[COVID-19 and vaccination: a global disruption]. / COVID-19 et vaccination : une dérégulation globale.

Coronavirus disease (COVID)-19 is an emerging pandemic infection whose significant ability to spread in a naïve population is well established. The first response of states to the COVID-19 outbreak was to impose lock-down and social barrier measures, such as wearing a surgical mask or social distancing. One of the consequences of this pandemic in terms of public health was the suspension or slowdown of infant vaccination campaigns, in almost all countries. The indirect effects of COVID-19 may therefore weigh on mortality from measles and polio in developing countries. In this pandemic chaos, the only hope lies in the rapid development of an effective vaccine against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, acceptance of this vaccine has not yet been won, as beyond the many unknowns that will inevitably weigh around such rapid development, skepticism among vaccine hesitants is growing.

TITLE: COVID-19 et vaccination : une dérégulation globale. ABSTRACT: La COVID-19 est une infection pandémique émergente dont l'importante capacité à se propager dans une population dénuée d'immunité n'est plus à prouver. La première réponse des États à la flambée de COVID-19 fut d'imposer un confinement et des mesures barrières, telles que le port du masque et la distanciation sociale. Une des répercussions de cette pandémie, en matière de santé publique, fut la suspension ou le ralentissement brusque des campagnes de vaccination des nourrissons, un peu partout dans le monde. Un des effets indirects de la COVID-19 est donc le risque de peser sur la mortalité mondiale, principalement via une recrudescence de la rougeole et de la poliomyélite, principalement dans les pays en voie de développement. Dans ce chaos potentiel, le seul espoir réside dans le développement rapide d'un vaccin efficace contre le SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2). Cependant, l'acceptation de ce vaccin par la population n'est pas évidente, car outre les nombreuses inconnues qui vont peser inévitablement dans le cas d'un développement très rapide du vaccin, le scepticisme des hésitants vaccinaux va à nouveau se développer.

COVID-19 and the kidney.

COVID-19 is primarily considered a respiratory illness, but the kidney may be one of the targets of SARS-CoV-2 infection, since the virus enters cells through the angiotensin-converting enzyme 2 receptor, which is found in abundance in the kidney. Information on kidney involvement in COVID-19 is limited but is evolving rapidly. This article discusses the pathogenesis of acute kidney injury (AKI) in COVID-19, its optimal management, and the impact of COVID-19 on patients with chronic kidney disease, patients with end-stage kidney disease on dialysis, and kidney transplant recipients.

Considerations for the Management of Oncology Patients During the COVID-19 Pandemic.

Worldwide incidence and mortality due to the coronavirus disease 2019 (COVID-19) pandemic is greatest in the United States, with the initial epicenter in New York. In Nassau County, New York, where we practice, our institution has had more than 2500 cases and has discharged from the hospital more than 1000 patients. As many academic and private institutions have swiftly shifted their clinical and research priorities to address the pandemic, data are emerging regarding both the impact of malignancy on COVID-19 outcomes as well as the challenges faced in assuring that cancer care remains unimpeded. Of concern, recent studies of cancer patients primarily in China and Italy have suggested that advanced malignancy is associated with increased susceptibility to severe COVID-19 infection. At present, more than 500 clinical trials are underway investigating the pathogenesis and treatment of COVID-19, including expanded use of oncology drugs, such as small molecular inhibitors of cytokine pathways. Here, we begin by reviewing the latest understanding of COVID-19 pathophysiology and then focus our attention on the impact of this virus on hematologic and oncologic practice. Finally, we highlight ongoing investigational treatment approaches that are so relevant to the care of oncology patients during this extraordinary pandemic.

The Importance of Telemedicine during COVID-19 Pandemic: A Focus on Diabetic Retinopathy.

Recently, telemedicine has become remarkably important, due to increased deployment and development of digital technologies. National and international guidelines should consider its inclusion in their updates. During the COVID-19 pandemic, mandatory social distancing and the lack of effective treatments has made telemedicine the safest interactive system between patients, both infected and uninfected, and clinicians. A few potential evidence-based scenarios for the application of telemedicine have been hypothesized. In particular, its use in diabetes and complication monitoring has been remarkably increasing, due to the high risk of poor prognosis. New evidence and technological improvements in telemedicine application in diabetic retinopathy (DR) have demonstrated efficacy and usefulness in screening. Moreover, despite an initial increase for devices and training costs, teleophthalmology demonstrated a good cost-to-efficacy ratio; however, no national screening program has yet focused on DR prevention and diagnosis. Lack of data during the COVID-19 pandemic strongly limits the possibility of tracing the real management of the disease, which is only conceivable from past evidence in normal conditions. The pandemic further stressed the importance of remote monitoring. However, the deployment of device and digital application used to increase screening of individuals and monitor progression of retinal disease needs to be easily accessible to general practitioners.

SARS-CoV-2 and the nose: Risks and implications for primary care.

BACKGROUND: General practitioners (GPs) have some of the highest rates of mortality from COVID-19 among healthcare workers. SARS-CoV-2 has unique properties that place GPs at particular risk. OBJECTIVE: The aim of this article is to discuss the nose-related features of SARS-CoV-2 that place GPs at risk, and to make recommendations pertinent to the safety and protection of primary healthcare physicians. DISCUSSION: The highest viral load of SARS-CoV-2 is in the nose and nasopharynx. It is often highest early in the illness, before the development of symptoms. Further, SARS-CoV-2 replicates and continues to shed in the nasopharynx long after the virus is no longer detectable in the lower respiratory tract. This places any physician performing examinations on, or procedures involving, the upper respiratory tract at risk for contracting COVID-19. New-onset hyposmia and dysgeusia are indicators for COVID-19 and should be included in screening protocols.

Insights from a global snapshot of the change in elective colorectal practice due to the COVID-19 pandemic.

BACKGROUND: There is a need to understand the impact of COVID-19 on colorectal cancer care globally and determine drivers of variation. OBJECTIVE: To evaluate COVID-19 impact on colorectal cancer services globally and identify predictors for behaviour change. DESIGN: An online survey of colorectal cancer service change globally in May and June 2020. PARTICIPANTS: Attending or consultant surgeons involved in the care of patients with colorectal cancer. MAIN OUTCOME MEASURES: Changes in the delivery of diagnostics (diagnostic endoscopy), imaging for staging, therapeutics and surgical technique in the management of colorectal cancer. Predictors of change included increased hospital bed stress, critical care bed stress, mortality and world region. RESULTS: 191 responses were included from surgeons in 159 centers across 46 countries, demonstrating widespread service reduction with global variation. Diagnostic endoscopy was reduced in 93% of responses, even with low hospital stress and mortality; whilst rising critical care bed stress triggered complete cessation (p = 0.02). Availability of CT and MRI fell by 40-41%, with MRI significantly reduced with high hospital stress. Neoadjuvant therapy use in rectal cancer changed in 48% of responses, where centers which had ceased surgery increased its use (62 vs 30%, p = 0.04) as did those with extended delays to surgery (p<0.001). High hospital and critical care bed stresses were associated with surgeons forming more stomas (p<0.04), using more experienced operators (p<0.003) and decreased laparoscopy use (critical care bed stress only, p<0.001). Patients were also more actively prioritized for resection, with increased importance of co-morbidities and ICU need. CONCLUSIONS: The COVID-19 pandemic was associated with severe restrictions in the availability of colorectal cancer services on a global scale, with significant variation in behaviours which cannot be fully accounted for by hospital burden or mortality.

Non-communicable diseases and inequalities increase risk of death among COVID-19 patients in Mexico.

BACKGROUND: The SARS-CoV-2 pandemic compounds Mexico's pre-existing challenges: very high levels of both non-communicable diseases (NCD) and social inequity. METHODS AND FINDINGS: Using data from national reporting of SARS-CoV-2 tested individuals, we estimated odds of hospitalization, intubation, and death based on pre-existing non-communicable diseases and socioeconomic indicators. We found that obesity, diabetes, and hypertension are positively associated with the three outcomes in a synergistic manner. The municipal poverty level is also positively associated with hospitalization and death. CONCLUSIONS: Mexico's response to COVID-19 is complicated by a synergistic double challenge: raging NCDs and extreme social inequity. The response to the current pandemic must take both into account both to be effective and to ensure that the burden of COVID-19 not falls disproportionately on those who are already disadvantaged.

Impact of COVID-19 epidemic curtailment strategies in selected Indian states: An analysis by reproduction number and doubling time with incidence modelling.

The Government of India in-network with the state governments has implemented the epidemic curtailment strategies inclusive of case-isolation, quarantine and lockdown in response to ongoing novel coronavirus (COVID-19) outbreak. In this manuscript, we attempt to estimate the impact of these steps across ten selected Indian states using crowd-sourced data. The trajectory of the outbreak was parameterized by the reproduction number (R0), doubling time, and growth rate. These parameters were estimated at two time-periods after the enforcement of the lockdown on 24th March 2020, i.e. 15 days into lockdown and 30 days into lockdown. The authors used a crowd sourced database which is available in the public domain. After preparing the data for analysis, R0 was estimated using maximum likelihood (ML) method which is based on the expectation minimum algorithm where the distribution probability of secondary cases is maximized using the serial interval discretization. The doubling time and growth rate were estimated by the natural log transformation of the exponential growth equation. The overall analysis shows decreasing trends in time-varying reproduction numbers (R(t)) and growth rate (with a few exceptions) and increasing trends in doubling time. The curtailment strategies employed by the Indian government seem to be effective in reducing the transmission parameters of the COVID-19 epidemic. The estimated R(t) are still above the threshold of 1, and the resultant absolute case numbers show an increase with time. Future curtailment and mitigation strategies thus may take into account these findings while formulating further course of action.

[To what extent Africa can limit the impact of the COVID-19 pandemic?] / Jusqu'où l'Afrique peut-elle limiter l'impact de la pandémie de COVID-19 ?

Following the onset of the global COVID-19 pandemic and the alerts issued by the World Health Organization, for several months attention has been focused on Africa as a potentially severely endangered continent. A sizable number of African countries, mainly low and middle income, suffer from limited available resources, especially in critical care, and COVID-19 is liable to overwhelm their already fragile health systems. To effectively manage what is shaping up as a multidimensional crisis, the challenge unquestionably goes beyond the necessary upgrading of public health infrastructures. It is also a matter of anticipating and taking timely action with regard to factors that may mitigate the propagation of SARS-CoV2 and thereby cushion the shock of the pandemic on the African continent. While some of these factors are largely unmanageable (climate, geography…), several others (socio-cultural, religious, audio-visual, and potentially political…) could be more or less effectively dealt with by African governments and populations.

COVID-19 mortality in Lombardy: the vulnerability of the oldest old and the resilience of male centenarians.

Italy was the first European nation to be affected by COVID-19. The biggest cluster of cases occurred in Lombardy, the most populous Italian region, and elderly men were the population hit in the hardest way. Besides its high infectivity, COVID-19 causes a severe cytokine storm and old people, especially those with comorbidities, appear to be the most vulnerable, presumably in connection to inflammaging. In centenarians inflammaging is much lower than predicted by their chronological age and females, presenting survival advantage in almost all centenarian populations, outnumber males, a phenomenon particularly evident in Northern Italy. Within this scenario, we wondered if: a) the COVID-19 mortality in centenarians was lower than that in people aged between 50 and 80 and b) the mortality from COVID-19 in nonagenarians and centenarians highlighted gender differences.We checked COVID-19-related vulnerability/mortality at the peak of infection (March 2020), using data on total deaths (i.e. not only confirmed COVID-19 cases). Our conclusion is that excess mortality increases steadily up to very old ages and at the same time men older than 90 years become relatively more resilient than age-matched females.

