WHO Clinical Research Articles

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic or mild/moderate symptoms to severe symptoms and death. The mechanisms underlying its clinical evolution are still unclear. Upon SARS-CoV-2 infection, host factors, such as the inflammasome system, are activated by the presence of the virus inside host cells. The search for COVID-19 risk factors is of relevance for clinical management. In this study, we investigated the impact of inflammasome single-nucleotide polymorphisms (SNPs) in SARS-CoV-2-infected individuals with distinct severity profiles at clinical presentation. Patients were divided into two groups according to disease severity at clinical presentation based on the WHO Clinical Progression Scale. Group 1 included patients with mild/moderate disease (WHO < 6; n = 76), and group 2 included patients with severe/critical COVID-19 (WHO ≥ 6; n = 357). Inpatients with moderate to severe/critical profiles were recruited and followed-up at Hospital Center for COVID-19 Pandemic – National Institute of Infectology (INI)/FIOCRUZ, RJ, Brazil, from June 2020 to March 2021. Patients with mild disease were recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, RJ, Brazil, in August 2020. Genotyping of 11 inflammasome SNPs was determined by real-time PCR. Protection and risk estimation were performed using unconditional logistic regression models. Significant differences in NLRP3 rs1539019 and CARD8 rs2043211 were observed between the two groups. Protection against disease severity was associated with the A/A genotype (ORadj = 0.36; P = 0.032), allele A (ORadj = 0.93; P = 0.010), or carrier-A (ORadj = 0.45; P = 0.027) in the NLRP3 rs1539019 polymorphism; A/T genotype (ORadj = 0.5; P = 0.045), allele T (ORadj = 0.93; P = 0.018), or carrier-T (ORadj = 0.48; P = 0.029) in the CARD8 rs2043211 polymorphism; and the A-C-G-C-C (ORadj = 0.11; P = 0.018), A-C-G-C-G (ORadj = 0.23; P = 0.003), C-C-G-C-C (ORadj = 0.37; P = 0.021), and C-T-G-A-C (ORadj = 0.04; P = 0.0473) in NLRP3 genetic haplotype variants. No significant associations were observed for the other polymorphisms. To the best of our knowledge, this is the first study demonstrating an association between CARD8 and NLRP3 inflammasome genetic variants and protection against COVID-19 severity, contributing to the discussion of the impact of inflammasomes on COVID-19 outcomes.

Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern in Children: A Single-Center Retrospective Cohort Study.

BackgroundRecent COVID-19 surges are attributed to emergence of more transmissible SARS-CoV-2 variants of concern (VOCs). The relative severity of VOCs in children is unknown.MethodsWe performed a single-center retrospective cohort study of children ≤18 years old diagnosed with COVID-19 from October 2020–February 2022 and whose SARS-CoV-2 isolate underwent Illumina sequencing. We measured the frequency of five markers of COVID-19 severity. Logistic regression models were fitted to estimate the odds of each severity marker with each VOC.ResultsAmong 714 children, 471 (66.0%) were infected with a VOC: 96 (13.4%) alpha, 38 (5.3%) gamma, 119 (16.7%) delta, and 215 (30.1%) omicron. High-risk medical conditions and increasing age were independently associated with COVID-19 severity. After adjusting for age, race, ethnicity, high-risk medical conditions, and COVID-19 community incidence, neither alpha, delta, nor omicron was associated with severe COVID-19. Gamma was independently associated with hospitalization (OR 6.7, 95% CI 2.0–22.1); pharmacologic treatment (OR 5.7, 95% CI 1.2–26.8); respiratory support (OR 11.9, 95% CI 2.7–62.4); and severe disease per the WHO Clinical Progression Scale (OR 11.7, 95% CI 2.1–90.5). Upon subgroup analyses, omicron was independently associated with ICU admission and severe disease per the WHO Clinical Progression Scale in children without SARS-CoV-2 immunization or prior COVID-19 infection.ConclusionsCompared to non-VOC COVID-19, the gamma VOC was independently associated with increased COVID-19 severity, as was omicron in children without SARS-CoV-2 immunization or prior COVID-19 infection. SARS-CoV-2 vaccination and prior COVID-19 prevented severe outcomes during the omicron surge.

