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Olfactory dysfunction test enables identification of COVID-19 infection

19th July 2021

Olfactory dysfunction is common in those with COVID-19 and a smell test can be used for the identification of infected individuals.

Olfactory dysfunction has been defined as the best predictor of infection with COVID-19. Moreover, in a study of 60 patients, 59 exhibited some dysfunction during a smell identification test. The study also revealed how only 58% of those tested had anosmia indicating in imperfect relationship between olfactory dysfunction and anosmia. It is possible therefore that the use of an inexpensive, rapid and sensitive method, based on olfactory dysfunction would be of potential value in identifying those with COVID-19. Based on this assumption, a team from the Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, US, sought to evaluate the prognostic value of a smell test for identifying those with COVID-19. The team enrolled healthy adults (18 years and over) from a single university campus screening site. Each of the participants were tested for olfactory dysfunction using a novel scent card (SAFER Diagnostics) and immediately followed up with a PCR test for COVID-19. The card itself contained several different scents under a scratch-off and sniff label and participants had eight options: grape, floral, blueberry, banana, mint, unsure or no scent. Using a QR code, the answers were processed electronically and an incorrect choice was labelled as olfactory dysfunction. The team collected participant demographics, medical history, any COVID-19 symptoms and a subjective smell test on a binary (yes/no) and a 10-point visual analogue scale, where 0 indicated no sense of smell and 10 was a normal sense of smell. Using regression analysis, the team assessed the association between the SAFER card and PCR test results, controlling for the presence of any other COVID-19-related symptoms such as fever, fatigue and cough.

Findings
A total of 163 participants were enrolled with a mean age of 31.6 years (56.3% male) with the majority (62.5%) of white ethnicity. There were 16 participants who tested positive for COVID-19 and 7 (4.8%) who tested negative. From the 16 who were PCR positive, 12 (75%) also failed the olfactory dysfunction test. A failed scent card screen was found to be the greatest predictor for COVID-19 positivity (odds ratio, OR = 80.24, 95% CI 14.77–435.90). The authors calculated that the smell test had a sensitivity for detecting COVID-19 of 75% and a specificity of 95.2%. When adding the presence of fatigue as an associated symptom, the sensitivity of the olfactory dysfunction test increased to 93.8% and the specificity to 89.8%. However, when either fever or cough were included, there was no increase in sensitivity. Interestingly, only 6 of the 16 who tested positive for COVID-19 presented with subjective anosmia.

In a discussion of their findings, the authors noted how their rapid olfactory dysfunction test was a valuable screening tool for COVID-19. Nevertheless, they recognised that not all patients experience olfactory dysfunction but that in the presence of fatigue, the test became more sensitive. The authors concluded by calling for future studies to include a larger participant cohort to better account for other olfactory dysfunction risk factors.

Citation
Said M et al. A Rapid Olfactory Test as a Potential Screening Tool for COVID-19. JAMA Otolaryngol Head Neck Surg.

CCK-A agonist reduces disease severity in moderate COVID

20th April 2021

A first-in-class CCK-A agonist has shown benefit in symptom reduction among those hospitalised with moderate COVID-19.

The dual action chemical entity, PNB001, has shown promise as a treatment for those hospitalised with COVID-19. The drug acts as both a cholecystokinin-A (CCK-A) agonist and CCK-B antagonist. Cholecystokinin is a peptide hormone originally identified in the gastrointestinal tract where it serves to mediate pancreatic secretion and contraction of the gall bladder. However, later work has revealed how there are two different types of CCK receptors, and PNB001 has been shown to have both analgesic and anti-inflammatory actions through binding with the different receptors termed A and B. It is the anti-inflammatory effect that is thought to be of greater relevance in COVID-19 and while human safety data on the drug proved to be satisfactory, to date, no trials had been undertaken with COVID-19 patients. In the present study, a team from PNB Vesper Life Science, Kerala, India (the manufacturer of PNB001), examined the impact of their new drug on disease severity scores among those hospitalised with COVID-19. Included patients had pneumonia but not severe disease (defined by an oxygen saturation of < 94%) on room air and with at least two recognised COVID-19 symptoms (e.g., fever, cough, dyspnoea). Excluded patients included those requiring mechanical ventilation. Individuals were randomised to receive either PNB001 (100mg three times daily) along with standard care (SC) or standard care alone which was consistent with India’s current clinical management protocol. Treatment with PNB001 was continued for 14 days and the primary outcome was the change in the 8-point WHO ordinal scale score for disease severity from baseline to day 14 and mortality at day 28.

Findings
A total of 40 patients (20 per arm) were recruited into the study with a mean age (in the PBN001 group) of 52.1 years (30% female). At baseline, both groups had an equal number of patients with a WHO scale score of 4 (i.e., oxygen by mask or nasal prongs). By day 14, the PNB001 group experienced a greater mean reduction in ordinal scale values (0.22 vs 1.12, PNB001 vs SC, p = 0.042) from baseline. For instance, at day 14, 17 (94.4%) vs 12 (70.6%) patients (PNB001 vs SC), had achieved a WHO scale score of 0 (no clinical or virological evidence of infection) and 1 vs 4 patients, maintained a WHO scale score of 4. However, day 28 mortality was similar in both groups although a higher proportion of patients given PNB001 were discharged from hospital by day 14 (19 vs 15, p = 0.048).

In their conclusion, the authors noted that PNB001 was well tolerated and that it showed significant clinical improvements when added to standard care in patients with moderate COVID-19. However, they also recognised the limitations of the study, i.e., a small sample size and the fact that while randomised, it was not blinded.

Citation
Lattmann E et al. Randomised, Comparative, Clinical Trial to Evaluate Efficacy and Safety of PNB001 in Moderate COVID-19 Patients. MedRxiv 2021