Asthma and Cacosmia Could Be Predictive Factors of Olfactory Dysfunction Persistence 9 Months after SARS-CoV-2 Infection: The ANOSVID Study.

Background. Long-term evolution data of olfactory disorders (OD) in COVID-19 are limited. Method. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from the first wave. The aim was to describe OD evolution, especially in patients with persistent OD (p-OD group) in comparison with patients with resolved OD (r-OD group). Results. Among 354 COVID-19 patients, 229 reported OD were included. Eighty-five percent of patients (n = 195) recovered from their OD within 90 days. However, 9.5 months (in average) after symptoms onset, OD were persisting in 93 patients (40.6%) and resolved in 136 patients (59.4%). In the p-OD group (n = 93), the mean age was 51.4 years (19-98) ± 20.2, and 65 patients (69.9%) were female; the three main comorbidities in the p-OD group were: asthma (20.4%, n = 19), allergic rhinitis (19.4%, n = 18), and arterial hypertension (16.1%, n = 15). Eleven patients (12%) presented anosmia, and 82 patients (88%) presented hyposmia. Asthma was more described in p-OD group than r-OD group (19 (20.4%) versus 10 (7.4%), p = 0.006). Cacosmia was more described in p-OD group than r-OD group (27 (29.0%) versus 18 (13.2%), p = 0.005). There was no significant difference between the two groups concerning other comorbidities and symptoms, clinical, biological, and imaging findings, and outcome or about the impact of OD on the quality of life of the patients between the p-OD group and r-OD group. sQOD-NS brief version score was 10.7 ± 5.89 and 12.0 ± 6.03, respectively (p = 0.137). Conclusion. Forty-one percent of patients with OD reported OD persistence 9.5 months after COVID-19 (hyposmia in 88% of cases). Asthma and cacosmia could be predictive factors of OD persistence.

Asthma and Cacosmia Could Be Predictive Factors of Olfactory Dysfunction Persistence 9 Months after SARS-CoV-2 Infection: The ANOSVID Study

Background. Long-term evolution data of olfactory disorders (OD) in COVID-19 are limited. Method. ANOSVID is a retrospective study in Nord Franche-ComtéHospital (France) that included COVID-19 patients from the first wave. The aim was to describe OD evolution, especially in patients with persistent OD (p-OD group) in comparison with patients with resolved OD (r-OD group). Results. Among 354 COVID-19 patients, 229 reported OD were included. Eighty-five percent of patients (n = 195) recovered from their OD within 90 days. However, 9.5 months (in average) after symptoms onset, OD were persisting in 93 patients (40.6%) and resolved in 136 patients (59.4%). In the p-OD group (n = 93), the mean age was 51.4 years (19–98) ±20.2, and 65 patients (69.9%) were female;the three main comorbidities in the p-OD group were: asthma (20.4%, n = 19), allergic rhinitis (19.4%, n = 18), and arterial hypertension (16.1%, n = 15). Eleven patients (12%) presented anosmia, and 82 patients (88%) presented hyposmia. Asthma was more described in p-OD group than r-OD group (19 (20.4%) versus 10 (7.4%), p = 0.006). Cacosmia was more described in p-OD group than r-OD group (27 (29.0%) versus 18 (13.2%), p = 0.005). There was no significant difference between the two groups concerning other comorbidities and symptoms, clinical, biological, and imaging findings, and outcome or about the impact of OD on the quality of life of the patients between the p-OD group and r-OD group. sQOD-NS brief version score was 10.7 ±5.89 and 12.0 ±6.03, respectively (p = 0.137). Conclusion. Forty-one percent of patients with OD reported OD persistence 9.5 months after COVID-19 (hyposmia in 88% of cases). Asthma and cacosmia could be predictive factors of OD persistence.

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

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.

Systematic Review and Subgroup Meta-analysis of Randomized Trials to Determine Tocilizumab's Place in COVID-19 Pneumonia.

INTRODUCTION: Tocilizumab randomized clinical trial results are heterogeneous because of the heterogenous population included in them. METHODS: We conducted a meta-analysis with subgroup meta-analysis (PRISMA guidelines) between severe and non-severe COVID-19. RESULTS: We included nine trials. Overall, the mortality rate was 24.5% (821/3357) in the tocilizumab group and 29.1% (908/3125) in the control group at day 28-30 (pooled OR, 0.85; 95% CI 0.76-0.96; p = 0.006). Considering the subgroup analysis, this benefit on mortality was confirmed and amplified in the severe COVID-19 group (pooled OR, 0.82; 95% CI 0.73-0.93; p = 0.001) but not in the non-severe COVID-19 group (pooled OR, 1.46; 95% CI 0.91-2.34; p = 0.12). For patients who were not mechanically ventilated at baseline (5523/6482), the pooled OR (0.74; 95% CI 0.64-0.85; p < 0.0001) for mechanical ventilation incidence at day 28-30 was in favor of tocilizumab (cumulative incidence of 14.8% versus 19.4% in tocilizumab and control arm, respectively). This benefit was confirmed in both subgroups, i.e., severe and non-severe COVID-19. CONCLUSION: Tocilizumab is an effective treatment in hospitalized patients with COVID-19 and hypoxemia by improving survival and decreasing mechanical ventilation requirement. The greatest benefit is observed in severe COVID-19.

