Trajectory of Viral RNA Load Among Persons With Incident SARS-CoV-2 G614 Infection (Wuhan Strain) in Association With COVID-19 Symptom Onset and Severity
Importance: The SARS-CoV-2 viral trajectory has not been well characterized in incident infections. These data are needed to inform natural history, prevention practices, and therapeutic development.
Objective: To characterize early SARS-CoV-2 viral RNA load (hereafter referred to as viral load) in individuals with incident infections in association with COVID-19 symptom onset and severity.
Design, Setting, and Participants: This prospective cohort study was a secondary data analysis of a remotely conducted study that enrolled 829 asymptomatic community-based participants recently exposed (<96 hours) to persons with SARS-CoV-2 from 41 US states from March 31 to August 21, 2020. Two cohorts were studied: (1) participants who were SARS-CoV-2 negative at baseline and tested positive during study follow-up, and (2) participants who had 2 or more positive swabs during follow-up, regardless of the initial (baseline) swab result. Participants collected daily midturbinate swab samples for SARS-CoV-2 RNA detection and maintained symptom diaries for 14 days.
Exposure: Laboratory-confirmed SARS-CoV-2 infection.
Main Outcomes and Measures: The observed SARS-CoV-2 viral load among incident infections was summarized, and piecewise linear mixed-effects models were used to estimate the characteristics of viral trajectories in association with COVID-19 symptom onset and severity.
Results: A total of 97 participants (55 women [57%]; median age, 37 years [IQR, 27-52 years]) developed incident infections during follow-up. Forty-two participants (43%) had viral shedding for 1 day (median peak viral load cycle threshold [Ct] value, 38.5 [95% CI, 38.3-39.0]), 18 (19%) for 2 to 6 days (median Ct value, 36.7 [95% CI, 30.2-38.1]), and 31 (32%) for 7 days or more (median Ct value, 18.3 [95% CI, 17.4-22.0]). The cycle threshold value has an inverse association with viral load. Six participants (6%) had 1 to 6 days of viral shedding with censored duration. The peak mean (SD) viral load was observed on day 3 of shedding (Ct value, 33.8 [95% CI, 31.9-35.6]). Based on the statistical models fitted to 129 participants (60 men [47%]; median age, 38 years [IQR, 25-54 years]) with 2 or more SARS-CoV-2-positive swab samples, persons reporting moderate or severe symptoms tended to have a higher peak mean viral load than those who were asymptomatic (Ct value, 23.3 [95% CI, 22.6-24.0] vs 30.7 [95% CI, 29.8-31.4]). Mild symptoms generally started within 1 day of peak viral load, and moderate or severe symptoms 2 days after peak viral load. All 535 sequenced samples detected the G614 variant (Wuhan strain).
Conclusions and Relevance: This cohort study suggests that having incident SARS-CoV-2 G614 infection was associated with a rapid viral load peak followed by slower decay. COVID-19 symptom onset generally coincided with peak viral load, which correlated positively with symptom severity. This longitudinal evaluation of the SARS-CoV-2 G614 with frequent molecular testing serves as a reference for comparing emergent viral lineages to inform clinical trial designs and public health strategies to contain the spread of the virus.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
JAMA network open - 5(2022), 1 vom: 04. Jan., Seite e2142796 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Stankiewicz Karita, Helen C [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 19.01.2022 Date Revised 01.07.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1001/jamanetworkopen.2021.42796 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM335414303 |
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| 100 | 1 | |a Stankiewicz Karita, Helen C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Trajectory of Viral RNA Load Among Persons With Incident SARS-CoV-2 G614 Infection (Wuhan Strain) in Association With COVID-19 Symptom Onset and Severity |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 19.01.2022 | ||
| 500 | |a Date Revised 01.07.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Importance: The SARS-CoV-2 viral trajectory has not been well characterized in incident infections. These data are needed to inform natural history, prevention practices, and therapeutic development | ||
| 520 | |a Objective: To characterize early SARS-CoV-2 viral RNA load (hereafter referred to as viral load) in individuals with incident infections in association with COVID-19 symptom onset and severity | ||
| 520 | |a Design, Setting, and Participants: This prospective cohort study was a secondary data analysis of a remotely conducted study that enrolled 829 asymptomatic community-based participants recently exposed (<96 hours) to persons with SARS-CoV-2 from 41 US states from March 31 to August 21, 2020. Two cohorts were studied: (1) participants who were SARS-CoV-2 negative at baseline and tested positive during study follow-up, and (2) participants who had 2 or more positive swabs during follow-up, regardless of the initial (baseline) swab result. Participants collected daily midturbinate swab samples for SARS-CoV-2 RNA detection and maintained symptom diaries for 14 days | ||
| 520 | |a Exposure: Laboratory-confirmed SARS-CoV-2 infection | ||
| 520 | |a Main Outcomes and Measures: The observed SARS-CoV-2 viral load among incident infections was summarized, and piecewise linear mixed-effects models were used to estimate the characteristics of viral trajectories in association with COVID-19 symptom onset and severity | ||
| 520 | |a Results: A total of 97 participants (55 women [57%]; median age, 37 years [IQR, 27-52 years]) developed incident infections during follow-up. Forty-two participants (43%) had viral shedding for 1 day (median peak viral load cycle threshold [Ct] value, 38.5 [95% CI, 38.3-39.0]), 18 (19%) for 2 to 6 days (median Ct value, 36.7 [95% CI, 30.2-38.1]), and 31 (32%) for 7 days or more (median Ct value, 18.3 [95% CI, 17.4-22.0]). The cycle threshold value has an inverse association with viral load. Six participants (6%) had 1 to 6 days of viral shedding with censored duration. The peak mean (SD) viral load was observed on day 3 of shedding (Ct value, 33.8 [95% CI, 31.9-35.6]). Based on the statistical models fitted to 129 participants (60 men [47%]; median age, 38 years [IQR, 25-54 years]) with 2 or more SARS-CoV-2-positive swab samples, persons reporting moderate or severe symptoms tended to have a higher peak mean viral load than those who were asymptomatic (Ct value, 23.3 [95% CI, 22.6-24.0] vs 30.7 [95% CI, 29.8-31.4]). Mild symptoms generally started within 1 day of peak viral load, and moderate or severe symptoms 2 days after peak viral load. All 535 sequenced samples detected the G614 variant (Wuhan strain) | ||
| 520 | |a Conclusions and Relevance: This cohort study suggests that having incident SARS-CoV-2 G614 infection was associated with a rapid viral load peak followed by slower decay. COVID-19 symptom onset generally coincided with peak viral load, which correlated positively with symptom severity. This longitudinal evaluation of the SARS-CoV-2 G614 with frequent molecular testing serves as a reference for comparing emergent viral lineages to inform clinical trial designs and public health strategies to contain the spread of the virus | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 700 | 1 | |a Dong, Tracy Q |e verfasserin |4 aut | |
| 700 | 1 | |a Johnston, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Neuzil, Kathleen M |e verfasserin |4 aut | |
| 700 | 1 | |a Paasche-Orlow, Michael K |e verfasserin |4 aut | |
| 700 | 1 | |a Kissinger, Patricia J |e verfasserin |4 aut | |
| 700 | 1 | |a Bershteyn, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Thorpe, Lorna E |e verfasserin |4 aut | |
| 700 | 1 | |a Deming, Meagan |e verfasserin |4 aut | |
| 700 | 1 | |a Kottkamp, Angelica |e verfasserin |4 aut | |
| 700 | 1 | |a Laufer, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Landovitz, Raphael J |e verfasserin |4 aut | |
| 700 | 1 | |a Luk, Alfred |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffman, Risa |e verfasserin |4 aut | |
| 700 | 1 | |a Roychoudhury, Pavitra |e verfasserin |4 aut | |
| 700 | 1 | |a Magaret, Craig A |e verfasserin |4 aut | |
| 700 | 1 | |a Greninger, Alexander L |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Meei-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Jerome, Keith R |e verfasserin |4 aut | |
| 700 | 1 | |a Wener, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Celum, Connie |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Helen Y |e verfasserin |4 aut | |
| 700 | 1 | |a Baeten, Jared M |e verfasserin |4 aut | |
| 700 | 1 | |a Wald, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Barnabas, Ruanne V |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Elizabeth R |e verfasserin |4 aut | |
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