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Schrempft, Stephanie, Pullen, Nick, Baysson, Hélène, Wisniak, Ania, Zaballa, María-Eugenia, Pennacchio, Francesco, Vollenweider, Peter, Marques-Vidal, Pedro, Preisig, Martin, Guessous, Idris, Stringhini, Silvia, Deborah, Amrein, Arm-Vernez, Isabelle, Azman, Andrew S.; Ba, Fatim, Bachmann, Delphine, Bal, Antoine, Balavoine, Jean-François, Balavoine, Michael, Barbe, Rémy P.; Baysson, Hélène, Beigbeder, Lison, Berthelot, Julie, Bleich, Patrick, Boehm, Livia, Bryand, Gaëlle, Bucolli, Viola, Chappuis, François, Collombet, Prune, Courvoisier, Delphine, Cudet, Alain, Davidovic, Vladimir, de Mestral Vargas, Carlos, D'Ippolito, Paola, Dubos, Richard, Dumont, Roxane, Eckerle, Isabella, El Merjani, Nacira, Flahault, Antoine, Francioli, Natalie, Frangville, Marion, Graindorge, Clément, Guessous, Idris, Harnal, Séverine, Hurst, Samia, Kaiser, Laurent, Kherad, Omar, Lamour, Julien, Lescuyer, Pierre, L'Huissier, François, Lombard, Fanny-Blanche, Loizeau, Andrea Jutta, Lorthe, Elsa, Martinez, Chantal, Ménard, Lucie, Menon, Lakshmi, Metral-Boffod, Ludovic, Meyer, Benjamin, Moulin, Alexandre, Nehme, Mayssam, Noël, Natacha, Pennacchio, Francesco, Perez-Saez, Javier, Pittet, Didier, Portier, Jane, Posfay-Barbe, Klara M.; Poulain, Géraldine, Pugin, Caroline, Pullen, Nick, Randrianandrasana, Zo Francia, Richard, Viviane, Rinaldi, Frederic, Rizzo, Jessica, Rochat, Deborah, Sakvarelidze, Irine, Samir, Khadija, Santa Ramirez, Hugo Alejandro, Schrempft, Stephanie, Semaani, Claire, Stringhini, Silvia, Testini, Stéphanie, Rivas, Deborah Urrutia, Verolet, Charlotte, Villers, Jennifer, Violot, Guillemette, Vuilleumier, Nicolas, Wisniak, Ania, Yerly, Sabine, Zaballa, María-Eugenia.
Journal of Psychiatric Research ; 2022.
Article in English | ScienceDirect | ID: covidwho-2165627

ABSTRACT

There are concerns about acute and long-term mental health effects of the COVID-19 pandemic. This study examined the prevalence and predictors of psychological distress before, during, and after a pandemic wave in Switzerland, 2021. Prevalence of psychological distress was estimated in adults aged 35–96 years using the General Health Questionnaire-12 administered in June 2021 (Specchio-COVID19 cohort, N = 3965), and compared to values from 2003 to 2006 (CoLaus;PsyCoLaus cohort, N = 5667). Anxiety and depression were assessed from February to June 2021 using the Generalised Anxiety Disorder scale-2 and the Patient Health Questionnaire-2, respectively. Prevalence of psychological distress in June 2021, after the pandemic wave (16.0% [95% CI, 14.6%–17.4%]) was comparable to pre-pandemic levels (15.1% [14.0%–16.2%]). Anxiety and depression were highest at the start of the pandemic wave in February 2021, and declined from February to June with the relaxation of measures. Predictors of psychological distress included being younger, female, a single parent, unemployed, a change in working hours or job loss in the past 6 months, greater perceived severity and contagiousness of COVID-19, and self-reported post COVID-19. By June 2021, following a pandemic wave, prevalence of psychological distress in Switzerland was closer to pre-pandemic levels. These findings highlight the need for additional mental health support during times of stricter government policies relating to COVID-19;yet they also suggest that individuals can adapt relatively quickly to the changing context.

