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1.
Frontiers in microbiology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1864069

ABSTRACT

The SARS-CoV-2 antigen-detecting rapid diagnostic test (Ag-RDTs) is an easy-to-use diagnostic tool to identify the contagious individuals and reduce the new infections. However, to be effective, Ag-RDTs require the detection of distinct variants of concern (VOC) with high analytical sensitivity. Here, we found that the VOC diverge at the nucleocapsid protein used by four commercial Ag-RDTs for the viral detection. Relative to the original D614G variant, there was a 10-fold loss of detection for the Delta and Alpha variants in certain Ag-RDTs, a reduction above the threshold required to isolate the viable virus. However, Beta and Omicron variants did not lose the detection capacity. As the new VOC arise, successful contact tracing requires continuous monitoring of Ag-RDTs performance.

2.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1863963

ABSTRACT

The role of T cells in the control of SARS-CoV-2 infection has been underestimated in favor of neutralizing antibodies. However, cellular immunity is essential for long-term viral control and protection from disease severity. To understand T-cell immunity in the absence of antibody generation we focused on a group of SARS-CoV-2 Non-Seroconvertors (NSC) recovered from infection. We performed an immune comparative analysis of SARS-CoV-2 infected individuals stratified by the absence or presence of seroconversion and disease severity. We report high levels of total naïve and low effector CD8+ T cells in NSC. Moreover, reduced levels of T-cell activation monitored by PD-1 and activation-induced markers were observed in the context of functional SARS-CoV-2 T-cell responses. Longitudinal data indicate the stability of the NSC phenotype over three months of follow-up after infection. Together, these data characterized distinctive immunological traits in NSC including skewed cellular distribution, low activation and functional SARS-CoV-2 T-cell responses. This data highlights the value of T-cell immune monitoring in populations with low seroconversion rates in response to SARS-CoV-2 infection and vaccination.

3.
Front Microbiol ; 13: 840757, 2022.
Article in English | MEDLINE | ID: covidwho-1862623

ABSTRACT

The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2.

4.
Age Ageing ; 51(5)2022 05 01.
Article in English | MEDLINE | ID: covidwho-1860799

ABSTRACT

BACKGROUND: SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine. METHODS: plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF. Neutralisation capacity was assessed in a pseudovirus neutralisation assay against the original WH1 and later B.1.617.2/Delta variants. A group of younger adults was used as a reference group. RESULTS: three months after vaccination, uninfected older adults presented reduced SARS-CoV-2-specific IgG levels and a significantly lower neutralisation capacity against the WH1 and Delta variants compared with vaccinated uninfected younger individuals. In contrast, COVID-19-recovered older adults showed significantly higher SARS-CoV-2-specific IgG levels after vaccination than their younger counterparts, whereas showing similar neutralisation activity against the WH1 virus and an increased neutralisation capacity against the Delta variant. Although, similarly to younger individuals, previously infected older adults elicit potent cross-reactive immune responses, higher quantities of SARS-CoV-2-specific IgG antibodies are required to reach the same neutralisation levels. CONCLUSIONS: although hybrid immunity seems to be active in previously infected older adults 3 months after mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected but vaccinated older residents of LTCF. These results suggest that a vaccine booster dose should be prioritised for this particularly vulnerable population.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , Long-Term Care , RNA, Messenger , Vaccination
5.
Front Immunol ; 13: 860215, 2022.
Article in English | MEDLINE | ID: covidwho-1847172

ABSTRACT

Background: Evidence on the determinants of the magnitude of humoral responses and neutralizing titers in individuals with mild COVID-19 is scarce. Methods: In this cohort study of mild COVID-19 patients, we assessed viral load (VL) by RT-qPCR at two/three time points during acute infection, and anti-SARS-CoV-2 antibodies by ELISA and plasma neutralizing responses using a pseudovirus assay at day 60. Results: Seventy-one individuals (65% female, median 42 years old) were recruited and grouped into high viral load (VL) >7.5 Log10 copies/mL (n=20), low, VL ≤7.5 Log10 copies/mL (n=22), or as Non-early seroconverters with a positive PCR (n=20), and healthy individuals with a negative PCR (n=9). Individuals with high or low VL showed similar titers of total neutralizing antibodies at day 60, irrespective of maximal VL or viral dynamics. Non-early seroconverters had lower antibody titers on day 60, albeit similar neutralizing activity as the groups with high or low VL. Longer symptom duration and older age were independently associated with increased humoral responses. Conclusions: In mild SARS-CoV-2-infected individuals, the duration of symptoms and age (but not VL) contribute to higher humoral responses.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , Cohort Studies , Female , Humans , Male
6.
Nat Commun ; 13(1): 2583, 2022 May 11.
Article in English | MEDLINE | ID: covidwho-1839524

ABSTRACT

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution. TRIAL REGISTRATION: Clinicaltrials.gov NCT04621123 and NCT04589949. REGISTRATION: NCT04621123 and NCT04589949 on https://www. CLINICALTRIALS: gov.


