[Preprint] Asymptomatic infection in a proof-of-concept longitudinal study on SARS-CoV-2 vaccine recipients, 2025, Shih et al.

[SNT Gatchaman]

Asymptomatic infection in a proof-of-concept longitudinal study on SARS-CoV-2 vaccine recipients

Spoiler: Authors

Chiaho Shih; You-Zhen Liao; Che-Yu Hsu; Ying-Chen Tsai; Ming-Yen Lin; Hsin-Ying Clair Chiou; Wen-Hui Kuan; Chih-Hsu Chang; An-Ting Liou; Yu-Chi Chou; Feng-Zu Sheen; Hsiang-Jung Lin; Jih-Jin Tsai; Ping-Chang Lin; Ming-Lung Yu; Wan-Long Chuang; Jia-Jung Lee; Jer-Ming Chang; Shang-Jyh Hwang; Justin Shih; Wen-Chun Hung; Ming-Feng Hou; Inn-Wen Chong; Yuh-Jyh Jong; Jung-San Chang

Individuals with asymptomatic SARS-CoV-2 infection can unknowingly transmit the virus, yet identifying such infections in vaccinated populations remains challenging.

We conducted a longitudinal study of 129 vaccine recipients immunized with various combinations of SARS-CoV-2 spike s protein vaccine platforms. Sera were collected before the first dose (v1), at 2 weeks (v7) and 6 months (v8) after the third dose. Taiwans first major COVID-19 outbreak occurred between v7 and v8. We measured anti-nucleocapsid (anti-N) and anti-S IgG antibody titers by ELISA and assessed virus-neutralizing activity using live virus and pseudovirus assays. By developing an iterative serial screening method, we identified asymptomatic infections among unconfirmed cases.

Our v7-v8 paired cohort resolved into three distinct groups: confirmed cases (21%), asymptomatic infections (17%), and uninfected cases (62%). In normalized v8 sera, confirmed cases exhibited an antiS+++/anti-N+++ phenotype, while uninfected cases showed an anti-S+/anti-N+ phenotype.

Statistical analysis validated a distinct asymptomatic group characterized by intermediate anti-S but baseline anti-N antibody levels (anti-S++/anti-N+). This approach enables more accurate estimates of infection prevalence and vaccine efficacy.

Web | DOI | PDF | Preprint: MedRxiv | Open Access

 

[Utsikt]

Almost a 1:1 ratio of confirmed (and presumably symptomatic) to asymptomatic cases.

The ration can’t be generalised, but it demonstrates why it’s difficult to get accurate data on the prevalence of lasting symptoms or ill health following an infection when a substantial share of the infected will be misclassified as uninfected.

 

[SNT Gatchaman]

it demonstrates why it’s difficult to get accurate data on the prevalence of lasting symptoms or ill health following an infection when a substantial share of the infected will be misclassified as uninfected.

And then you get Association of Self-reported COVID-19 Infection and SARS-CoV-2 Serology Test Results With Persistent Physical Symptoms Among French Adults During the COVID-19 Pandemic (2022) —

The findings of this cross-sectional analysis of a large, population-based French cohort suggest that persistent physical symptoms after COVID-19 infection may be associated more with the belief in having been infected with SARS-CoV-2 than with having laboratory-confirmed COVID-19 infection.

the belief in having had COVID-19 infection may have increased the likelihood of symptoms, either directly by affecting perception or indirectly by prompting maladaptive health behaviors, such as physical activity reduction or dietary exclusion. These mechanisms are thought to contribute to the long-described persistence of physical symptoms after acute infections.

our results suggest that further research regarding persistent physical symptoms after COVID-19 infection should also consider mechanisms that may not be specific to the SARSCoV-2 virus. From a clinical perspective, patients in this situation should be offered a medical evaluation to prevent their symptoms being erroneously attributed to COVID-19 infection and to identify cognitive and behavioral mechanisms that may be targeted to relieve the symptoms.

 

[Utsikt]

And then you get Association of Self-reported COVID-19 Infection and SARS-CoV-2 Serology Test Results With Persistent Physical Symptoms Among French Adults During the COVID-19 Pandemic (2022) —

To quote yourself from that thread:

The problem seems to come down to the potential false negative rate for the serology test. They are assuming accuracy of serology testing and concluding the patients have abnormal beliefs. I think this is going to prove to be an incredible error of inference.

Non-seroconversion or early seroreconversion following previous positive PCR seems unusually high for this virus. 36-37% seems to be the commonly quoted figures. I've also seen comment about positive nucleocapsid but negative spike serology down the line from infection also - I can't find a reference to support this though, so if anyone has come across this already, please post.