ALSO, THERE ARE 1259 00:49:25,200 --> 00:49:27,320 DIFFERENT TYPES OF IMMUNO 1260 00:49:27,320 --> 00:49:28,680 COMPROMISED, THERE ARE PEOPLE 1261 00:49:28,680 --> 00:49:31,080 WHO STILL HAVE PARTS OF THEIR 1262 00:49:31,080 --> 00:49:33,480 IMMUNE SYSTEM THAT DOES 1263 00:49:33,480 --> 00:49:34,520 FUNCTION, IT'S--THERE ARE 1264 00:49:34,520 --> 00:49:37,360 DIFFERENT ASSPEBTS, YOU KNOW THE 1265 00:49:37,360 --> 00:49:39,520 DIFFERENT CASES THAT LISTED THEY 1266 00:49:39,520 --> 00:49:43,800 DON'T ALL HAVE THE SAME SORT OF 1267 00:49:43,800 --> 00:49:44,200 IMMUNO COMPROMISE. 1268 00:49:44,200 --> 00:49:46,840 AND WHAT YOU CAN IMAGINE IN 1269 00:49:46,840 --> 00:49:48,680 SOMEBODY THAT WOULD BE HEAVILY 1270 00:49:48,680 --> 00:49:51,080 IMMUNO SUPPRESSED, IS THAT THE 1271 00:49:51,080 --> 00:49:53,560 VIRUS DOES REPLICATE, BUT IF YOU 1272 00:49:53,560 --> 00:49:55,520 HAVE NO IMMUNE PRESSURE AT ALL, 1273 00:49:55,520 --> 00:49:57,880 THIS SIGNIFY HAVE YOU SEEN COULD 1274 00:49:57,880 --> 00:49:59,760 JUST ACCUMULATE RANDOM MUTATIONS 1275 00:49:59,760 --> 00:50:01,440 THAT ARE--YOU KNOW THAT CAN BE 1276 00:50:01,440 --> 00:50:02,560 COMPLETELY NEUTRAL AND THEY 1277 00:50:02,560 --> 00:50:03,800 NEVER GET PUDGIERED BECAUSE 1278 00:50:03,800 --> 00:50:09,960 THERE'S NO PRESSURE FOR THEM TO 1279 00:50:09,960 --> 00:50:10,440 BE PUDGIERED, RIGHT? 1280 00:50:10,440 --> 00:50:12,320 BUT IF YOU HAVE PARTIAL 1281 00:50:12,320 --> 00:50:14,080 IMMUNITY, YOU CAN SEE SOME 1282 00:50:14,080 --> 00:50:15,400 SELECTION PRESSURE THAT HAS 1283 00:50:15,400 --> 00:50:18,880 OCCURRED SO CAN YOU ARGUE THAT 1284 00:50:18,880 --> 00:50:20,080 IN AN IMMUNO COMPETENT PERSON 1285 00:50:20,080 --> 00:50:21,360 YOU COULD ALSO HAVE MUTATIONS 1286 00:50:21,360 --> 00:50:25,800 THAT HAPPEN BECAUSE THE VIRUS IS 1287 00:50:25,800 --> 00:50:28,320 TRYING TO EVADE A VERY STRONG 1288 00:50:28,320 --> 00:50:32,080 IMMUNE RESPONSE OF AN IMMUNO 1289 00:50:32,080 --> 00:50:33,960 COMPETENT PERSON BUT THE 1290 00:50:33,960 --> 00:50:35,360 SARS-COV-2 IS AN ACUTE INFECTION 1291 00:50:35,360 --> 00:50:37,320 SO THAT THE VIRUS DOESN'T HAVE 1292 00:50:37,320 --> 00:50:41,280 THAT MUCH TIME TO EVOLVE WITHIN 1293 00:50:41,280 --> 00:50:43,040 AN ACUTE INFECTION. 1294 00:50:43,040 --> 00:50:46,240 AND SO, THAT'S WHY THERE'S SORT 1295 00:50:46,240 --> 00:50:49,000 OF THIS BALANCE BETWEEN LONG 1296 00:50:49,000 --> 00:50:51,520 INFECTION, LOW IMMUNE PRESSURE, 1297 00:50:51,520 --> 00:50:52,240 SHORT INFECTION, STRONG IMMUNE 1298 00:50:52,240 --> 00:50:54,480 PRESSURE AND THERE MAY BE 1299 00:50:54,480 --> 00:50:55,280 SOMETHING IN BETWEEN THAT COULD 1300 00:50:55,280 --> 00:51:00,960 LEAD TO SOME OF THESE VARIANTS 1301 00:51:00,960 --> 00:51:01,680 OF CONCERN. 