The Sensitivity and Specificity of WHO clinical Staging in Predicting Cd4 Cell Counts in HIV Infected Patients at the Police Hospital in Accra, Ghana

Introduction : Initiating an HIV positive client on ART is an important step in the care of PLHIV. Due to a shortage of CD4 machines and reagents, the WHO clinical staging guideline is widely used to determine when to initiate ART in developing countries.Objective : To determine whether WHO clinical staging is predictive of CD4 of 350 in initiation of ART in patients presenting at the Police Hospital ART clinic.Methods : We reviewed the records of clients on ART, from 2010 to 2012 and compared the WHO clinical staging and CD4 counts at their first visit to the clinic. Pregnant women, hepatitis B infected patients and children below fifteen were excluded from the study.Results : Two hundred and five PLHIVs were eligible for inclusion in the study. Sensitivity of the WHO Clinical staging to predict initiation of ART was 44% and specificity 87%. Positive predictive power was 83% and Negative predictive power was 51%.Conclusion : Almost 50% of those needing ART as per CD4 count were classified as WHO stage 1 or 2. This means that about half of those deemed not qualified to start ART by WHO clinical staging actually needed to be initiated on ART. Access to CD4 machines andreagents must be increased to minimize delay in start of treatment for patients.

Observations on 73 Vaccine breakthrough COVID-19 infected patients and its individualized homeopathic treatment

Background: Since the initiation of vaccine rollout, breakthrough COVID-19 infections have been reported. While conventional therapy is the accepted mode of treatment, there has been little recognition of the role played by the alternative therapies like homeopathy. The purposes of this study were to identify the clinico-symptomatic profile of the vaccine breakthrough covid-19 infections and to assess the response of individualized homoeopathic treatment in these breakthrough cases.&#x0D; Methods: A retrospective data analysis of patients treated with homoeopathic medicines who confirmed the breakthrough infection criteria: positive infection ≥14 days after completion of both the recommended doses of an authorized COVID-19 vaccine was conducted. IBM SPSS Statistics 21.0 was used for data analysis with a p-value below 0.05 defined as significant. WHO Clinical Progression Scale and Outcome in Relation to Impact on Daily Living score were used as outcome measures.&#x0D; Results: In total 73 cases were reported to be vaccine breakthrough infections. The median recovery time reported in the data set was 9 ± 2 days. While 5 patients dropped out, 68 (93.15%) patients responded positively to homeopathic treatment, and 55 (75.34%) recovered completely with normalized serological markers/ nasal swabs/ HRCT Chest. About 29 (39.72%) of these presented with mild clinical manifestations, 26 (35.61%) moderate, 17 (23.28%) severe and 1 (1.36%) was critical. 10 homeopathic remedies were prescribed to these 73 patients. Majority of the patients attained an ORIDL score of 4. Maximum patients reported a WHO clinical Progression score of 3. Statistical analysis showed a significant response to homeopathic treatment in the study group.&#x0D; Conclusion: Vaccine breakthrough cases occur in a fraction of vaccinated people. Despite the limited number of study subjects, homoeopathy showed some promising results in the present setup. The response rate was highest in the moderate and severe cases which suggest the importance of consideration of alternative medicine in the current pandemic. Further exploratory research studies and comparative clinical trials may be encouraged.

The impact of key secular trends during the first three waves the COVID-19 pandemic

ImportancePatient age, comorbidity burden, and disease severity at presentation are the major factors associated with surviving COVID-19. Hospital-level factors including ICU occupancy may confer additional risk to individual patients, particularly at times of maximal stress on healthcare systems. The interaction of patient- and hospital-level factors over time during pandemic disease remains an area of active exploration. ObjectiveTo determine the impact of patient and hospital risk factors during episodic surges, characterize severity distribution between waves, and evaluate patient-level impact of ICU capacity on COVID-19 survivorship. DesignRetrospective cohort study. SettingFour acute care hospitals within an integrated healthcare network in San Diego, California. ParticipantsAll patients (18+ y.o.) admitted with a positive PCR test for SARS-CoV-2 or ICD-10 code for COVID-19 from March 1, 2020 through June 30, 2021. Main Outcome(s) and Measure(s)Patient survivorship and length of stay. ResultsSix thousand eight hundred fifty-one patients were evaluated in this large cohort series. Patient level factors associated with mortality included: severity at admission (WHO Clinical Progression Score [WCPS]), age, gender, BMI, marital status, language preference, Elixhauser score, elevated laboratory (d-dimer, ferritin, LDH) or lower absolute lymphocyte count. When adjusting for patient age alone, survivorship during surges was also inversely associated with ICU occupancy, though this correlation was not present when adjusted for patient-level factors. Conclusions and RelevancePatient age, comorbidity burden, and severity at the time of presentation are the major factors associated with surviving COVID-19. Hospital-level factors including ICU occupancy may confer additional risk to individual patients, particularly at times of maximal stress on healthcare systems.

Efficacy and safety of nelarabine in patients with relapsed or refractory T-cell acute lymphoblastic leukemia: a systematic review and meta-analysis.

Nelarabine is approved for the treatment of relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) patients who relapse following at least two different chemotherapy regimens. Previous studies have evaluated the efficacy and safety of nelarabine with chemotherapy in the treatment of R/R T-ALL. However, the results are inconsistent. This review aimed to summarize findings on efficacy and safety data in R/R T-ALL patients administered with the drug nelarabine. The present review conducted a comprehensive search of MEDLINE (via PubMed), WHO Clinical Trial Registry, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials until 15 January 2022. Thirteen studies fulfilled the eligibility criteria with a total of 2508 patients. The efficacy of nelarabine was studied in terms of complete remission (CR) and partial remission (PR). Included studies reported overall random-effects pooled prevalence of CR and PR were 37.2 (95% CI: 22.8, 51.5) and 10.2 (95% CI: 4.9, 15.5), respectively. Most common adverse events associated with nelarabine were neutropenia, thrombocytopenia, fatigue, infections, and reversible peripheral neuropathy. Nelarabine is being used as salvage therapy as a bridge to hematopoietic stem cell transplantation and the findings of this meta-analysis indicate that it is an effective and safe treatment to be used in addition to the first-line treatment for R/R T-ALL.

Efficacy and safety of ultra-low dose inhaled melphalan in the treatment of hospitalized patients with COVID-19

Background. One of the most important components of COVID-19 therapy is the suppression of the hyperergic immune response. There is an urgent need of creating the optimal tactics of efficient and safe anti-inflammatory therapy. A new method of treatment of COVID-19 with inhalation of ultra-low (non-cytotoxic) doses of the alkylating drug melphalan is proposed, based on previous experimental, preclinical, and clinical data on its use in severe bronchial asthma.The aim. To evaluate the efficacy and safety of inhalation of ultra-low doses of melphalan in hospitalized patients with COVID-19-associated lung damage.Materials and methods. A prospective, open, controlled, blind for the central expert study was conducted. Sixty adult patients were included, 30 patients were consecutively admitted to the hospital and received nebulized inhalations of 0.1 mg of melphalan for 7 days. Thirty patients of the control group were selected by an independent expert retrospectively using the computer algorithm for selecting «close» patients based on the «case-control» principle. The primary endpoints were the dynamics on the WHO Clinical Improvement Scale and the dynamics of dyspnea according to the modified Borg scale, secondary – assessment of adverse events, dynamics of indicators of clinical, biochemical blood tests, lungs computed tomography data from the beginning of inhalations in the melphalan group and from the corresponding day in the control group.Results. Inhalations of melphalan led to a significant improvement in the clinical condition of patients according to the WHO scale, decrease in the intensity of dyspnea on day 7 of treatment and by the time of discharge, a significant anti-inflammatory effect. Adverse events and dynamics of laboratory parameters did not differ from the control group.Conclusion. The method of treatment of COVID-19 by inhalation of ultra-low doses of the alkylating drug melphalan is safe and leads to a significant clinical improvement of hospitalized patients with COVID-19-associated lung damage.

Machine learning-based model for prediction of clinical deterioration in hospitalized patients by COVID 19

Despite the publication of great number of tools to aid decisions in COVID-19 patients, there is a lack of good instruments to predict clinical deterioration. COVID19-Osakidetza is a prospective cohort study recruiting COVID-19 patients. We collected information from baseline to discharge on: sociodemographic characteristics, comorbidities and associated medications, vital signs, treatment received and lab test results. Outcome was need for intensive ventilatory support (with at least standard high-flow oxygen face mask with a reservoir bag for at least 6 h and need for more intensive therapy afterwards or Optiflow high-flow nasal cannula or noninvasive or invasive mechanical ventilation) and/or admission to a critical care unit and/or death during hospitalization. We developed a Catboost model summarizing the findings using Shapley Additive Explanations. Performance of the model was assessed using area under the receiver operating characteristic and prediction recall curves (AUROC and AUPRC respectively) and calibrated using the Hosmer–Lemeshow test. Overall, 1568 patients were included in the derivation cohort and 956 in the (external) validation cohort. The percentages of patients who reached the composite endpoint were 23.3% vs 20% respectively. The strongest predictors of clinical deterioration were arterial blood oxygen pressure, followed by age, levels of several markers of inflammation (procalcitonin, LDH, CRP) and alterations in blood count and coagulation. Some medications, namely, ATC AO2 (antiacids) and N05 (neuroleptics) were also among the group of main predictors, together with C03 (diuretics). In the validation set, the CatBoost AUROC was 0.79, AUPRC 0.21 and Hosmer–Lemeshow test statistic 0.36. We present a machine learning-based prediction model with excellent performance properties to implement in EHRs. Our main goal was to predict progression to a score of 5 or higher on the WHO Clinical Progression Scale before patients required mechanical ventilation. Future steps are to externally validate the model in other settings and in a cohort from a different period and to apply the algorithm in clinical practice.Registration: ClinicalTrials.gov Identifier: NCT04463706.

Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease (CLARITY): statistical analysis plan for a randomised controlled Bayesian adaptive sample size trial

The CLARITY trial (Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease) is a two-arm, multi-centre, randomised controlled trial being run in India and Australia that investigates the effectiveness of angiotensin receptor blockers in addition to standard care compared to placebo (in Indian sites) with standard care in reducing the duration and severity of lung failure in patients with COVID-19. The trial was designed as a Bayesian adaptive sample size trial with regular planned analyses where pre-specified decision rules will be assessed to determine whether the trial should be stopped due to sufficient evidence of treatment effectiveness or futility. Here, we describe the statistical analysis plan for the trial and define the pre-specified decision rules, including those that could lead to the trial being halted. The primary outcome is clinical status on a 7-point ordinal scale adapted from the WHO Clinical Progression scale assessed at day 14. The primary analysis will follow the intention-to-treat principle. A Bayesian adaptive trial design was selected because there is considerable uncertainty about the extent of potential benefit of this treatment.Trial registrationClinicalTrials.gov NCT04394117. Registered on 19 May 2020Clinical Trial Registry of India CTRI/2020/07/026831Version and revisionsVersion 1.0. No revisions.

Metformin Use in Relation to Clinical Outcomes and Hyperinflammatory Syndrome Among COVID-19 Patients With Type 2 Diabetes: A Propensity Score Analysis of a Territory-Wide Cohort.

AimThis study was conducted in order to evaluate the association between metformin use and clinical outcomes in type 2 diabetes mellitus (T2DM) patients hospitalized with coronavirus disease 2019 (COVID-19).MethodsPatients with T2DM with confirmed diagnosis of COVID-19 and admitted between January 21, 2020, and January 31, 2021 in Hong Kong were identified in our cohort. Exposure was defined as metformin use within 90 days prior to admission until hospital discharge for COVID-19. Primary outcome was defined as clinical improvement of ≥1 point on the WHO Clinical Progression Scale (CPS). Other outcomes were hospital discharge, recovery, in-hospital death, acidosis, hyperinflammatory syndrome, length of hospitalization, and changes in WHO CPS score.ResultsMetformin use was associated with greater odds of clinical improvement (OR = 2.74, p = 0.009), hospital discharge (OR = 2.26, p = 0.009), and recovery (OR = 2.54, p = 0.005), in addition to lower odds of hyperinflammatory syndrome (OR = 0.71, p = 0.021) and death (OR = 0.41, p = 0.010) than control. Patients on metformin treatment had a shorter hospital stay (−2.76 days, p = 0.017) than their control counterparts. The average WHO CPS scores were significantly lower in metformin users than non-users since day 15 (p < 0.001). However, metformin use was associated with higher odds of acidosis.ConclusionsMetformin use was associated with lower mortality and lower odds for hyperinflammatory syndrome. This provides additional insights into the potential mechanisms of the benefits of metformin use in T2DM patients with COVID-19.

Clinical and epidemiological aspects of patients infected with SARS-CoV-2 variants: a case-control study

Objective: To compare the clinical outcomes of patients infected with SARS-CoV-2 variants with patients infected with the original strain. Methods: This is a case control study comparing cases of COVID-19 patients infected with SARS-CoV-2 variants of concern identified by genomic sequencing, with a control group of 62 patients randomly selected from a COVID-19 database of patients diagnosed prior to the emergence of these variants. Findings: In the 40 patients infected with variants, the predominant (52.5%) was P.1 variant. The variant group presented more arthralgia (p=0.015), hyporexia (p=0.006), nausea/vomiting (p=0.048), and mental confusion (p=0.029), the last not identified in the control group. There were no significant differences in comorbidities or demographic data between the groups. Severe disease, according to the WHO Clinical Progression Scale, was identified only in those infected with the variants, as well as high-flow oxygen therapy and ICU admission (p=0.05). The two deaths reported in the study were in patients infected with the variants. Conclusions: The worst outcomes were observed in the group infected with SARS-CoV-2 variants, although no significant differences in comorbidities or demographics date were observed between the groups.

Rehabilitation of People With Chronic Spinal Cord Injury Using a Laparoscopically Implanted Neurostimulator: Impact on Mobility and Urinary, Anorectal, and Sexual Functions

ObjectivesThis study aimed to assess the impact of the laparoscopic implantation of neuromodulation electrodes (Possover-LION procedure) on mobility and on sexual, urinary, and anorectal functions of people with chronic spinal cord injury (SCI). Material and MethodsLongitudinal analysis of 30 patients with chronic SCI (21 ASIA impairment scale (AIS) A, eight AIS B, and one AIS C) submitted to the Possover-LION procedure for bilateral neuromodulation of femoral, sciatic, and pudendal nerves. Assessments were performed before the surgical procedure and at 3, 6, and 12 months postoperatively. The primary outcome was evolution in walking, measured by the Walking Index for Spinal Cord Injury score, preoperatively and at 12 months. Secondary outcomes were changes in overall mobility (Mobility Assessment Tool for Evaluation of Rehabilitation score), urinary function and quality of life (Qualiveen questionnaire), and bowel (time for bowel emptying proceedings and Wexner’s Fecal Incontinence Severity Index [FISI]) and sexual functions (International Index of Erectile Function for men and Female Sexual Function Index for women). Surgical time, intraoperative bleeding, and perioperative complications were also recorded. ResultsQualitatively, 18 of 25 (72%) patients with thoracic injury and 3 of 5 (60%) patients with cervical injury managed to establish a walker-assisted gait at one-year follow-up (p < 0.0001). A total of 11 (47.8%) have improved in their urinary incontinence (p < 0.0001), and seven (30.4%) improved their enuresis (p = 0.0156). The FISI improved from a median of 9 points preoperatively to 5.5 at 12 months (p = 0.0056). Of note, 20 of 28 (71.4%) patients reported an improvement on genital sensitivity at 12 months postoperatively (p < 0.0001), but this was not reflected in sexual quality-of-life questionnaires. ConclusionsPatients experienced improved mobility and genital sensitivity and a reduction in the number of urinary and fecal incontinence episodes. By demonstrating reproducible outcomes and safety, this study helps establish the Possover-LION procedure as an addition to the therapeutic armamentarium for the rehabilitation of patients with chronic SCI. Clinical Trial RegistrationThis study was registered at the WHO Clinical Trials Database through the Brazilian Registry of Clinical Trials—REBEC (Universal Tracking Number: U1111-1261-4428).