Subject(s)
COVID-19 , Bayes Theorem , COVID-19/therapy , Humans , Immunization, Passive , Middle Aged , Multicenter Studies as Topic , Outpatients , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
7.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335426

ABSTRACT

Purpose: Mass vaccination campaigns have reduced the incidence and severity of COVID-19. However, there is limited information about how patients with predominantly antibody-deficiencies (PAD) respond to COVID-19 vaccination. Here, we evaluated humoral and cellular responses developed in SARS-CoV-2-naïve PAD individuals after three mRNA-1273 vaccine doses. Methods Patients and healthy controls (HCs) were immunized at week 0 (w0) and w4. PAD individuals received an additional dose at w24. Blood samples were collected at w0, w4, w8, w24, and/or w28. We determined levels of anti-Spike and anti-RBD antibodies, Spike-specific IgG avidity, and neutralizing activity (Wuhan-Hu-1, Delta, and Omicron variants). Cellular responses were evaluated by IFN-γ ELISpot and flow cytometry. Results Unclassified primary antibody-deficiency patients (unPAD, n = 9) and HCs developed comparable vaccine-induced humoral responses. However, common variable immunodeficiency patients (CVID, n = 12) showed lower antibody responses than HCs. While the frequency of Spike-specific CD4 + T cells was similar between PAD patients and HCs, CD8 + T cells responses were reduced in CVID individuals. Both PAD groups showed lower levels of Spike-specific IFN-γ-producing T-cells. Combined immunodeficiency (CID, n = 1) and thymoma with immunodeficiency (TID, n = 1) patients developed cellular but not humoral responses after two immunizations. The third vaccine dose boosted humoral responses in most PAD patients, but had little effect on cellular immunity. Conclusion mRNA-1273 vaccine-induced immune responses in PAD individuals are heterogeneous, depend on the type and degree of antibody-deficiency, and should be immunomonitored to define a personalized vaccination strategy.

8.
Lancet Reg Health Eur ; 15: 100337, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1829137

ABSTRACT

BACKGROUND: Many countries have resumed mass-gathering events like music festivals, despite the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading. In this study, we aimed to assess the effect of two mass-gathering outdoor events, held during a peak of SARS-CoV-2 transmission, on COVID-19 incidence. METHODS: This was a retrospective, population-based control-matched analysis. The study population included attendees to two outdoor music festivals held in Catalonia (North-East Spain). The primary objective was to compare the incidence of COVID-19 within the 3-to-10 days following the event between attendees and a population-based control group. FINDINGS: The analysis included 18,275 and 27,347 attendees to the first and second festivals, respectively, and their corresponding controls. The post-festival 7-day cumulative COVID-19 incidence among attendees and controls was 4.14% (95% CI 3.86-4.44) vs. 1.69% (1.51-1.88) for the first festival (RR 2.46; 2.16-2.80), and 2.42% (2.35-2.61) and 1.10% (0.99-1.2) for the second festival (RR 2.19; 1.92-2.51). COVID-19 incidence among immunized individuals was also two-fold higher in attendees than in controls. Previous COVID-19 infection, vaccination, and adequate mask-wearing were significantly associated with a lower risk of COVID-19 infection after the events. INTERPRETATION: Despite the proven effectiveness of preventive measures such as Ag-RDT screening, mask-wearing and vaccination, caution should be taken when holding these events during a period of high community SARS-CoV-2 transmission. FUNDING: Crowdfunding campaign YoMeCorono (https://www.yomecorono.com/) and the Generalitat de Catalunya.

