Cardiovascular Safety of Hydroxychloroquine-Azithromycin in 424 COVID-19 Patients.

Background and Objectives: Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular, the potential of prolong cardiac repolarization when using this combination has been discussed. Materials and Methods: We report a pragmatic and simple safety approach which we implemented among the first patients treated for COVID-19 in our center in early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) > 500 ms, hypokalemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 h of the initial prescription. Results: Among the 424 consecutive adult patients (mean age 46.3 ± 16.1 years; 216 women), 21.5% patients were followed in conventional wards and 78.5% in a day-care unit. A total of 11 patients (2.6%) had contraindications to the HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after 2 days of treatment (p = 0.003). QTc prolongation was particularly observed in female outpatients <65 years old without cardiovascular disease. Ten patients (2.4%) developed QTc prolongation > 60 ms, and none had QTc > 500 ms. Conclusions: This report does not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, it shows that a simple initial assessment of patient medical history, electrocardiogram (ECG), and kalemia identifies contraindicated patients and enables the safe treatment of COVID-19 patients with HCQ-AZ. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are applied.

SARS-CoV-2 Reinfection and Severity of the Disease: A Systematic Review and Meta-Analysis.

Since the discovery of SARS-CoV-2, changes in genotype and reinfection with different variants have been observed in COVID-19-recovered patients, raising questions around the clinical pattern and severity of primary infection and reinfection. In this systematic review, we summarize the results of 23 studies addressing SARS-CoV-2 reinfections. A total of 23,231 reinfected patients were included, with pooled estimated reinfection rates ranging from 0.1 to 6.8%. Reinfections were more prevalent during the Omicron variant period. The mean age of reinfected patients was 38.0 ± 6. years and females were predominant among reinfected patients (M/F = 0.8). The most common symptoms during the first and second infection were fever (41.1%), cough (35.7% and 44.6%), myalgia (34.5% and 33.3%), fatigue (23.8% and 25.6%), and headaches (24.4% and 21.4%). No significant differences of clinical pattern were observed between primary infection and reinfection. No significant differences in the severity of infection were observed between primary infection and reinfection. Being female, being a patient with comorbidities, lacking anti-nucleocapsid IgG after the first infection, being infected during the Delta and Omicron wave, and being unvaccinated were associated with a higher risk of reinfection. Conflicting age-related findings were found in two studies. Reinfection with SARS-CoV-2 suggests that natural immunity is not long-lasting in COVID-19 patients.

The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule.

The nature and dynamics of mutations associated with the emergence, spread, and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant ("Marseille-4") for 10 months since its onset in July 2020. Here, we analyzed and classified into subvariants and lineages 7453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1 ± 1.4 months, during which 4.1 ± 2.6 mutations accumulated. Growth rate was 0.079 ± 0.045, varying from 0.010 to 0.173. Most of the lineages exhibited a bell-shaped distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marseille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in SARS-CoV-2 of mink and in the Alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.

First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France.

The SARS-CoV-2 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants have recently emerged worldwide. To date, the 21L/BA.2 Omicron variant has remained very minority globally but became predominant in Denmark instead of the 21K/BA.1 variant. Here, we describe the first cases diagnosed with this variant in south-eastern France. We identified 13 cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travelers returning from Tanzania. Overall, viral genomes displayed a mean (±standard deviation) number of 65.9 ± 2.5 (range, 61-69) nucleotide substitutions and 31.0 ± 8.3 (27-50) nucleotide deletions, resulting in 49.6 ± 2.2 (45-52) amino acid substitutions (including 28 in the spike protein) and 12.4 ± 1.1 (12-15) amino acid deletions. Phylogeny showed the distribution in three different clusters of these genomes, which were most closely related to genomes from England and South Africa, from Singapore and Nepal, or from France and Denmark. Structural predictions highlighted a significant enlargement and flattening of the surface of the 21L/BA.2 N-terminal domain of the spike protein compared to that of the 21K/BA.1 Omicron variant, which may facilitate initial viral interactions with lipid rafts. Close surveillance is needed at global, country, and center scales to monitor the incidence and clinical outcome of the 21L/BA.2 Omicron variant.

Diaphragm dysfunction after severe COVID-19: An ultrasound study.