Tocilizumab in COVID-19 pneumonia: Practical proposals based on a narrative review of randomised trials.

In this article, we express our opinion about tocilizumab as an effective treatment in coronavirus disease 2019, based on a narrative review and a deep analysis of tocilizumab randomised trial results. Eight trials were included. No one was in favour for controlled arm about main endpoint of death or mechanical ventilation incidence at day 28-30. Five trials on heterogenous populations seem to not demonstrate tocilizumab efficacy, but showed encouraging results in subgroup analysis on severe/critical patients (in favour for tocilizumab). Trials on severe/critical COVID-19 pneumonia as REMAP-CAP and RECOVERY showed mortality benefit of tocilizumab administration; CORIMUNO, REMAP-CAP and RECOVERY showed that tocilizumab decreased the incidence of mechanical ventilation. No safety signal about tocilizumab used was noticed in all trials. We concluded that tocilizumab reduces mortality and mechanical ventilation requirement if administered with the right timing in COVID-19 pneumonia. The challenge now is to define the optimal group and timing for tocilizumab benefit and we suggest that: (i) tocilizumab has a place in treatment of severe/critical COVID-19 pneumonia, with a high level of O2 flow or noninvasive ventilation or high flow nasal cannula; (ii) possibly early after intubation in patients on mechanical ventilation. Initiating tocilizumab in critically ill patients early before irreversible respiratory failure, especially in patients at an inflammatory stage could be the key to successful outcome.

Angioedema and COVID-19: A New Dermatological Manifestation?

The main localization of SARS-CoV-2 infection is the respiratory tract. Digestive and otorhinolaryngological localizations are also reported. More recently, dermatological manifestations have been reported during Coronavirus disease-19 (COVID-19). We report a case of a labial angioedema in a patient with confirmed COVID-19.

Is There Still a Place for Tocilizumab in Coronavirus Disease 2019?

In this article, we sought to summarize the available evidence of tocilizumab as a treatment for coronavirus disease 2019. Recent tocilizumab randomized trials have not shown clear evidence of efficacy, especially on mortality, in contrast to observational studies. These clinical trials focus on a heterogeneous population of patients (clinical severity and inflammatory stage), and this is possibly one of the reasons that explain heterogeneity of results. However, these same trials have shown some evidence that tocilizumab may reduce intensive care unit admissions and/or mechanical ventilation incidence, which are huge challenges in the severe acute respiratory syndrome coronavirus 2 pandemic. Future clinical trials with primary endpoint built on this assumption are needed (1) to confirm whether tocilizumab reduces mechanical ventilation requirement and (2) to describe the right patient population and optimal timing for tocilizumab administration. Finding the optimal timing for tocilizumab administration and the group of patients who are susceptible to having the greatest benefit are probably the main challenge.

New loss of smell and taste: Uncommon symptoms in COVID-19 patients on Nord Franche-Comte cluster, France.

BACKGROUND: New loss of smell or taste was not included as common symptoms of COVID-19 until March 2020 when the pandemic started in Western countries. We want to describe the prevalence and features of anosmia and dysgeusia in COVID-19 patients. METHODS: We retrospectively investigated the clinical features of confirmed cases of COVID-19 in Nord Franche-Comté Hospital, Trevenans, France, between March, 1st and March, 14th 2020. We used SARS-CoV-2 real time RT-PCR in respiratory samples to confirm the cases. RESULTS: Of 70 patient enrolled, the mean age was 57.0 years and 29 patients (41%) were men. Median Charlson comorbidity index was 1.70(±2.5). Twenty-seven (39%) patients had pneumonia. Fatigue (93% [65]), cough (80% [55]) and fever (77% [54]) were the three main symptoms. Neurologic symptoms were present in more than half of the patients: anosmia (53% [37]) and dysgeusia (48% [34]). The mean duration of anosmia was 7.4 (±5, [1-21]) days, 51% (36/70) recovered before 28 days of evolution. Only one patient with anosmia had not recovered at the end of the follow-up. Patients with anosmia had less often a pneumonia (10/37 vs 17/33, p = 0.036), were less often hospitalized (13/37 vs 20/33, p = 0.033) and needed less often oxygen therapy (6/37 vs 17/33, p = 0.002) than patients without anosmia. There were no statistically differences for viral load between patients with anosmia and patients without anosmia (5.5 [2.0-8.6] vs 5.3 [2.1-8.5] log copies/ml respectively, p = 0.670). The fatality of COVID-19 in our study was 6% with four deaths. CONCLUSIONS: Anosmia and dysgeusia are present in half of COVID-19 patients. The mean duration of anosmia was 7 days and the outcome seems favorable in less than 28 days.