An open labeled, randomized, controlled clinical study to evaluate the efficacy of Torchnil capsules and Febcin tablet as add-on therapy for Covid-19 patients

ObjectivesThis study was conducted to evaluate the efficacy and safety of Cap. Torchnil & Tab. Febcin when given as add-on therapy to Covid19 positive patients with moderate disease. Material and methodsFollowing written informed consent, patients were randomized to receive Cap. Torchnil & Tab. Febcin in addition to standard of care (SOC) [Add-on Group] or only SOC [SOC Group] for 14 days. Effect on clinical symptoms, WHO Clinical Assessment scale, hospital stay duration, time to Covid negative report, Sp02 levels and biomarkers was assessed during admission and relapse rate, if any, post discharge for 3 months. Results193 patients were screened and 150 completed the study, 77 in Add-on Group and 73 in SOC Group. Improvement in Covid related symptoms, WHO Assessment scale, time to covid negative report and duration of hospital stay was observed earlier in Add-on Group. Statistically significant fall in biomarker levels viz. CPK, D-dimer and IL-6 values at Day 14 and LDH levels at Days 7 & 14 was observed in Add-on Group. Improvement in Sp02 levels was also seen earlier in Add-on Group. Only 2 patients complained of acidity. Post discharge, 91 patients (49 from Add-on group and 42 from SOC group) came for physical visits. All these patients were clinically stable with no evidence of relapse. ConclusionThe study results thus showed that Cap. Torchnil and Tab. Febcin were effective and safe when given as add-on therapy to SOC in the clinical management of patients with moderate Covid-19 disease.

MRNA Covid-19 vaccines in pregnancy: A systematic review.

Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses. Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20-22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described. There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio. The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed. PROSPERO (CRD42021261684).

High-dose immunoglobulins from convalescent donors for patients hospitalised with COVID-19

High-dose immunoglobulins from convalescent donors for patients hospitalised with COVID-19

Interleukin-1 blocking agents for treating COVID-19.

Interleukin-1 blocking agents for treating COVID-19.

Effect of dexamethasone in patients with ARDS and COVID-19 (REMED trial)\u2014study protocol for a prospective, multi-centre, open-label, parallel-group, randomized controlled trial

BackgroundSince December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids.MethodsREMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1–5, followed by dexamethasone 10 mg on days 6–10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic.DiscussionWe aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety.Trial registrationEudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020

SARS-CoV2 infection in symptomatic patients: interest of serological tests and predictors of mortality: experience of DR Congo

BackgroundIn symptomatic patients, the diagnostic approach of COVID-19 should be holistic. We aimed to evaluate the concordance between RT-PCR and serological tests (IgM/IgG), and identify the factors that best predict mortality (clinical stages or viral load).MethodsThe study included 242 patients referred to the University hospital of Kinshasa for suspected COVID-19, dyspnea or ARDS between June 1st, 2020 and August 02, 2020. Both antibody-SARS-CoV2 IgM/IgG and RT-PCR method were performed on the day of admission to hospital. The clinical stages were established according to the COVID-19 WHO classification. The viral load was expressed by the CtN2 (cycle threshold value of the nucleoproteins) and the CtE (envelope) genes of SARS- CoV-2 detected using GeneXpert. Kappa test and Cox regression were used as appropriate.ResultsThe GeneXpert was positive in 74 patients (30.6%). Seventy two patients (29.8%) had positive IgM and 34 patients (14.0%) had positive IgG. The combination of RT-PCR and serological tests made it possible to treat 104 patients as having COVID-19, which represented an increase in cases of around 41% compared to the result based on GeneXpert alone. The comparison between the two tests has shown that 57 patients (23.5%) had discordant results. The Kappa coefficient was 0.451 (p < 0.001). We recorded 23 deaths (22.1%) among the COVID-19 patients vs 8 deaths (5.8%) among other patients. The severe-critical clinical stage increased the risk of mortality vs. mild-moderate stage (aHR: 26.8, p < 0.001). The values of CtE and CtN2 did not influence mortality significantly.ConclusionIn symptomatic patients, serological tests are a support which makes it possible to refer patients to the dedicated COVID-19 units and treat a greater number of COVID-19 patients. WHO Clinical classification seems to predict mortality better than SARS-Cov2 viral load.

Progression to a severe form of COVID-19 among patients with chronic respiratory diseases

RationaleViral respiratory infections, including SARS-CoV-2 infection, can trigger respiratory symptoms among patients suffering from chronic respiratory diseases, leading to exacerbations and hospitalizations. Despite the tropism of SARS-CoV-2 into the respiratory tract, chronic respiratory diseases do not seem to be risk factors for severe forms of COVID-19. ObjectivesTo assess whether hospitalized patients for COVID-19 with chronic respiratory diseases were at lower risk of developing a severe form than other patients. MethodsThis French study included patients admitted to hospital in COVID-19 ward, suffering from a SARS-CoV-2 infection, diagnosed on RT-PCR or chest computed tomography associated with clinical symptoms, from March 15 to June 30, 2020. Ambulatory patients who were tested in the emergency department and patients with severe hypoxaemia requiring intensive care were not included. All data were collected from electronic medical records up to discharge of the patient. Main Results617 patients were included: 125 with a chronic respiratory disease, mainly chronic obstructive pulmonary disease (45%) and asthma (30%). The percentage of patients scoring 6 or higher on the WHO Clinical Progression Scale during hospital stay was lower in patients with chronic respiratory disease compared to those without chronic respiratory disease (21.6% versus 31.3%, respectively, p = 0.03). Among patients with chronic respiratory disease, temperature above 38 °C on admission (OR 16.88 (95% CI 4.01–71.00)), lymphopenia (OR 5.08 (1.25–20.72)), CPAP therapy (OR 4.46 (1.04–19.17)) and age (OR 1.09 (1.02–1.16)) were associated with an increased risk to reach a score of 6 or above. ConclusionsHospital admissions in COVID-19 ward of patients suffering from chronic respiratory diseases are at lower risk of developing a severe form of COVID- 19, especially in patients with chronic obstructive pulmonary disease or asthma. Prospective studies would confirm our results and allow to better organize the follow-up of these patients in a pandemic period.

EFFICACY, IMMUNOGENICITY AND SIDE EFFECT OF COVID-19 VACCINE ON PREGNANT AND LACTATING WOMEN: A SYSTEMATIC REVIEW

Purpose: To investigate the efficacy, immunogenicity, and side effect of the Covid-19 vaccine on pregnant and lactating women. Methods: We obtained 1366 articles from 7 databases such as PubMed, Google Scholar, ScienceDirect, Cochrane Library, EU Clinical Trials Register, ClinicalTrials.gov, the WHO Clinical Trial Registry. The search terms were “Covid-19 Vaccine”, “Sars-Cov-2 Vaccine”, “Vaccine Efficacy”, “Vaccine Immunogenicity”, “Vaccine Side Effect“, “Pregnant Women”, and “Lactating Women”. Study selection and study quality appraisal were guided by Joanna Briggs Institute (JBI). Results: Fifteen articles were included. Vaccinated pregnant women had a lower risk of Covid-19 infection. Immune responses were detected in maternal blood, cord blood, and breast milk. The T-cell had the potential to against viral variants. Covid-19 vaccination resulted in low disruption among lactating women. There was no difference in side effects between pregnant and nonpregnant women. Conclusions: Covid-19 vaccine lowered infection risk and robust immune responses among pregnant and lactating women.