{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:13:13Z","timestamp":1773007993025,"version":"3.50.1"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,2,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Current guidelines recommend that individuals with moderate COVID-19 disease isolate for 5 days after the first appearance of symptoms or a positive SARS-CoV-2 test. It would be useful to understand the time course of infectious virus production and its correlation with virus detection using a rapid antigen test (RAT) or quantitative reverse transcriptase (qRT)-PCR. In a phase 2 study, 242 vaccinated patients with COVID-19 and at low risk for progression to severe disease initiated 5 days of treatment with pomotrelvir (PBI-0451, a SARS-CoV-2 main protease inhibitor) or placebo within 5 days after symptom onset. The primary endpoint, the proportion of subjects with SARS-CoV-2 viral titers below the limit of detection on Day 3 of treatment in the pomotrelvir versus placebo groups, was not met. No between-group differences in SARS-CoV-2 clearance or symptom resolution or alleviation were observed. Additional analyses evaluated the dynamics of SARS-CoV-2 replication in mid-turbinate nasal swabs and saliva samples using infectious virus assay (IVA), RAT, and qRT-PCR. SARS-CoV-2 cleared rapidly, with negative results first determined by IVA (TCID\n            <jats:sub>50<\/jats:sub>\n            below the limit of detection), followed by the RAT (negative for SARS-CoV-2 N antigen), and qRT-PCR (RNA below the limit of detection), which suggests that delayed initiation of treatment (up to 5 days after symptom onset) may have contributed to the lack of treatment response. Symptom resolution lagged behind viral clearance assessed by IVA and RAT. These data support reliance on a negative RAT to determine when an individual is no longer producing infectious virus and may end isolation.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>A phase 2 double-blind, placebo-controlled study was performed evaluating pomotrelvir, a SARS-CoV-2 Mpro inhibitor, compared with placebo in 242 non-hospitalized, vaccinated, symptomatic adults with COVID-19 (Omicron). No improvement in the decrease of viral replication or relief of symptoms was observed between the two groups when treatment was initiated \u22653 days after symptom onset. These results suggest that future COVID-19 antiviral studies using a similar patient population may need to initiate treatment earlier, like influenza studies. This is the first study to prospectively evaluate SARS-CoV-2 viral dynamics and the time to viral clearance in a significant number of patients using concurrently obtained results from an infectious virus assay, a rapid antigen test (RAT), and a qRT-PCR assay over a 15-day time course. These results suggest that a negative RAT assay is a good indicator of loss of infectious virus and the ability to return to normal activities.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.02980-23","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T14:01:36Z","timestamp":1704895296000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["SARS-CoV-2 viral dynamics in a placebo-controlled phase 2 study of patients infected with the SARS-CoV-2 Omicron variant and treated with pomotrelvir"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3909-6578","authenticated-orcid":false,"given":"Katyna","family":"Borroto-Esoda","sequence":"first","affiliation":[{"name":"Pardes BioSciences Inc., Carlsbad, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wilfret","sequence":"additional","affiliation":[{"name":"Pardes BioSciences Inc., Carlsbad, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Tong","sequence":"additional","affiliation":[{"name":"Pardes BioSciences Inc., Carlsbad, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Plummer","sequence":"additional","affiliation":[{"name":"Pardes BioSciences Inc., Carlsbad, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Kearney","sequence":"additional","affiliation":[{"name":"Pardes BioSciences Inc., Carlsbad, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8460-9857","authenticated-orcid":false,"given":"Ann D.","family":"Kwong","sequence":"additional","affiliation":[{"name":"Pardes BioSciences Inc., Carlsbad, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","unstructured":"Wang L Berger NA Kaelber DC Davis PB Volkow ND Xu R. 2022. COVID infection rates clinical outcomes and racial\/ethnic and gender disparities before and after Omicron emerged in the US. Infectious diseases (except HIV\/AIDS):2022.02.21.22271300. doi:10.1101\/2022.02.21.22271300","DOI":"10.1101\/2022.02.21.22271300"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04411-y"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c01451"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04389-z"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02138-x"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2022.07.005"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00462-7"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.5888\/pcd18.210123"},{"key":"e_1_3_4_10_2","volume-title":"PBI-0451: an orally administered 3CL protease inhibitor of SARS-CoV-2 for COVID-19","author":"Kearney BP","year":"2022","unstructured":"KearneyBP, PlummerA, WolfgangGHI, Turnquist D, Marshall MR, Pruijssers A, Stevens LJ, Hughes TM, Kook S, Denison M, Schwabe C, Lopatin U, Arnold LD. 2022. Conference on retroviruses and opportunistic infections, poster 00470. PBI-0451: an orally administered 3CL protease inhibitor of SARS-CoV-2 for COVID-19"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-020-02958-1"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02351-21"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2022.1827"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2022.07.010"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abl7430"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac933"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2205944"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2021.10.039"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02881-20"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2342-5"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(22)00226-0"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00697-22"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716197"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02980-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02980-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T14:06:44Z","timestamp":1707228404000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.02980-23"}},"subtitle":[],"editor":[{"given":"Anne","family":"Piantadosi","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,6]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,6]]}},"alternative-id":["10.1128\/spectrum.02980-23"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.02980-23","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,6]]},"assertion":[{"value":"2023-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02980-23"}}