Inquilinus limosus Bacteremia in Lung Transplant Recipient after SARS-CoV-2 Infection.

Inquilinus limosus is an environmental bacterium associated with respiratory tract colonization in cystic fibrosis patients. We report a case of I. limosus bacteremia in a patient in France who received a lung transplant and experienced chronic graft dysfunction and SARS-CoV-2 infection. This case suggests I. limosus displays virulence factors associated with invasion.

COVID-19 epidemic peaks distribution in the United-States of America, from epidemiological modeling to public health policies.

COVID-19 prediction models are characterized by uncertainties due to fluctuating parameters, such as changes in infection or recovery rates. While deterministic models often predict epidemic peaks too early, incorporating these fluctuations into the SIR model can provide a more accurate representation of peak timing. Predicting R0, the basic reproduction number, remains a major challenge with significant implications for government policy and strategy. In this study, we propose a tool for policy makers to show the effects of possible fluctuations in policy strategies on different R0 levels. Results show that epidemic peaks in the United States occur at varying dates, up to 50, 87, and 82 days from the beginning of the second, third, and fourth waves. Our findings suggest that inaccurate predictions and public health policies may result from underestimating fluctuations in infection or recovery rates. Therefore, incorporating fluctuations into SIR models should be considered when predicting epidemic peak times to inform appropriate public health responses.

Geo-epidemiological approach of the COVID-19 pandemic in France and in Europe for public health policies.

The spread of the COVID-19 pandemic has shown great heterogeneity between countries that merits investigation. There is a need to better highlight the variability in the pandemic trajectories in different geographic areas. By using openly available data from 'GitHub' COVID-19 dataset for Europe and from the official dataset of France for the period 2020 to 2021, I present the three COVID-19 waves in France and Europe in maps. The epidemic trends across areas display different evolutions for different time periods. National and European public health authorities will be able to improve allocation of resources for more effective public health measures based on geo-epidemiological analyses.

The COVID-19 Pandemic and the Migrant Population for HIV Diagnosis and Care Follow-Up: They Are Left Behind.

The coronavirus 2019 (COVID-19) pandemic has posed numerous worldwide challenges. The level of social vulnerability of the migrant population is disproportionately higher than other populations. Recent reports have shown that the access to care for the migrant population (i.e., non-French nationality patients) were greatly impacted during this pandemic. Thus, we would like to highlight the significant impact of the COVID-19 pandemic on care follow-up in those migrant people infected with HIV who receive HIV care in France. Two groups of patients were defined: that is, patients with continuous care and patients with a loss of follow-up of at least one year during the COVID-19 pandemic. Among 672 HIV patients, 19 (2.7%) patients were lost to follow-up for at least one year during the COVID-19 pandemic. We found no significant difference for gender (p = 0.332) or age (p = 0.115) between the two groups. However, patients with a loss of follow-up were mainly migrants rather than from the other group (p < 0.001), and the same results were observed for the nation of birth (89.5% vs. 44%, p < 0.001). In our hospital, most of the patients who were living abroad but had HIV care in France before the COVID epidemic (mainly retired migrants) were lost to follow-up during the COVID-19 pandemic. To date, most of them have not resumed HIV care in France and we do not know their present situation. We can only observe that the COVID-19 pandemic has predominately disrupted the HIV care of migrant populations. Do not let them be left behind!

Cannabidiol and SARS-CoV-2 Infection.

