The prevalence of chemosensory dysfunction in patients with COVID-19 varies greatly between populations. It is unclear whether such differences are due to factors at the level of the human host, or at the level of the coronavirus, or both. At the host level, the entry proteins which allow virus binding and entry have variants with distinct properties, and the frequency of such variants differs between ethnicities. At the level of the virus, the D614G mutation enhances virus entry to the host cell. Since the two virus strains (D614 and G614) coexisted in the first six months of the pandemic in most populations, it has been difficult to distinguish between contributions of the virus and contributions of the host for anosmia. To answer this question, we conducted a systematic review and meta-analysis of studies in South Asian populations when either the D614 or the G614 virus was dominant. We show that populations infected predominantly with the G614 virus had a much higher prevalence of anosmia (pooled prevalence of 31.8%) compared with the same ethnic populations infected mostly with the D614 virus strain (pooled anosmia prevalence of 5.3%). We conclude that the D614G mutation is a major contributing factor that increases the prevalence of anosmia in COVID-19, and that this enhanced effect on olfaction constitutes a previously unrecognized phenotype of the D614G mutation. The new virus strains that have additional mutations on the background of the D614G mutation can be expected to cause a similarly increased prevalence of chemosensory dysfunctions.

The D614G Virus Mutation Enhances Anosmia in COVID-19 Patients: Evidence from a Systematic Review and Meta-analysis of Studies from South Asia.

The prevalence of chemosensory dysfunction in patients with COVID-19 varies greatly between populations. It is unclear whether such differences are due to factors at the level of the human host, or at the level of the coronavirus, or both. At the host level, the entry proteins which allow virus binding and entry have variants with distinct properties, and the frequency of such variants differs between ethnicities. At the level of the virus, the D614G mutation enhances virus entry to the host cell. Since the two virus strains (D614 and G614) co-existed in the first six months of the pandemic in most populations, it has been difficult to distinguish between contributions of the virus and contributions of the host for anosmia. To answer this question, we conducted a systematic review and meta-analysis of studies in South Asian populations when either the D614 or the G614 virus was dominant. We show that populations infected predominantly with the G614 virus had a much higher prevalence of anosmia (pooled prevalence of 31.8%) compared with the same ethnic populations infected mostly with the D614 virus strain (pooled anosmia prevalence of 5.3%). We conclude that the D614G mutation is a major contributing factor that increases the prevalence of anosmia in COVID-19, and that this enhanced effect on olfaction constitutes a previously unrecognized phenotype of the D614G mutation. The new virus strains that have additional mutations on the background of the D614G mutation can be expected to cause a similarly increased prevalence of chemosensory dysfunctions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/21261934v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@f2cc42org.highwire.dtl.DTLVardef@401e43org.highwire.dtl.DTLVardef@182e7d1org.highwire.dtl.DTLVardef@1414d2a_HPS_FORMAT_FIGEXP M_FIG C_FIG

https://medrxiv.org/content/10.1101/2021.08.11.21261934v1.full.pdf

The D614G virus mutation enhances anosmia in COVID-19 patients: Evidence from a systematic review and meta-analysis of studies from South Asia

Neurological consequences of COVID-19 and brain related pathogenic mechanisms: A new challenge for neuroscience

Olfactory disorders (OD) pathogenesis, underlying conditions, and prognostic in coronavirus disease 2019 (COVID‐19) remain partially described. ANOSVID is a retrospective study in Nord Franche‐Comté Hospital (France) that included COVID‐19 patients from March 1 2020 to May 31 2020. The aim was to compare COVID‐19 patients with OD (OD group) and patients without OD (no‐OD group). A second analysis compared patients with anosmia (high OD group) and patients with hyposmia or no OD (low or no‐OD group). The OD group presented less cardiovascular and other respiratory diseases compared to the no‐OD group (odds ratio [OR] = 0.536 [0.293–0.981], p = 0.041 and OR = 0.222 [0.056–0.874], p = 0.037 respectively). Moreover, history of malignancy was less present in the high OD group compared with the low or no‐OD group (OR = 0.170 [0.064–0.455], p < 0.001). The main associated symptoms (OR > 5) with OD were loss of taste (OR = 24.059 [13.474–42.959], p = 0.000) and cacosmia (OR = 5.821 [2.246–15.085], p < 0.001). Most of all ORs decreased in the second analysis, especially for general, digestive, and ENT symptoms. Only two ORs increased: headache (OR = 2.697 [1.746–4.167], p < 0.001) and facial pain (OR = 2.901 [1.441–5.842], p = 0.002). The high OD group had a higher creatinine clearance CKD than the low or no‐OD group (89.0 ± 21.1 vs. 81.0 ± 20.5, p = 0.040). No significant difference was found concerning the virological, radiological, and severity criteria. OD patients seem to have less comorbidity, especially better cardiovascular and renal function. Associated symptoms with OD were mostly neurological symptoms. We did not find a significant relationship between OD and less severity in COVID‐19 possibly due to methodological bias.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347548

