tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2023 Dec 2;10(12)
fad598.
doi: 10.1093/ofid/ofad598. eCollection 2023 Dec. Nasopharyngeal Viral Load Is the Major Driver of Incident Antibody Immune Response to SARS-CoV-2 Infection
Meng Xu[SUP] 1 [/SUP], Meagan P O'Brien[SUP] 1 [/SUP], Andrea T Hooper[SUP] 1 [/SUP], Eduardo Forleo-Neto[SUP] 1 [/SUP], Flonza Isa[SUP] 1 [/SUP], Peijie Hou[SUP] 1 [/SUP], Kuo-Chen Chan[SUP] 1 [/SUP], Myron S Cohen[SUP] 2 [/SUP], Mary A Marovich[SUP] 3 [/SUP], Jennifer D Hamilton[SUP] 1 [/SUP], Boaz Hirshberg[SUP] 1 [/SUP], Gary A Herman[SUP] 1 [/SUP], Bret J Musser[SUP] 1 [/SUP]
Affiliations
Background: Virologic determinants of seroconversion to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were defined in a post hoc analysis of prospectively studied vaccine- and infection-naïve individuals at high risk for coronavirus disease 2019 (COVID-19).
Methods: This phase 3 COVID-19 prevention trial (NCT04452318) with casirivimab and imdevimab was conducted in July 2020-February 2021, before widespread vaccine availability. Placebo-treated participants who were uninfected (SARS-CoV-2 quantitative reverse transcription polymerase chain reaction [RT-qPCR] negative) and seronegative were assessed weekly for 28 days (efficacy assessment period [EAP]) for COVID-19 symptoms and SARS-CoV-2 infection by RT-qPCR of nasopharyngeal swab samples and for serostatus by antinucleocapsid immunoglobulin (Ig) G. Regression-based modeling, including causal mediation analysis, estimated the effects of viral load on seroconversion.
Results: Of 157/1069 (14.7%) uninfected and seronegative (for antispike IgG, antispike IgA, and antinucleocapsid IgG) participants who became infected during the EAP, 105 (65%) seroconverted. The mean (SD) maximum viral load of seroconverters was 7.23 (1.68) log[SUB]10[/SUB] copies/mL vs 4.8 (2.2) log[SUB]10[/SUB] copies/mL in those who remained seronegative; viral loads of ∼6.0log[SUB]10[/SUB] copies/mL better predicted seroconversion. The mean of the maximum viral load was 7.11 log[SUB]10 [/SUB]copies/mL in symptomatic participants vs 5.58 log[SUB]10 [/SUB]copies/mL in asymptomatic participants. The mean duration of detectable viral load was longer in seroconverted vs seronegative participants: 3.24 vs 1.63 weeks.
Conclusions: Maximum SARS-CoV-2 viral load is a major driver of seroconversion and symptomatic COVID-19, with high viral loads (∼6.0 log[SUB]10 [/SUB]copies/mL) better predicting seroconversion. Serology underestimates infection rates, incidence, and prevalence of SARS-CoV-2 infection.
Keywords: COVID-19; SARS-CoV-2; antibody immune responses; causal mediation analysis; neutralizing monoclonal antibodies.
. 2023 Dec 2;10(12)
fad598.doi: 10.1093/ofid/ofad598. eCollection 2023 Dec. Nasopharyngeal Viral Load Is the Major Driver of Incident Antibody Immune Response to SARS-CoV-2 Infection
Meng Xu[SUP] 1 [/SUP], Meagan P O'Brien[SUP] 1 [/SUP], Andrea T Hooper[SUP] 1 [/SUP], Eduardo Forleo-Neto[SUP] 1 [/SUP], Flonza Isa[SUP] 1 [/SUP], Peijie Hou[SUP] 1 [/SUP], Kuo-Chen Chan[SUP] 1 [/SUP], Myron S Cohen[SUP] 2 [/SUP], Mary A Marovich[SUP] 3 [/SUP], Jennifer D Hamilton[SUP] 1 [/SUP], Boaz Hirshberg[SUP] 1 [/SUP], Gary A Herman[SUP] 1 [/SUP], Bret J Musser[SUP] 1 [/SUP]
Affiliations
- PMID: 38111750
- PMCID: PMC10727195
- DOI: 10.1093/ofid/ofad598
Background: Virologic determinants of seroconversion to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were defined in a post hoc analysis of prospectively studied vaccine- and infection-naïve individuals at high risk for coronavirus disease 2019 (COVID-19).
Methods: This phase 3 COVID-19 prevention trial (NCT04452318) with casirivimab and imdevimab was conducted in July 2020-February 2021, before widespread vaccine availability. Placebo-treated participants who were uninfected (SARS-CoV-2 quantitative reverse transcription polymerase chain reaction [RT-qPCR] negative) and seronegative were assessed weekly for 28 days (efficacy assessment period [EAP]) for COVID-19 symptoms and SARS-CoV-2 infection by RT-qPCR of nasopharyngeal swab samples and for serostatus by antinucleocapsid immunoglobulin (Ig) G. Regression-based modeling, including causal mediation analysis, estimated the effects of viral load on seroconversion.
Results: Of 157/1069 (14.7%) uninfected and seronegative (for antispike IgG, antispike IgA, and antinucleocapsid IgG) participants who became infected during the EAP, 105 (65%) seroconverted. The mean (SD) maximum viral load of seroconverters was 7.23 (1.68) log[SUB]10[/SUB] copies/mL vs 4.8 (2.2) log[SUB]10[/SUB] copies/mL in those who remained seronegative; viral loads of ∼6.0log[SUB]10[/SUB] copies/mL better predicted seroconversion. The mean of the maximum viral load was 7.11 log[SUB]10 [/SUB]copies/mL in symptomatic participants vs 5.58 log[SUB]10 [/SUB]copies/mL in asymptomatic participants. The mean duration of detectable viral load was longer in seroconverted vs seronegative participants: 3.24 vs 1.63 weeks.
Conclusions: Maximum SARS-CoV-2 viral load is a major driver of seroconversion and symptomatic COVID-19, with high viral loads (∼6.0 log[SUB]10 [/SUB]copies/mL) better predicting seroconversion. Serology underestimates infection rates, incidence, and prevalence of SARS-CoV-2 infection.
Keywords: COVID-19; SARS-CoV-2; antibody immune responses; causal mediation analysis; neutralizing monoclonal antibodies.