Cannabidiol (CBD) can prevent the inflammatory response of SARS-CoV-2 spike protein in Caco-2-cells. This action is coupled with the inhibition of IL-1beta, IL-6, IL-18, and TNF-alpha, responsible for the inflammatory process during SARS-CoV-2 infection. CBD can act on the different proteins encoded by SARS-CoV-2 and as an antiviral agent to prevent the viral infection. Furthermore, recent studies have shown the possible action of CBD as an antagonist of cytokine release syndromes. In the SARS-CoV-2 pathophysiology, the angiotensin-converting enzyme 2 (ACE2) seems to be the key cell receptor for SARS-CoV-2 infection. The WNT/ß-catenin pathway and PPARγ interact in an opposite manner in many diseases, including SARS-CoV-2 infection. CBD exerts its activity through the interaction with PPARγ in SARS-CoV-2 infection. Thus, we can hypothesize that CBD may counteract the inflammatory process of SARS-CoV-2 by its interactions with both ACE2 and the interplay between the WNT/ß-catenin pathway and PPARγ. Vaccines are the only way to prevent COVID-19, but it appears important to find therapeutic complements to treat patients already affected by SARS-CoV-2 infection. The possible role of CBD should be investigated by clinical trials to show its effectiveness.

Heterogeneity of the COVID-19 Pandemic in the United States of America: A Geo-Epidemiological Perspective

The spread of the COVID-19 pandemic has shown great heterogeneity between regions of countries, e. g., in the United States of America (USA). With the growing of the worldwide COVID-19 pandemic, there is a need to better highlight the variability in the trajectory of this disease in different worldwide geographic areas. Indeed, the epidemic trends across areas can display completely different evolution at a given time. Geo-epidemiological analyses using data, that are publicly available, could be a major topic to help governments and public administrations to implement health policies. Geo-epidemiological analyses could provide a basis for the implementation of relevant public health policies. With the COVID-19 pandemic, geo-epidemiological analyses can be readily utilized by policy interventions and USA public health authorities to highlight geographic areas of particular concern and enhance the allocation of resources.

Dysautonomia and Implications for Anosmia in Long COVID-19 Disease.

Long COVID-19 patients often reported anosmia as one of the predominant persisting symptoms. Recent findings have shown that anosmia is associated with neurological dysregulations. However, the involvement of the autonomic nervous system (ANS), which can aggregate all the long COVID-19 neurological symptoms, including anosmia, has not received much attention in the literature. Dysautonomia is characterized by the failure of the activities of components in the ANS. Long COVID-19 anosmia fatigue could result from damage to olfactory sensory neurons, leading to an augmentation in the resistance to cerebrospinal fluid outflow by the cribriform plate, and further causing congestion of the glymphatic system with subsequent toxic build-up in the brain. Studies have shown that anosmia was an important neurologic symptom described in long COVID-19 in association with potential COVID-19 neurotropism. SARS-CoV-2 can either travel via peripheral blood vessels causing endothelial dysfunction, triggering coagulation cascade and multiple organ dysfunction, or reach the systemic circulation and take a different route to the blood-brain barrier, damaging the blood-brain barrier and leading to neuroinflammation and neuronal excitotoxicity. SARS-CoV-2 entry via the olfactory epithelium and the increase in the expression of TMPRSS2 with ACE2 facilitates SARS-CoV-2 neurotropism and then dysautonomia in long COVID-19 patients. Due to this effect, patients with anosmia persisting 3 months after COVID-19 diagnosis showed extensive destruction of the olfactory epithelium. Persistent anosmia observed among long COVID-19 patients may be involved by a cascade of effects generated by dysautonomia leading to ACE2 antibodies enhancing a persistent immune activation.

Delayed epidemic peak caused by infection and recovery rate fluctuations.

Forecasting epidemic scenarios has been critical to many decision-makers in imposing various public health interventions. Despite progresses in determining the magnitude and timing of epidemics, epidemic peak time predictions for H1N1 and COVID-19 were inaccurate, with the peaks delayed with respect to predictions. Here, we show that infection and recovery rate fluctuations play a critical role in peak timing. Using a susceptible-infected-recovered model with daily fluctuations on control parameters, we show that infection counts follow a lognormal distribution at the beginning of an epidemic wave, similar to price distributions for financial assets. The epidemic peak time of the stochastic solution exhibits an inverse Gaussian probability distribution, fitting the spread of the epidemic peak times observed across Italian regions. We also show that, for a given basic reproduction number R0, the deterministic model anticipates the peak with respect to the most probable and average peak time of the stochastic model. The epidemic peak time distribution allows one for a robust estimation of the epidemic evolution. Considering these results, we believe that the parameters' dynamical fluctuations are paramount to accurately predict the epidemic peak time and should be introduced in epidemiological models.

