3 Risk of Bias and Limitations
When analysing data related to COVID-19 positivity it is important to recognise the sensitivity of the test is variable. Bronchoalveolar lavage is the most sensitive test (93%) whilst nasal swabs (63%) and pharyngeal swabs (46%) have lower positive rates14. Moein et al, who conducted the UPSIT, case control study and Mao et al were the only authors to report the technique and anatomical location of their Polymerase Chain Reaction (PCR) analysis of COVID-19 status. Moien et al used nasal aspirates or washes and Mao et al’s group used throat swabs . Due to the relatively low sensitivity of the test used there will be a proportion of false negatives that will falsely lower the incidence of COVID-19 positivity in the OD groups.
The majority of the responses to questionnaires were received using remotely using electronic response forms of mobile based applications which will cause selection bias. Younger more technologically interactive cohort are more likely to interact and this sub-group seem to be less affected by COVID-19 when compared to older age groups who have a higher morbidity and mortality. For example, Menni et al(in an unpublished paper made available before peer review) who used a mobile based application, report an average age of 41.48 (CI = 13.77) for those in their non-PCR-tested group, including over 1.5million people. Hospitalised populations are also less likely to interact with these methods due to their disease severity, internet connection or associated interventional treatments.
Cross-sectional questionnaires and case series are prone to bias due to influence of confounding variables, assessment of patients at different time points relative to their exposure and reporting bias. In case series specifically consecutive patients often missed in data collection. In these studies, however the researchers are simply presenting patient factors and associated symptoms rather than treatments or interventions and their subsequent effects or outcomes and this observational nature could help to reduce observer bias. In studies that were conducted requiring historical data from the patients there is a risk of recall bias and under-reporting or inaccuracies of symptoms specifically where onset and duration of symptoms is involved.