Taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

Global population genetics and diversity in the TAS2R bitter taste receptor family.

Bitter taste receptors (TAS2Rs) are noted for their role in perception, and mounting evidence suggests that they mediate responses to compounds entering airways, gut, and other tissues. The importance of these roles suggests that TAS2Rs have been under pressure from natural selection. To determine the extent of variation in TAS2Rs on a global scale and its implications for human evolution and behavior, we analyzed patterns of diversity in the complete 25 gene repertoire of human TAS2Rs in ∼2,500 subjects representing worldwide populations. Across the TAS2R family as a whole, we observed 721 single nucleotide polymorphisms (SNPs) including 494 nonsynonymous SNPs along with 40 indels and gained and lost start and stop codons. In addition, computational predictions identified 169 variants particularly likely to affect receptor function, making them candidate sources of phenotypic variation. Diversity levels ranged widely among loci, with the number of segregating sites ranging from 17 to 41 with a mean of 32 among genes and per nucleotide heterozygosity (π) ranging from 0.02% to 0.36% with a mean of 0.12%. F ST ranged from 0.01 to 0.26 with a mean of 0.13, pointing to modest differentiation among populations. Comparisons of observed π and F ST values with their genome wide distributions revealed that most fell between the 5th and 95th percentiles and were thus consistent with expectations. Further, tests for natural selection using Tajima's D statistic revealed only two loci departing from expectations given D's genome wide distribution. These patterns are consistent with an overall relaxation of selective pressure on TAS2Rs in the course of recent human evolution.

Taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 241 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,897 COVID-19-positive patients, 39.2% reported taste dysfunction (95% confidence interval: 35.34%-43.12%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 18) versus self-report (n = 223) methodologies (Q = 0.57, df = 1, P = 0.45). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

Worldwide diversity, association potential, and natural selection in the superimposed taste genes, CD36 and GNAT3.

CD36 and GNAT3 mediate taste responses, with CD36 acting as a lipid detector and GNAT3 acting as the α subunit of gustducin, a G protein governing sweet, savory, and bitter transduction. Strikingly, the genes encoding CD36 and GNAT3 are genomically superimposed, with CD36 completely encompassing GNAT3. To characterize genetic variation across the CD36-GNAT3 region, its implications for phenotypic diversity, and its recent evolution, we analyzed from ~2,500 worldwide subjects sequenced by the 1000 Genomes Project (1000GP). CD36-GNAT3 harbored extensive diversity including 8,688 single-nucleotide polymorphisms (SNPs), 414 indels, and other complex variants. Sliding window analyses revealed that nucleotide diversity and population differentiation across CD36-GNAT3 were consistent with genome-wide trends in the 1000GP (π = 0.10%, P = 0.64; FST = 9.0%, P = 0.57). In addition, functional predictions using SIFT and PolyPhen-2 identified 60 variants likely to alter protein function, and they were in weak linkage disequilibrium (r2 < 0.17), suggesting their effects are largely independent. However, the frequencies of predicted functional variants were low (P¯ = 0.0013), indicating their contributions to phenotypic variance on population scales are limited. Tests using Tajima's D statistic revealed that pressures from natural selection have been relaxed across most of CD36-GNAT3 during its recent history (0.39 < P < 0.67). However, CD36 exons showed signs of local adaptation consistent with prior reports (P < 0.035). Thus, CD36 and GNAT3 harbor numerous variants predicted to affect taste sensitivity, but most are rare and phenotypic variance on a population level is likely mediated by a small number of sites.

Taste loss as a distinct symptom of COVID-19: A systematic review and meta-analysis.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19, taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 241 meeting all inclusion criteria. Additionally, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct prevalence measures of taste loss would be the most valid because they avoid the taste/smell confusion of self-report. The meta-analysis showed that, among 138,897 COVID-19-positive patients, 39.2% reported taste dysfunction (95% CI: 35.34-43.12%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 18) versus self-report (n = 223) methodologies (Q = 0.57, df = 1, p = 0.45). Generally, males reported lower rates of taste loss than did females and taste loss was highest in middle-aged groups. Thus, taste loss is a bona fide symptom COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

Bitter taste receptors: Genes, evolution and health.

Bitter taste perception plays vital roles in animal behavior and fitness. By signaling the presence of toxins in foods, particularly noxious defense compounds found in plants, it enables animals to avoid exposure. In vertebrates, bitter perception is initiated by TAS2Rs, a family of G protein-coupled receptors expressed on the surface of taste buds. There, oriented toward the interior of the mouth, they monitor the contents of foods, drinks and other substances as they are ingested. When bitter compounds are encountered, TAS2Rs respond by triggering neural pathways leading to sensation. The importance of this role placed TAS2Rs under selective pressures in the course of their evolution, leaving signatures in patterns of gene gain and loss, sequence polymorphism, and population structure consistent with vertebrates' diverse feeding ecologies. The protective value of bitter taste is reduced in modern humans because contemporary food supplies are safe and abundant. However, this is not always the case. Some crops, particularly in the developing world, retain surprisingly high toxicity and bitterness remains an important measure of safety. Bitter perception also shapes health through its influence on preference driven behaviors such as diet choice, alcohol intake and tobacco use. Further, allelic variation in TAS2Rs is extensive, leading to individual differences in taste sensitivity that drive these behaviors, shaping susceptibility to disease. Thus, bitter taste perception occupies a critical intersection between ancient evolutionary processes and modern human health.

Objective Sensory Testing Methods Reveal a Higher Prevalence of Olfactory Loss in COVID-19-Positive Patients Compared to Subjective Methods: A Systematic Review and Meta-Analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify the causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords "COVID-19," "smell," and/or "olfaction." We included any study that quantified smell loss (anosmia and hyposmia) as a symptom of COVID-19. Studies were grouped and compared based on the type of method used to measure smell loss-subjective measures, such as self-reported smell loss, versus objective measures using rated stimuli-to determine if prevalence differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbances. We identified 34 articles quantifying anosmia as a symptom of COVID-19 (6 objective and 28 subjective), collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4-89.2%) and 44% with subjective measurements (95% CI of 32.2-57.0%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2; the use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss.

Objective sensory testing methods reveal a higher prevalence of olfactory loss in COVID-19-positive patients compared to subjective methods: A systematic review and meta-analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence, from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords "COVID-19," "smell," and/or "olfaction." We included any study that quantified olfactory loss as a symptom of COVID-19. Studies were grouped and compared based on the type of method used to measure smell loss-subjective measures such as self-reported smell loss versus objective measures using rated stimuli-to determine if prevalence rate differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbance rates. We identified 34 articles quantifying anosmia as a symptom of COVID-19, collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4-89.2%) and 45% with subjective measurements (95% CI of 31.1-58.5%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2; the use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss.