Symptoms and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Positivity in the General Population in the United Kingdom
Authors: Vihta Karina Doris , Pouwels Koen B , Peto Tim E A , Pritchard Emma , Eyre David W , House Thomas , Gethings Owen , Studley Ruth , Rourke Emma , Cook Duncan , Diamond Ian , Crook Derrick , Matthews Philippa C , Stoesser Nicole , Walker Ann Sarah ,   COVID-19 Infection Survey, Rourke Emma , Studley Ruth , Thomas Tina , Ayoubkhani Daniel , Black Russell , Felton Antonio , Crees Megan , Jones Joel , Lloyd Lina , Sunderland Esther , Sarah Walker Ann , Crook Derrick , Matthews Philippa C , Peto Tim , Pritchard Emma , Stoesser Nicole , Vihta Karina Doris , Wei Jia , Howarth Alison , Doherty George , Kavanagh James , Chau Kevin K , Cameron Sarah , Tamblin-Hopper Phoebe , Wolna Magda , Brown Rachael , Hatch Stephanie B , Ebner Daniel , Martins Ferreira Lucas , Christott Thomas , Marsden Brian D , Dejnirattisai Wanwisa , Mongkolsapaya Juthathip , Hoosdally Sarah , Cornall Richard , Stuart David I , Jones E Yvonne , Screaton Gavin , Pouwels Koen , Eyre David W , Lythgoe Katrina , Bonsall David , Golubchik Tanya , Fryer Helen , Bell John , Newton John , Robotham Julie , Birrell Paul , Jordan Helena , Sheppard Tim , Athey Graham , Moody Dan , Curry Leigh , Brereton Pamela , Hay Jodie , Van Steenhouse Harper , Godsmark Anna , Morris George , Mallick Bobby , Eeles Phil , Cox Stuart , Paddon Kevin , James Tim , Cameron Sarah , Tamblin-Hopper Phoebe , Wolna Magda , Brown Rachael , Lee Jessica 
Published: November 2021

Abstract

Background
“Classic” symptoms (cough, fever, loss of taste/smell) prompt severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing in the United Kingdom. Studies have assessed the ability of different symptoms to identify infection, but few have compared symptoms over time (reflecting variants) and by vaccination status.

Methods
Using the COVID-19 Infection Survey, sampling households across the United Kingdom, we compared symptoms in PCR-positives vs PCR-negatives, evaluating sensitivity of combinations of 12 symptoms (percentage symptomatic PCR-positives reporting specific symptoms) and tests per case (TPC) (PCR-positives or PCR-negatives reporting specific symptoms/ PCR-positives reporting specific symptoms).

Results
Between April 2020 and August 2021, 27 869 SARS-CoV-2 PCR-positive episodes occurred in 27 692 participants (median 42 years), of whom 13 427 (48%) self-reported symptoms (“symptomatic PCR-positives”). The comparator comprised 3 806 692 test-negative visits (457 215 participants); 130 612 (3%) self-reported symptoms (“symptomatic PCR-negatives”). Symptom reporting in PCR-positives varied by age, sex, and ethnicity, and over time, reflecting changes in prevalence of viral variants, incidental changes (eg, seasonal pathogens (with sore throat increasing in PCR-positives and PCR-negatives from April 2021), schools reopening) and vaccination rollout. After May 2021 when Delta emerged, headache and fever substantially increased in PCR-positives, but not PCR-negatives. Sensitivity of symptom-based detection increased from 74% using “classic” symptoms, to 81% adding fatigue/weakness, and 90% including all 8 additional symptoms. However, this increased TPC from 4.6 to 5.3 to 8.7.

Conclusions
Expanded symptom combinations may provide modest benefits for sensitivity of PCR-based case detection, but this will vary between settings and over time, and increases tests/case. Large-scale changes to targeted PCR-testing approaches require careful evaluation given substantial resource and infrastructure implications.