Is diffusion of SARS-CoV-2 variants of concern associated with different symptoms?

Dear Editor,

Although the spread of coronavirus disease 2019 (COVID-19) seems to be slowing down in many countries as consequence of widespread vaccination, the gradual accumulation of non-synonymous mutations within the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has lead to appearance of variants of concern (VOCs), characterized by greater infectivity and/or potential of immune evasion especially from anti-SARS-CoV-2 neutralizing antibodies elicited after COVID-19 vaccination. In a recent report, Fantini et al. have proposed an interesting health approach for anticipating COVID-19 outbreaks, based on an index of transmissibility (T-index), calculated from parameters of coronavirus binding to host cells. Although this strategy seems indeed promising, previous evidence has been garnered that easier and more accessible tools such infodemiology, which relies on investigating the volume of Web searches for specific COVID-19 symptoms, may be effective in anticipating local COVID-19 epidemiological trends, , provided that symptoms caused by the emerging VOCs remain constant over time.

With the aim of establishing whether COVID-19 symptoms may have changed over time after introduction of new SARS-CoV-2 VOCs, we conducted an electronic search in Google Trends (Google Inc. Mountain View, CA, US) for the most common self-reported symptoms in patients with SARS-CoV-2 infection, using the Italian search terms “tosse” (cough), “raffreddore” (cold), “mal di testa” (headache) and “febbre” (fever). The country option was set to “Italy”, and the search period ranged between March 1, 2020 to present time (July 7, 2021). The data were downloaded as weekly Google Trends Score (GTS) for all these keywords, thus mirroring the cumulative volume of Google searches recorded for each specific term during the previous week. The GTS was then normalized (i.e., expressed as “ratio”) for the number of COVID-19 diagnoses recorded in Italy during the same week, as officially reported by the Italian National Institute of Health (Istituto Superiore di Sanità; ISS). The correlation between the GTS of the four symptoms was carried out with Spearman's test. The statistical analysis was performed with analyze-it (analyze-it Software Ltd, Leeds, UK). The study was conducted in accordance with the Declaration of Helsinki, under the terms of relevant local legislation. This analysis was based on electronic searches in the unrestricted, publicly available national repositories, and thereby no informed consent or Ethical Committee approvals were required.

The results of this analysis are shown in Fig. 1 . As concerns the local diffusion of VOCs in Italy according to ISS data, variants bearing the D614G mutation have replaced the prototype Wuhan strain between April and May 2020, the alpha (B1.1.7) variant has become largely prevalent (over 80% of COVID-19 cases) between February and March 2021, whilst the prevalence of the delta variant (B.1.617.2) has displayed a dramatic increase in May/June 2021. Irrespective of this evolving epidemiological trend, the normalized GTS of the four symptoms has followed a virtually overlapping trend over time, without exhibiting substantial differences (Fig. 1). The absence of a time-dependent variation in the prevalence of COVID-19 symptoms is reflected by highly significant Spearman's correlations among all normalized GTS for all symptoms (all r ≥ 0.94 and p < 0.001), as reported in Table 1 .

Fig. 1

Google searches for the most common symptoms of coronavirus disease 2019 (COVID-19) between March 1, 2020 and July 7, 2021. Results are expressed as weekly Google trends score (GTS) normalized for the number of new COVID-19 cases recorded during the same week.

Table 1

Spearman's correlation between volume of Google searches for the most common symptoms of coronavirus disease 2019 (COVID-19) between March 1, 2020 and July 7, 2021. Results are expressed as weekly Google trends score (GTS) normalized for the number of new COVID-19 cases recorded during the same week.

Symptoms	Cold	Headache	Fever
Cough	0.96 (95% CI, 0.94–0.98; p < 0.001)	0.97 (0.95–0.98; p < 0.001)	0.99 (0.99–0.99; p < 0.001)
Cold	–	0.94 (0.90–0.98; p < 0.001)	0.96 (0.93–0.97; p < 0.001)
Headache	–	–	0.98 (0.97–0.99; p < 0.001)

The results of our analysis of normalized GTS for the most common searched COVID-19 symptoms recorded over time in Italy reveals that the progressive introduction of new strains and VOCs in the country was not seemingly associated with significant changes in the primary clinical picture, at least as reflected by the volume of Web searches and Internet interrogations for the most common self-reported COVID-19 symptoms. Therefore, the use of an infodemiology-based approach remains seemingly valuable for monitoring viral epidemiology and anticipating possible outbreaks.

Funding

None declared.

Declaration of Competing Interest

The authors have no relevant competing interest to disclose in relation to this work.