Background: SARS-CoV-2 infection can impair diaphragm function at the acute phase but the frequency of diaphragm dysfunction after recovery from COVID-19 remains unknown. Materials and methods: This study was carried out on patients reporting persistent respiratory symptoms 3-4 months after severe COVID-19 pneumonia. The included patients were selected from a medical consultation designed to screen for recovery after acute infection. Respiratory function was assessed by a pulmonary function test, and diaphragm function was studied by ultrasonography. Results: In total, 132 patients (85M, 47W) were recruited from the medical consultation. During the acute phase of the infection, the severity of the clinical status led to ICU admission for 58 patients (44%). Diaphragm dysfunction (DD) was detected by ultrasonography in 13 patients, two of whom suffered from hemidiaphragm paralysis. Patients with DD had more frequently muscle pain complaints and had a higher frequency of prior cardiothoracic or upper abdominal surgery than patients with normal diaphragm function. Pulmonary function testing revealed a significant decrease in lung volumes and DLCO and the dyspnea scores (mMRC and Borg10 scores) were significantly increased in patients with DD. Improvement in respiratory function was recorded in seven out of nine patients assessed 6 months after the first ultrasound examination. Conclusion: Assessment of diaphragm function by ultrasonography after severe COVID-19 pneumonia revealed signs of dysfunction in 10% of our population. In some cases, ultrasound examination probably discovered an un-recognized pre-existing DD. COVID-19 nonetheless contributed to impairment of diaphragm function. Prolonged respiratory physiotherapy led to improvement in respiratory function in most patients. Clinical trial registration: [www.cnil.fr], identifier [#PADS20-207].

A rapid, easy, and scalable whole blood monocyte CD169 assay for outpatient screening during SARS-CoV-2 outbreak, and potentially other emerging disease outbreaks.

Objective: The COVID-19 corona virus disease outbreak is globally challenging health systems and societies. Its diagnosis relies on molecular methods, with drawbacks revealed by mass screening. Upregulation of neutrophil CD64 or monocyte CD169 has been abundantly reported as markers of bacterial or acute viral infection, respectively. We evaluated the sensitivity of an easy, one-step whole blood flow cytometry assay to measure these markers within 10 min, as a potential screening test for COVID-19 patients. Methods: Patients (n = 177) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were tested on 10 µL blood and results were compared with reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Results: We observed 98% and 100% sensitivity in early-stage (n = 52) and asymptomatic patients (n = 9), respectively. Late-stage patients, who presented for a second control RT-qPCR, were negative for both assays in most cases. Conversely, neutrophil CD64 expression was unchanged in 75% of cases, without significant differences between groups. Conclusion: Monocyte CD169 evaluation was highly sensitive for detecting SARS-CoV-2 infection in first-presentation patients; and it returns to basal level upon infection clearance. The potential ease of fingerprick collection, minimal time-to-result, and low cost rank this biomarker measurement as a potential viral disease screening tool, including COVID-19. When the virus prevalence in the tested population is usually low (1%-10%), such an approach could increase the testing capacity 10 to 100-fold, with the same limited molecular testing resources, which could focus on confirmation purposes only.

Outcomes of 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020: A Monocentric Retrospective Analysis.

Objectives: We evaluated the 6-week mortality of SARS-CoV-2 hospitalized patients treated using a standardized protocol in 2020 in Marseille, France. Methods: A retrospective monocentric cohort study was conducted in the standard hospital wards at the Institut Hospitalo-Universitaire Méditerranée Infection, between March and December 2020 in adults with SARS-CoV-2 PCR-proven infection. Results: Of the 2111 hospitalized patients (median age, 67 [IQR 55-79] years; 1154 [54.7%] men), 271 were transferred to the intensive care unit (12.8%) and 239 died (11.3%; the mean age of patients who died was 81.2 (±9.9)). Treatment with hydroxychloroquine plus azithromycin (HCQ-AZ), used in 1270 patients, was an independent protective factor against death (0.68 [0.52 - 0.88]). This effect was consistent for all subgroups of age, comorbidities, severity of the disease and comedications with zinc or corticosteroids. Zinc was independently protective against death (0.39 [0.23 - 0.67]), in a subgroup analysis of patients treated with HCQ-AZ without dexamethasone. The use of high-flow oxygen therapy in elderly patients who were not eligible for intensive care unit transfer saved 19 patients (33.9%). Conclusions: In our 2020 cohort, treating COVID-19 with HCQ-AZ was associated with lower mortality. These results need to be analyzed in the context of academic discussions about observational studies versus randomized clinical trials. More data will deserve to be analyzed in the SARS-Cov 2 variants, vaccination and post-vaccination era.