9.
Front Public Health ; 10: 778110, 2022.
Article in English | MEDLINE | ID: covidwho-1775983

ABSTRACT

Background: Schistosomiasis among migrant populations in Europe is an underdiagnosed infection, yet delayed treatment may have serious long-term consequences. In this study we aimed to characterize the clinical manifestations of Schistosoma infection among migrant women, and the degree of underdiagnosis. Methods: We carried out a prospective cross-sectional study among a migrant population living in the North Metropolitan Barcelona area and coming from schistosomiasis-endemic countries. We obtained clinical, laboratory and socio-demographic data from electronic clinical records, as well as information about years of residence and previous attendance at health services. Blood sample was obtained and schistosomiasis exposure was assessed using a specific ELISA serological test. Results: Four hundred and five patients from schistosomiasis-endemic regions were screened, of whom 51 (12.6%) were female. Seropositivity prevalence was 54.8%, but considering women alone we found a prevalence of 58.8% (30 out of 51). The median age of the 51 women was 41.0 years [IQR (35-48)] and the median period of residence in the European Union was 13 years [IQR (10-16)]. Schistosoma-positive women (N = 30) showed a higher prevalence of gynecological signs and symptoms compared to the seronegative women (96.4 vs. 66.6%, p = 0.005). Among seropositive women, the median number of visits to Sexual and Reproductive Health unit prior to diagnosis of schistosomiasis was 41 [IQR (18-65)]. Conclusion: The high prevalence of signs and symptoms among seropositive women and number of previous visits suggest a high rate of underdiagnosis and/or delayed diagnosis of Schistosoma infection, particularly female genital schistosomiasis, among migrant females.


Subject(s)
Genital Diseases, Female , Schistosomiasis , Transients and Migrants , Adult , Cross-Sectional Studies , Europe/epidemiology , Female , Genital Diseases, Female/diagnosis , Genital Diseases, Female/ethnology , Genital Diseases, Female/parasitology , Humans , Middle Aged , Pilot Projects , Prospective Studies , Schistosomiasis/diagnosis , Schistosomiasis/ethnology
10.
Antiviral Res ; 200: 105270, 2022 04.
Article in English | MEDLINE | ID: covidwho-1763566

ABSTRACT

The pandemic caused by the new coronavirus SARS-CoV-2 has made evident the need for broad-spectrum, efficient antiviral treatments to combat emerging and re-emerging viruses. Plitidepsin is an antitumor agent of marine origin that has also shown a potent pre-clinical efficacy against SARS-CoV-2. Plitidepsin targets the host protein eEF1A (eukaryotic translation elongation factor 1 alpha) and affects viral infection at an early, post-entry step. Because electron microscopy is a valuable tool to study virus-cell interactions and the mechanism of action of antiviral drugs, in this work we have used transmission electron microscopy (TEM) to evaluate the effects of plitidepsin in SARS-CoV-2 infection in cultured Vero E6 cells 24 and 48h post-infection. In the absence of plitidepsin, TEM morphological analysis showed double-membrane vesicles (DMVs), organelles that support coronavirus genome replication, single-membrane vesicles with viral particles, large vacuoles with groups of viruses and numerous extracellular virions attached to the plasma membrane. When treated with plitidepsin, no viral structures were found in SARS-CoV-2-infected Vero E6 cells. Immunogold detection of SARS-CoV-2 nucleocapsid (N) protein and double-stranded RNA (dsRNA) provided clear signals in cells infected in the absence of plitidepsin, but complete absence in cells infected and treated with plitidepsin. The present study shows that plitidepsin blocks the biogenesis of viral replication organelles and the morphogenesis of virus progeny. Electron microscopy morphological analysis coupled to immunogold labeling of SARS-CoV-2 products offers a unique approach to understand how antivirals such as plitidepsin work.


Subject(s)
COVID-19 , Depsipeptides , Animals , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Chlorocebus aethiops , Depsipeptides/pharmacology , Peptides, Cyclic , SARS-CoV-2 , Vero Cells , Virus Replication
11.
Cell Rep Med ; 3(2): 100523, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1751231

ABSTRACT

To understand the determinants of long-term immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the concurrent impact of vaccination and emerging variants, we follow a prospective cohort of 332 patients with coronavirus disease 2019 (COVID-19) over more than a year after symptom onset. We evaluate plasma-neutralizing activity using HIV-based pseudoviruses expressing the spike of different SARS-CoV-2 variants and analyze them longitudinally using mixed-effects models. Long-term neutralizing activity is stable beyond 1 year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while the responses of non-hospitalized individuals are dominated by long-lived B cells. In both groups, vaccination boosts responses to natural infection. Long-term (>300 days from infection) responses in unvaccinated participants show a reduced efficacy against beta, but not alpha nor delta, variants. Multivariate analysis identifies the severity of primary infection as an independent determinant of higher magnitude and lower relative cross-neutralization activity of long-term neutralizing responses.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Severity of Illness Index , Adult , Aged , B-Lymphocytes/immunology , COVID-19/blood , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/therapeutic use , Female , Follow-Up Studies , Humans , Immunologic Memory , Kinetics , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Spike Glycoprotein, Coronavirus/immunology , Treatment Outcome , Vaccination/methods , Young Adult
12.
Biomed Opt Express ; 13(3): 1609-1619, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1741990

ABSTRACT

Current diagnostics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection heavily rely on reverse transcription-polymerase chain reaction (RT-PCR) or on rapid antigen detection tests. The former suffers from long time-to-result and high cost while the latter from poor sensitivity. Therefore, it is crucial to develop rapid, sensitive, robust, and inexpensive methods for SARS-CoV-2 testing. Herein, we report a novel optofluidic technology, a flow-virometry reader (FVR), for fast and reliable SARS-CoV-2 detection in saliva samples. A small microfluidic chip together with a laser-pumped optical head detects the presence of viruses tagged with fluorescent antibodies directly from saliva samples. The technology has been validated using clinical samples with high sensitivity (91.2%) and specificity (90%). Thanks also to its short time-to-result (<30 min) and small size (25 × 30 × 13 cm), which can be further reduced in the future, it is a strong alternative to existing tests, especially for point-of-care (POC) and low resource settings.

13.
J Infect Dis ; 225(6): 938-946, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1740891

ABSTRACT

BACKGROUND: Although coronavirus disease 2019 (COVID-19) vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need. METHODS: Functional characterization of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus-induced cytotoxicity, median tissue culture infectious dose [TCID50] reduction, and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA [1], Italy [1], and Spain [2]; 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1, and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated. RESULTS: All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all 4 methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. The hIG (IgG type) induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25-100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins. CONCLUSIONS: Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.


Subject(s)
Antibodies, Viral/immunology , Antibody-Dependent Cell Cytotoxicity , COVID-19/blood , COVID-19/therapy , Phagocytosis/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/blood , COVID-19/immunology , Humans , Immunization, Passive , Immunoglobulin G/blood , Immunoglobulin G/immunology , Spike Glycoprotein, Coronavirus/genetics
14.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329353

ABSTRACT

Background: Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and defence strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months.MethodsWe established a cohort of 769 health professionals including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2. We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. Findings: 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time.Interpretation: IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 13 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. Funding Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04;NCT04885478)

15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315814

ABSTRACT

Background: The epidemiological situation generated by COVID-19 has cast into sharp relief the delicate balance between public health priorities and the economy, with businesses obliged to toe a line between employee health and continued production. In an effort to detect as many cases as possible, isolate contacts, cut transmission chains and limit the spread of the virus in the workplace, mass testing strategies have been implemented in both public health and industrial contexts to minimize the risk of disruption in activity. Objective: To evaluate the economic impact of mass workplace testing strategy as carried out by a large automotive company in Catalonia in terms of health and healthcare resource savings. Methodology: Analysis of health costs and impacts based on the estimation of mortality and morbidity avoided because of screening and the resulting savings in healthcare costs. Results: The economic impact of the mass workplace testing strategies (using both PCR and RAT tests) was approximately €10.44 per test performed or €5,575.49 per positive detected. 38% of this figure corresponds to savings derived from better use of health resources (hospital beds, ICU beds and follow-up of infected cases), while the remaining 62% corresponds to improved health rates due to avoided morbidity and mortality. In scenarios with higher positivity rates and a greater impact of the infection on health and the use of health resources, these results could be up to ten times higher (€130.24 per test performed or €69,565.59 per positive detected). Conclusion: In the context of COVID-19, preventive actions carried out by the private sector to safeguard industrial production also have concomitant public benefits in the form of savings in healthcare costs. Thus, governmental bodies need to recognize the value of implementing such strategies in private settings and facilitate them through, for example, subsidies.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315813

ABSTRACT

The epidemiological situation generated by COVID-19 has highlighted the importance of applying non-pharmacological measures. Among these, mass screening of the asymptomatic general population has been established as a priority strategy by carrying out diagnostic tests to limit the spread of the virus. In this article, we aim to evaluate the economic impact of mass COVID-19 screenings of an asymptomatic population through a Cost-Benefit Analysis based on the estimated total costs of mass screening versus health gains and associated health costs avoided. Excluding the value of monetized health, the Benefit-Cost ratio was estimated at approximately 0.45. However, if monetized health is included in the calculation, the ratio is close to 1.20. The monetization of health is the critical element that tips the scales in favour of the desirability of screening. Screenings with the highest return are those that maximize the percentage of positives detected.