1302 00:51:01,680 --> 00:51:03,040 >> SO HERE'S A FOLLOW UP 1303 00:51:03,040 --> 00:51:04,480 QUESTION FROM DR. COLLINS, YOU 1304 00:51:04,480 --> 00:51:06,520 ANSWERED SORT OF THE FIRST PART 1305 00:51:06,520 --> 00:51:08,200 SO WOULDN'T THE SELECTION IN AN 1306 00:51:08,200 --> 00:51:10,280 IMMUNE ON O COMPROMISE PATIENT 1307 00:51:10,280 --> 00:51:12,560 BE DIFFERENT THAN IN AN ANIMAL 1308 00:51:12,560 --> 00:51:17,520 AND ALSO AS YOU MENTIONED IN AN 1309 00:51:17,520 --> 00:51:19,560 IMMUNO COMPROMISED PERSON? 1310 00:51:19,560 --> 00:51:20,520 BUT DOESN'T OMICRON FIT 1 OF 1311 00:51:20,520 --> 00:51:22,080 THESE BETTER THAN THE OTHER? 1312 00:51:22,080 --> 00:51:23,080 >> THAT'S A VERY GOOD QUESTION, 1313 00:51:23,080 --> 00:51:28,280 IT'S NOT CLEAR TO ME WHICH 1 1314 00:51:28,280 --> 00:51:29,120 FITS BETTER. 1315 00:51:29,120 --> 00:51:34,680 THERE'S SOME ARGUING FOR THE 1316 00:51:34,680 --> 00:51:35,480 ANIMAL RESERVOIR HYPOTHESIS AND 1317 00:51:35,480 --> 00:51:37,880 I DON'T KNOW HOW STRONG THE 1318 00:51:37,880 --> 00:51:40,520 EVIDENCE IS FOR THAT AT THIS 1319 00:51:40,520 --> 00:51:42,480 POINT, JUST LIKE I'M NOT SURE 1320 00:51:42,480 --> 00:51:44,640 THE EVIDENCE IS ALL THERE EITHER 1321 00:51:44,640 --> 00:51:48,320 FOR THE IMMUNO COMPROMISED 1322 00:51:48,320 --> 00:51:49,040 PATIENT HYPOTHESIS. 1323 00:51:49,040 --> 00:51:51,640 SO, I DON'T KNOW, I DON'T KNOW 1324 00:51:51,640 --> 00:51:52,560 WHAT THE ANSWER IS. 1325 00:51:52,560 --> 00:51:57,200 I THINK THERE HAS BEEN A LITTLE 1326 00:51:57,200 --> 00:51:58,240 BIT MORE--INITIALLY IT WAS 1327 00:51:58,240 --> 00:52:01,720 THOUGHT, I REMEMBER WHEN OMICOON 1328 00:52:01,720 --> 00:52:03,560 CAME OUT, THE ANIMAL RESERVOIR 1329 00:52:03,560 --> 00:52:06,560 PEOPLE WERE LIKE, YOU MUST BE 1330 00:52:06,560 --> 00:52:07,520 ANIMAL RESERVOIR AND OTHERS WERE 1331 00:52:07,520 --> 00:52:10,080 SAYING I HAVE NO IDEA BUT AT 1332 00:52:10,080 --> 00:52:13,480 THIS POINT, I THINK IT'S 50/50 1333 00:52:13,480 --> 00:52:17,320 MAYBE, YOU KNOW, WHERE IT CAME 1334 00:52:17,320 --> 00:52:18,280 FROM. 1335 00:52:18,280 --> 00:52:18,680 >> GOTCHA. 1336 00:52:18,680 --> 00:52:19,880 ALL RIGHT, LET'S GO OVER TO 1337 00:52:19,880 --> 00:52:21,280 QUESTIONS ABOUT THE IMMUNE 1338 00:52:21,280 --> 00:52:21,480 SYSTEM. 1339 00:52:21,480 --> 00:52:22,480 SO THE FIRST PRESENTATION 1340 00:52:22,480 --> 00:52:24,560 FOCUSED ON THE ROLE OF 1341 00:52:24,560 --> 00:52:25,600 ANTIBODIES IN INFECTION, COULD 1342 00:52:25,600 --> 00:52:28,720 YOU COMMENT ON THE ROLE OF VIRUS 1343 00:52:28,720 --> 00:52:29,880 SPECIFIC T-CELLS, IN CLEARING 1344 00:52:29,880 --> 00:52:36,280 AND HOW THAT MIGHT AFFECT THIS 1345 00:52:36,280 --> 00:52:36,520 PROCESS. 