Analysis of SARS-CoV-2 Variants From 24,181 Patients Exemplifies the Role of Globalization and Zoonosis in Pandemics.

After the end of the first epidemic episode of SARS-CoV-2 infections, as cases began to rise again during the summer of 2020, we at IHU Méditerranée Infection in Marseille, France, intensified the genomic surveillance of SARS-CoV-2, and described the first viral variants. In this study, we compared the incidence curves of SARS-CoV-2-associated deaths in different countries and reported the classification of SARS-CoV-2 variants detected in our institute, as well as the kinetics and sources of the infections. We used mortality collected from a COVID-19 data repository for 221 countries. Viral variants were defined based on ≥5 hallmark mutations along the whole genome shared by ≥30 genomes. SARS-CoV-2 genotype was determined for 24,181 patients using next-generation genome and gene sequencing (in 47 and 11% of cases, respectively) or variant-specific qPCR (in 42% of cases). Sixteen variants were identified by analyzing viral genomes from 9,788 SARS-CoV-2-diagnosed patients. Our data show that since the first SARS-CoV-2 epidemic episode in Marseille, importation through travel from abroad was documented for seven of the new variants. In addition, for the B.1.160 variant of Pangolin classification (a.k.a. Marseille-4), we suspect transmission from farm minks. In conclusion, we observed that the successive epidemic peaks of SARS-CoV-2 infections are not linked to rebounds of viral genotypes that are already present but to newly introduced variants. We thus suggest that border control is the best mean of combating this type of introduction, and that intensive control of mink farms is also necessary to prevent the emergence of new variants generated in this animal reservoir.

Who Were Hospitalized Deceased Patients from COVID-19 During the First Year of Pandemic? Retrospective Analysis of 1104 Deceased Patients in South of France.

INTRODUCTION: Following the first year of the COVID-19 pandemic, a complete analysis of the characteristics of the deceased hospitalized patients was performed, to identify factors related to premature mortality and to compare patient profiles according to the epidemic periods. METHODS: Retrospective analysis of 1104 deceased patients in two University Hospitals in South-eastern France, between March 1, 2020 and March 12, 2021 from Hospital's electronic medical records was performed. RESULTS: Mean age was 80 years (± 11.1) and 10% of the deceased were younger than 65 years with specific comorbidities, e.g., genetic conditions, metastatic cancer, or massive obesity. Among the three clusters identified, two clusters (75% of deceased patients) include very elderly patients with numerous comorbidities, and differ by their proportion of dependent institutionalized patients. The third cluster is made up of younger patients with fewer but severe comorbidities. Deceased patients' profiles varied according to the epidemic periods: during the first period (March-June 2020), more patients were institutionalized. The second period (September-December2020) coincided with a higher mortality rate. CONCLUSIONS: This study confirmed that most patients hospitalized and dying from COVID-19 were frail, i.e., elderly and/or highly comorbid and that the small proportion of young patients had severe comorbidities.

Culture and identification of a "Deltamicron" SARS-CoV-2 in a three cases cluster in southern France.

Multiple SARS-CoV-2 variants have successively, or concomitantly spread worldwide since the summer of 2020. A few co-infections with different variants were reported and genetic recombinations, common among coronaviruses, were reported or suspected based on co-detection of signature mutations of different variants in a given genome. Here we report three infections in southern France with a Delta 21J_AY.4-Omicron 21K/BA.1 "Deltamicron" recombinant. The hybrid genome harbors signature mutations of the two lineages, supported by a mean sequencing depth of 1163-1421 reads and a mean nucleotide diversity of 0.1%-0.6%. It is composed of the near full-length spike gene (from codons 156-179) of an Omicron 21K/BA.1 variant in a Delta 21J/AY.4 lineage backbone. Importantly, we cultured an isolate of this recombinant and sequenced its genome. It was observed by scanning electron microscopy. As it is misidentified with current variant screening quantitative polymerase chain reaction (qPCR), we designed and implemented for routine diagnosis a specific duplex qPCR. Finally, structural analysis of the recombinant spike suggested its hybrid content could optimize viral binding to the host cell membrane. These findings prompt further studies of the virological, epidemiological, and clinical features of this recombinant.

