In response to the COVID-19 pandemic, many governments have taken drastic measures to avoid an overflow of intensive care units. Accurate metrics of disease spread are critical for the reopening strategies. Here, we show that self-reports of smell/taste changes are more closely associated with hospital overload and are earlier markers of the spread of infection of SARS-CoV-2 than current governmental indicators. We also report a decrease in self-reports of new onset smell/taste changes as early as 5 days after lockdown enforcement. Cross-country comparisons demonstrate that countries that adopted the most stringent lockdown measures had faster declines in new reports of smell/taste changes following lockdown than a country that adopted less stringent lockdown measures. We propose that an increase in the incidence of sudden smell and taste change in the general population may be used as an indicator of COVID-19 spread in the population.

G protein-coupled receptors (GPCRs) conserve common structural folds and activation mechanisms, yet their ligand spectra and functions are highly diverse. This work investigated how the amino-acid sequences of olfactory receptors (ORs)—the largest GPCR family—encode diversified responses to various ligands. We established a proteochemometric (PCM) model based on OR sequence similarities and ligand physicochemical features to predict OR responses to odorants using supervised machine learning. The PCM model was constructed with the aid of site-directed mutagenesis, in vitro functional assays, and molecular simulations. We found that the ligand selectivity of the ORs is mostly encoded in the residues up to 8 Å around the orthosteric pocket. Subsequent predictions using Random Forest (RF) showed a hit rate of up to 58%, as assessed by in vitro functional assays of 111 ORs and 7 odorants of distinct scaffolds. Sixty-four new OR–odorant pairs were discovered, and 25 ORs were deorphanized here. The best model demonstrated a 56% deorphanization rate. The PCM-RF approach will accelerate OR–odorant mapping and OR deorphanization.