1346 00:52:36,520 --> 00:52:38,560 SAME QUESTION FOR ME, SO I'M NOT 1347 00:52:38,560 --> 00:52:43,080 AN IMMUNOLOGYST SO I WON'T BE 1348 00:52:43,080 --> 00:52:46,080 ABLE TO DETAIL BUT WHAT I THINK 1349 00:52:46,080 --> 00:52:51,280 IS CLEAR IS THAT IN IMMUNO 1350 00:52:51,280 --> 00:52:54,480 COMPETENT PATIENTS, THAT WHAT 1351 00:52:54,480 --> 00:52:55,440 CORRELATES WITH CLINICAL 1352 00:52:55,440 --> 00:52:56,720 IMPROVEMENT IS THE FORMATION OF 1353 00:52:56,720 --> 00:52:59,560 ANTIBODIES AND I THINK THAT'S 1354 00:52:59,560 --> 00:53:00,360 VERY CLEAR. 1355 00:53:00,360 --> 00:53:01,720 IT'S ALWAYS BEEN VERY CLEAR FROM 1356 00:53:01,720 --> 00:53:03,280 THE BEGINNING AND THAT IT'S ALSO 1357 00:53:03,280 --> 00:53:07,480 VERY CLEAR THAT THE PATIENTS WHO 1358 00:53:07,480 --> 00:53:11,280 ARE--WHO DON'T HAVE THAT 1359 00:53:11,280 --> 00:53:12,640 ANTIBODY PRODUCTION JUST DO NOT 1360 00:53:12,640 --> 00:53:16,640 DO WELL AND SO, AGAIN, I THINK 1361 00:53:16,640 --> 00:53:20,080 MOST OF THESE PATIENTS WHO HAVE 1362 00:53:20,080 --> 00:53:21,720 B-CELL DEPLETION HAVE SOME 1363 00:53:21,720 --> 00:53:24,400 T-CELL IMPAIRMENT AS WELL. 1364 00:53:24,400 --> 00:53:26,040 SO, BUT AGAIN THE SPECIFIC ROLE 1365 00:53:26,040 --> 00:53:28,040 OF THE T-CELLS UNFORTUNATELY I 1366 00:53:28,040 --> 00:53:41,960 CAN'T--I CAN'T TOUCH ON BUT 1367 00:53:41,960 --> 00:53:43,840 CLEARLY--SO I THINK, YOU KNOW 1368 00:53:43,840 --> 00:53:45,120 T-CELLS ARE CLEARLY IMPORTANT AS 1369 00:53:45,120 --> 00:53:48,720 WELL, BUT OF COURSE I CAN'T SAY 1370 00:53:48,720 --> 00:53:49,840 MORE ABOUT THAT. 1371 00:53:49,840 --> 00:53:53,280 >> OKAY, THE NIH PATIENT WITH 1372 00:53:53,280 --> 00:53:54,520 PROLONGED SARS-COV-2 INFECTION 1373 00:53:54,520 --> 00:53:57,160 WAS NEGATIVE IN THEIR MP SWABS 1374 00:53:57,160 --> 00:53:59,080 BUT POSITIVE IN THE BALL, CAN 1375 00:53:59,080 --> 00:54:00,280 YOU SPEAK OUT, DO YOU KNOW HOW 1376 00:54:00,280 --> 00:54:01,560 OFTEN THAT OCCURS AND DOES THIS 1377 00:54:01,560 --> 00:54:03,320 LEAD TO US MISSING OTHER 1378 00:54:03,320 --> 00:54:03,760 INFECTED PEOPLE? 1379 00:54:03,760 --> 00:54:07,800 SORE IS IT LIMITED TO THE 1380 00:54:07,800 --> 00:54:08,560 SEVERELY IMMUNO COMPROMISED? 1381 00:54:08,560 --> 00:54:11,080 AND ALSO IS THIS IMPACTED AT ALL 1382 00:54:11,080 --> 00:54:11,640 BY VARIANTS? 1383 00:54:11,640 --> 00:54:13,080 >> SO YEAH, I CAN ANSWER THE 1384 00:54:13,080 --> 00:54:13,520 FIRST PART. 1385 00:54:13,520 --> 00:54:15,400 I DON'T KNOW HOW FREQUENTLY IT 1386 00:54:15,400 --> 00:54:16,800 HAPPENS BUT IT HAPPENS NOT 1387 00:54:16,800 --> 00:54:24,040 INFETAL COMPARTMENT - 1388 00:54:24,040 --> 00:54:25,640 -INFREQUENTLY AND IT 1389 00:54:25,640 --> 00:54:27,280 HAPPENS IN IMMUNO COMPROMISED 1390 00:54:27,280 --> 00:54:27,680 PATIENTS AS WELL. 1391 00:54:27,680 --> 00:54:29,080 AND WHEN THIS HAPPENED WE 1392 00:54:29,080 --> 00:54:30,320 STARTED TO TALKING TO COLLEAGUES 1393 00:54:30,320 --> 00:54:31,600 AT OTHER INSTITUTIONS WHO SAID 1394 