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.

COVEVOL: Natural Evolution at 6 Months of COVID-19.

Many studies have investigated post-COVID symptoms, but the predictors of symptom persistence remain unknown. The objective was to describe the natural course of the disease at 6 months and to identify possible factors favoring the resurgence or persistence of these symptoms. COVEVOL is a retrospective observational descriptive study of 74 patients. All patients with positive SARS-CoV-2 PCR from March 2020 were included. We compared a group with symptom persistence (PS group) with another group without symptom persistence (no-PS group). Fifty-three out of seventy-four patients (71.62%) described at least one persistent symptom at 6 months of SARS-CoV-2 infection. In the PS group, 56.6% were women and the average age was 54.7 years old [21-89.2] ± 16.9. The main symptoms were asthenia (56.6%, n = 30), dyspnea (34%, n = 18), anxiety (32.1% n = 17), anosmia (24.5%, n = 13) and agueusia (15.1% n = 8). Ten patients (13.51%) presented a resurgence in symptoms. Patients in the PS group were older (p = 0.0048), had a higher BMI (p = 0.0071), and were more frequently hospitalized (p = 0.0359) compared to the no-PS group. Odynophagia and nasal obstruction were less present in the inaugural symptoms of COVID-19 in the PS group (p = 0.0202 and p = 0.0332). Persistent post-COVID syndromes are common and identification of contributing factors is necessary for understanding this phenomenon and appropriate management.

Post-COVID-19 Syndrome: Nine Months after SARS-CoV-2 Infection in a Cohort of 354 Patients: Data from the First Wave of COVID-19 in Nord Franche-Comté Hospital, France.

(1) Background. Post-COVID-19 syndrome is defined as the persistence of symptoms after confirmed SARS-CoV-2 infection. (2) Methods. ANOSVID is an observational retrospective study in Nord Franche-Comté Hospital in France that included adult COVID-19 patients confirmed by RT-PCR from 1 March 2020 to 31 May 2020. The aim was to describe patients with post-COVID-19 syndrome with persistent symptoms (PS group) and to compare them with the patients without persistent symptoms (no-PS group). (3) Results. Of the 354 COVID-19 patients, 35.9% (n = 127) reported persistence of at least one symptom after a mean of 289.1 ± 24.5 days after symptom onset. Moreover, 115 patients reported a recurrence of symptoms after recovery, and only 12 patients reported continuous symptoms. The mean age of patients was 48.6 years (19-93) ± 19.4, and 81 patients (63.8%) were female. Patients in the PS group had a longer duration of symptoms of initial acute SARS-CoV-2 infection than patients in the no-PS group (respectively, 57.1 ± 82.1 days versus 29.7 ± 42.1 days, p < 0.001). A majority of patients (n = 104, 81.9%) reported three or more symptoms. The most prevalent persistent symptoms were loss of smell (74.0%, n = 94), fatigue (53.5%, n = 68), loss of taste (31.5%, n = 40), and dyspnea (30.7%, n = 39). These were followed by pain symptoms (26.8% (n = 34), 26.0% (n = 33), 24.4% (n = 31); headache, arthralgia, and myalgia, respectively). More than half of patients reporting persistent symptoms (58%, n = 73) were healthcare workers (HCWs). Among outpatients, this population was more present in the PS group than the no-PS group ((86.6%) n = 71/82 versus (72.2%) n = 109/151, p = 0.012). Post-COVID-19 syndrome was more frequent in patients with a past history of chronic rhinosinusitis (8.7% (n = 11%) versus 1.3% (n = 3), p < 0.001). No significant difference was found regarding clinical characteristics and outcome, laboratory, imaging findings, and treatment received in the two groups. (4) Conclusions. More than a third of our COVID-19 patients presented persistent symptoms after SARS-CoV-2 infection, particularly through loss of smell, loss of taste, fatigue, and dyspnea, with a high prevalence in HCWs among COVID-19 outpatients.

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.

Recurrence of COVID-19 after recovery ? A case series in health care workers, France.

We describe 3 cases of coronavirus disease 2019 in health care workers in France involving presumed clinical and microbiological recurrence after recovery. All patients were immunocompetent with clinical mild form. These cases highlight the possibility of coronavirus disease-recurrence.

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.

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).