Physiological discrimination and correlation between olfactory and gustatory dysfunction in long-term COVID-19.

The spread of the SARS-CoV-2 virus produces a new disease termed COVID-19, the underlying physiological mechanisms of which are still being understood. Characteristic of the infection is the compromising of taste and smell. There is a persistent need to discriminate the dysfunctions and correlation between taste and smell, which are probably epiphenomena of other concealed conditions. Anosmic and ageusic long-term COVID-19 patients were re-evaluated after 1 year using a Volabolomic approach with an e-nose recording system coupled with olfactometric and gustometric tests. Here a range of sensory arrangements was found, from normal taste and smell to complete losses. The following patterns of olfactory threshold (OT)-taste threshold-olfactory uni- and cross-modal perception were found anosmia-severe hypogeusia-anosmia; hyposmia-hypogeusia-severe hyposmia; normosmia-ageusia-hyposmia; severe hyposmia -normogeusia-normosmia. There is a strong correlation between OT and olfactory uni- and cross-modal perception, a moderate correlation between olfactory and taste threshold and no correlation between OT and taste threshold. In conclusion, this study provides evidence for the feasibility of testing the chemical senses to directly objectify function in order to discriminate taste from olfactory impairment. Furthermore, it allows to hypothesize a long-term effect of the virus due to neuroinvasion through, probably, the olfactory system with injury in the related multisensory areas of taste and smell.

COVID-19 Smell Impairment and Crosstalk with Hypoxia Physiology.

Since its apomorphic appearance in 2019, severe acute respiratory syndrome Coronavirus type 2 (SARS-CoV-2) nowadays circulates as a plesiomorphic human virus in several synapomorphic variants. The respiratory tract is the most important site of infection, the viral effects in the lungs are well described, and more than half of the patients could develop shortness of breath and dyspnea and require ventilatory support. The physiological sign of this condition is the decrease in the partial pressure of oxygen in the blood, leading to acute hypoxia, which could be a factor in the disease. In severe patients, we recorded several physiological parameters: breath frequency (BF), partial pressure of oxygen in the blood (pO2), partial pressure of carbon dioxide in the blood (pCO2), hemoglobin (Hb), heart rate (HR), and blood pressure in correlation with the olfactory threshold. We found significant correlations between reduced olfactory threshold with pO2 and hemoglobin levels, changes in heart rate, and increased HR and pCO2. These results suggest that COVID-19 causes an impaired sense of smell that decreases in threshold corresponding to the disease severity.

Unmasking the 'Asymptomatic' COVID-19: A Nose Question.

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has high infectivity, often masked by asymptomatic carriers, which allows it to spread rapidly and become a pandemic. Attempts to slow the pandemic at this stage depend on the ability to unmask asymptomatic carriers. The rapid diagnosis of active coronavirus disease 2019 (COVID-19) infection is one of the cornerstones of pandemic control, as the nasal cavity is the main gateway for SARS-CoV-2 entry and altered sense of smell is a feature of the current virus. In the present study, we therefore tested the olfactory threshold coupled with heart-lung parameters in subjects undergoing traditional molecular testing, resulting in a significantly different score between asymptomatic subjects and healthy controls. In total, 82% of asymptomatic positives showed olfactory impairment; of these, 46% had severe hyposmia and 7% had anosmia, while in the control 9% had severe hyposmia and 0% had anosmia, respectively, which agrees with heart rate, breathing rate, and blood pressure parameter variations. The olfactory test coupled with physiological parameters may help to identify asymptomatic people. In conclusion, our results suggest that most asymptomatic individuals could be unmasked by mass olfactory rapid threshold screening and then referred to traditional slower diagnostic tests.

Italian Expert Consensus on Clinical and Therapeutic Management of Multiple Chemical Sensitivity (MCS).