00:54:31,600 --> 00:54:33,040 OH YEAH, WE SEE THIS, WE HAVE 1395 00:54:33,040 --> 00:54:34,440 PATIENT WHO IS COME IN AND YOU 1396 00:54:34,440 --> 00:54:35,760 KNOW WE SWAB THEM, THEY'RE 1397 00:54:35,760 --> 00:54:36,960 NEGATIVE AND THEN YOU ACTUALLY 1398 00:54:36,960 --> 00:54:38,040 LOOK FOR DEEPER SAMPLES AND 1399 00:54:38,040 --> 00:54:39,040 THEY'RE POSITIVE AND I THINK 1400 00:54:39,040 --> 00:54:40,080 WHAT'S HAPPENING THERE IS JUST 1401 00:54:40,080 --> 00:54:44,080 THAT YOU KNOW PEOPLE WILL HAVE 1402 00:54:44,080 --> 00:54:48,280 MORE VIRUS IN DIFFERENT PARTS OF 1403 00:54:48,280 --> 00:54:50,080 THEIR AIRWAY AND THAT'S WHY WE 1404 00:54:50,080 --> 00:54:52,040 DO GO LOOKING FOR DEEPER AIR WAY 1405 00:54:52,040 --> 00:54:53,680 SAMPLES WHEN WE SUSPECT SARKINGS 1406 00:54:53,680 --> 00:54:55,200 KICKOFF 2 INFECTION BUT WE HAVE 1407 00:54:55,200 --> 00:54:57,080 NEGATIVE TESTING AND WE DO THAT 1408 00:54:57,080 --> 00:54:58,360 ON A REGULAR BASIS. 1409 00:54:58,360 --> 00:55:00,840 AND THERE ARE SOME PATIENTS WE 1410 00:55:00,840 --> 00:55:03,080 DON'T TRUST, DO NOT HAVE 1411 00:55:03,080 --> 00:55:04,160 SARS-COV-2 INFECTION UNTIL WE 1412 00:55:04,160 --> 00:55:05,480 GET THOSE SAMPLES AND THOSE MAKE 1413 00:55:05,480 --> 00:55:08,800 US FEEL BETTER WHEN THEY'RE 1414 00:55:08,800 --> 00:55:09,280 NEGATIVE. 1415 00:55:09,280 --> 00:55:12,680 SO I THINK IT'S PECULIAR THAT 1416 00:55:12,680 --> 00:55:16,800 AFTER THE BALL THAT SHE THEN HAD 1417 00:55:16,800 --> 00:55:19,120 POSITIVE ORAL AND 1418 00:55:19,120 --> 00:55:19,840 NASO-PHARYNGIAL SWABS. 1419 00:55:19,840 --> 00:55:21,280 I CAN'T EXPLAIN THAT, I'M NOT 1420 00:55:21,280 --> 00:55:22,440 SURE WHAT HAPPENED THERE OTHER 1421 00:55:22,440 --> 00:55:25,680 THAN PERHAPS WE WERE JUST 1422 00:55:25,680 --> 00:55:27,360 GETTING DEEPER INTO HER 1423 00:55:27,360 --> 00:55:29,800 INFECTION AND IT'S SUDDENLY 1424 00:55:29,800 --> 00:55:31,280 BECAME POSITIVE, I'M REALLY NOT 1425 00:55:31,280 --> 00:55:31,520 SURE. 1426 00:55:31,520 --> 00:55:33,280 I THINK WHAT WAS INTERESTING IN 1427 00:55:33,280 --> 00:55:35,040 THIS PATIENT IS THAT IF WE 1428 00:55:35,040 --> 00:55:38,720 LOOKING BACK ON IT, IF WE HAD 1429 00:55:38,720 --> 00:55:40,480 HAD BALL SAMPLES, WHEN SHE WAS 1430 00:55:40,480 --> 00:55:43,920 HAVING THESE MILD SYMPTOMS WHICH 1431 00:55:43,920 --> 00:55:46,680 WE HAD BROUGHT UP BUT AGAIN IT'S 1432 00:55:46,680 --> 00:55:47,760 AN INVASIVE PROCEDURE AND 1433 00:55:47,760 --> 00:55:48,880 DECLINED IT, MAYBE WE WOULD HAVE 1434 00:55:48,880 --> 00:55:51,080 BEEN TIPPED OFF EARLIER THAT HER 1435 00:55:51,080 --> 00:55:52,600 VIRAL LOAD MAY HAVE BEEN HIGHER, 1436 00:55:52,600 --> 00:55:54,680 YOU KNOW DEEP DOWN IN HER LUNGS 1437 00:55:54,680 --> 00:55:56,320 AND MAYBE WE WOULD HAVE THOUGHT 1438 00:55:56,320 --> 00:55:59,320 DIFFERENTLY ABOUT THIS CASE. 1439 00:55:59,320 --> 00:56:00,720 I THINK--I KNOW I WOULD HAVE 1440 00:56:00,720 --> 00:56:04,440 THOUGHT DIFFERENTLY ABOUT THE 1441 00:56:04,440 --> 00:56:04,640 CASE. 1442 00:56:04,640 --> 00:56:06,440 SO, TO ANSWER THE QUESTION, WE 1443 00:56:06,440 --> 00:56:08,600 DO SEE THIS, I RECENTLY WAS AT 1444 00:56:08,600 --> 00:56:09,560 ANOTHER HOSPITAL LAST WEEKEND 1445 00:56:09,560 --> 00:56:11,400 AND I HAD THE SAME SITUATION A 1446 00:56:11,400 --> 00:56:15,320 PATIENT WHO JUST KEPT TESTING 1447 00:56:15,320 --> 00:56:18,640 NEGATIVE AND THANKFULLY, KEPT ON 1448 00:56:18,640 --> 00:56:20,280 ISOLATION BECAUSE THEY ENDED UP 1449 00:56:20,280 --> 00:56:22,800 BEING POSITIVE ON A BALL. 1450 00:56:22,800 --> 00:56:23,880 ARE WE MISSING PEOPLE? 1451 00:56:23,880 --> 00:56:27,360 I HOPE NOT BECAUSE I THINK 1452 00:56:27,360 --> 00:56:28,680 EVERYBODY IS SO CAREFUL NOW AND 1453 00:56:28,680 --> 00:56:30,360 ESPECIALLY IN THE HOSPITAL 1454 00:56:30,360 --> 00:56:33,280 SETTING, PEOPLE ARE KEPT ON 1455 00:56:33,280 --> 00:56:34,400 ISOLATION WHEN THERE'S SUSPICION 1456 00:56:34,400 --> 00:56:38,560 EVEN WITH NEGATIVE TESTING. 1457 00:56:38,560 --> 00:56:40,400 >> SO RELATED WHAT HAPPENS TO 1458 00:56:40,400 --> 00:56:42,080 THIS PARTICULAR PATIENT'S 1459 00:56:42,080 --> 00:56:43,640 ORGANIZING PNEUMONIA ONCE THE 1460 00:56:43,640 --> 00:56:44,080 VIRUS WAS CLEARED? 1461 00:56:44,080 --> 00:56:46,680 BUT THEN ALSO WHAT WAS THE--WHY 1462 00:56:46,680 --> 00:56:48,960 DOES THE CDC GUIDANCE FOR 1463 00:56:48,960 --> 00:56:51,200 OUTPATIENT IMMUNO COMPROMISED 1464 00:56:51,200 --> 00:56:55,000 PATIENTS SUGGEST ISOLATION FOR A 1465 00:56:55,000 --> 00:56:55,880 MINIMUM OF 10-20 DAYS? 1466 00:56:55,880 --> 00:56:58,840 DO YOU THINK THIS IS TOO SHORT? 1467 00:56:58,840 --> 00:56:59,800 >> YEAH, SO FOR THE FIRST 1468 00:56:59,800 --> 00:57:01,160 QUESTION FOR THE ORGANIZING 1469 00:57:01,160 --> 00:57:02,080 PNEUMONIA, I THINK WHAT HAPPENED 1470 00:57:02,080 --> 00:57:06,840 IN OUR PATIENT IS THAT YOU KNOW 1471 00:57:06,840 --> 00:57:09,280 SHE--I THINK MAYBE SHE HAD A 1472 00:57:09,280 --> 00:57:10,400 COMPONENT OF ORGANIZING 1473 00:57:10,400 --> 00:57:12,080 PNEUMONIA WHICH IS JUST AN 1474 00:57:12,080 --> 00:57:13,680 IMMUNE DRIVEN PROCESS OF TRYING 1475 00:57:13,680 --> 00:57:15,320 TO HEAL THE LUNG BUT CAUSING 1476 00:57:15,320 --> 00:57:18,640 DAMAGE AT THE SAME TIME BUT I 1477 00:57:18,640 --> 00:57:21,920 THINK--I THINK HER SYMPTOMS WERE 1478 00:57:21,920 --> 00:57:22,480 ACTUALLY FROM SARS-COV-2. 1479 00:57:22,480 --> 00:57:23,560 BECAUSE I THINK WHEN WE CLEARED 1480 00:57:23,560 --> 00:57:25,480 THAT VIRUS OR INFLAMMATORY 1481 00:57:25,480 --> 00:57:28,680 MARKERS THAT HAD NEVER BEEN 1482 00:57:28,680 --> 00:57:29,120 NORMAL, NORMALIZED. 