Automatic Deep-Learning Segmentation of Epicardial Adipose Tissue from Low-Dose Chest CT and Prognosis Impact on COVID-19.

BACKGROUND: To develop a deep-learning (DL) pipeline that allowed an automated segmentation of epicardial adipose tissue (EAT) from low-dose computed tomography (LDCT) and investigate the link between EAT and COVID-19 clinical outcomes. METHODS: This monocentric retrospective study included 353 patients: 95 for training, 20 for testing, and 238 for prognosis evaluation. EAT segmentation was obtained after thresholding on a manually segmented pericardial volume. The model was evaluated with Dice coefficient (DSC), inter-and intraobserver reproducibility, and clinical measures. Uni-and multi-variate analyzes were conducted to assess the prognosis value of the EAT volume, EAT extent, and lung lesion extent on clinical outcomes, including hospitalization, oxygen therapy, intensive care unit admission and death. RESULTS: The mean DSC for EAT volumes was 0.85 ± 0.05. For EAT volume, the mean absolute error was 11.7 ± 8.1 cm3 with a non-significant bias of -4.0 ± 13.9 cm3 and a correlation of 0.963 with the manual measures (p < 0.01). The multivariate model providing the higher AUC to predict adverse outcome include both EAT extent and lung lesion extent (AUC = 0.805). CONCLUSIONS: A DL algorithm was developed and evaluated to obtain reproducible and precise EAT segmentation on LDCT. EAT extent in association with lung lesion extent was associated with adverse clinical outcomes with an AUC = 0.805.

Value and prognostic impact of a deep learning segmentation model of COVID-19 lung lesions on low-dose chest CT

Objectives 1) To develop a deep learning (DL) pipeline allowing quantification of COVID-19 pulmonary lesions on low-dose computed tomography (LDCT). 2) To assess the prognostic value of DL-driven lesion quantification. Methods This monocentric retrospective study included training and test datasets taken from 144 and 30 patients, respectively. The reference was the manual segmentation of 3 labels: normal lung, ground-glass opacity(GGO) and consolidation(Cons). Model performance was evaluated with technical metrics, disease volume and extent. Intra- and interobserver agreement were recorded. The prognostic value of DL-driven disease extent was assessed in 1621 distinct patients using C-statistics. The end point was a combined outcome defined as death, hospitalization>10 days, intensive care unit hospitalization or oxygen therapy. Results The Dice coefficients for lesion (GGO+Cons) segmentations were 0.75±0.08, exceeding the values for human interobserver (0.70±0.08;0.70±0.10) and intraobserver measures (0.72±0.09). DL-driven lesion quantification had a stronger correlation with the reference than inter- or intraobserver measures. After stepwise selection and adjustment for clinical characteristics, quantification significantly increased the prognostic accuracy of the model (0.82 vs. 0.90;p<0.0001). Conclusions A DL-driven model can provide reproducible and accurate segmentation of COVID-19 lesions on LDCT. Automatic lesion quantification has independent prognostic value for the identification of high-risk patients.

Long-Term Persistence of Olfactory and Gustatory Disorders in COVID-19 Patients.

Smell and taste disorders are frequent symptoms during acute COVID-19 and may persist long after the resolution of the initial phase. This study aims to estimate the proportion and risk factors for smell and/or taste disorders at the onset of symptoms and their persistence after more than 6 months of follow-up in COVID-19 patients. We analyzed a prospective cohort of COVID-19 patients admitted to our institute in Marseille, France in early 2020. After being discharged from the hospital, patients with smell and/or taste disorders were contacted for a telephone interview. Logistic regression analysis was performed to determine the risk factors for smell and/or taste disorders. A total of 3,737 patients were included, of whom 1,676 reported smell and/or taste disorders at the onset of symptoms. Taste and/or smell disorders were independently associated with being younger and female, a lower likelihood of suffering from diabetes, cardiovascular diseases and cancer, a longer delay between the onset of symptoms and consultation, and non-severe forms of COVID-19 at admission. Of the 605 patients with smell and/or taste disorders who were followed-up, 154 (25.5%) reported the persistence of symptoms for more than 6 months. At the time of follow-up, being female, having a chronic respiratory disease and using angiotensin-converting enzyme inhibitors (ACEis) were factors independently associated with the persistence of smell and/or taste disorders. In conclusion, the long-term persistence of olfactory and gustative disorders is frequent among COVID-19 patients, notably affecting female patients and patients who suffered from chronic respiratory diseases before infection. The role of ACEis needs to be further evaluated in larger numbers of patients.

