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1.
Vaccines (Basel) ; 10(5)2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1847412

ABSTRACT

Information regarding the efficacy of the recombinant adenovirus type-5-vectored (CanSino Bio) vaccine against the COVID-19 disease in a real-life setting is limited. A retrospective cohort study was carried out in the teaching university community of the metropolitan area of Monterrey, Mexico, through a four-section survey, and during the COVID-19 delta wave. Determination of IgG antibodies against SARS-CoV-2 spike (S) protein was performed in a subset of participants vaccinated with CanSino Bio. A total of 7468 teachers responded to the survey, and 6695 of them were fully vaccinated. Of those, 72.7% had CanSino Bio, 10.3% Pfizer, 8.4% AstraZeneca, 1.2% Moderna, and 2.7% others. Symptomatic breakthrough infections were recorded in those vaccinated with CanSino Bio (4.1%), AstraZeneca (2.1%), and Pfizer (2.2%). No difference was found between CanSino Bio and other vaccines regarding hospitalization, the need for mechanical ventilation, and death. For CanSino Bio recipients, anti-S antibodies were >50 AU/mL in 73.2%. In conclusion, primary breakthrough symptomatic infections were higher in the CanSino vaccinated group compared to other brands. Individuals with a previous infection had higher antibody levels than those who were reinfected and without infection. A boosted dose of CanSino is recommended for those individuals without a previous infection.

2.
Microb Drug Resist ; 28(3): 338-345, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1722178

ABSTRACT

Aim: This study aims to assess the changes in antimicrobial resistance among some critical and high-priority microorganisms collected previously and during the coronavirus disease 2019 (COVID-19) pandemic in Mexico. Methods: We collected antimicrobial susceptibility data for critical and high-priority microorganisms from blood, urine, respiratory samples, and from all specimens, in which the pathogen may be considered a causative agent. Data were stratified and compared for two periods: 2019 versus 2020 and second semester 2019 (prepandemic) versus the second semester 2020 (pandemic). Results: In the analysis of second semester 2019 versus the second semester 2020, in blood samples, increased resistance to oxacillin (15.2% vs. 36.9%), erythromycin (25.7% vs. 42.8%), and clindamycin (24.8% vs. 43.3%) (p ≤ 0.01) was detected for Staphylococcus aureus, to imipenem (13% vs. 23.4%) and meropenem (11.2% vs. 21.4) (p ≤ 0.01), for Klebsiella pneumoniae. In all specimens, increased ampicillin and tetracycline resistance was detected for Enterococcus faecium (p ≤ 0.01). In cefepime, meropenem, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Escherichia coli; and in piperacillin-tazobactam, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Pseudomonas aeruginosa. Conclusion: Antimicrobial resistance increased in Mexico during the COVID-19 pandemic. The increase in oxacillin resistance for S. aureus and carbapenem resistance for K. pneumoniae recovered from blood specimens deserves special attention. In addition, an increase in erythromycin resistance in S. aureus was detected, which may be associated with high azithromycin use. In general, for Acinetobacter baumannii and P. aeruginosa, increasing resistance rates were detected.


Subject(s)
Bacterial Infections/epidemiology , Bacterial Infections/microbiology , COVID-19/epidemiology , Drug Resistance, Multiple, Bacterial , Humans , Mexico/epidemiology , Microbial Sensitivity Tests , Pandemics , SARS-CoV-2
3.
J Med Virol ; 94(6): 2402-2413, 2022 06.
Article in English | MEDLINE | ID: covidwho-1718416

ABSTRACT

The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.


Subject(s)
COVID-19 , Asia , COVID-19/epidemiology , Europe/epidemiology , Humans , SARS-CoV-2 , Socioeconomic Factors
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309482