1483 00:57:29,120 --> 00:57:31,240 AND SHE NO LONGER NEEDED OXYGEN 1484 00:57:31,240 --> 00:57:33,160 AND I THINK THAT THE ENTIRE TIME 1485 00:57:33,160 --> 00:57:36,040 WE WERE SEEING THIS WAS COVID 1486 00:57:36,040 --> 00:57:37,040 THE ENTIRE TIME. 1487 00:57:37,040 --> 00:57:38,720 WE DID WEAN HER STEROIDS SO WHEN 1488 00:57:38,720 --> 00:57:40,600 YOU PUT SOMEONE ON STEROIDS YOU 1489 00:57:40,600 --> 00:57:41,880 CAN'T JUST STOP THEM IMMEDIATELY 1490 00:57:41,880 --> 00:57:44,200 AND SHE SHE WAS ON SOME STEROIDS 1491 00:57:44,200 --> 00:57:48,000 FOR A COUPLE OF WEEKS WHILE 1492 00:57:48,000 --> 00:57:49,920 WE'RE WEANING THEM DOWN AND SO 1493 00:57:49,920 --> 00:57:51,920 SHE DID GET SOME TREATMENT FOR 1494 00:57:51,920 --> 00:57:52,880 ORGANIZING PNEUMONIA BUT I THINK 1495 00:57:52,880 --> 00:57:54,920 AT THE END OF THE DAY, THIS WAS 1496 00:57:54,920 --> 00:57:56,760 REALLY MOSTLY DRICH BY THE 1497 00:57:56,760 --> 00:57:57,280 VIRUS. 1498 00:57:57,280 --> 00:58:02,560 --DRICH --DRIVEN BY THE VIRUS. 1499 00:58:02,560 --> 00:58:04,520 THE SECOND WAS ABOUT ISOLATION, 1500 00:58:04,520 --> 00:58:06,280 I THINK THE REASON IT'S LONGER 1501 00:58:06,280 --> 00:58:08,880 FOR PATIENTS THAT ARE IMMUNO 1502 00:58:08,880 --> 00:58:10,600 COMPROMISE -ED IS BECAUSE WE 1503 00:58:10,600 --> 00:58:11,720 KNOW PATIENTS HAVE LONGER 1504 00:58:11,720 --> 00:58:13,560 INFECTIONS AND THEY TEND TO HAVE 1505 00:58:13,560 --> 00:58:15,040 REPLICATING VIRUS FOR LONGER AND 1506 00:58:15,040 --> 00:58:17,680 THAT'S WHERE THAT 20 DAYS COMES 1507 00:58:17,680 --> 00:58:19,240 FROM. 1508 00:58:19,240 --> 00:58:21,280 DO I THINK IT'S TOO SHORT? 1509 00:58:21,280 --> 00:58:24,800 WELL THE CDC DOES SAY IN IMMUNO 1510 00:58:24,800 --> 00:58:26,120 COMPROMISED PATIENTS IT SHOULD 1511 00:58:26,120 --> 00:58:27,880 BE AT LEAST 20 DAYS BUT TALK TO 1512 00:58:27,880 --> 00:58:29,720 AN INFECT YOWZ DISEASE 1513 00:58:29,720 --> 00:58:30,680 SPECIALIST BUT THEN WE ARE LEFT 1514 00:58:30,680 --> 00:58:33,080 WITH TRYING TO FIGURE THIS OUT 1515 00:58:33,080 --> 00:58:37,360 AND THAT'S YOU KNOW THAT'S WHERE 1516 00:58:37,360 --> 00:58:39,680 IT GETS COMPLICATED WHERE IN A 1517 00:58:39,680 --> 00:58:52,800 HOSPITAL YOU CAN ASK FOR SOME OF 1518 00:58:52,800 --> 00:58:55,440 THESE SPECIALIZED--ELODIE, AND 1519 00:58:55,440 --> 00:58:56,720 DR. DASS IN NLM AND ASKING THEM 1520 00:58:56,720 --> 00:58:58,600 ABOUT CT VALUES AND WHAT THEIR 1521 00:58:58,600 --> 00:59:00,040 THOUGHTS ARE ON WHAT'S GOING ON, 1522 00:59:00,040 --> 00:59:02,560 SO, DO I THINK IT'S TOO SHORT? 1523 00:59:02,560 --> 00:59:04,880 FOR SOME IT IS AND FOR SOME IT'S 1524 00:59:04,880 --> 00:59:05,360 NOT? 1525 00:59:05,360 --> 00:59:08,920 THERE'S REALLY NO CLEAR ANSWER 1526 00:59:08,920 --> 00:59:09,160 THERE. 1527 00:59:09,160 --> 00:59:11,880 I THINK FOR SOME IT'S CLEARLY 1528 00:59:11,880 --> 00:59:13,080 TOO SHORT. 