Olfactory dysfunction in COVID‐19, new insights from a cohort of 353 patients: The ANOSVID study

The most effective method of limiting the coronavirus disease pandemic of 2019 (COVID-19) is vaccination. For the determination of the comparative efficacy and safety of COVID-19 vaccines and their platforms during the pre-Delta era, a systematic review and network meta-analysis was conducted. The MEDLINE, Embase, and MedRxiv databases were searched, and the gray literature was manually searched up to 8 July 2021. The review includes the phase II and III randomized controlled trials (RCTs) that assessed the efficacy, immunogenicity, and safety of the COVID-19 vaccines. The network meta-analysis used a Bayesian model and used the surface under the cumulative ranking to rank the comparisons between the vaccines. All included studies were quality appraised according to their design, and the heterogeneity of the analyses was assessed using I2. In terms of vaccine efficacy, the mRNA-1273 vaccine ranked the highest, and the CoronaVac vaccine ranked the lowest. The mRNA-1273 ranked the highest for neutralizing antibody responses to live SARS-CoV-2. The WIV04 vaccine was associated with the lowest incidence of both local and systemic adverse reactions. All studies except one had a low to moderate risk of bias. The mRNA platform vaccines showed higher efficacy and more adverse reactions than the other vaccines.

/pdf/efficacy-immunogenicity-and-safety-of-covid-19-vaccines-in-1zkq6qki.pdf

Efficacy, Immunogenicity, and Safety of COVID-19 Vaccines in Randomized Control Trials in the Pre-Delta Era: A Systematic Review and Network Meta-Analysis

Anecdotal evidence suggests that the severity of coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is likely to be distinguished by variations in loss of smell (LOS). Thus, we conducted a meta-analysis of 45 articles that include a total of 42,120 COVID-19 patients from 17 different countries to demonstrate that severely ill or hospitalized COVID-19 patients have a lesser chance of experiencing LOS than non-severely ill or non-hospitalized COVID-19 patients (odds ratio = 0.527 [95% CI 0.373-0.744; p < 0.001] and 0.283 [95% CI 0.173-0.462; p < 0.001], respectively). We also proposed a possible mechanism underlying the association of COVID-19 severity with anosmia, which may explain why patients without sense of smell develop severe COVID-19. Variations in LOS according to the severity of COVID-19 is a global phenomenon, with few exceptions. Since severely ill patients have a lower rate of anosmia, patients without anosmia should be monitored more closely in the early stages of COVID-19, for early diagnosis of severity of illness. An understanding of how the severity of COVID-19 infection and LOS are associated has profound implications for the clinical management and mitigation strategies for the disease.

/pdf/is-loss-of-smell-an-early-predictor-of-covid-19-severity-a-3ezfuuxzip.pdf

Is loss of smell an early predictor of COVID-19 severity: a systematic review and meta-analysis.

Absolute oral and subcutaneous bioavailability of ortho-topolin riboside in mice.

/pdf/european-regulatory-science-and-regulatory-science-expert-43dbadibhq.pdf

Hocheol Shin

Papers

Is loss of smell an early predictor of COVID-19 severity: a systematic review and meta-analysis.

Absolute oral and subcutaneous bioavailability of ortho-topolin riboside in mice.

European Regulatory Science and Regulatory Science Expert Training Project