A novel Monte Carlo simulation procedure for modelling COVID-19 spread over time.

The coronavirus disease 2019 (COVID-19) has now spread throughout most countries in the world causing heavy life losses and damaging social-economic impacts. Following a stochastic point process modelling approach, a Monte Carlo simulation model was developed to represent the COVID-19 spread dynamics. First, we examined various expected performances (theoretical properties) of the simulation model assuming a number of arbitrarily defined scenarios. Simulation studies were then performed on the real COVID-19 data reported (over the period of 1 March to 1 May) for Australia and United Kingdom (UK). Given the initial number of COVID-19 infection active cases were around 10 for both countries, the model estimated that the number of active cases would peak around 29 March in Australia (≈ 1,700 cases) and around 22 April in UK (≈ 22,860 cases); ultimately the total confirmed cases could sum to 6,790 for Australia in about 75 days and 206,480 for UK in about 105 days. The results of the estimated COVID-19 reproduction numbers were consistent with what was reported in the literature. This simulation model was considered an effective and adaptable decision making/what-if analysis tool in battling COVID-19 in the immediate need, and for modelling any other infectious diseases in the future.

Disease progression of cancer patients during COVID-19 pandemic: a comprehensive analytical strategy by time-dependent modelling.

BACKGROUND: As the whole world is experiencing the cascading effect of a new pandemic, almost every aspect of modern life has been disrupted. Because of health emergencies during this period, widespread fear has resulted in compromised patient safety, especially for patients with cancer. It is very challenging to treat such cancer patients because of the complexity of providing care and treatment, along with COVID-19. Hence, an effective treatment comparison strategy is needed. We need to have a handy tool to understand cancer progression in this unprecedented scenario. Linking different events of cancer progression is the need of the hour. It is a huge challenge for the development of new methodology. METHODS: This article explores the time lag effect and makes a statistical inference about the best experimental arm using Accelerated Failure Time (AFT) model and regression methods. The work is presented as the occurrence of other events as a hazard rate after the first event (relapse). The time lag effect between the events is linked and analysed. RESULTS: The results were presented as a comprehensive analytical strategy by joining all disease progression. An AFT model applied with the transition states, and the dependency structure between the gap times was used by the auto-regression model. The effects of arms were compared using the coefficient of auto-regression and accelerated failure time (AFT) models. CONCLUSIONS: We provide the solutions to overcome the issue with intervals between two consecutive events in motivating head and neck cancer (HNC) data. COVID-19 is not going to leave us soon. We have to conduct several cancer clinical trials in the presence of COVID-19. A comprehensive analytical strategy to analyse cancer clinical trial data during COVID-19 pandemic is presented.

ESMO management and treatment adapted recommendations in the COVID-19 era: gynaecological malignancies.

The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients' outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients' general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines.

Multi-Criteria Decision Analysis to prioritize hospital admission of patients affected by COVID-19 in low-resource settings with hospital-bed shortage.

OBJECTIVE: To use Multi-Criteria Decision Analysis (MCDA) to determine weights for eleven criteria in order to prioritize COVID-19 non-critical patients for admission to hospital in healthcare settings with limited resources. METHODS: The MCDA was applied in two main steps: specification of criteria for prioritizing COVID-19 patients (and levels within each criterion); and determination of weights for the criteria based on experts' knowledge and experience in managing COVID-19 patients, via an online survey. Criteria were selected based on available COVID-19 evidence with a focus on low- and middle-income countries (LMICs). RESULTS: The most important criteria (mean weights, summing to 100%) are: PaO2 (16.3%); peripheral O2 saturation (15.9%); chest X-ray (14.1%); Modified Early Warning Score-MEWS (11.4%); respiratory rate (9.5%); comorbidities (6.5%); living with vulnerable people (6.4%); body mass index (5.6%); duration of symptoms before hospital evaluation (5.4%); CRP (5.1%); and age (3.8%). CONCLUSIONS: At the beginning of a new pandemic, when evidence for disease predictors is limited or unavailable and effective national contingency plans are difficult to establish, the MCDA prioritization model could play a pivotal role in improving the response of health systems.