1529 00:59:13,080 --> 00:59:15,400 BUT IT DEPENDS. 1530 00:59:15,400 --> 00:59:16,680 >> GREAT, SO IT'S 1:00 O'CLOCK. 1531 00:59:16,680 --> 00:59:18,240 IT'S THERE ARE MORE QUESTIONS SO 1532 00:59:18,240 --> 00:59:20,720 IF YOU DON'T MIND I'M GOING TO 1533 00:59:20,720 --> 00:59:27,480 ASK A FEW MORE IF THAT'S OKAY. 1534 00:59:27,480 --> 00:59:27,720 EXCELLENT. 1535 00:59:27,720 --> 00:59:27,920 OKAY. 1536 00:59:27,920 --> 00:59:29,000 >> SO THERE WAS A REQUESTY ABOUT 1537 00:59:29,000 --> 00:59:33,960 ANY CONCERN THAT THE USE OF MUTE 1538 00:59:33,960 --> 00:59:38,640 O GENICS AS [INDISCERNIBLE] 1539 00:59:38,640 --> 00:59:39,400 ELEVATE CONCERNS? 1540 00:59:39,400 --> 00:59:41,200 WHAT DATA DO WE NEED TO INSURE 1541 00:59:41,200 --> 00:59:43,440 THAT THIS ISN'T HAPPENING IN 1542 00:59:43,440 --> 00:59:45,680 HEALTHY OR IMMUNO COMPROMISED 1543 00:59:45,680 --> 00:59:45,920 PATIENTS? 1544 00:59:45,920 --> 00:59:47,720 >> YEAH, I THINK THE DATA WILL 1545 00:59:47,720 --> 00:59:50,160 BE LOOKING AT THE VIRUSES AND 1546 00:59:50,160 --> 00:59:55,040 JUST LOOKING AT WHETHER THERE 1547 00:59:55,040 --> 00:59:58,760 ARE MUTATIONS FOR ANY ANTIVIRAL, 1548 00:59:58,760 --> 01:00:01,280 YOU'RE ALWAYS LOOKING AT 1549 01:00:01,280 --> 01:00:01,760 ANTIVIRAL RESISTANCE. 1550 01:00:01,760 --> 01:00:05,840 I DON'T KNOW IF THAT DEPENDS 1551 01:00:05,840 --> 01:00:06,680 WHAT WAS TARGETED OR THE 1552 01:00:06,680 --> 01:00:08,680 PARTICULAR 1 IS THE ACTUAL 1553 01:00:08,680 --> 01:00:11,880 POLYMER ACE THAT IS TARGETED SO 1554 01:00:11,880 --> 01:00:16,640 I THINK WE'LL JUST BE LOOKING. 1555 01:00:16,640 --> 01:00:17,080 >> GREAT. 1556 01:00:17,080 --> 01:00:18,720 CAN YOU SPEAK A LITTLE ABOUT WHY 1557 01:00:18,720 --> 01:00:22,520 THERE MIGHT BE MORE SELECTION 1558 01:00:22,520 --> 01:00:24,520 FOR ANDROGENIC CHANGE OR SOMEONE 1559 01:00:24,520 --> 01:00:27,920 WHO'S NOT RECEIVING THERAPEUTIC 1560 01:00:27,920 --> 01:00:28,360 ANTIBODIES. 1561 01:00:28,360 --> 01:00:31,080 >> SO I DON'T KNOW WHY THERE 1562 01:00:31,080 --> 01:00:34,520 WOULD BE NECESSARILY MORE, IT 1563 01:00:34,520 --> 01:00:38,640 SEEMS THERE ARE ANDROGENIC 1564 01:00:38,640 --> 01:00:40,520 CHANGES THAT OCCUR AND YOU KNOW 1565 01:00:40,520 --> 01:00:41,080 I DON'T KNOW. 1566 01:00:41,080 --> 01:00:42,920 I DON'T KNOW WHY WE WOULD EVEN 1567 01:00:42,920 --> 01:00:47,560 SEE SOME OF THESE LIKE OMICRON, 1568 01:00:47,560 --> 01:00:50,000 THESE ANTIGENIC SITES IF IT IS 1569 01:00:50,000 --> 01:00:51,080 AN IMMUNO COMPROMISED PERSON, 1570 01:00:51,080 --> 01:00:54,480 WHY YOU WOULD SEE SOME OF THESE 1571 01:00:54,480 --> 01:00:55,840 MUTATED SITES SO I DON'T KNOW 1572 01:00:55,840 --> 01:00:56,320 THE ANSWER. 