Worldwide use of HPV self-sampling for cervical cancer screening.

An increasing body of evidence supports the validity of self-sampling as an alternative to clinician collection for primary Human Papillomavirus (HPV) screening. Self-sampling effectively reaches underscreened women and can be a powerful strategy in low- and high-resource settings for all target ages. This work aims to summarize the current use of HPV self-sampling worldwide. It is part of a larger project that describes cervical cancer screening programmes and produces standardized coverage estimates worldwide. A systematic review of the literature and official documents supplemented with a formal World Health Organisation country consultation was conducted. Findings show that the global use of HPV self-sampling is still limited. Only 17 (12%) of countries with identified screening programs recommend its use, nine as the primary collection method, and eight to reach underscreened populations. We identified 10 pilots evaluating the switch to self-sampling in well-established screening programs. The global use of self-sampling is likely to increase in the coming years. COVID-19's pandemic has prompted efforts to accelerate HPV self-sampling introduction globally, and it is now considered a key element in scaling up screening coverage. The information generated by the early experiences can be beneficial for decision-making in both new and existing programs.

Wearing masks from the age of 6 to counter the spread of COVID-19 in French schools

The start of the school year in September 2020 in France, during the COVID-19 pandemic, was accompanied by debates on the value of wearing masks in primary school. This work discusses the interest of wearing masks from the age of 6, in the light of the scientific knowledge updated until early November 2020 and of French specificities. Literature shows that children are contaminated and account for at least 11% of COVID-19 cases. This rate is increasing: it was lower in studies carried out during periods of confinement, school holidays or low circulation of the virus. Children are contaminants for all age groups. Nowadays, there is no scientific data supporting a risk associated with children wearing a mask. The risk-benefit balance is therefore clearly in favour of the generalised use of masks for children. The compulsory wearing of masks by children, whatever their age (from the age of 6 in schools), can only be more effective than no measures at all.

Tocilizumab for treating COVID pneumonia: Analysis of effectiveness and security

Background and importance Tocilizumab (TCZ) is an immunosuppressor drug, IL-6 inhibitor, indicated for the treatment of rheumatoid arthritis and cytokine release syndrome associated with CAR T cell therapy. It was proposed as a compassionate treatment for severe COVID-19 due to its potential benefit as anticytokine therapy with IL-6 as the target, one of the most relevant cytokines involved in the cytokine storm induced by COVID-19. Aim and objectives The main objective was to evaluate TCZ security and effectiveness in the treatment of COVID-19 pneumonia. Material and methods A retrospective observational study was conducted in patients with COVID-19 pneumonia treated with TCZ from 20 March to 20 May 2020 at a tertiary hospital. Study variables were: age, sex, need for invasive and noninvasive ventilation, intubation days and oxygen therapy. Days in inpatient care, admission to intensive care units (ICU) and time spent there, adverse reactions and deaths were also obtained. Data were recollected from the electronic clinical records. Results Data from 59 COVID-19 patients were collected in this study between March and May 2020. Median age (maxmin) was 62.4 (48-74) years and 76.3% of patients were men. Comorbidities were: hypertension in 37.3%, dyslipidaemia in 20.3% and diabetes in 15.2%. Six patients had asthma and 5 had cardiopathy. 72 hours after TCZ administration, 54.2% of patients had respiratory improvement with a reduced need for oxygen therapy, 32.2% had stabilisation of their condition and 13.6% had worsening of their condition, requiring orotracheal intubation. Seven days after TCZ administration, 44 had clinical improvement with a reduced need for oxygen therapy, 6 remained stable with VNI and 9 had worsening of their condition (6 passed out, 3 were admitted to the ICU). TCZ was well tolerated with no adverse effects detected. 28 days after TCZ administration, mortality was 15.2%, 69.6% were discharged and 15.2% remained in hospital at the end of the study. Conclusion and relevance The results of the study showed that TCZ was effective and safe in patients with COVID-19 pneumonia. Patient outcomes were favourable in most cases. During admission, patients showed clinical improvement with a reduced need for invasive ventilation and oxygen therapy. Due to the potential bias (patients received different treatments before and after TCZ) and the small sample size, it is necessary to confirm these results in controlled clinical trials.