Assessment of risk conferred by coding and regulatory variations of TMPRSS2 and CD26 in susceptibility to SARS-CoV-2 infection in human.

At present, more than 200 countries and territories are directly affected by the coronavirus disease-19 (COVID-19) pandemic. Incidence and case fatality rate are significantly higher among elderly individuals (age>60 years), type 2 diabetes and hypertension patients. Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection. We hypothesised that common variants from TMPRSS2 and CD26 may play critical role in infection susceptibility of predisposed population or group of individuals. Coding (missense) and regulatory variants from TMPRSS2 and CD26 were studied across 26 global populations. Two missense and five regulatory SNPs were identified to have differential allelic frequency. Significant linkage disequilibrium (LD) signature was observed in different populations. Modelled protein-protein interaction (PPI) predicted strong molecular interaction between these two receptors and SARS-CoV-2 spike protein (S1 domain). However, two missense SNPs, rs12329760 (TMPRSS2) and rs1129599 (CD26), were not found to be involved physically in the said interaction. Four regulatory variants (rs112657409, rs11910678, rs77675406 and rs713400) from TMPRSS2 were found to influence the expression of TMPRSS2 and pathologically relevant MX1. rs13015258 a 50 UTR variant from CD26 have significant role in regulation of expression of key regulatory genes that could be involved in SARS-CoV-2 internalization. Overexpression of CD26 through epigenetic modification at rs13015258-C allele was found critical and could explain the higher SARS-CoV-2 infected fatality rate among type 2 diabetes.

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review.

IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. OBSERVATIONS: SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. CONCLUSIONS AND RELEVANCE: As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

Azithromycin in COVID-19 Patients: Pharmacological Mechanism, Clinical Evidence and Prescribing Guidelines.

The global COVID-19 pandemic has led to a race to find medications that can improve the prognosis of the disease. Azithromycin, in association with hydroxychloroquine or chloroquine, has been proposed as one such medication. The aim of this review is to describe the pharmacological mechanism, clinical evidence and prescribing guidelines concerning azithromycin in COVID-19 patients. There is weak evidence on the antiviral and immunomodulating effects of azithromycin, which in addition is not based on results from COVID-19 patients specifically. Therefore, this antibacterial should be considered only as empirical treatment of community-acquired pneumonia (CAP), although not all current treatment guidelines are in agreement. After the initial expectations raised by a small trial, more recent evidence has raised serious safety concerns on the use of hydroxychloroquine or chloroquine with azithromycin to treat COVID-19 patients, as all these drugs have arrhythmogenic potential. The World Health Organization has not made recommendations suggesting the use of azithromycin with hydroxychloroquine or chloroquine as treatment for COVID-19, but some national organisations have taken a different position, recommending this as first-line treatment. Several scientific societies, including the American College of Cardiology, have cautioned about the risks of this treatment in view of the lack of evidence concerning its benefits.

CAR T-cell treatment during the COVID-19 pandemic: Management strategies and challenges.

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly across the world. Currently, the COVID-19 pandemic is affecting the continuity of essential routine healthcare services and procedures, including chimeric antigen receptor T-cell (CAR-T) therapy, a life-saving option for patients with relapsed/refractory (R/R) hematologic malignancies. Due to the rapid disease progression of hematological malignancies, there is an urgent need to manufacture and utilize CAR T-cells. However, CAR-T treatment has become extraordinarily challenging during this COVID-19 pandemic. Thus, many medical and technical factors must now be taken into consideration before, during, and after CAR-T therapy. The purpose of this review is to provide brief suggestions for rational decision-making strategies in evaluating and selecting CAR T-cell treatment and appropriate CAR T-cell products, and protective strategies for medical staff and patients to prevent infection in the midst of the current COVID-19 pandemic.