2.
The Lancet Regional Health - Europe ; : 100547, 2022.
Article in English | ScienceDirect | ID: covidwho-2131784

ABSTRACT

Summary Background More than two years into the COVID-19 pandemic, most of the population has developed anti-SARS-CoV-2 antibodies from infection and/or vaccination. However, public health decision-making is hindered by the lack of up-to-date and precise characterization of the immune landscape in the population. Here, we estimated anti-SARS-CoV-2 antibodies seroprevalence and cross-variant neutralization capacity after Omicron became dominant in Geneva, Switzerland. Methods We conducted a population-based serosurvey between April 29 and June 9, 2022, recruiting children and adults of all ages from age-stratified random samples of the general population of Geneva, Switzerland. We tested for anti-SARS-CoV-2 antibodies using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein, and for antibody neutralization capacity against different SARS-CoV-2 variants using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. We estimated seroprevalence and neutralization capacity using a Bayesian modeling framework accounting for the demographics, vaccination, and infection statuses of the Geneva population. Findings Among the 2521 individuals included in the analysis, the estimated total antibodies seroprevalence was 93.8% (95% CrI 93.1–94.5), including 72.4% (70.0–74.7) for infection-induced antibodies. Estimates of neutralizing antibodies in a representative subsample (N = 1160) ranged from 79.5% (77.1–81.8) against the Alpha variant to 46.7% (43.0–50.4) against the Omicron BA.4/BA.5 subvariants. Despite having high seroprevalence of infection-induced antibodies (76.7% [69.7–83.0] for ages 0–5 years, 90.5% [86.5–94.1] for ages 6–11 years), children aged <12 years had substantially lower neutralizing activity than older participants, particularly against Omicron subvariants. Overall, vaccination was associated with higher neutralizing activity against pre-Omicron variants. Vaccine booster alongside recent infection was associated with higher neutralizing activity against Omicron subvariants. Interpretation While most of the Geneva population has developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, less than half has neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection confers the greatest neutralization capacity, including against Omicron. Funding General Directorate of Health in Geneva canton, Private Foundation of the Geneva University Hospitals, European Commission (“CoVICIS” grant), and a private foundation advised by CARIGEST SA.

3.
Nat Commun ; 13(1): 7086, 2022 Nov 29.
Article in English | MEDLINE | ID: covidwho-2133428

ABSTRACT

Post-COVID syndrome remains poorly studied in children and adolescents. Here, we aimed to investigate the prevalence and risk factors of pediatric post-COVID in a population-based sample, stratifying by serological status. Children from the SEROCoV-KIDS cohort study (State of Geneva, Switzerland), aged 6 months to 17 years, were tested for anti-SARS-CoV-2 N antibodies (December 2021-February 2022) and parents filled in a questionnaire on persistent symptoms in their children (lasting over 12 weeks) compatible with post-COVID. Of 1034 children tested, 570 (55.1%) were seropositive. The sex- and age-adjusted prevalence of persistent symptoms among seropositive children was 9.1% (95%CI: 6.7;11.8) and 5.0% (95%CI: 3.0;7.1) among seronegatives, with an adjusted prevalence difference (ΔaPrev) of 4.1% (95%CI: 1.1;7.3). Stratifying per age group, only adolescents displayed a substantial risk of having post-COVID symptoms (ΔaPrev = 8.3%, 95%CI: 3.5;13.5). Identified risk factors for post-COVID syndrome were older age, having a lower socioeconomic status and suffering from chronic health conditions, especially asthma. Our findings show that a significant proportion of seropositive children, particularly adolescents, experienced persistent COVID symptoms. While there is a need for further investigations, growing evidence of pediatric post-COVID urges early screening and primary care management.

6.
Int J Prison Health ; ahead-of-print(ahead-of-print)2022 10 24.
Article in English | MEDLINE | ID: covidwho-2087989

ABSTRACT

PURPOSE: Prisons can be epicentres of infectious diseases. However, empirical evidence on the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in prison is still scarce. This study aims to estimate the seroprevalence rates of anti-SARS-CoV-2 in the largest and most crowded Swiss prison and compare them with the seroprevalence rate in the general population. DESIGN/METHODOLOGY/APPROACH: A cross-sectional study was conducted in June 2020, one month after the first wave of SARS-CoV-2 in Switzerland. Groups included: people living in detention (PLDs) detained before the beginning of the pandemic (n = 116), PLDs incarcerated after the beginning of the pandemic (n = 61), prison staff and prison healthcare workers (n = 227) and a sample from the general population in the same time period (n = 3,404). The authors assessed anti-SARS-CoV-2 IgG antibodies. FINDINGS: PLDs who were incarcerated before the beginning of the pandemic had a significantly lower seroprevalence rate [0.9%, confidence interval (CI)95%: 0.1%-5.9%] compared to the general population (6.3%, CI 95%: 5.6-7.3%) (p = 0.041). The differences between PLDs who were incarcerated before and other groups were marginally significant (PLDs incarcerated after the beginning of the pandemic: 6.6%, CI 95%: 2.5%-16.6%, p = 0.063; prison staff CI 95%: 4.8%, 2.7%-8.6%, p = 0.093). The seroprevalence of prison staff was only slightly and non-significantly lower than that of the general population. ORIGINALITY/VALUE: During the first wave, despite overcrowding and interaction with the community, the prison was not a hotspot of SARS-CoV-2 infection. Preventive measures probably helped avoiding clusters of infection. The authors suggest that preventive measures that impact social welfare could be relaxed when overall circulation in the community is low to prevent the negative impact of isolation.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Seroepidemiologic Studies , COVID-19/epidemiology , Cross-Sectional Studies , Switzerland/epidemiology , Antibodies, Viral , Immunoglobulin G
7.
Antiviral Res ; 208: 105452, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2085918

