Classic trio of COVID-19 symptoms miss about 30 percent of cases

The triad of symptoms—fever, coughs, and anosmia/aguesia—used to screen patients for lab testing for the novel coronavirus disease (COVID-19) may be underpowered, according to a new study. Instead, additional symptom combinations may help maximize case capture and resource efficiency.

“The proposed approach enables the selection of symptom combinations to maximize the capture of cases without overwhelming laboratory capacity,” the researchers said. “Our findings may help to optimize the choice of triggering symptoms for diagnostic work-up in COVID-19 vaccine efficacy trials or in a wider public health setting.”

UK (n=122,305) and US (n=3,162) users of the COVID-19 Symptom Study app participated in the study; all had reported new-onset symptoms followed by a reverse transcriptase-polymerase chain reaction (RT-PCR) test within 7 days. The researchers calculated the sensitivity and specificity of different symptom combinations, as well as the number of RT-PCR tests needed to identify a positive case.

COVID-19 was positively confirmed in 1,202 and 79 patients in the UK and US users, respectively. Looking at each symptom individually, headache and fatigue had the highest sensitivity at 3 days in the UK cohort, yielding values of 67 percent and 65 percent, respectively. This remained true even at 7 days, and when the analysis was replicated in the US cohort. [J Infect 2021;doi:10.1016/j.jinf.2021.02.015]

Anosmia/ageusia only provided 22-percent and 49-percent sensitivities at 3 and 7 days, respectively, in the UK cohort. It had the most efficient test per case (TPC), however, at 20 and 10 at the respective time points.

Testing instead for symptom combinations, the researchers found that within 3 days of symptom onset, cough or dyspnoea was present in 49 percent of individuals who would eventually test positive for COVID-19. Adding fever to the assessment battery increased sensitivity to 60 percent, while the final inclusion of anosmia/ageusia bumped the sensitivity up slightly to 69 percent.

By 7 days, the classic trifecta of COVID-19 symptoms could identify only 84 percent of positive cases.

Incorporating headache and fatigue to the symptom inventory resulted in a 92-percent increase in COVID-19 cases identified at day 3 and improved to 97 percent at day 7.

However, maximizing symptom efficacy came with efficiency trade-offs. At day 3, TPC doubled from 42 using the classic COVID-19 symptoms to 85 when applying the extended symptoms. The same was true for day 7 (TPC 42 to 81). “Thus, an increase in sensitivity comes at a cost,” the researchers said.

“In situations where there is a limited testing capacity, we provide a range of optimal symptom combinations that could be used, given different target numbers of TPC identified,” they said. “This finding may prove useful for COVID-19 vaccine developers or in public health settings when deciding which symptoms should trigger testing to optimise financial and logistical resource utilization.”