An Immunogenicity Report for the Comparison between Heterologous and Homologous Prime-Boost Schedules with ChAdOx1-S and BNT162b2 Vaccines.

BACKGROUND: There is a small amount of immunological data on COVID-19 heterologous vaccination schedules in humans. We assessed the immunogenicity of BNT162b2 (Pfizer/BioNTech) administered as a second dose in healthcare workers primed with ChAdOx1-S (Vaxzevria, AstraZeneca). METHODS: 197 healthcare workers were included in a monocentric observational study in Foch hospital, France, between June and July 2021. The main outcome was the immunogenicity measured by serum SARS-CoV-2 IgG antibodies. RESULTS: 130 participants received the ChAdOx1-S/BNT vaccine and 67 received the BNT/BNT vaccine. The geometric mean of IgG antibodies was significantly higher in the BNT/BNT vaccine group compared to the ChAdOx1-S/BNT vaccine group, namely 10,734.9, 95% CI (9141.1-12,589.3) vs. 7268.6, 95% CI (6501.3-8128.3), respectively (p < 0.001). However, after adjustment for time duration between the prime and second vaccinations, no significant difference was observed (p = 0.181). A negative correlation between antibody levels and time duration between second dose and serology test was observed for the BNT/BNT vaccine (p < 0.001), which remained significant after adjustment for all covariates (p < 0.001), but not for the ChAdOx1-S/BNT vaccine (p = 0.467). CONCLUSIONS: Heterologous and homologous schedules of ChAdOx1-S and BNT vaccines present robust immune responses after the second vaccination. The results observed were equivalent after adjustment for covariates and emphasize the importance of flexibility in deploying mRNA and viral vectored vaccines. Nevertheless, applying the ChAdOx1-S schedule vaccination for the heterologous second dose of BNT was associated with decreased IgG antibody levels compared to the homologous BNT/BNT vaccination.

Clinical characterization of dysautonomia in long COVID-19 patients.

Increasing numbers of COVID-19 patients, continue to experience symptoms months after recovering from mild cases of COVID-19. Amongst these symptoms, several are related to neurological manifestations, including fatigue, anosmia, hypogeusia, headaches and hypoxia. However, the involvement of the autonomic nervous system, expressed by a dysautonomia, which can aggregate all these neurological symptoms has not been prominently reported. Here, we hypothesize that dysautonomia, could occur in secondary COVID-19 infection, also referred to as "long COVID" infection. 39 participants were included from December 2020 to January 2021 for assessment by the Department of physical medicine to enhance their physical capabilities: 12 participants with COVID-19 diagnosis and fatigue, 15 participants with COVID-19 diagnosis without fatigue and 12 control participants without COVID-19 diagnosis and without fatigue. Heart rate variability (HRV) during a change in position is commonly measured to diagnose autonomic dysregulation. In this cohort, to reflect HRV, parasympathetic/sympathetic balance was estimated using the NOL index, a multiparameter artificial intelligence-driven index calculated from extracted physiological signals by the PMD-200 pain monitoring system. Repeated-measures mixed-models testing group effect were performed to analyze NOL index changes over time between groups. A significant NOL index dissociation over time between long COVID-19 participants with fatigue and control participants was observed (p = 0.046). A trend towards significant NOL index dissociation over time was observed between long COVID-19 participants without fatigue and control participants (p = 0.109). No difference over time was observed between the two groups of long COVID-19 participants (p = 0.904). Long COVID-19 participants with fatigue may exhibit a dysautonomia characterized by dysregulation of the HRV, that is reflected by the NOL index measurements, compared to control participants. Dysautonomia may explain the persistent symptoms observed in long COVID-19 patients, such as fatigue and hypoxia. Trial registration: The study was approved by the Foch IRB: IRB00012437 (Approval Number: 20-12-02) on December 16, 2020.