1573 01:00:56,320 --> 01:00:57,640 >> OKAY, I THINK WE WRAP UP WITH 1574 01:00:57,640 --> 01:00:59,080 THE LAST 1 HERE, DO WE KNOW HOW 1575 01:00:59,080 --> 01:01:00,680 TD TYPES AND LOCATIONS OF 1576 01:01:00,680 --> 01:01:02,760 MUTATIONS FOR THE DIFFERENT 1577 01:01:02,760 --> 01:01:04,680 VARIANTS IMPACT THE SEVERITY OR 1578 01:01:04,680 --> 01:01:07,520 LOCALIZATION OF THE DISEASE FOR 1579 01:01:07,520 --> 01:01:08,840 IMMUNO COMPETENT INDIVIDUALS 1580 01:01:08,840 --> 01:01:09,880 AS--AGAIN WE SAW TAKEN--THEY 1581 01:01:09,880 --> 01:01:12,240 DELTA WAS NOR SEVERE THAT 1582 01:01:12,240 --> 01:01:13,520 OMICRON SEEMS TO BE. 1583 01:01:13,520 --> 01:01:15,960 >> DO YOU MEAN THE LOCATIONS AS 1584 01:01:15,960 --> 01:01:17,920 IN THE TISSUE TROPISM, OR IF 1585 01:01:17,920 --> 01:01:20,400 THERE ARE PARTS THAT THE 1586 01:01:20,400 --> 01:01:21,200 RESPIRATORY TRACK. 1587 01:01:21,200 --> 01:01:24,360 SO THERE ARE FOR EXAMPLE, IF YOU 1588 01:01:24,360 --> 01:01:28,200 LOOK AT OMICRON, THERE ARE 1589 01:01:28,200 --> 01:01:29,160 SPECIFIC POSITIONS THAT ARE 1590 01:01:29,160 --> 01:01:30,480 ASSOCIATED SO FOR EXAMPLE, THE 1591 01:01:30,480 --> 01:01:32,840 WAY THE VIRUS ENTERS THE CELLS, 1592 01:01:32,840 --> 01:01:34,280 THE RECEPTORS IT USES. 1593 01:01:34,280 --> 01:01:36,440 IT USES A SLIGHTLY DIFFERENT 1594 01:01:36,440 --> 01:01:38,280 ENTRY PATHWAY AND SO IT'S 1595 01:01:38,280 --> 01:01:40,240 THOUGHT THAT THE CELLS THAT WE 1596 01:01:40,240 --> 01:01:44,200 HAVE IN OUR LOWER LUNGS OR THE 1597 01:01:44,200 --> 01:01:46,440 LOWER RESPIRATORY TRACT DON'T 1598 01:01:46,440 --> 01:01:47,720 HAVE NECESSARILY THE RIGHT 1599 01:01:47,720 --> 01:01:51,440 PATHWAYS FOR THE VIRUS TO ENTER 1600 01:01:51,440 --> 01:01:53,480 SO THAT THE VIRUS TENDS TO 1601 01:01:53,480 --> 01:01:56,120 INFECT MOSTLY CELLS FROM THE 1602 01:01:56,120 --> 01:01:57,040 UPPER RESPIRATORY TRACT. 1603 01:01:57,040 --> 01:02:00,320 SO THERE ARE SPECIFIC MUTATIONS 1604 01:02:00,320 --> 01:02:03,520 LIKE THAT BUT WILL DETERMINE 1605 01:02:03,520 --> 01:02:08,440 DISEASE SEVERITY BECAUSE OF THE 1606 01:02:08,440 --> 01:02:11,080 TROAPISM OR THE LOCATION THAT'S 1607 01:02:11,080 --> 01:02:12,440 AFFECTED BY THE VIRUSES, SO 1608 01:02:12,440 --> 01:02:13,920 THERE ARE MUTATIONS THAT HAVE 1609 01:02:13,920 --> 01:02:15,920 BEEN ASSOCIATED WITH THAT 1610 01:02:15,920 --> 01:02:17,240 SPECIFICALLY, YES. 1611 01:02:17,240 --> 01:02:17,560 >> GREAT. 1612 01:02:17,560 --> 01:02:18,440 ALL RIGHT, WELL THANK YOU BOTH 1613 01:02:18,440 --> 01:02:21,040 VERY MUCH, THIS IS AN EXCELLENT 1614 01:02:21,040 --> 01:02:23,280 TALK AND CHECK BACK LATER TO SEE 1615 01:02:23,280 --> 01:02:24,680 WHAT THE NEXT COVID TALK WILL 1616 01:02:24,680 --> 01:02:26,120 BE, WE HAVE A FEW MORE LINED UP 1617 01:02:26,120 --> 01:02:29,600 AND WE WILL SEE YOU ALL NEXT 1618 01:02:29,600 --> 01:02:29,800 TIME. 1619 01:02:29,800 --> 00:00:00,000 >> THANK YOU.