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In-center maintenance hemodialysis (HD) patients are at high risk of acquiring coronavirus disease 2019 (COVID-19) by cross-contamination inside the unit. The aim of this study was to assess retrospectively the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the very first pandemic phase (March-July 2020) in a cohort of in-center maintenance HD patients and in nurses the same HD facility, using a phylogenetic approach. All SARS-CoV-2 quantitative reverse-transcription polymerase chain reaction positive patients and nurses from our HD unit-respectively 10 out of 98, and 8 out of 58- and two other positive patients dialyzed in our self-care unit were included. Whole-genome viral sequencing and phylogenetic analysis supported the cluster investigation. Five positive patients were usually dialyzed in the same room and same shift before their COVID-19 diagnosis was made. Viral sequencing performed on 4/5 patients' swabs showed no phylogenetic link between their viruses. The fifth patient (whose virus could not be sequenced) was dialyzed at the end of the dialysis room and was treated by a different nurse than the one in charge of the other patients. Three nurses shared the same virus detected in both self-care patients (one of them had been transferred to our in-center facility). The epidemiologically strongly suspected intra-unit cluster could be ruled out by viral genome sequencing. The infection control policy did not allow inter-patient contamination within the HD facility, in contrast to evidence of moderate dissemination within the nursing staff and in the satellite unit. Epidemiologic data without phylogenetic confirmation might mislead the interpretation of the dynamics of viral spreading within congregate settings.

The kinetics of IgG antibodies after coronavirus disease 2019 (COVID‐19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgG antibody levels and time to seronegativation during the follow‐up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow‐up of severe or critical laboratory‐proven COVID‐19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti‐spike and anti‐nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID‐19 therapeutics on IgG levels were assessed through linear regression using a mixed‐effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age (p = 0.005) and decreased significantly over time (p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) (p = 0.0026) and lower IgG levels in immunocompromised patients (p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID‐19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short‐term corticotherapy does not. Those data improve the understanding of SARS‐CoV‐2 serology while further research should determine the determinants of long‐term seroprotection., Highlights Anti‐SARS‐CoV‐2 IgG antibody levels measured during follow‐up of severe and critical COVID‐19 were studied. We analyzed the influence of time, demographics, clinical and paraclinical characteristics and COVID‐19 treatments on specific IgG levels and time to seronegativation. Time and immunodepression were associated to reduced IgG levels at follow‐up, while age and BMI were associated to increased levels. Corticosteroids given as short‐term treatment for COVID‐19 did not show influence. BMI and immunodepression were respectively associated with decreased and increased rates of seronegativation.

BackgroundThe viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice.MethodsONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients.ResultsTwenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P ConclusionSystemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.

Objective: To determine the early electrocardiographic changes in a cohort of ambulatory cameroonian COVID-19 patients treated with hydroxychlo- roquine and Azithromycin. Design: Prospective study. Setting: Treatment centres of the city of Yaounde, Cameroon, from May 7th to 24th 2020. Participants: We enrolled 51 consecutive confirmed COVID-19 on RT-PCR who having mild forms of COVID-19 and treated by hydroxychloroquine 200 mg twice daily during seven #days plus Azithromycin 500 mg the first day and 250 mg the remaining 4 days as per national standard. Main Outcomes Measures: The primary end-point was the change in QTc interval between day 0 (D0), day 3 (D3) and day 7 (D7). Secondary endpoints were changes in all other cardiac electrical conductivity patterns and the occurrence of clinical arrhythmic events during the course of treatment. Results: The population (29 men and 22 women) was aged 39 ± 11 years (range 17 to 61 years). Mean Tisdale score was 3.35 ± 0.48. No significant change from baseline (D0) of QTc was observed at D7 (429 ± 27 ms at D0 versus 396 ± 26 ms at D7; p = 0.27). A reduction of heart rate was observed between the D0 and D7 (75 ± 13 bpm versus 70 ± 13 bpm, p = 0.02) with increased QRS duration between D0 and D7 (95 ± 10 ms versus 102 ± 17 ms, p = 0.004). No symptomatic arrhythmic events occurred during the treatment course. Conclusions: No life-threatening modification of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with hydroxychloroquine and azithromycin. Studies are needed in critical-ill and older patients.

Background and aims We describe the characteristics and short-term prognosis of in-patients with diabetes and COVID-19 admitted to a Belgian academic care center. Methods We retrospectively reviewed the data on admission from patients with known or newly-diagnosed diabetes and confirmed COVID-19. First, survivors were compared to non-survivors to study the predictive factors of in-hospital death in patients with diabetes. Secondly, diabetic patients with SARS-CoV-2 pneumonia were matched for age and sex with non-diabetic patients with SARS-CoV-2 pneumonia, to study the prognosis and predictive factors of in-hospital death related to diabetes. Results Seventy-three diabetic patients were included. Mean age was 69 (±14) years. Women accounted for 52%. Most patients had type 2 diabetes (89.0%), long-term complications of hyperglycemia (59.1%), and hypertension (80.8%). The case-fatality rate (CFR) was 15%. Non-survivors had more severe pneumonia based on imaging (p 0.029) and were less often treated with metformin (p 0.036). In patients with SARS-CoV-2 pneumonia, CFR was 15.6% in diabetic (n = 64) and 25.0% in non-diabetic patients (n = 128), the difference being non-significant (p 0.194). Predictive factors of in-hospital death were elevated white blood cells count (HR 9.4, CI 1.50–58.8, p 0.016) and severe pneumonia on imaging (HR 25.0, CI 1.34–466, p 0.031) in diabetic patients, and cognitive impairment (HR 5.80, CI 1.61–20.9, p 0.007) and cardiovascular disease (HR 5.63, CI 1.54–20.6, p 0.009) in non-diabetic patients. Conclusion In this monocentric cohort from Belgium, diabetic in-patients with COVID-19 had mostly type 2 diabetes, prevalent hyperglycemia-related vascular complications and comorbidities including hypertension. In this cohort, the CFR was not statistically different between patients with and without diabetes., Highlights • Obesity concerns half of the patients with diabetes and COVID-19. • Body mass index and HbA1c do not influence mortality. • Severe pneumonia on imaging predicts death in patients with diabetes and COVID-19. • Case fatality rate was similar in patients with and without diabetes.

Telomeres are non-coding DNA sequences that protect chromosome ends and shorten with age. Short telomere length (TL) is associated with chronic diseases and immunosenescence. The main risk factor for mortality of coronavirus disease 2019 (COVID-19) is older age, but outcome is very heterogeneous among individuals of the same age group. Therefore, we hypothesized that TL influences COVID-19-related outcomes. In a prospective study, we measured TL by Flow-FISH in 70 hospitalized COVID-19 patients and compared TL distribution with our reference cohort of 491 healthy volunteers. We also correlated TL with baseline clinical and biological parameters. We stained autopsy lung tissue from six non-survivor COVID-19 patients to detect senescence-associated β-galactosidase activity, a marker of cellular aging. We found a significantly higher proportion of patients with short telomeres (

BACKGROUND: The diagnosis of cutaneous leishmaniasis (CL) is often difficult because of the diversity of clinical presentations, its often-misleading appearance and the very long incubation period (time between the endemic stay and the onset of skin lesions). CASE: We report the case of an otherwise healthy 67-year-old man who presented with inflammatory skin lesions on the scalp and face for the past 7 years. The lesions were first mistaken as cutaneous sarcoidosis, mycobacterial infection, and cutaneous lymphoma. Finally, the diagnosis was made by RT-PCR analysis on a punch-biopsy specimen, which was positive for Leishmania infantum. DISCUSSION AND CONCLUSION: To date, the choice of treatment for complex cutaneous leishmaniases is based on the Leishmania species. Our patient successfully responded to liposomal amphotericin B.

Background and Objective: In the absence of characterization on pharmacokinetics and reference concentrations for hydroxychloroquine in COVID-19 patients, the dose and treatment duration for hydrochloroquine are currently empirical, mainly based on in vitro data, and may vary across national guidelines and clinical study protocols. The aim of this paper is to describe the pharmacokinetics of hydroxychloroquine in COVID-19 patients, considered to be a key step toward its dosing optimization. Methods: We have developed a population pharmacokinetic model for hydroxychloroquine in COVID-19 patients using prospectively collected pharmacokinetic data from patients either enrolled in a clinical trial or treated with hydroxychloroquine as part of standard of care in two tertiary Belgian hospitals. Results: The final population pharmacokinetic model was a one-compartment model with first-order absorption and elimination. The estimated parameter values were 9.3/h, 860.8 L, and 15.7 L/h for the absorption rate constant, the central compartment volume, and the clearance, respectively. The bioavailability factor was fixed to 0.74 based on previously published models. Model validations by bootstraps, prediction corrected visual predictive checks, and normalized prediction distribution errors gave satisfactory results. Simulations were performed to compare the exposure obtained with alternative dosing regimens. Conclusion: The developed models provide useful insight for the dosing optimization of hydroxychloroquine in COVID-19 patients. The present results should be used in conjunction with exposure-efficacy and exposure-safety data to inform optimal dosing of hydroxychloroquine in COVID-19., SCOPUS: ar.j, info:eu-repo/semantics/published

Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder characterized by hyperimmune response. The mortality is high despite progress being made in the diagnosis and treatment of the disease. This review aimed to update knowledge on adult HLH pathophysiology, identify the numerous causes and help clinicians make early diagnosis and initiate treatment. Using Embase, we searched relevant articles published from 1 January 2010 to 31 October 2019, with the MESH term ‘haemophagocytic lymphohistiocytosis; macrophagic activation syndrome, adult’. The mean age at presentation is about 50 years, with a male predominance. The most frequent disease associations are haematological diseases, viral or bacterial infections and autoimmune diseases. The pathophysiologic mechanism is probably the combination of inherited genetic mutations and extrinsic triggers. The mortality rate is 26.5–74.8%. HScore is more efficient than HLH-2004 criteria to identify HLH, with diagnostic sensitivity and specificity 90% and 79%, respectively. 18-fluorodeoxyglucose positron emission tomography–computed tomography is potentially useful for detecting underlying disease and the extent of secondary HLH. Disease-specific treatment should be given as soon as possible. Treatment with corticosteroids combined or not with etoposide is the mainstay of treatment. Monoclonal antibodies and JAK pathway inhibitors show promise of being effective. In adult HLH, infectious diseases, autoimmune disease and malignancy should be suspected so that disease-specific treatment can be given promptly. Treatment with corticosteroids combined or not with etoposide is the mainstay of treatment, but new therapies show promise of being effective.

SARS-CoV-2 vaccines offered great hope in controlling the worldwide COVID-19 pandemic. At present, SARS-CoV-2 vaccines have shown excellent efficacy to prevent COVID-19 but immunocompromised patients were left-off most vaccine clinical trials albeit their extreme vulnerability. Indeed, immunosuppression is associated with a higher risk of developing severe COVID-19 with mortality rates over 30% reported in patients with hematologic malignancies (HM). [...]