Multiple chemical sensitivity (MCS) is a multisystem, recurrent, environmental disorder that flares in response to different exposures (i.e., pesticides, solvents, toxic metals and molds) under the threshold limit value (TLV) calculated for age and gender in the general population. MCS is a syndrome characterized by cutaneous, allergic, gastrointestinal, rheumatological, endocrinological, cardiological and neurological signs and symptoms. We performed a systematic review of the literature to summarize the current clinical and therapeutic evidence and then oriented an eDelphi consensus. Four main research domains were identified (diagnosis, treatment, hospitalization and emergency) and discussed by 10 experts and an MCS patient. Thus, the first Italian MCS consensus had the double aim: (a) to improve MCS knowledge among healthcare workers and patients by standardizing the clinical and therapeutic management to MCS patients; and (b) to improve and shed light on MCS misconceptions not supported by evidence-based medicine (EBM).

Electrophysiological and olfactometric evaluation of long-term COVID-19.

COVID-19 is a public health emergency with cases increasing globally. Its clinical manifestations range from asymptomatic and acute respiratory disease to multiple organ dysfunction syndromes and effects of COVID-19 in the long term. Interestingly, regardless of variant, all COVID-19 share impairment of the sense of smell and taste. We would like to report, as far as we know, the first comprehensive neurophysiological evaluation of the long-term effects of SARS-CoV-2 on the olfactory system with potential-related neurological damage. The case report concerns a military doctor, with a monitored health history, infected in April 2020 by the first wave of the epidemic expansion while on military duty in Codogno (Milan). In this subject, we find the electrophysiological signal in the periphery, while its correlate is absent in the olfactory bulb region than in whole brain recordings. In agreement with this result is the lack of metabolic signs of brain activation under olfactory stimulation. Consequently, quantitative and qualitative diagnoses of anosmia were made by means of olfactometric tests. We strongly suggest a comprehensive series of olfactometric tests from the first sign of COVID-19 and subsequent patient assessments. In conclusion, electrophysiological and metabolic tests of olfactory function have made it possible to study the long-term effects and the establishment of neurological consequences.

Smell and Taste in Severe CoViD-19: Self-Reported vs. Testing.

One of the most striking reported symptoms in CoViD-19 is loss of smell and taste. The frequency of these impairments and their specificity as a potential central nervous system function biomarker are of great interest as a diagnostic clue for CoViD-19 infection as opposed to other similar symptomatologic diseases and because of their implication in viral pathogenesis. Here severe CoViD-19 was investigated by comparing self-report vs. testing of smell and taste, thus the objective severity of olfactory impairment and their possible correlation with other symptoms. Because a significant discrepancy between smell and taste testing vs. self-report results (p < 0.001) emerges in our result, we performed a statistical analysis highlighting disagreement among normosmia (p < 0.05), hyposmia, severe hyposmia, and anosmia (p < 0.001) and, in hypogeusia and severe hypogeusia, while no differences are observed in normogeusia and ageusia. Therefore, we analyzed the olfactory threshold by an objective test revealing the distribution of hyposmic (34%), severe hyposmic (48%), and anosmic (13%) patients in severe CoViD-19. In severe CoViD-19 patients, taste is lost in 4.3% of normosmic individuals, 31.9% of hyposmic individuals, 46.8% of severe hyposmic individuals, and 17% of anosmic individuals. Moreover, 95% of 100 CoViD-19 patients objectively tested were affected by smell dysfunction, while 47% were affected by taste dysfunction. Furthermore, analysis by objective testing also highlighted that the severity of smell dysfunction in CoViD-19 subjects did not correlate with age and sex. In conclusion, we report by objective testing that the majority of CoViD-19 patients report severe anosmia, that most of the subjects have olfactory impairment rather than taste impairment, and, finally, that the olfactory impairment correlate with symptom onset and hospitalization (p < 0.05). Patients who exhibit severe olfactory impairment had been hospitalized for about a week from symptom onset; double time has taken place in subjects with normosmia. Our results may be limited by the relatively small number of study participants, but these suggest by objective testing that hyposmia, severe hyposmia, and anosmia may relate directly to infection severity and neurological damage. The smell test assessment could be a potential screening symptom that might contribute to the decision to test suspected cases or guide quarantine instructions, further therapeutic approach, and evaluation of neurological damage.