Inflammatory parameter analysis in severe COVID-19 patients treated with tocilizumab

Background and importance Tocilizumab (TCZ) is an immunosuppressor drug, IL-6 inhibitor, indicated for the treatment of rheumatoid arthritis and cytokine release syndrome associated with CAR T cell therapy. It was proposed as a compassionate treatment for severe COVID-19 due to its potential benefit as anticytokine therapy with IL-6 as the target, one of the most relevant cytokines involved in the cytokine storm induced by COVID-19. Aim and objectives The main objective was to evaluate TCZ effectiveness in the modification of inflammatory parameters in severe COVID-19 patients. Material and methods A retrospective observational study was conducted in 46 patients with COVID-19 admitted to an intensive care unit (ICU) and treated with TCZ from 20 March to 20 May 2020 at a tertiary hospital. Variables analysed were: age, sex, levels of IL-6, C reactive protein (CRP), ferritin, lymphocytes count and D-dimer on days 0, 1, 3, 7 and 14 after TCZ administration. Days in the ICU, deaths and patient outcomes were also obtained. Results Median age was 64 years and 67.4% of patients were men. IL-6 levels on day 0 were 293 pg/mL, peaking at 416 pg/mL on day 3 and decreasing to 241.9 pg/mL on day 7. CRP levels increased above the normal range (median 53.35 mg/L on day 0) in all patients before initiation of therapy with TCZ and decreased on day 7 (median 3 mg/L). Serum ferritin decreased from 1798 mg/L on day 1 to 1197.5 mg/L on day 7 before TCZ. Lymphocyte count increased from 570 to 1365 lymphocytes/mL on day 7. D-dimer level on day 0 was 2008 ng/mL and increased to 3910 ng/mL on day 7 and decreased to 1723 ng/mL on day 14. Length in ICU stay was 16.4 days compared with the mean stay of the total number of ICU COVID patients, which was 26.1 days. Mortality was 19.6%, 15.2% remained in hospital at the end of the study and 65.2% were discharged. Conclusion and relevance The results showed an improvement in inflammatory markers with TCZ treatment, as well as a decrease in length of stay in the ICU, similar to findings reported in the literature. Nevertheless, because of potential bias due to patients receiving different treatments before and after TCZ and the small sample size, it is necessary to confirm these results in controlled clinical studies.

Experience of the use of baricitinib in COVID-19 pneumonia

Background and importance Baricitinib is an immunosuppressive agent included as one of the therapeutic options for COVID-19 in the Spanish protocol Agencia Española del Medicamento y Productos Sanitarios. Aim and objectives The objective was to assess the effectiveness of this drug in hospitalised but non-critically ill patients. Material and methods An observational retrospective study was conducted in a third level hospital from 26 March to 5 May. Inclusion criteria were: hospitalised patients diagnosed with COVID-19 pneumonia and treated with baricitinib. Data collected were: age, gender, comorbidities, severe pneumonia diagnosis, ferritin and interleukin 6 (IL-6) prior to the beginning of treatment with baricitinib, standard of care according to the hospital's protocol, concomitant treatment with anakinra, duration of treatment with baricitinib, average hospital stay (AHS), deaths and hospital discharges. The data were collected from the electronic medical records and the hospital's management department. Results 171 patients treated with baricitinib were included, with an average age of 69.5 (34-96) years. 71.3% (122) were men. 87.1% (149) had comorbidities and 73.1% (125) were diagnosed with a severe pneumonia, with 25% of them dying (31). Median duration of treatment with baricitinib was 5 days (1- 12). AHS for the baricitinib group was 14.60 (3-47) days, and AHS for the whole sample of patients diagnosed with COVID- 19 pneumonia was 17.2 days. 23.4% (40) of patients had high levels of ferritin (>2500 UI/L). Among them, 87.5% (35) were discharged and 12.5% (5) died. IL-6 levels were high (>40 U/ L) in 29.8% (51) of patients, <40 U/L in 37.4% (64) and not measured in 32.7% (56). In the group with high IL-6 levels, 70.6% (36) were discharged and 29.4% (15) died. Among those with normal levels of IL-6, 93.8% (60) were discharged and 6.3% (4) died. 84.2% (144) of baricitinib patients were also treated with the SoC. During the hospital stay, 31.0% (53) of patients were treated with anakinra and baricitinib, 83.0% (44) were discharged and 17.0% (9) died. Global mortality of the whole sample of patients diagnosed with COVID-19 pneumonia was 18.1% (31). Conclusion and relevance AHS for baricitinib patients was shorter than for the whole sample of COVID-19 patients. The percentage of patients with high levels of IL-6 was superior to that of patients with high ferritin, with mortality greater in patients with IL-6 >40 UI/L. Hence IL-6 level appears to be a better prognostic factor of mortality than ferritin. This could also be related to a greater patient's immune response. Regarding treatment effectiveness, mortality of patients who were treated with SoC plus baricitinib was similar to that of patients treated with anakinra plus baricitinib.