Background HIV patients face considerable acute and chronic healthcare needs and battling the HIV epidemic remains of the utmost importance. By focusing on health outcomes in relation to the cost of care, value-based healthcare (VBHC) proposes a strategy to optimize quality of care and cost-efficiency. Its implementation may provide an answer to the increasing pressure to optimize spending in healthcare while improving patient outcomes. This paper describes a pragmatic value-based healthcare framework for HIV care. Methods A value-based HIV healthcare framework was developed during a series of roundtable discussions bringing together 16 clinical stakeholder representatives from the Belgian HIV reference centers and 2 VBHC specialists. Each round of discussions was focused on a central question translating a concept or idea to the next level of practical implementation: 1) how can VBHC principles be translated into value-based HIV care drivers; 2) how can these value-based HIV care divers be translated into value-based care objectives and activities; and 3) how can value-based HIV care objectives and activities be translated into value-based care indicators. Value drivers were linked to concrete objectives and activities using a logical framework approach. Finally, specific, measurable, and acceptable structure, process and outcomes indicators were defined to complement the framework. Results Our framework identifies 4 core value areas where HIV care would benefit most from improvements: Prevention, improvement of the cascade of care, providing patient-centered HIV care and sustaining a state-of-the-art HIV disease management context. These 4 core value areas were translated into 12 actionable core value objectives. For each objective, example activities were proposed. Indicators are suggested for each level of the framework (outcome indicators for value areas and objectives, process indicators for suggested activities). Conclusions This framework approach outlines how to define a patient- and public health centered value-based HIV care paradigm. It proposes how to translate core value drivers to practical objectives and activities and suggests defining indicators that can be used to track and improve the framework’s implementation in practice.

Jean Cyr Yombi,1 Halil Yildiz,1 Claire Beguin,2 Laurence Habimana2 1Department of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, Brussels, 1200, Belgium; 2Department of Medical Informatics and Statistics, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, 1200, BelgiumCorrespondence: Jean Cyr YombiDepartment of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, Brussels, 1200, BelgiumTel +3227641902Fax +3227641046Email Jean.yombi@uclouvain.beBackground: Preliminary reports described a reduction in non-COVID admissions during the first wave of the pandemic including some of critical diseases such as cancer, myocardial and cerebral infarction.Objective: The aim of our study was to evaluate the impact of the COVID-19 pandemic on non-COVID in-hospital admissions in a large academic center in Belgium.Materials and Methods: We performed a retrospective study of non-COVID-19 in-hospital admissions during the first two waves of the COVID-19 pandemic. The average number of admissions per week in 2020 has been compared to that of the same period in 2019 and 2018. Comparisons were made first for all admissions, then by disease groups, using the classification of APRDRG, and then by diagnoses using ICD-10-CM classification.Results: Overall in-hospital admissions were reduced by around 39% and 29% during the first and the second waves of the COVID-19 pandemic respectively compared to 2018 and 2019. No significant difference was found between the average number of admissions in the early-COVID and the pre-COVID baseline period during the two waves. The average number of admissions was significantly reduced in the peak-COVID period compared to the baseline (first wave: 332 versus 763 admissions/week, p< 0.01, − 57%; second wave: 496 versus 788 admissions/week, p< 0.01, − 37%), as well as in the late-COVID period compared to the baseline (first wave: 412 versus 763 admissions/week, p< 0.01, − 46%; second wave: 470 versus 788 admissions/week, p< 0.01, − 40%). Cancer, myocardial and cerebral infarction admissions were not statistically reduced during the the two waves of COVID pandemic compared to the pre-COVID period.Conclusion: Our study shows that non-COVID in-hospital admissions rates were substantially reduced during the first two waves of COVID-19 pandemic. In our study, cancer, myocardial and cerebral infarction admissions were not statistically reduced, which was not in accordance to what was described in the literature.Keywords: COVID-19 pandemic, non-COVID-19 admissions, SARS-COV-2

Aims Low haemoglobin (Hb) at admission has been identified as a risk factor for mortality for elderly patients with hip fractures in some studies. However, this remains controversial. This study aims to analyze the association between Hb level at admission and mortality in elderly patients with hip fracture undergoing surgery. Patients and Methods All consecutive patients (prospective database) admitted with hip fracture operated in a tertiary hospital between 2012 and 2016 were analyzed. We collected patient characteristics, time to surgery, duration and type of surgery, comorbidities, Hb at admission, nadir of Hb after surgery, the use and amount of red blood cells (RBCs) transfusion products, postoperative complications, and death. The main outcome measures were mortality at 30 days, 90 days, 180 days, and one year after surgery. Results We included 829 patients; the mean age was 81 years (sd 11). Mortality at 30 days, 90 days, 180 days, and one year was 5.7%, 12.3%, 18.1%, and 23.5%, respectively. The highest mortality was observed in patients aged over 80 years (162/557, 29%) and in male patients (85/267, 32%). Survival at 90 days, 180 days, and one year after surgery was significantly lower in patients with a Hb level below 120 g/l at admission. In multivariate analysis, Hb level below 120 g/l at admission was found to be an independent factor associated with mortality (adjusted hazard ratio (aHR) 1.68 (95% confidence interval (CI) 1.22 to 2.31); p = 0.001), along with age (aHR 1.06 (95% CI 1.04 to 1.06); p < 0.001), male sex (aHR 2.19 (95% CI 1.61 to 2.96); p < 0.001), and need for RBC transfusions (aHR 1.10 (95% CI 1.02 to 1.19); p = 0.01). Conclusion Our results suggest that low Hb at admission along with age and RBC transfusions is significantly associated with short- and long-term mortality after hip fracture surgery, independently of comorbidity confounders. Further studies should be performed to understand how preoperative Hb could be taken into account in perioperative management. Cite this article: Bone Joint J 2019;101-B:1122–1128.

We report the case of a 51 year-old female who complained of jaundice and weight loss. At the time of presentation, she had been in remission from a stage 2a ductal breast carcinoma for 58 months. The clinical presentation was suggestive of a primary pancreas cancer with liver metastases and retroperitoneal lymph nodes. We performed liver and pancreas biopsies that demonstrate a relapse of her old breast carcinoma with positive hormone receptors and HER2 positive. Conservative treatment by chemotherapy was given with Paclitaxel - Trastuzumab and Pertuzumab. Pancreatic metastases are uncommon. Furthermore, pancreatic metastases from breast cancer are very rare. We performed a review of the literature and found 48 cases of pancreatic metastases from breast cancer. We would like to highlight by this case that when a pancreatic lesion appears, in patients with a past history of cancer, physicians must not forget the possibility of metastases from primary tumor even if the initial stage, of the tumor, is low. However the diagnosis is not always easy. If liver and pancreatic lesions occur simultaneously, the clinical presentation can mimic metastatic primary pancreatic cancer. Therefore performing biopsy is highly recommended for making the correct diagnosis and also for the staging of the disease and the choice of the best treatment according to immunohistochemical analysis.

Place: United States

During the last decade, many studies have assessed the performance of malaria tests on non-invasively collected specimens, but no systematic review has hitherto estimated the overall performance of these tests. We report here the first meta-analysis estimating the diagnostic performance of malaria diagnostic tests performed on saliva, urine, faeces, skin odour ('sniff and tell') and hair, using either microscopy or PCR on blood sample as reference test., info:eu-repo/semantics/published

This study aims to evaluate SARS-CoV-2 seroprevalence among health care workers (HCWs) and to assess self-reported risk factors for seropositivity. A total of 3255 HCWs were included and the overall seroprevalence was 7.8%. The likelihood of seropositivity was higher in participants reporting any COVID-19 symptoms within the last 4 months (OR 8.32, 95% CI 5.83-11.88, P < 0.001). Being a female HCW (OR 1.32, 95% CI 1.11-2.32, P < 0.01), having a cohabitant who was infected with SARS-CoV-2 (OR 2.55, 95% CI 1.78-3.66 P < 0.001) or a cohabitant who was a nursing home caregiver (OR 3.71, 95% CI 1.59-8.65, P = 0.002) were independently associated with an increased risk of seropositivity. Working in a COVID-19 unit (OR 1.64, 95% CI 1.21-2.23, P < 0.001) and being exposed to a SARS-CoV-2 infected co-worker (OR 1.30,95% CI 0.97-1.74, P = 0.016) resulted in higher seropositivity rate. Even if in-hospital exposure may play a significant role, increased infection risk is most likely attributable to household contact.

BACKGROUND: The impact of the COVID-19 pandemic on functional exercise capacity seemed quickly clinically evident. The objective of this study was to assess the functional exercise capacity of patients with severe COVID-19 and to evaluate the effect of a telerehabilitation program in the specific context of the COVID-19 pandemic. METHOD: Patients hospitalized for severe or critical COVID-19 were recruited. The functional exercise capacity (1-min sit-to-stand test (STST)) was prospectively quantified at discharge. A telerehabilitation program was then proposed. A control group was composed with the patients refusing the program. RESULTS: At discharge, none of the 48 recruited patients had a STST higher than the 50th percentile and 77% of them were below the 2.5th percentile. SpO2 was 92.6 ± 3.0% after STST and 15 patients had oxygen desaturation. After 3-months of follow-up, the number of repetitions during STST significantly increased either in telerehabilitation (n = 14) (p < 0.001) or in control groups (n = 13) (p = 0.002) but only one patient had a result higher than the 50th percentile (in Telerehabilitation group) and 37% of them were still under the 2.5th percentile for this result. The improvement was significantly and clinically greater after the telerehabilitation program (p = 0.005). No adverse events were reported by the patients during the program. CONCLUSIONS: Patients hospitalized for COVID-19 have a low functional exercise capacity at discharge and the recovery after three months is poor. The feasibility and the effect of a simple telerehabilitation program were verified, this program being able to substantially improve the functional recovery after three months.

The first wave of coronavirus disease 2019 (COVID-19) was particularly dramatic for kidney transplant recipients (KTRs) around the world.1 A recent European registry study showed 28-day mortality and intensive care unit (ICU) admission rates at 22% and 21%, respectively.2 In the United States, a multicenter cohort study revealed a 28-day mortality rate at 18%.3 Fortunately, patients from our tertiary KT center were less impacted with mortality and ICU admission rates at 11% and 11%, respectively. [...]

Introduction Haemophagocytic lymphohistiocytosis (HLH) is a severe disorder with high mortality. The aim of this review is to update clinical management of relapsed/refractory HLH in adults, with a focus on current and new therapies. Methods We searched relevant articles in Embase and PUBMED with the MESH term “hemophagocytic lymphohistiocytosis; refractory; relapsing; adult.” Results One hundred eight papers were found; of these, 22 were retained for this review. The treatment of HLH in adult is based on the HLH-94 regimen. The response rate is lower than in pediatric patients, and 20–30% are refractory to this therapy. DEP regimen and allogenic hematopoietic stem cell transplantation (HSCT) are associated with complete response and partial response in 27% and 49.2%, respectively. However, many patients fail to achieve a stable condition before HSCT, and mortality is higher in them. New drugs have been developed, such as emapalumab, ruxolitinib, and alemtuzumab, and they may be used as bridges to the curative HSCT. They are relatively well tolerated and have few or mild side effects. With these agents, the rate of partial response ranges from 14.2% to 100%, while the rate of complete response is highly variable according to study and medication used. The number of patients who achieved HSCT ranged from 44.8% to 77%, with a survival rate of 55.9% to 100%. However, the populations in these studies are mainly composed of mixed-age patients (pediatric and adult patients), and studies including only adult patients are scarce. Conclusion Relapsed or refractory HLH in adult patients is associated with poor outcome, and consolidation with HSCT may be required in some cases. Mortality related to HSCT is mainly due to active HLH disease before HSCT and post HSCT complications. New drugs, such as empalumab, ruxolitinib, and alemtuzumab are interesting since these agents may be used as bridges to HSCT with increases in the numbers of patients proceeding to HSCT and survival rate.

In the early stage of the COVID-19 pandemic, Belgian health authorities endorsed the interim guidelines for the treatment of COVID-19 pneumonia: hydroxychloroquine (HCQ) recommended for treatment of hospitalized patients with moderate to severe disease. As a growing number of patients were admitted, inevitably, our internal medicine team questioned the efficacy and safety of HCQ, especially with regard to cardiac side effects. In parallel with our concerns, data regarding the safety and efficacy of HCQ were published, with discordant results and debate in the medical community. Media coverage of the possible risks and benefits of HCQ use in COVID-19 also caused confusion amongst the public. In this Perspectives in Rheumatology article, we review the use and safety of HCQ in autoimmune disease and its putative efficacy and toxicity in COVID-19. Finally, we share our concern about the future of this widely used and inexpensive drug after the COVID-19 pandemic has passed.

Dear Editor, Hypoxaemia is a typical feature of the coronavirus disease 2019 (COVID-19). The rapid rise in the number of patients requiring oxygen therapy during the pandemic may cause a sharp increase in oxygen demands and potential threats of supply disruption, particularly in developing countries1 or nursing homes. Moreover, the use of elevated oxygen flows via nasal cannula raises concerns about exhaled air dispersion distance and the potential risk of generating aerosols [...]

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is particularly life threatening in patients with kidney failure under dialysis, with mortality rate at 28 days of 21.2% in the ERA-EDTA registry and 25% in the ERACODA (European Renal Association COVID-19 Database) database. [...]

Many innovations, such as long-acting agents, new delivery modalities (injectable and nanoparticles), and novel paradigms (immunotherapy or dual therapy), have been introduced to facilitate the administration of antiretroviral treatment (ART) to patients infected with HIV and improve their adherence and quality of life without altering the drugs' effectiveness. Studies have investigated the use of intermittent treatment, especially weekends-off ART in HIV-suppressed patients. In this review, we analyzed data concerning intermittent ART to help determine if this strategy is reasonable for the management of patients living with HIV. The results of early studies, in 2007-2015, were encouraging, but the studies were flawed because of the small number of patients included, the absence of a control arm, and random designs with variable patterns of ART administration. From 2016, studies have included more patients, and some are prospective, randomized controlled studies. While non-nucleoside reverse transcriptase inhibitors have been most studied, treatment with integrase inhibitors also has been reported, with the findings that viral resistance did not appear when treatment failed with dolutegravir but not with raltegravir. The most recent study, QUATUOR, found that a 4-day on, 3-day off pattern was non-inferior to the continuous pattern (7 days on). Better-quality studies with long-term follow-up (96 weeks or more) are needed to determine the validity of intermittent treatment and the optimal regimens and monitoring to be used in the management of viro-logically suppressed patients living with HIV.

Background: At first less impacted than the rest of the world, African countries, including Cameroon, are also facing the spread of COVID-19. Objective: This study aimed to analyze the spread of the COVID-19 in Cameroon, one of the most affected countries in sub-Saharan Africa. Methods: We used the data from the Africa Centre for Disease Control and Prevention, reporting the number of confirmed cases and deaths, and analyzed the regularity of tests and confirmed cases and compared those numbers with neighboring countries. We tested different phenomenological models to model the early phase of the outbreak. Results: Since the first reported cases on the 7th of March, 18,662 people have been diagnosed with COVID-19 as of the 24th of August, 186,243 tests have been performed, and 408 deaths have been recorded. New cases have been recorded only in 50% of the days since the first reported cases. There are considerable disparities in the reporting of daily cases, making it difficult to interpret these numbers and to model the evolution of the pandemic with the phenomenological models. Conclusion: Currently, following the finding from this study, it is challenging to predict the evolution of the pandemic and to make comparisons between countries as screening measures are so sparse. Monitoring should be performed regularly to provide a more accurate estimate of the situation and allocate healthcare resources more efficiently., info:eu-repo/semantics/published

Since December 2019, we have been in the battlefield with a new threat to the humanity, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), characterized by viral pneumonia. It may be asymptomatic or cause various symptoms, ranging from flu-like symptoms to acute respiratory distress syndrome and eventually death. At present, the only reliable test for COVID-19 diagnosis is quantitative reverse transcriptase-polymerase chain reaction. Assessing the immune response against SARS-CoV-2 could increase the detection sensitivity of infected population. Hereby, we report the performances of a fully automated chemiluminescent immunoassay (CLIA) on 276 serum samples. One hundred samples obtained from COVID-19 negative subjects (COVID-19 free) were analyzed to evaluate the diagnostic specificity of antibody (Ab) detection. Thereafter, 176 samples obtained from 125 patients with confirmed COVID-19 (COVID-19 patients) were selected to assess the diagnostic sensitivity of the CLIA. All samples were analyzed on MAGLUMI 800 platform. All COVID-19 free samples had Ab levels below the cutoff values. Hence, the diagnostic specificity was estimated at 100% (95% confidence interval [CI] = 96.3-100.0; positive predictive value = 100%). By the 18th day from the onset of symptoms, we reached an optimal diagnostic sensitivity (more than 95.0%) In fact, the diagnostic sensitivity increased over time and between 15 and 25 days after symptoms onset, reached 95.5% (95% CI = 84.9-99.2). The new automated CLIA analyzer appeared to be a robust and reliable method to measure specific Ab against COVID-19 at high throughput. Our data suggest that combining Ab and nucleic acid detection could increase diagnostic sensitivity.

Dear Editor, Cancer has been shown to be associated with higher risk of COVID-19 complications [1]. However, data on patients with COVID-19 and an underlying hematological disease as well as on specific risks factors in this particularly immunocompromised population are scarce [2–5]. We conducted a retrospective study in a tertiary center of 1000 beds with a hematology reference center. Our ethics committee approved the study (N° CEHF 2020/06AVR/201). Between March 13 and May 15, 2020 a total of 375 consecutive patients were hospitalized with COVID-19 and among them 13 (3.4%) met the inclusion criteria of having an underlying hematological disease. [...]

Patients on in-center maintenance hemodialysis (HD) are at potentially high risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]) inside the HD unit, due to social contacts during the frequent HD sessions. Data concerning the dynamics of anti–SARS-CoV-2 antibodies in patients on HD are scarce. [...]

Background Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations. Methods Consecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated. Results Of the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients. Conclusions In SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity.

TO THE EDITOR, When a patient is hospitalizated with COVID-19, prediction of the risk of development of severe or critical illness is of great importance [1]. Several risk scores have been described such as COVID-GRAM [2], National Early Warning Score 2 (NEWS 2) [3] and 4C mortality score [4]. [...]

Halil Yildiz,1,&ast; Diego Castanares-Zapatero,2,&ast; Guillaume Pierman,1 Lucie Pothen,1 Julien De Greef,1 Frank Aboubakar Nana,3 Hector Rodriguez-Villalobos,4 Leila Belkhir,1 Jean Cyr Yombi1 1Department of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium; 2Department of Intensive Care Unit, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium; 3Department of Pneumology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium; 4Department of Microbiology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium&ast;These authors contributed equally to this workCorrespondence: Halil YildizDepartment of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 10 avenue hippocrate, Brussels, BelgiumTel +3227641902Fax +3227641046Email halil.yildiz@uclouvain.beIntroduction: The neutrophil-to-lymphocyte ratio (NLR) could be a predictive factor of severe COVID-19. However, most relevant studies are retrospective, and the optimal NLR cut-off point has not been determined. The objective of our research was identification and validation of the best NLR cut-off value on admission that could predict high in-hospital mortality in COVID-19 patients.Methods: Medical files of all patients admitted for COVID-19 pneumonia in our dedicated COVID-units between March and April 2020 (derivation cohort) and between October and December 2020 (validation cohort) were reviewed.Results: Two hundred ninety-nine patients were included in the study (198 in the derivation and 101 in the validation cohort, respectively). Youden’s J statistic in the derivation cohort determined the optimal cut-off value for the performance of NLR at admission to predict mortality in hospitalized patients with COVID-19. The NLR cut-off value of 5.94 had a sensitivity of 62% and specificity of 64%. In ROC curve analysis, the AUC was 0.665 [95% CI 0.530– 0.801, p= 0.025]. In the validation cohort, the best predictive cut-off value of NLR was 6.4, which corresponded to a sensitivity of 63% and a specificity of 64% with AUC 0.766 [95% CI 0.651– 0.881, p < 0.001]. When the NLR cut-off value of 5.94 was applied in the validation cohort, there was no significant difference in death and survival in comparison with the derivation NLR cut-off. Net reclassification improvement (NRI) analysis showed no significant classification change in outcome between both NLR cut-off values (NRI:0.012, p=0.31).Conclusion: In prospective analysis, an NLR value of 5.94 predicted high in-hospital mortality upon admission in patients hospitalized for COVID-19 pneumonia.Keywords: neutrophil-to-lymphocyte ratio, coronavirus disease, SARS-CoV-2 infection, COVID-19, risk factors, laboratory markers

TO THE EDITORS, We recently reported that almost all maintenance hemodialysis (MHD) patients mount specific antibodies within a month of COVID-19 onset. However, evidence concerning the immunogenicity of SARS-CoV-2 vaccines in this immunodeficient population is scarce. [...]

Background The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration ClinicalTrials.gov NCT04429854 .Registered on 12 June 2020 - Retrospectively registered., info:eu-repo/semantics/published

Background The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is unknown.Methods ONCOSARS-1 was a prospective, single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were included. All patients (n=363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients.Results Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (PP=0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (PConclusion Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.

Background: Patients with coronavirus disease (COVID-19) can develop severe hypoxemia. Meeting the soaring demands of oxygen may be a challenge. Objective: To test the efficacy of an easily handmade system, the double-trunk mask (DTM), in reducing oxygen consumption while maintaining patient’s oxygenation level. Methods: Hospitalized adults with COVID-19 and hypoxemia treated with low-flow oxygen therapy we recruited. The standard oxygen delivery system was replaced by the DTM with nasal cannula for 30 minutes with an oxygen output adapted to maintain an identical oxygen saturation by pulse oximetry. The standard oxygen delivery system was then reinstated for 30 minutes. Primary outcome was the absolute change in oxygen flow between the standard delivery systems and the DTM. Secondary outcomes were changes in blood gases, vital parameters and patient comfort. Results: Eleven patients were analyzed (mean age 61 years; 27% male). Compared with standard delivery systems, the oxygen output was significantly reduced with the DTM (median, 5 vs 1.5 L/min (95% CI -4 to -1.5, p=0.003)) when oxygen saturation and arterial oxygen tension remained stable. The DTM was also associated with a significant but slight increase in arterial carbon dioxide tension (median, 36 mmHg vs 37 mmHg, p=0.006), and respiratory rate (median, 26 vs 30 breaths/min, p=0.05). Other parameters were unaltered. The DTM was generally judged less comfortable than the baseline oxygen delivery system, especially in patients requiring low oxygen flow at baseline. Conclusions: The DTM is a simple and efficient system to reduce oxygen consumption. This may have clinical implications in places where oxygen supplies are limited.

ObjectiveTo determine the early electrocardiographic changes in a cohort of ambulatory cameroonian COVID-19 patients treated with hydroxychloroquine and Azithromycin.DesignProspective study.SettingTreatment centres of the city of Yaounde, Cameroon, from May 7th to 24th 2020.ParticipantsWe enrolled 51 consecutive confirmed COVID-19 on RT-PCR who having mild forms of COVID-19 and treated by hydroxychloroquine 200mg twice daily during seven days plus Azithromycin 500 mg the first day and 250 mg the remaining 4 days as per national standard.Main outcomes measuresThe primary end-point was the change in QTc interval between day 0 (D0), day 3 (D3) and day 7 (D7). Secondary endpoints were changes in all other cardiac electrical conductivity patterns and the occurrence of clinical arrhythmic events during the course of treatment.ResultsThe population (29 men and 22 women) was aged 39 ± 11 years (range 17 to 61 years). Mean Tisdale score was 3.35±0.48. No significant change from baseline (D0) of QTc was observed at D7 (429±27 ms at D0 versus 396±26 ms at D7; p=0.27). A reduction of heart rate was observed between the D0 and D7 (75±13 bpm versus 70±13 bpm, p = 0.02) with increased QRS duration between D0 and D7 (95±10 ms versus 102±17 ms, p = 0.004). No symptomatic arrhythmic events occurred during the treatment course.ConclusionsNo life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with hydroxychloroquine and azithromycin. Studies are needed in critical-ill and older patients.

To the editors of the Pan African Medical Journal Coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome (SARS-CoV-2) is a global public health problem with major economic and social consequence of tremendous importance. Since the identification of its first case in Wuhan, Hubei, China in end December 2019, the exponential and rapid spread of the disease over all continents led the World Health Organization (WHO) to declare a pandemic in March, 11, 2020. Since, then several governement and non-governmental organizations pay a serious attention on this pandemic [1]. Moreover, the rapid spread of the pandemic is very challenging for its control by placing enormous pressure on all health care systems worldwide [2], and on frontline healthcare workers who are rapidly altering their professional responsibilities to help meet hospital needs. Limitation of staff members, redeployment of healthcare providers in the COVID-19 units, priority allocation of material and financial resources to fight COVID-19, limitation of the number of outpatient consultations have all contributed to a global health economic crisis [3]. It is estimated that health care workers (HCW) comprise between 4% and 19% of all reported COVID-19 cases in Europe and China [4]. Their risk of being contaminated is particulary high when treating non diagnose COVID-19 people due to shortage in the material of testing and further increased by the suboptimal personal protective equipment (PPE) available for health personnel in low-and middle-income countries (LMICs) [5]. Surgeons are particularly affected due to the wide variety of procedures they perform, many of which are conducted routinely in the outpatient setting. Urgent measures are warranted to avert health specialist from being infected or dying of COVID-19. This ensures that we have readily available healthy surgeons, anesthesiologists, intensivists and nurses for an adequate perioperative management of COVI-19 patients with surgical pathologies. Considering the important role of surgical teams during the COVID-19 pandemic many scientific societies have set-up guidelines to curb the prevalence of COVID-19 among surgical teams. Some of these recommendations strategies include postponing all elective surgical procedures, triage of patients to identify those at risk of COVID-19, compulsory surgical care of COVID-19 patients surgical emergencies, a constant supply of adequate PPE for the surgical team, wearing of a face mask by the COVID-19 patient during the entire surgical intervention. Designated COVID-19 operating areas (COA) must be allocated for COVID-19 patients requiring an emergency surgery. Patients transit to and from the COA must be as quick as possible [6]. Zheng L and colleagues have also put forth a protocol of emergency surgery based on three level of stratified risks: (i) For confirmed and suspected COVID-19 patients, surgeons need to report to the hospital´s epidemiology department, infection control department, and operating room before they undergo surgery and then transfer a separate path to a negative pressure room, then to an isolation area. (ii) For high-risk COVID-19 patients who have to undergo surgery, after their preoperative preparation is completed, the anesthesiologist, nurse, and surgeon all follow protective measures for anesthesia and surgical procedures. After the surgery, the patients return to the original isolation ward according to the original transfer route. (iii) For low-risk COVID-19 patients, the general protection measures are needed for anesthesia and surgical procedures. After the operation, patients are transferred to their original ward according to the original transfer route [7]. In LLCs, surgical interventions are generally expensive for the general population [8] and the reduction of elective surgery may contribute to inflate this cost. Of note, the setting in which surgical interventions are performed, might be an important risk to acquire COVID-19. Thus, it is urgent to propose some practical strategies and resource-sensitive and context specific guidelines to reduce the spread of the disease in the operating room. Pending to resource availability and constraints, these strategic recommendations could be summarized in nine points as follow: 1) Adequate triage of all patients who undergo surgical intervention by assessing fever or respiratory signs; 2) Addressing all suspected patients to a specific unit for rapid diagnostic testing; 3) Interim cancelation of postponing of all elective surgery for confirmed cases; 4) Multidisciplinary operative staff meeting should be organized by video-communications or webinars; 5) Social distancing during clinical examination ; 6) Patients should wear their masks during all the peri-operative time (pre-operative consultation, during the entire surgical intervention and thereafter in the post-operative recovery unit) ; 7) The surgical team should have a constant and readily supply of PPE; 8) Sterilization of all surgical equipments and the operating room after surgery, especially after operating COVID-19 confirmed case; 9) Restrictions of family and friends visits to the patient in the postoperative period. A few couples of days succeeding the COVID-19 confinement in some high-income countries the pandemic of higher risk of transmission of COVID-19 increased in the general population as well as several surgical services given that no curative treatment nor vaccine for COVID-19 has been discovered yet. Hence, the surgical workforce or surgical team is continuously being re-inforced through psychological support to prevent physical and emotional exhaustion; enhancing their healthcare leadership and capacity building skills; regular clear communication between surgeons, between surgeons and anesthesiologists and between the surgical team and surgical patients; continuous refresher courses for the surgical teams on PPE; securing enough PPE to protect both the surgical patient and surgical team; continuous compliance to preventive measures such as hand washing before and after surgery; respecting social distancing during the surgical intervention [9]. While emergency surgical procedures will need to continue to be performed using PPE, elective or non-essential surgeries might still remain unfeasible in LMICs due to a shortage of PPE for the surgical human resources [10]. The following checklist proposed by the Royal College of Surgeons in the UK should help in prioritization of surgical interventions and resources adapted to local healthcare system: adequate timing for elective surgery, adequate supply and use of PPE, availability of interdependent service like anesthesiology, critical care or pathology; availability of local testing kits or laboratories for COVID-19, availability of an accurate assessment of the surgical workload by surgical sub-specialties, provision of a minimal risk environment that includes ward areas, operating room and post-anesthesia care units with adequate facilities to care for COVID-19 patients with surgical pathologies as well as to avert infection amongst the surgical team; adequate theatre capacity to meet the surgical service demands; ensuring an adequate supply of a surgical workforce in good physical and mental health; local coordination and availability of recovery management team in place (with multi-professional and multidisciplinary clinical input), to provide coordination and oversight of relevant policies and communications [9]. In poor resource settings, this flexible tool could also be used in order to limit spread of COVID-19 infection in surgical context. Conclusion COVID-19 is a real public health challenge for global healthcare system, impacting severely surgical services. This devastating pandemic calls for urgent readaption and reorientation of health policies and health system to comply with the incident pressing health needs in LMICs. This include implementation of practical context-specific and resources-sensitive guidelines to curb and reduce the transmission rate of SARS-CoV-2 infection to the surgical teams and improve the surgical care of COVID-19 patients living in underserved settings, even during and early after this pandemic. Competing interests All authors declare no competing interests.

To The Editor, During the COVID-19 pandemic, eosinopenia was described by Li et al. as a hallmark of this infection in patients presenting with fever [1]. For the prediction of positive SARS-CoV-2 cases (diagnosis based on RT-PCR), eosinopenia has a sensitivity of 74.7% and specificity of 68.7% with the area under the curve AUC of 0.717. The combination of eosinopenia and raised hs-CRP yielded a sensitivity of 67·9% and specificity of 78·2% (AUC = 0·730). [...]

Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with COVID-19, as attested by low-molecular-weight proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of uric acid (46%) or phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular necrosis, intraluminal debris, and a marked decrease in the expression of megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of respiratory failure requiring invasive mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into COVID-19 severity and outcome., Graphical abstract

Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.

The Malian pharmacovigilance program has been associated with modest growth over the past years. The purpose of this chapter is to assess the current state of pharmacovigilance (PV) in Mali and the adverse drug reactions reported to the National Pharmacovigilance Center of Mali. The profiles and number of adverse drug reactions (ADRs), the degree of toxicity, and the WHO and Naranjo scores are evaluated. We found that three university teaching hospitals in Mali conducted such PV studies. Our results showed that although there is a recognition of the need for PV, the practice was very limited. Only 67.6% of participant practitioners had an accepted knowledge for PV and its methodology. This situation is attributed to the insufficient knowledge about what can or should be reported in PV and a lack of a reliable notification process. Nevertheless, this study highlighted the profile of commonly used ADRs and the problems inherent to systematic reporting.

In December, 2019, a new acute respiratory syndrome appeared in Wuhan, China. The disease, later named COVID19, is caused by a new coronavirus (SARS-CoV-2) [1e3]. Clinical presentation is mild in about 80%, moderate to severe in 15% and critical in 5% of cases. [...]

Objectives As severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic is increasing its victims on a global scale with recurring outbreaks, it remains of outmost importance to rapidly identify people requiring an intensive care unit (ICU) hospitalization. The aim of this study was to identify Coronavirus Disease 2019 (COVID-19) biomarkers, to investigate their correlation with disease severity and to evaluate their usefulness for follow-up. Methods Fifty patients diagnosed with SARS-Cov-2 were included in March 2020. Clinical and biological data were collected at admission, during hospitalization and one month after discharge. Patients were divided into two severity groups: non-ICU (28) and ICU and/or death (22) to stratify the risk. Results Blood parameters in COVID-19 patients at admission showed increased C-reactive protein (CRP) (100%), ferritin (92%), lactate dehydrogenase (LDH) (80%), white blood cell (WBC) count (26%) with lymphopenia (52%) and eosinopenia (98%). There were significant differences in levels of CRP, ferritin, D-dimers, fibrinogen, lymphocyte count, neutrophil count and neutrophil-to-lymphocyte ratio (NLR) among the two severity groups. Mapping of biomarker’s kinetics distinguished early and late parameters. CRP, ferritin, LDH, lymphopenia and eosinopenia were present upon admission with a peak at the first week. Late biomarkers such as anemia, neutrophilia and elevated liver biomarkers appeared after one week with a peak at three weeks of hospitalization. Conclusions We confirmed that high-values of CRP, NLR, D-dimers, ferritin as well as lymphopenia and eosinopenia were consistently found and are good markers for risk stratification. Kinetics of these biomarkers correlate well with COVID-19 severity. Close monitoring of early and late biomarkers is crucial in the management of critical patients to avoid preventable deaths.