Flu Watch (2006–2011) and Virus Watch (2020–2022) are household community cohort studies investigating the epidemiology, clinical features, risk factors for transmission and immunity to influenza and SARS-CoV-2 respectively. Both cohorts recruited all members of participating households and followed them up with weekly surveys commencing on symptom occurrence.
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Flu Watch
Flu Watch was a household community cohort study following up entire households across England during six influenza seasons including three periods of seasonal influenza (winters 2006–2007, 2007–2008 and 2008–2009) and the first three waves of the 2009 influenza pandemic (summer 2009, autumn‐winter 2009/2010 and winter 2010/2011). 5 484 participants were followed up for 118 158 person‐weeks11. Participants were asked to submit nasal swabs on day two of any illness that was a “cough, cold, sore throat, or flu-like illness”. These were examined using polymerase chain reaction (PCR). All samples were analysed for influenza infection. At different times in the study, rhinovirus, RSV and seasonal coronavirus were also tested for using PCR. Only respiratory and constitutional symptoms were considered for this analysis (i.e. sore throat, cough, runny nose, sneezing, fever, headache, fatigue). Full details of the Flu Watch methodology have been previously published12.
Virus Watch
Virus Watch is a household community cohort study following up entire households in England and Wales since mid-June 2020. By February 2022, 58 566 individuals in 28 495 households had registered to take part in the study. Participants submitted weekly online surveys reporting the date of any respiratory, constitutional, gastrointestinal, ocular, or skin symptoms experienced and the dates and results of any testing for SARS-CoV-2 by lateral flow test (LFT) or PCR. Symptoms included for the analysis were: cough, dry cough, sore throat, blocked nose, runny nose, sneezing, sinus pain, fever, fatigue, headache, muscle ache, loss of smell and loss of taste. The Virus Watch study protocol is available online13.
Data processing
For both studies, symptom data were extracted and grouped into illness episodes. Tests with no symptoms reported were excluded in both studies. The start date of an illness episode was defined as the first day any symptoms were reported, and the end date was the final day of reported symptoms. A seven-day washout period in which no symptoms were reported was used to identify separate illness episodes.
In Virus Watch, swab results were matched to illnesses that were within seven days of the illness start date. In addition to self-reported SARS-CoV-2 test results, test results from the UK Second-Generation Surveillance System (SGSS) dataset were linked to the Virus Watch dataset. Participant data were linked over time and between databases using the unique personal identifier recorded at all interactions with the English National Health Service (NHS), full name, date of birth and home address. SGSS contains SARS-CoV-2 test results during Pillar 1 (testing patients in secondary care) and Pillar 2 (community testing).
SARS-CoV-2 variant designation
Testing (by LFT or PCR) detects the presence of SARS-CoV-2 but, unlike RNA sequencing, does not identify the variant. Therefore, using national surveillance data14, we designated a variant to a case if that variant was making up at least 75% of all regional sequenced genomes at the time of the case’s symptom onset. Illnesses in regions and weeks that did not have a dominant variant reaching at least 75% of all sequenced genomes were excluded. Variants are defined as per the UK Health Secretary Agency (UKHSA) definition and wild-type refers to all SARS-CoV-2 variants circulating before the Alpha variant14.
Analysis
We present symptom profiles of individuals with confirmed SARS-CoV-2 (n = 10 986), seasonal coronavirus (HCoV-NL63, HCoV-OC43, and HCoV-229E) (n = 191), influenza (n = 222), RSV (n = 84) and rhinovirus (n = 283) and compare the proportion of symptoms experienced during illnesses.
We also compare the compatibility of the WHO case definition for ARI (sudden onset of symptoms with cough and/or sore throat and/or runny nose) and WHO case definition for ILI (fever > = 38 °C and cough).
As a sensitivity analysis to account for the fact that Flu Watch samples were submitted from anyone with cough, sore throat, cold or flu-like illness, whereas the national COVID-19 testing program encouraged submission of samples from all those with persistent cough, fever or loss of sense of smell or taste, we restricted SARS-CoV-2 cases to those submitted from participants who met the definition for ARI (Appendix 1).
We ran multiple multivariate logistic regressions to describe the odds of experiencing different respiratory and constitutional symptoms by SARS-CoV-2 VOC. Our primary exposure was SARS-CoV-2 variant strain (wild-type, Alpha, Delta, Omicron BA1, Omicron BA2) with Omicron BA5 as variant of reference. We controlled for known confounders reported in the literature including sex, age, clinal vulnerability and natural or vaccine induced immunity15,16,17. Clinical vulnerability status was derived from self-reported data on immunosuppressive therapy, cancer diagnoses, and chronic disease status. Participants were considered to have past exposure (and therefore some degree of immunity) to SARS-CoV-2 if they reported a SARS-CoV-2 positive illness or vaccination between 90- and 14- days prior symptom onset. This time window was based on the UK Health Security Agency (UKHSA) and the European Centre for Disease Control (ECDC) reports on SARS-CoV-2 immune response and immunity15,17.
Ethics
The Virus Watch study was approved by the Hampstead NHS Health Research Authority Ethics Committee. Ethics approval number—20/HRA/2320. All members of participating households provided informed consent for themselves and, where relevant, for children that they were responsible for. This was electronically collected during registration. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. All methods were performed in accordance with the relevant guidelines and regulations.