Introduction of the SARS-CoV-2 Beta variant from Comoros into the Marseille geographical area.

BACKGROUND: We describe the epidemiology of the first cases diagnosed in our institute of infections with the SARS-CoV-2 Beta variant and how this variant was imported to Marseille. METHODS: The Beta variant was identified based on analyses of sequences of viral genomes or of a spike gene fragment obtained by next-generation sequencing using Illumina technology, or by a real-time reverse-transcription-PCR (qPCR) specific of the Beta variant. RESULTS: The first patient diagnosed as infected with the SARS-CoV-2 Beta variant was sampled on January 15, 2021. Twenty-nine patients were diagnosed in January 2021 (two weeks). Fifteen (52%) patients were of Comorian nationality. Eight (28%) had travelled abroad, including six who had returned from Comoros. Phylogeny based on SARS-CoV-2 genomes from 11 of these patients and their best BLAST hits from the GISAID database showed that seven patients, including the four returning from Comoros, were clustered with 27 other genomes from GISAID that included the six first Beta variant genomes described in Comoros in January 2021. CONCLUSIONS: Our analyses highlight that, as for the case of other SARS-CoV-2 variants that have been diagnosed in Marseille, the Beta variant was imported to Marseille through travel from abroad. It had limited spread in our geographical area.

SARS-CoV-2 Vaccination and Protection Against Clinical Disease: A Retrospective Study, Bouches-du-Rhône District, Southern France, 2021.

From January 18th to August 13th, 2021, 13,804 unvaccinated and 1,156 patients who had received at least one COVID-19 vaccine dose were tested qPCR-positive for SARS-CoV-2 in our center. Among vaccinated patients, 949, 205 and 2 had received a single, two or three vaccine doses, respectively. Most patients (80.3%) had received the Pfizer-BioNTech vaccine. The SARS-CoV-2 variants infecting vaccinated patients varied over time, reflecting those circulating in the Marseille area, with a predominance of the Marseille-4/20A.EU2 variant from weeks 3 to 6, of the Alpha/20I variant from weeks 7 to 25, and of the Delta/21A variant from week 26. SARS-CoV-2 infection was significantly more likely to occur in the first 13 days post-vaccine injection in those who received a single dose (48.9%) than two doses (27.4%, p< 10-3). Among 161 patients considered as fully vaccinated, i.e., >14 days after the completion of the vaccinal scheme (one dose for Johnson and Johnson and two doses for Pfizer/BioNTech, Moderna and Sputnik vaccines), 10 (6.2%) required hospitalization and four (2.5%) died. Risks of complications increased with age in a nonlinear pattern, with a first breakpoint at 54, 33, and 53 years for death, transfer to ICU, and hospitalization, respectively. Among patients infected by the Delta/21A or Alpha/20I variants, partial or complete vaccination exhibited a protective effect with a risk divided by 3.1 for mortality in patients ≥ 55 years, by 2.8 for ICU transfer in patients ≥ 34 years, and by 1.8 for hospitalization in patients ≥ 54 years. Compared to partial vaccination, complete vaccination provided an even stronger protective effect, confirming effectiveness to prevent severe forms of COVID-19.

Exploratory Study on Application of MALDI-TOF-MS to Detect SARS-CoV-2 Infection in Human Saliva.