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315734

ABSTRACT

The banning of mass-gathering indoor events to prevent SARS-CoV-2 spread cause an important impact on local economies. We designed a randomized-controlled open-label trial to assess the effectiveness of a comprehensive preventive intervention for a mass-gathering indoor event (a live concert) based on systematic screening of attendees with antigen-detecting rapid diagnostic tests, use of facial mask, and adequate air ventilation. According to a RT-PCR test performed on day 8 after the event, none of the 465 assistants in the experimental arm (i.e., event attendants) became infected by SARS-CoV-2 (observed incidence 0%;Bayesian estimated incidence 0.14%;95%CI: 0% to 0.61%) versus 2 out of 495 controls (not entering into the event) (0.31%;95%CI: 0.04% to 0.73%). No significant differences were observed between the estimated incidence in the two study arms. Our study provides evidence on the safety of indoor mass-gathering events conducted during a COVID-19 outbreak under a comprehensive preventive intervention. (ClinicalTrials.gov number, NCT04668625)

19.
Lancet Respir Med ; 10(3): 278-288, 2022 03.
Article in English | MEDLINE | ID: covidwho-1671366

ABSTRACT

BACKGROUND: Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio ≥6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0·9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log10 copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123. FINDINGS: Between Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4·4 days (SD 1·4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1·05 [95% CI 0·78 to 1·41]). The mean change in viral load from baseline to day 7 was -2·41 log10 copies per mL (SD 1·32) with convalescent plasma and -2·32 log10 copies per mL (1·43) with placebo (crude difference -0·10 log10 copies per mL [95% CI -0·35 to 0·15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention. INTERPRETATION: Methylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded. FUNDING: Grifols, Crowdfunding campaign YoMeCorono.


Subject(s)
COVID-19 , Methylene Blue , Adult , COVID-19/therapy , COVID-19 Vaccines , Double-Blind Method , Humans , Immunization, Passive , Middle Aged , Outpatients , SARS-CoV-2 , Treatment Outcome
20.
Sci Rep ; 12(1): 640, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621277

ABSTRACT

COVID-19 pathophysiology is currently not fully understood, reliable prognostic factors remain elusive, and few specific therapeutic strategies have been proposed. In this scenario, availability of biomarkers is a priority. MS-based Proteomics techniques were used to profile the proteome of 81 plasma samples extracted in four consecutive days from 23 hospitalized COVID-19 associated pneumonia patients. Samples from 10 subjects that reached a critical condition during their hospital stay and 10 matched non-severe controls were drawn before the administration of any COVID-19 specific treatment and used to identify potential biomarkers of COVID-19 prognosis. Additionally, we compared the proteome of five patients before and after glucocorticoids and tocilizumab treatment, to assess the changes induced by the therapy on our selected candidates. Forty-two proteins were differentially expressed between patients' evolution groups at 10% FDR. Twelve proteins showed lower levels in critical patients (fold-changes 1.20-3.58), of which OAS3 and COG5 found their expression increased after COVID-19 specific therapy. Most of the 30 proteins over-expressed in critical patients (fold-changes 1.17-4.43) were linked to inflammation, coagulation, lipids metabolism, complement or immunoglobulins, and a third of them decreased their expression after treatment. We propose a set of candidate proteins for biomarkers of COVID-19 prognosis at the time of hospital admission. The study design employed is distinctive from previous works and aimed to optimize the chances of the candidates to be validated in confirmatory studies and, eventually, to play a useful role in the clinical practice.


Subject(s)
Blood Proteins , COVID-19/blood , COVID-19/diagnosis , Hospitalization , Aged , Aged, 80 and over , Biomarkers/blood , Disease Progression , Female , Humans , Male , Mass Spectrometry , Middle Aged , Prospective Studies , Proteome
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