The key role of the level of ACE2 gene expression in SARS-CoV-2 infection.

SARS-CoV-2 more readily affects the elderly, especially as they present co-morbidities. In the COVID-19 pathogeny, ACE2 appears to be the key cell receptor for SARS-CoV-2 to infect humans. The level of ACE2 gene expression influences the susceptibility of contracting SARS-CoV-2. In circumstances in which the ACE2 level is low, the incidence of Covid-19 seems to be fewer. Two clinical patterns illustrate this observation, i. e., in infants and in Alzheimer's disease (AD). Very young children and AD patients get little COVID-19, in part probably due to decreased expression of ACE2. The determination of the nasal level of ACE2 gene expression could provide a useful scale to predict the susceptibility to contract the SARS-CoV-2 infection.

Interplay of Opposing Effects of the WNT/ß-Catenin Pathway and PPARγ and Implications for SARS-CoV2 Treatment.

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has quickly reached pandemic proportions. Cytokine profiles observed in COVID-19 patients have revealed increased levels of IL-1ß, IL-2, IL-6, and TNF-α and increased NF-κB pathway activity. Recent evidence has shown that the upregulation of the WNT/ß-catenin pathway is associated with inflammation, resulting in a cytokine storm in ARDS (acute respire distress syndrome) and especially in COVID-19 patients. Several studies have shown that the WNT/ß-catenin pathway interacts with PPARγ in an opposing interplay in numerous diseases. Furthermore, recent studies have highlighted the interesting role of PPARγ agonists as modulators of inflammatory and immunomodulatory drugs through the targeting of the cytokine storm in COVID-19 patients. SARS-CoV2 infection presents a decrease in the angiotensin-converting enzyme 2 (ACE2) associated with the upregulation of the WNT/ß-catenin pathway. SARS-Cov2 may invade human organs besides the lungs through the expression of ACE2. Evidence has highlighted the fact that PPARγ agonists can increase ACE2 expression, suggesting a possible role for PPARγ agonists in the treatment of COVID-19. This review therefore focuses on the opposing interplay between the canonical WNT/ß-catenin pathway and PPARγ in SARS-CoV2 infection and the potential beneficial role of PPARγ agonists in this context.

COVID-19 Vaccine Hesitancy among French People Living with HIV.

People living with HIV are a high-risk population concerning the coronavirus 19 (COVID-19) infection, with a poorer prognosis. It is important to achieve high COVID-19 vaccination coverage rates in this group as soon as possible. This project used self-reporting to assess vaccine hesitancy and acceptance among people living with HIV towards the novel COVID-19 vaccine. Sixty-eight (28.7%) participants among the 237 declared their hesitancy to be vaccinated against COVID-19. Participants who expressed concerns about their health (p < 0.001), the requirement of mandatory COVID-19 vaccination (p = 0.017), and their chronic disease status (p = 0.026) were independently associated with the acceptance of vaccination. Conversely, participants presenting general vaccine refusal (p < 0.001), concerns about the serious side effects of COVID-19 vaccines (p < 0.001), and those already thinking having an immune status to COVID-19 (p = 0.008) were independently associated with COVID-19 vaccine hesitancy. Our results suggest that vaccine strategy would be more successful in France with a communication strategy emphasizing the collective benefits of herd immunity in the population living with HIV and reassuring patients with chronic diseases about the safety of the proposed vaccines.

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis.

BACKGROUND: High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters. METHODS: The TOCICOVID study included a prospective cohort of patients aged 16-80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology. RESULTS: Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25-0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36-0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31-1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17-2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22-2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group. CONCLUSION: These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.