exclude: true --- class: top left hide-count background-image: url(img/sarscov2_cdc_blur_crop.png) background-size: cover .move-top20[ .title-text[<span style='font-size:1.0em'>COVID-19</span>] .title-subtext[<span style='font-size:1.0em'>A Case of Prolonged Infection<br> & Organizing Pneumonia</span>] ] .callout-url-leftcorner[ .title-nametext[ Brendan J. Kelly, MD, MS Infectious Diseases, Epidemiology & Microbiology University of Pennsylvania 08 December 2022 ] ] .footnote-right[<span style='color: white'>photo: CDC @unsplash</span>] --- exclude: true ## Disclosures .pad-left[ - No conflicts of interest. - Research supported by: - NIAID K23 AI121485 - CDC BAA 200-2021-10986 ] --- ## History of Present Illness .pad-left[ - 74yo W with hypothyroidism, mantle cell lymphoma s/p obinutuzumab/zanubrutinib (anti-CD20 / tyrosine-kinase inhibitor) admitted with COVID-19 and organizing pneumonia - Reportedly SARS-CoV-2 positive since May 2022 despite COVID vaccine * 4 - Presented July 2022 with fevers, hypoxia, bilateral groundglass opacities - Concern for drug-induced organizing pneumonia / pneumonitis - Held zanubrutinib; started high-dose prednisone, home O2, T/S ppx July 2022 ] --- ## History of Present Illness .pad-left[ - Empiric abx (levo, amox-clav) & fail to wean steroids through fall 2022 - Readmit Sep-Oct 2022 and s/p remdesivir treatment (9/28) - Readmit Nov 2022, s/p bebtelivumab (10/25) & baracitinib (10/30) - "After starting the baricitinib... oxygen requirement dramatically improved" and discharged from the hospital with plan for a prednisone taper - 17 days post-discharge, returned because O2sat to 70% despite 5L O2 by NC; also with recurrent fevers to 102F ] --- exclude: true ## SARS-CoV-2 Ct Values Over Time .center[ <img src="figs/p_ct_pre.png" width="6400" height="80%" style="display: block; margin: auto;" /> ] --- background-image: url("figs/p_ct_pre.png") background-position: center background-size: contain --- ## Chest Imaging: July 2022 .center[ <img src="img/dr_ct_2022-07.png" width="60%" style="display: block; margin: auto;" /> ] --- ## Chest Imaging: August 2022 .center[ <img src="img/dr_ct_2022-08.png" width="60%" style="display: block; margin: auto;" /> ] --- ## Chest Imaging: Early October 2022 .center[ <img src="img/dr_ct_2022-10a.png" width="60%" style="display: block; margin: auto;" /> ] --- ## Chest Imaging: Late October 2022 .center[ <img src="img/dr_ct_2022-10b.png" width="60%" style="display: block; margin: auto;" /> ] --- ## Chest Imaging: Early November 2022 .center[ <img src="img/dr_ct_2022-11a.png" width="60%" style="display: block; margin: auto;" /> ] --- ## Chest Imaging: Late November 2022 - Admission .center[ <img src="img/dr_ct_2022-11b.png" width="60%" style="display: block; margin: auto;" /> ] --- ## Chest Imaging: Late November 2022 - Admission .pad-left[ - No pulmonary embolism. - Redemonstration of diffuse migrating patchy opacities, grossly unchanged compared to prior, most in keeping with organizing pneumonia, potentially related to ongoing COVID-19 infection or drug toxicity. ] --- ## A Recent Case Report .pad-left[ - "A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, intravenous (IV) remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to full recovery." - "The patient's hypoxemia resolved quickly after initiation of nirmatrelvir/ritonavir on HD6. Nares swab SARS-CoV-2 PCR was negative on HD7 and serum PCR on HD8. By HD14 he was weaned off supplemental oxygen and chest CT showed persistent but improved areas of GGO." ] .footnote-left[[Najjar-Debbiny R et al _CID_ 2022](https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac443/6599020); [Ford ES et al _CID_ 2022](https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac868/6795102)] --- exclude: true ## Najjar-Debbiny et al _CID_ 2022 .center[ ] .footnote-left[[Najjar-Debbiny R et al _CID_ 2022](https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac443/6599020)] --- exclude: true ## Ford et al _CID_ 2022 .center[ ] .footnote-left[[Ford ES et al _CID_ 2022](https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac868/6795102)] --- ## Single-Patient IND .pad-left[ - Tried to get nirmatrelvir-ritonavir 11/23/2022... - EUA restricts nirmatrelvir-ritonavir to outpatients without severe disease - Thanksgiving & outpatient pharmacy stock unavailable 11/24/2022 - emergency, single-patient IND #164918 on 11/25/2022 - **Thank you** to Aasith Villavicencio Paz, MD & Jessica Phung, PharmD - **Thank you** to Meghan Gattie, PharmD @ FDA ] --- background-image: url("figs/p_combined.png") background-position: center background-size: contain --- background-image: url("figs/p_ct_post.png") background-position: center background-size: contain --- ## Chest Imaging: December 2022 .center[ <img src="img/dr_ct_2022-12.png" width="60%" style="display: block; margin: auto;" /> ] --- ## Chest Imaging: December 2022 .pad-left[ - Improved diffuse severe lung disease though with some new sites of disease. - Resultant and increased areas of traction bronchiectasis suggesting fibrosis. ] --- exclude: true ## Acknowledgements .pull-left[ - __ARES Group @ Penn__ Laurel Glaser, Kyle Rodino, Sean Loughrey, Laura Cowden, Magda Wernovsky, Jessie Gunoskey, Jennifer Han, Erik Clarke, Michael David, Matt Ziegler, Lauren Dutcher, Ebbing Lautenbach, Jim Harrigan - __Bushman Laboratory @ Penn__ Arwa Abbas, Aoife Roche, Andrew Marques, Aubrey Bailey, John Everett, Rick Bushman - __PennCHOP Microbiome Program__ Lisa Mattei, Casey Hofstaedter, Huanjia Zhang, Kyle Bittinger ] .pull-right[ - __Collman Laboratory @ Penn__ Ize Imai, Aurea Simon Soro, John McGinniss, Ron Collman - __Division of ID @ Penn__ Ian Frank, Pablo Tebas, Robert Gross, Emily Blumberg - __Rutgers University & Penn DBEI__ Jason Roy, Arman Oganisian - __CDC Prevention Epicenters__ Clifford McDonald, Alison Laufer Halpin - __Funding__ <u>CDC</u>: BAAs 200-2016-91964, 200-2018-02919, 200-2021-10986, 200-2021-10986 & <u>NIAID</u>: K23 AI121485 ] .center[ ### brendank@pennmedicine.upenn.edu ] --- class: middle center hide-count background-image: url(img/sarscov2_cdc_blur_crop.png) background-size: cover .title-subtext[Questions?] --- exclude: true class: middle center hide-count background-image: url(img/sarscov2_cdc_blur_crop.png) background-size: cover .title-subtext[Questions?] .callout-url-bottom[ .fade-in[<span style="font-size:0.5em; color:white">slides ↓ </span>] <span style="link-color:white">[bjklab.org](http://www.bjklab.org)</span> ]