COVID-19: comparative clinical features and outcome in 114 patients with or without pneumonia (Nord Franche-Comte Hospital, France).

COVID-19 patients (n = 114) were included (55 patients with pneumonia (group P) and 59 without pneumonia (group NP). Patients in group P were older (69 (±17) years vs 46 (±16); p < 0.001) with a male predominance (58.2% vs 27.1%; p < 0.001). The symptoms which were statistically more frequents in patients with pneumonia were fever ≥ 38 °C (93% vs 70%; p = 0.002) and dyspnea (73% vs 22%; p < 0.001). Symptoms such as facial headache (42% vs 15%; p = 0.001), sore throat (39% vs 16%; p = 0.007), dysgeusia (61% vs 33%; p = 0.003), anosmia (63% vs 31%; p = 0.001) were statistically more frequents in patients without pneumonia.

Impact of tocilizumab on mortality and/or invasive mechanical ventilation requirement in a cohort of 206 COVID-19 patients.

INTRODUCTION: No therapy has proven to be effective yet to reduce mortality and/or invasive mechanical ventilation (IMV) requirement in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment. METHODS: We conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: mortality and/or IMV requirement. RESULTS: Thirty patients were treated with TCZ and 176 patients were treated without TCZ. TCZ was used in patients in critical condition (oxygen therapy flow at TCZ onset was 10.5 L/min and 14/30 patients had ≥ 50% lung involvement on CT scan) as a rescue treatment (8/30 patients who died were not admitted in USC in regard to their comorbidities). However, mortality and/or IMV requirement were lower in patients with TCZ than in patients without TCZ (27% vs 52%, p = 0.009). CONCLUSION: Despite the small sample size in the TCZ group, this result suggests that TCZ reduces mortality and/or IMV requirement in patients with severe SARS-CoV-2 pneumonia. This notion needs to be confirmed and spread in the medical community.

Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster.

Clinical descriptions about influenza-like illnesses (ILI) in COVID-19 seem non-specific. We aimed to compare the clinical features of COVID-19 and influenza. We retrospectively investigated the clinical features and outcomes of confirmed cases of COVID-19 and influenza in Nord Franche-Comté Hospital between February 26th and March 14th 2020. We used SARS-CoV-2 RT-PCR and influenza virus A/B RT-PCR in respiratory samples to confirm the diagnosis. We included 124 patients. The mean age was 59 (±19 [19-98]) years with 69% female. 70 patients with COVID-19 and 54 patients with influenza A/B. Regarding age, sex and comorbidities, no differences were found between the two groups except a lower Charlson index in COVID-19 group (2 [±2.5] vs 3 [±2.4],p = 0.003). Anosmia (53% vs 17%,p < 0.001), dysgeusia (49% vs 20%,p = 0.001), diarrhea (40% vs 20%,p = 0.021), frontal headache (26% vs 9%,p = 0.021) and bilateral cracklings sounds (24% vs 9%,p = 0.034) were statistically more frequent in COVID-19. Sputum production (52% vs 29%,p = 0.010), dyspnea (59% vs 34%,p = 0.007), sore throat (44% vs 20%,p = 0.006), conjunctival hyperhemia (30% vs 4%,p < 0.001), tearing (24% vs 6%,p = 0.004), vomiting (22% vs 3%,p = 0.001) and rhonchi sounds (17% vs 1%,p = 0.002) were more frequent with influenza infection. We described several clinical differences which can help the clinicians during the co-circulation of influenza and SARS-CoV-2.

Diarrhea: An underestimated symptom in Coronavirus disease 2019.

In a retrospective study in the Nord Franche-Comté hospital conducted between March 1st and March 17th 2020, and compared to the review of Li et al., diarrhea was a main symptom in patients with COVID-19. Out of the 114 patients, 55 (48%) had diarrhea; it was the fifth most common symptom. In the group of patients with diarrhea, the median age was 56 years (±18) and 32 (58%) were female. Only 2 patients (3.6%) had a past history of inflammatory bowel disease. Fifty-six percent of patients (n=30/54) were hospitalised. Diarrhea appeared 4.5 days (±1.8) after the onset of the first other symptoms in COVID-19. Of the 55 patients with diarrhea, 29 (52.7%) had at least one simultaneous gastrointestinal (GI) symptom other than diarrhea. Twenty-five patients (45.5%) had nausea, 19 patients (34.5%) had abdominal pain and 9 (16.3%) had vomiting. Myalgia, sore throat, sneezing and the other GI symptoms were statistically more frequent in the group with diarrhea than in the group without diarrhea (P<0.05).