ABSTRACT

Background: Seroprevalence of anti-SARS-CoV-2 antibodies is now available in several world regions to better estimate transmission dynamics. However, to date, there is no epidemiological data regarding anti-SARS-CoV-2 prevalence in Mexico. Therefore, we aimed to determine the prevalence of anti-SARS-CoV-2 antibodies and define the clinical and demographic characteristics associated with seroprevalence in a institutionalized population. Methods: : We conducted a serological survey in Ciudad Guadalupe, NL, Mexico. Institutionalized employees voluntarily participated during July 2020. Demographic and clinical characteristics were collected at the time of blood sampling to analyze the associated characteristics. IgM/IgG antibodies were determined using a qualitative chemiluminescent immunoassay. We reported the raw and the adjusted seroprevalence for test performance characteristics. Descriptive statistics were used for categorical and continuous variables. Statistical significance was tested using the Chi-squared test, Student’s t-test and the Mann-Whitney. Logistic regression models and the odds ratios (adjusted and unadjusted) were used to estimate the association of demographic and clinical characteristics. Results: : Of the 3,268 participants included, 193 (5.9%, 95% CI 5.1-6.8) tested positive for IgM/IgG against SARS-CoV-2. Adjusted prevalence by the immunoassay diagnostic performance resulted in a prevalence of 5.7 (95% CI 4.9-6.6). Gender, city of residence, and comorbidities did not show any association with having IgM/IgG antibodies. A total of 114 out of 193 (59.1%) subjects with a positive test were asymptomatic, and the odds of being positive were higher in those who reported symptoms of COVID-19 in the previous four weeks to the survey (OR 4.1, 95% CI 2.9-5.5). Conclusions: : There is a low rate of SARS-CoV-2 infection among institutionalized employees that have continuously been working during the pandemic. Six in ten infections were asymptomatic, and seroprevalence is low and still far from herd immunity. Epidemiological surveillance and preventive measures should be mandatory.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318969

ABSTRACT

Background: Preliminary reports show that nosocomial SARS-CoV-2 infection is not associated with increased mortality compared with community acquired infection. Methods: Retrospective comparison of COVID-19 adult patients who were classified according to probable time of acquisition of SARS-CoV-2 and symptom onset. Data from hospitalized patients that were hospitalized in non-COVID-19 areas were reviewed.All patients were classified as community-acquired/Community-onset (CA-CO), Community- acquired/hospital-onset (CA-HO) and Hospital-acquired/Hospital-onset (HA-HO) cases. All patients without respiratory symptoms were tested on day one and if negative, hospitalized in non-COVID-19 areas. Results: We identified 59 patients that fulfilled the definition of CA-HO or HA-HO COVID-19. Patients in the CA-CO group were less likely to have multiple comorbidities than the patients in the CA-HO and HA-HO groups. Mortality was lower in the CA-CO group (21.8%) compared to the other groups, although it did not reach statistical significance. Discussion: We identified 9 clusters of HA-HO cases arising from multiple-bed rooms from the non-COVID-19 areas. There was no significant difference for HA-HO COVID-19 between patients placed in a common-room bed compared to patients placed on single bed rooms (p=.19). Nevertheless, the RR for HA-HO COVID-19 was 105 (95% CI 62.9 to 177.6) for patients treated in a common-room allocating another COVID-19-detected patient within the immediate 24 h time frame (P=<0.01). Conclusion: Hospital-acquired COVID-19 is newly described and poses a challenge for infection control. We identified small clusters related to multiple-bed rooms from non-COVID-19 hospitalization wards and propose a simple time-based classification for hospital surveillance and isolation precautions.

6.
Viruses ; 14(1)2022 01 14.
Article in English | MEDLINE | ID: covidwho-1625198

ABSTRACT

SARS-CoV-2 variants of concern (VOCs) or of interest (VOIs) causing vaccine breakthrough infections pose an increased risk to worldwide public health. An observational case-control study was performed of SARS-CoV-2 vaccine breakthrough infections in hospitalized or ambulatory patients in Monterrey, Mexico, from April through August 2021. Vaccination breakthrough was defined as a SARS-CoV-2 infection that occurred any time after 7 days of inoculation with partial (e.g., first dose of two-dose vaccines) or complete immunization (e.g., second dose of two-dose vaccines or single-dose vaccine, accordingly). Case group patients (n = 53) had partial or complete vaccination schemes with CanSino (45%), Sinovac (19%), Pfizer/BioNTech (15%), and AstraZeneca/Oxford (15%). CanSino was administered most frequently in ambulatory patients (p < 0.01). The control group (n = 19) received no COVID-19 vaccines. Among SARS-CoV-2 variants detected by whole-genome sequencing, VOC Delta B.1.617.2 predominated in vaccinated ambulatory patients (p < 0.01) and AY.4 in hospitalized patients (p = 0.04); VOI Mu B.1.621 was detected in four (7.55%) vaccinated patients. SARS-CoV-2 breakthrough infections in our hospital occurred mostly in patients vaccinated with CanSino due to the higher prevalence of CanSino vaccine administration in our population. These patients developed mild COVID-19 symptoms not requiring hospitalization. The significance of this study lies on the detection of SARS-CoV-2 variants compromising the efficacy of local immunization therapies in Monterrey, Mexico.


Subject(s)
COVID-19/virology , SARS-CoV-2/isolation & purification , Adult , Aged , COVID-19/epidemiology , COVID-19 Vaccines , Case-Control Studies , Female , Hospitalization , Hospitals, University , Humans , Male , Mexico/epidemiology , Middle Aged , Phylogeny , Prevalence , SARS-CoV-2/classification , SARS-CoV-2/genetics , Vaccination , Whole Genome Sequencing
8.
Microb Drug Resist ; 28(3): 338-345, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1555726

ABSTRACT

Aim: This study aims to assess the changes in antimicrobial resistance among some critical and high-priority microorganisms collected previously and during the coronavirus disease 2019 (COVID-19) pandemic in Mexico. Methods: We collected antimicrobial susceptibility data for critical and high-priority microorganisms from blood, urine, respiratory samples, and from all specimens, in which the pathogen may be considered a causative agent. Data were stratified and compared for two periods: 2019 versus 2020 and second semester 2019 (prepandemic) versus the second semester 2020 (pandemic). Results: In the analysis of second semester 2019 versus the second semester 2020, in blood samples, increased resistance to oxacillin (15.2% vs. 36.9%), erythromycin (25.7% vs. 42.8%), and clindamycin (24.8% vs. 43.3%) (p ≤ 0.01) was detected for Staphylococcus aureus, to imipenem (13% vs. 23.4%) and meropenem (11.2% vs. 21.4) (p ≤ 0.01), for Klebsiella pneumoniae. In all specimens, increased ampicillin and tetracycline resistance was detected for Enterococcus faecium (p ≤ 0.01). In cefepime, meropenem, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Escherichia coli; and in piperacillin-tazobactam, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Pseudomonas aeruginosa. Conclusion: Antimicrobial resistance increased in Mexico during the COVID-19 pandemic. The increase in oxacillin resistance for S. aureus and carbapenem resistance for K. pneumoniae recovered from blood specimens deserves special attention. In addition, an increase in erythromycin resistance in S. aureus was detected, which may be associated with high azithromycin use. In general, for Acinetobacter baumannii and P. aeruginosa, increasing resistance rates were detected.


Subject(s)
Bacterial Infections/epidemiology , Bacterial Infections/microbiology , COVID-19/epidemiology , Drug Resistance, Multiple, Bacterial , Humans , Mexico/epidemiology , Microbial Sensitivity Tests , Pandemics , SARS-CoV-2
9.
BMC Infect Dis ; 21(1): 1170, 2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1526605

ABSTRACT

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.


Subject(s)
COVID-19 , COVID-19/therapy , Humans , Immunization, Passive , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
11.
BMC Infect Dis ; 21(1): 835, 2021 Aug 19.
Article in English | MEDLINE | ID: covidwho-1365330

ABSTRACT

BACKGROUND: Seroprevalence of anti-SARS-CoV-2 antibodies is now available in several world regions to better estimate transmission dynamics. However, to date, there is no epidemiological data regarding anti-SARS-CoV-2 prevalence in Mexico. Therefore, we aimed to determine the prevalence of anti-SARS-CoV-2 antibodies and define the clinical and demographic characteristics associated with seroprevalence. METHODS: We conducted a cross-sectional serological survey in Ciudad Guadalupe, NL, Mexico. City government employees voluntarily participated during July 2020. Demographic and clinical characteristics were collected at the time of blood sampling to analyze the associated characteristics. IgM/IgG antibodies were determined using a qualitative chemiluminescent immunoassay. Descriptive statistics were used for categorical and continuous variables. Statistical significance was tested using the Chi-squared test, Student's t-test and the Mann-Whitney. Logistic regression models and the odds ratios (adjusted and unadjusted) were used to estimate the association of demographic and clinical characteristics. RESULTS: Of the 3,268 participants included, 193 (5.9%, 95% CI 5.1-6.8) tested positive for IgM/IgG against SARS-CoV-2. Sex, city of residence, and comorbidities did not show any association with having IgM/IgG antibodies. A total of 114 out of 193 (59.1%) subjects with a positive test were asymptomatic, and the odds of being positive were higher in those who reported symptoms of COVID-19 in the previous four weeks to the survey (OR 4.1, 95% CI 2.9-5.5). CONCLUSIONS: There is a low rate of SARS-CoV-2 infection among government employees that have continuously been working during the pandemic. Six in ten infections were asymptomatic, and seroprevalence is low and still far from herd immunity. Epidemiological surveillance and preventive measures should be mandatory.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/epidemiology , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/isolation & purification , Antibodies, Viral/blood , COVID-19/immunology , Cross-Sectional Studies , Humans , Mexico/epidemiology , Pandemics , Prevalence , SARS-CoV-2/immunology , Seroepidemiologic Studies
12.
J Microbiol Immunol Infect ; 54(5): 787-793, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1293986

ABSTRACT

OBJECTIVE: We aimed to analyze clinical outcomes from patients with severe COVID-19 pneumonia that received either baricitinib plus dexamethasone or dexamethasone monotherapy. METHODOLOGY: We performed a retrospective comparative study. Data from hospitalized patients with severe COVID-19 pneumonia (saturation <93%, bilateral pulmonary infiltrates) that were treated with baricitinib plus dexamethasone or dexamethasone were collected. Our primary objective was to compare overall mortality and secondly to compare progression to mechanical ventilation and over infection rates. RESULTS: A total of 793 patients were assessed for inclusion criteria, 596 were excluded and 197 were analyzed for primary outcome: 123 in the baricitinib plus dexamethasone group and 74 in the dexamethasone monotherapy group. The mean age was 59.9 years (SD ± 14.5) and 62.1% (123/197) were male. 42.9% (85/197) of the cases required ICU admission and 25.8% (51/197) underwent invasive mechanical ventilation (IMV). Overall thirty-day mortality was 27.9% (55/197); Mortality was significantly lower in the baricitinib plus dexamethasone group compared to the dexamethasone monotherapy group (20.3% vs 40.5%, P = <.05). There was no difference in hospital acquired infections between both groups. CONCLUSION: Thirty-day mortality was significantly lower in patients with COVID-19 pneumonia treated with baricitinib plus dexamethasone versus dexamethasone monotherapy. No difference was observed in progression to invasive mechanical ventilation and hospital acquired infections.


Subject(s)
Azetidines/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Aged , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/drug effects
13.
Trials ; 22(1): 1, 2021 Jan 04.
Article in English | MEDLINE | ID: covidwho-1060153

ABSTRACT

OBJECTIVES: Conestat alfa, a recombinant human C1 esterase inhibitor, is a multi-target inhibitor of inflammatory cascades including the complement, the kinin-kallikrein and the contact activation system. The study objective is to investigate the efficacy and safety of conestat alfa in improving disease severity and short-term outcome in COVID-19 patients with pulmonary disease. TRIAL DESIGN: This study is an investigator-initiated, randomized (2:1 ratio), open-label, parallel-group, controlled, multi-center, phase 2a clinical trial. PARTICIPANTS: This trial is conducted in 3 hospitals in Switzerland, 1 hospital in Brazil and 1 hospital in Mexico (academic and non-academic). All patients with confirmed SARS-CoV-2 infection requiring hospitalization for at least 3 calendar days for severe COVID-19 will be screened for study eligibility. INCLUSION CRITERIA: - Signed informed consent - Age 18-85 years - Evidence of pulmonary involvement on CT scan or X-ray of the chest - Duration of symptoms associated with COVID-19 ≤ 10 days - At least one of the following risk factors for progression to mechanical ventilation on the day of enrolment: 1) Arterial hypertension 2) ≥ 50 years 3) Obesity (BMI ≥ 30 kg/m2) 4) History of cardiovascular disease 5) Chronic pulmonary disease 6) Chronic renal disease 7) C-reactive protein > 35mg/L 8) Oxygen saturation at rest of ≤ 94% when breathing ambient air Exclusion criteria: - Incapacity or inability to provide informed consent - Contraindications to the class of drugs under investigation (C1 esterase inhibitor) - Treatment with tocilizumab or another IL-6R or IL-6 inhibitor before enrolment - History or suspicion of allergy to rabbits - Pregnancy or breast feeding - Active or anticipated treatment with any other complement inhibitor - Liver cirrhosis (any Child-Pugh score) - Admission to an ICU on the day or anticipated within the next 24 hours of enrolment - Invasive or non-invasive ventilation - Participation in another study with any investigational drug within the 30 days prior to enrolment - Enrolment of the study investigators, their family members, employees and other closely related or dependent persons INTERVENTION AND COMPARATOR: Patients randomized to the experimental arm will receive conestat alfa in addition to standard of care (SOC). Conestat alfa (8400 U followed by 4200 U every 8 hours) will be administered as a slow intravenous injection (5-10 minutes) over a 72-hour period (i.e. 9 administrations in total). The first conestat alfa treatment will be administered on the day of enrolment. The control group will receive SOC only. SOC treatment will be administered according to local institutional guidelines, including supplemental oxygen, antibiotics, corticosteroids, remdesivir, and anticoagulation. MAIN OUTCOMES: The primary endpoint of this trial is disease severity on day 7 after enrolment assessed by an adapted WHO Ordinal Scale for Clinical Improvement (score 0 will be omitted and score 6 and 7 will be combined) from 1 (no limitation of activities) to 7 (death). Secondary outcomes include (i) the time to clinical improvement (time from randomization to an improvement of two points on the WHO ordinal scale or discharge from hospital) within 14 days after enrolment, (ii) the proportion of participants alive and not having required invasive or non-invasive ventilation at 14 days after enrolment and (iii) the proportion of subjects without an acute lung injury (defined by PaO2/FiO2 ratio of ≤300mmHg) within 14 days after enrolment. Exploratory outcomes include virological clearance, C1 esterase inhibitor pharmacokinetics and changes in routine laboratory parameters and inflammatory proteins. RANDOMISATION: Subjects will be randomised in a 2:1 ratio to treatment with conestat alfa in addition to SOC or SOC only. Randomization is performed via an interactive web response system (SecuTrial®). BLINDING (MASKING): In this open-label trial, participants, caregivers and outcome assessors are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We will randomise approximately 120 individuals (80 in the active treatment arm, 40 in the SOC group). Two interim analyses after 40 and 80 patients are planned according to the Pocock adjusted levels αp = 0.0221. The results of the interim analysis will allow adjustment of the sample size (Lehmacher, Wassmer, 1999). TRIAL STATUS: PROTECT-COVID-19 protocol version 3.0 (July 07 2020). Participant recruitment started on July 30 2020 in one center (Basel, Switzerland, first participant included on August 06 2020). In four of five study centers patients are actively recruited. Participation of the fifth study center (Mexico) is anticipated by mid December 2020. Completion of trial recruitment depends on the development of the SARS-CoV-2 pandemic. TRIAL REGISTRATION: Clinicaltrials.gov, number: NCT04414631 , registered on 4 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/drug therapy , Complement C1 Inhibitor Protein/administration & dosage , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , Clinical Trials, Phase II as Topic , Complement C1 Inhibitor Protein/adverse effects , Complement C1 Inhibitor Protein/pharmacokinetics , Drug Administration Schedule , Female , Humans , Injections, Intravenous/methods , Male , Mexico , Middle Aged , Multicenter Studies as Topic , Pilot Projects , Randomized Controlled Trials as Topic , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/pharmacokinetics , Severity of Illness Index , Switzerland , Treatment Outcome , Young Adult
14.
Trials ; 22(1): 1, 2021 Jan 04.
Article in English | MEDLINE | ID: covidwho-1007150

ABSTRACT

OBJECTIVES: Conestat alfa, a recombinant human C1 esterase inhibitor, is a multi-target inhibitor of inflammatory cascades including the complement, the kinin-kallikrein and the contact activation system. The study objective is to investigate the efficacy and safety of conestat alfa in improving disease severity and short-term outcome in COVID-19 patients with pulmonary disease. TRIAL DESIGN: This study is an investigator-initiated, randomized (2:1 ratio), open-label, parallel-group, controlled, multi-center, phase 2a clinical trial. PARTICIPANTS: This trial is conducted in 3 hospitals in Switzerland, 1 hospital in Brazil and 1 hospital in Mexico (academic and non-academic). All patients with confirmed SARS-CoV-2 infection requiring hospitalization for at least 3 calendar days for severe COVID-19 will be screened for study eligibility. INCLUSION CRITERIA: - Signed informed consent - Age 18-85 years - Evidence of pulmonary involvement on CT scan or X-ray of the chest - Duration of symptoms associated with COVID-19 ≤ 10 days - At least one of the following risk factors for progression to mechanical ventilation on the day of enrolment: 1) Arterial hypertension 2) ≥ 50 years 3) Obesity (BMI ≥ 30 kg/m2) 4) History of cardiovascular disease 5) Chronic pulmonary disease 6) Chronic renal disease 7) C-reactive protein > 35mg/L 8) Oxygen saturation at rest of ≤ 94% when breathing ambient air Exclusion criteria: - Incapacity or inability to provide informed consent - Contraindications to the class of drugs under investigation (C1 esterase inhibitor) - Treatment with tocilizumab or another IL-6R or IL-6 inhibitor before enrolment - History or suspicion of allergy to rabbits - Pregnancy or breast feeding - Active or anticipated treatment with any other complement inhibitor - Liver cirrhosis (any Child-Pugh score) - Admission to an ICU on the day or anticipated within the next 24 hours of enrolment - Invasive or non-invasive ventilation - Participation in another study with any investigational drug within the 30 days prior to enrolment - Enrolment of the study investigators, their family members, employees and other closely related or dependent persons INTERVENTION AND COMPARATOR: Patients randomized to the experimental arm will receive conestat alfa in addition to standard of care (SOC). Conestat alfa (8400 U followed by 4200 U every 8 hours) will be administered as a slow intravenous injection (5-10 minutes) over a 72-hour period (i.e. 9 administrations in total). The first conestat alfa treatment will be administered on the day of enrolment. The control group will receive SOC only. SOC treatment will be administered according to local institutional guidelines, including supplemental oxygen, antibiotics, corticosteroids, remdesivir, and anticoagulation. MAIN OUTCOMES: The primary endpoint of this trial is disease severity on day 7 after enrolment assessed by an adapted WHO Ordinal Scale for Clinical Improvement (score 0 will be omitted and score 6 and 7 will be combined) from 1 (no limitation of activities) to 7 (death). Secondary outcomes include (i) the time to clinical improvement (time from randomization to an improvement of two points on the WHO ordinal scale or discharge from hospital) within 14 days after enrolment, (ii) the proportion of participants alive and not having required invasive or non-invasive ventilation at 14 days after enrolment and (iii) the proportion of subjects without an acute lung injury (defined by PaO2/FiO2 ratio of ≤300mmHg) within 14 days after enrolment. Exploratory outcomes include virological clearance, C1 esterase inhibitor pharmacokinetics and changes in routine laboratory parameters and inflammatory proteins. RANDOMISATION: Subjects will be randomised in a 2:1 ratio to treatment with conestat alfa in addition to SOC or SOC only. Randomization is performed via an interactive web response system (SecuTrial®). BLINDING (MASKING): In this open-label trial, participants, caregivers and outcome assessors are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We will randomise approximately 120 individuals (80 in the active treatment arm, 40 in the SOC group). Two interim analyses after 40 and 80 patients are planned according to the Pocock adjusted levels αp = 0.0221. The results of the interim analysis will allow adjustment of the sample size (Lehmacher, Wassmer, 1999). TRIAL STATUS: PROTECT-COVID-19 protocol version 3.0 (July 07 2020). Participant recruitment started on July 30 2020 in one center (Basel, Switzerland, first participant included on August 06 2020). In four of five study centers patients are actively recruited. Participation of the fifth study center (Mexico) is anticipated by mid December 2020. Completion of trial recruitment depends on the development of the SARS-CoV-2 pandemic. TRIAL REGISTRATION: Clinicaltrials.gov, number: NCT04414631 , registered on 4 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/drug therapy , Complement C1 Inhibitor Protein/administration & dosage , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , Clinical Trials, Phase II as Topic , Complement C1 Inhibitor Protein/adverse effects , Complement C1 Inhibitor Protein/pharmacokinetics , Drug Administration Schedule , Female , Humans , Injections, Intravenous/methods , Male , Mexico , Middle Aged , Multicenter Studies as Topic , Pilot Projects , Randomized Controlled Trials as Topic , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/pharmacokinetics , Severity of Illness Index , Switzerland , Treatment Outcome , Young Adult
15.
Braz. j. infect. dis ; 24(3):261-263, 2020.
Article in English | LILACS (Americas), Grey literature | ID: grc-742302