SARS-CoV-2 has caused a large outbreak since its emergence in December 2019. COVID-19 diagnosis became a priority so as to isolate and treat infected individuals in order to break the contamination chain. Currently, the reference test for COVID-19 diagnosis is the molecular detection (RT-qPCR) of the virus from nasopharyngeal swab (NPS) samples. Although this sensitive and specific test remains the gold standard, it has several limitations, such as the invasive collection method, the relative high cost and the duration of the test. Moreover, the material shortage to perform tests due to the discrepancy between the high demand for tests and the production capacities puts additional constraints on RT-qPCR. Here, we propose a PCR-free method for diagnosing SARS-CoV-2 based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling and machine learning (ML) models from salivary samples. Kinetic saliva samples were collected at enrollment and ten and thirty days later (D0, D10 and D30), to assess the classification performance of the ML models compared to the molecular tests performed on NPS specimens. Spectra were generated using an optimized protocol of saliva collection and successive quality control steps were developed to ensure the reliability of spectra. A total of 360 averaged spectra were included in the study. At D0, the comparison of MS spectra from SARS-CoV-2 positive patients (n = 105) with healthy healthcare controls (n = 51) revealed nine peaks that significantly distinguished the two groups. Among the five ML models tested, support vector machine with linear kernel (SVM-LK) provided the best performance on the training dataset (accuracy = 85.2%, sensitivity = 85.1%, specificity = 85.3%, F1-Score = 85.1%). The application of the SVM-LK model on independent datasets confirmed its performances with 88.9% and 80.8% of correct classification for samples collected at D0 and D30, respectively. Conversely, at D10, the proportion of correct classification had fallen to 64.3%. The analysis of saliva samples by MALDI-TOF MS and ML appears as an interesting supplementary tool for COVID-19 diagnosis, despite the mitigated results obtained for convalescent patients (D10).

Life-years lost by COVID-19 patients in public hospitals of Marseille (APHM-South-Eastern France): a limited death toll: a retrospective analysis.

OBJECTIVE: Between 1 March and 15 June, France experienced the first wave of the COVID-19 pandemic, during which 29 549 deaths occurred among COVID-19 patients, 17 250 of whom died in hospital. Our hypothesis is that crude mortality rates are not sufficient to assess the impact of the epidemic on public health. The objective of this paper is to estimate the potential years of life lost (YLL) of patients who died from COVID-19. METHOD: We realised a retrospective analysis of the exhaustive sample of COVID-19 PCR-positive patients who died in public hospitals of Marseille during this first wave. Data on demographic characteristics, comorbidities and care pathways were collected from medical records. The Charlson Comorbidity Index (CCI) was used to assess what would have been the probability of dying within 1 year of these patients in the absence of COVID-19 and to estimate total YLL. RESULTS: Among the 1631 patients who were hospitalised for COVID-19, 178 patients died, at an average age of 80 years. According to CCI, 88.8% of the deceased patients had an 85% probability of dying within 1 year before COVID-19. Among the 11.2% who had a lower CCI probability, 18 out of 20 had at least one additional comorbidity known to be a major risk factor of mortality in COVID-19 disease. Cumulative total number of YLL was estimated to be 541 in this deceased population, that is, an average of 3 YLL. CONCLUSION: Although our results should be interpreted with caution, this analysis confirms that mortality due to COVID-19 translates into a limited number of YLL due to both old age and preexisting comorbidities in the most vulnerable patients. This fact should be better considered in public health management of the pandemic both for risk communication and design of the most appropriate protective measures.

Incidence and Outcome of Coinfections with SARS-CoV-2 and Rhinovirus.

BACKGROUND: We aimed to compare the clinical severity in patients who were coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and rhinovirus or monoinfected with a single one of these viruses. METHODS: The study period ranged from 1 March 2020 to 28 February 2021 (one year). SARS-CoV-2 and other respiratory viruses were identified by real-time reverse-transcription-PCR as part of the routine work at Marseille University hospitals. Bacterial and fungal infections were detected by standard methods. Clinical data were retrospectively collected from medical files. This study was approved by the ethical committee of our institute. RESULTS: A total of 6034/15,157 (40%) tested patients were positive for at least one respiratory virus. Ninety-three (4.3%) SARS-CoV-2-infected patients were coinfected with another respiratory virus, with rhinovirus being the most frequent (62/93, 67%). Patients coinfected with SARS-CoV-2 and rhinovirus were significantly more likely to report a cough than those with SARS-CoV-2 monoinfection (62% vs. 31%; p = 0.0008). In addition, they were also significantly more likely to report dyspnea than patients with rhinovirus monoinfection (45% vs. 36%; p = 0.02). They were also more likely to be transferred to an intensive care unit and to die than patients with rhinovirus monoinfection (16% vs. 5% and 7% vs. 2%, respectively) but these differences were not statistically significant. CONCLUSIONS: A close surveillance and investigation of the co-incidence and interactions of SARS-CoV-2 and other respiratory viruses is needed. The possible higher risk of increased clinical severity in SARS-CoV-2-positive patients coinfected with rhinovirus warrants further large scale studies.