Encephalopathy and encephalitis during acute SARS-CoV-2 infection. Spanish Society of Neurology COVID-19 Registry. / Encefalopatías y encefalitis durante la infección aguda por SARS-CoV2. Registro de la Sociedad Española de Neurología SEN COVID-19.

OBJECTIVES: Since the beginning of the COVID-19 pandemic, the Spanish Society of Neurology has run a registry of patients with neurological involvement for the purpose of informing clinical neurologists. Encephalopathy and encephalitis were among the most frequently reported complications. In this study, we analyse the characteristics of these complications. PATIENTS AND METHODS: We conducted a retrospective, descriptive, observational, multicentre study of patients with symptoms compatible with encephalitis or encephalopathy, entered in the Spanish Society of Neurology's COVID-19 Registry from 17 March to 6 June 2020. RESULTS: A total of 232 patients with neurological symptoms were registered, including 51 cases of encephalopathy or encephalitis (21.9%). None of these patients were healthcare professionals. The most frequent syndromes were mild or moderate confusion (33%) and severe encephalopathy or coma (9.8%). The mean time between onset of infection and onset of neurological symptoms was 8.02 days. Lumbar puncture was performed in 60.8% of patients, with positive PCR results for SARS-CoV-2 in only one case. Brain MRI studies were performed in 47% of patients, with alterations detected in 7.8% of these. EEG studies were performed in 41.3% of cases, detecting alterations in 61.9%. CONCLUSIONS: Encephalopathy and encephalitis are among the complications most frequently reported in the registry. More than one-third of patients presented mild or moderate confusional syndrome. The mean time from onset of infection to onset of neurological symptoms was 8 days (up to 24hours earlier in women than in men). EEG was the most sensitive test in these patients, with very few cases presenting alterations in neuroimaging studies. All patients treated with boluses of corticosteroids or immunoglobulins progressed favourably.

Smell and Taste Dysfunction in COVID-19 Is Associated With Younger Age in Ambulatory Settings: A Multicenter Cross-Sectional Study.

BACKGROUND AND OBJECTIVE: Since the initial anecdotal reports of coronavirus disease 2019 (COVID-19) from China, a growing number of studies have reported on smell and/or taste dysfunction (STD). Objective: The aim of our study was to investigate the frequency and severity of STD in COVID-19 patients and to evaluate the association with demographic characteristics, hospital admission, symptoms, comorbidities, and blood biomarkers. METHODS: We performed a multicenter cross-sectional study on patients who were positive for SARS-CoV-2 (n=846) and controls (n=143) from 15 Spanish hospitals. Data on STD were collected prospectively using an in-person survey. The severity of STD was categorized using a visual analog scale. We analyzed time to onset, recovery rate, time to recovery, hospital admission, pneumonia, comorbidities, smoking, and symptoms. RESULTS: STD was at least 2-fold more common in COVID-19-positive patients than in controls. COVID-19-positive hospitalized patients were older, with a lower frequency of STD, and recovered earlier than outpatients. Analysis stratified by severity of STD showed that more than half of COVID-19 patients presented severe loss of smell (53.7%) or taste (52.2%); both senses were impaired in >90%. In the multivariate analysis, older age (>60 years), being hospitalized, and increased C-reactive protein were associated with a better sense of smell and/or taste. COVID-19-positive patients reported improvement in smell (45.6%) and taste (46.1%) at the time of the survey; in 90.6% this was within 2 weeks of infection. CONCLUSION: STD is a common symptom in COVID-19 and presents mainly in young and nonhospitalized patients. More studies are needed to evaluate follow-up of chemosensory impairment.

[Multifocal encephalitis as a neurological manifestation of COVID-19 infection]. / Encefalitis multifocal como manifestación neurológica de la infección por COVID-19.

TITLE: Encefalitis multifocal como manifestación neurológica de la infección por COVID-19.

Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study.

OBJECTIVES: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Singleton pregnancies with COVID-19 at >20+0  weeks. METHODS: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. MAIN OUTCOME MEASURES: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. RESULTS: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. CONCLUSIONS: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. TWEETABLE ABSTRACT: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.