ABSTRACT

ABSTRACT While the outbreak has reached every region of the world, it is undeniable that countries in the southern hemisphere seem to be less affected, where cases have been reported, these have been imported and travel related. We analyzed the climate temperature from various regions according to their current ongoing human-to-human transmission status. We studied 3 groups;Group 1, 10 provinces from China with majority of COVID-19 cases;Group 2, areas where continuous horizontal transmission outside of China had been reported;and group 3, areas where imported cases had been detected and no horizontal transmission had been documented after at least seven days since the first case was reported. The regions without ongoing human-to-human transmission showed significantly higher temperatures when compared to China and countries with ongoing human-to-human transmission, with over an 11-degree difference. The average rainfall during the study period was significantly higher in those regions without OHHT when compared to the Chinese provinces with ongoing human-to-human transmission and the regions with active transmission of SARS-CoV-2. Our findings show statistically significant differences between regions with ongoing human-to-human transmission of COVID-19 cases compared to those regions without horizontal transmission. This phenomenon could have implications in the behavior of the ongoing COVID-19 outbreak in the following months.

17.
Cardiol Res ; 11(4): 260-265, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-610168

ABSTRACT

Although coronavirus disease 2019 (COVID-19) manifests in most cases with respiratory symptoms, other presentations can occur. Direct damage to the cardiovascular system has been reported and recently, acute myocardial injury has been identified as a risk factor for mortality. Transthoracic echocardiography is a non-invasive tool that allows the detection of myocardial damage with validated markers (left ventricular ejection fraction and global longitudinal strain). Herein, we present the echocardiographic findings in four patients with COVID-19. All cases had acute respiratory distress syndrome (100%). Three out of four had elevated levels of creatine kinase and creatine kinase myocardial band. One case had ventricular concentric remodeling (25%). All cases (100%) had altered ventricular function: two had a reduced ejection fraction (50%) and, of those available for global longitudinal strain analysis, all had abnormal global longitudinal strain (100%). One case was found to have a tricuspid vegetation of 12 × 10 mm with no other manifestation of endocarditis. All of our cases had left ventricular dysfunction as assessed by echocardiography. One of our patients had a vegetation in the tricuspid valve. Two of our cases had a reduced ejection fraction. The importance of acute cardiac injury in COVID-19 has recently been established. A recent study found it to be an independent risk factor for mortality in patients with this disease. Information regarding echocardiographic characteristics of this population is scarce. Further research to elucidate the impact of these characteristics on morbidity and mortality is urgently needed.

18.
Braz J Infect Dis ; 24(3): 261-263, 2020.
Article in English | MEDLINE | ID: covidwho-165377

ABSTRACT

While the outbreak has reached every region of the world, it is undeniable that countries in the southern hemisphere seem to be less affected, where cases have been reported, these have been imported and travel related. We analyzed the climate temperature from various regions according to their current ongoing human-to-human transmission status. We studied 3 groups; Group 1, 10 provinces from China with majority of COVID-19 cases; Group 2, areas where continuous horizontal transmission outside of China had been reported; and group 3, areas where imported cases had been detected and no horizontal transmission had been documented after at least seven days since the first case was reported. The regions without ongoing human-to-human transmission showed significantly higher temperatures when compared to China and countries with ongoing human-to-human transmission, with over an 11-degree difference. The average rainfall during the study period was significantly higher in those regions without OHHT when compared to the Chinese provinces with ongoing human-to-human transmission and the regions with active transmission of SARS-CoV-2. Our findings show statistically significant differences between regions with ongoing human-to-human transmission of COVID-19 cases compared to those regions without horizontal transmission. This phenomenon could have implications in the behavior of the ongoing COVID-19 outbreak in the following months.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Temperature , Betacoronavirus , COVID-19 , China , Coronavirus Infections/transmission , Humans , Pandemics , Pneumonia, Viral/transmission , SARS-CoV-2
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