ABSTRACT

SARS-CoV-2 is currently causing an unprecedented pandemic. While vaccines are massively deployed, we still lack effective large-scale antiviral therapies. In the quest for antivirals targeting conserved structures, we focused on molecules able to bind viral RNA secondary structures. Aminoglycosides are a class of antibiotics known to interact with the ribosomal RNA of both prokaryotes and eukaryotes and have previously been shown to exert antiviral activities by interacting with viral RNA. Here we show that the aminoglycoside geneticin is endowed with antiviral activity against all tested variants of SARS-CoV-2, in different cell lines and in a respiratory tissue model at non-toxic concentrations. The mechanism of action is an early inhibition of RNA replication and protein expression related to a decrease in the efficiency of the -1 programmed ribosomal frameshift (PRF) signal of SARS-CoV-2. Using in silico modeling, we have identified a potential binding site of geneticin in the pseudoknot of frameshift RNA motif. Moreover, we have selected, through virtual screening, additional RNA binding compounds, interacting with the same site with increased potency.


Subject(s)
COVID-19 , Frameshifting, Ribosomal , Humans , SARS-CoV-2/genetics , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , RNA, Viral/metabolism , COVID-19/drug therapy
8.
Int J Infect Dis ; 2022 Sep 30.
Article in English | MEDLINE | ID: covidwho-2049309

ABSTRACT

OBJECTIVE: To describe long-COVID symptoms among older adults, and to assess risk factors for two common long-COVID symptoms: fatigue and dyspnea. METHODS: Multicenter prospective cohort study, conducted in Israel, Switzerland, Spain, and Italy. Included were individuals at least 30 days since COVID-19 diagnosis. We compared long-COVID symptoms between elderly individuals (age>65 years) and younger population (18-65 years); and conducted univariate and multivariable analyses for predictors of long-COVID fatigue and dyspnea. RESULTS: 2333 individuals were evaluated at an average of 5 months [146 days (95% CI 142-150)] following COVID-19 onset. Mean age was 51 and 20.5% were>65 years. Older adults were more likely to be symptomatic, with most common symptoms being fatigue (38%) and dyspnea (30%). They were more likely to complain of cough and arthralgia, and have abnormal chest imaging and pulmonary function tests. Independent risk factors for long-COVID fatigue and dyspnea included female gender, obesity, and closer proximity to COVID-19 diagnosis; older age was not an independent predictor. CONCLUSIONS: Older individuals with long-COVID, have different persisting symptoms, with more pronounced pulmonary impairment. Women and individuals with obesity are at risk. Further research is warranted to investigate the natural history of long-COVID among the elderly population and to assess possible interventions aimed at promoting rehabilitation and well-being.

9.
Transfusion ; 62(10): 1997-2011, 2022 10.
Article in English | MEDLINE | ID: covidwho-2019638

ABSTRACT

BACKGROUND: Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics. STUDY DESIGN AND METHODS: In a single-center hypothesis-generating prospective case-control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID-19 pneumonia received 2 × 200 ml pathogen-reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28-day mortality, and dCCP -related adverse events in recipients. RESULTS: Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP-related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV-2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS-CoV-2 antigens over 14-21 days post dCCP in all except 4 immunosuppressed recipients. DISCUSSION: PRT did not impact dCCP anti-virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post-transfusion antibody responses indicate the need for controlled trials using well-characterized dCCP with informative assays.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Case-Control Studies , Humans , Immunization, Passive , Middle Aged
10.
PLoS One ; 17(8): e0272663, 2022.
Article in English | MEDLINE | ID: covidwho-1993491

ABSTRACT

OBJECTIVES: To report a prospective epidemiological, virological and serological investigation of a SARS-CoV-2 outbreak in a primary school. METHODS: As part of a longitudinal, prospective, school-based surveillance study, this investigation involved repeated testing of 73 pupils, 9 teachers, 13 non-teaching staff and 26 household members of participants who tested positive, with rapid antigen tests and/or RT-PCR (Day 0-2 and Day 5-7), serologies on dried capillary blood samples (Day 0-2 and Day 30), contact tracing interviews and SARS-CoV-2 whole genome sequencing. RESULTS: We identified 20 children (aged 4 to 6 years from 4 school classes), 2 teachers and a total of 4 household members who were infected by the Alpha variant during this outbreak. Infection attack rates were between 11.8 and 62.0% among pupils from the 4 school classes, 22.2% among teachers and 0% among non-teaching staff. Secondary attack rate among household members was 15.4%. Symptoms were reported by 63% of infected children, 100% of teachers and 50% of household members. All analysed sequences but one showed 100% identity. Serological tests detected 8 seroconversions unidentified by SARS-CoV-2 virological tests. CONCLUSIONS: This study confirmed child-to-child and child-to-adult SARS-CoV-2 transmission and introduction into households. Effective measures to limit transmission in schools have the potential to reduce the overall community circulation.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , Child , Disease Outbreaks , Humans , Longitudinal Studies , Prospective Studies , SARS-CoV-2/genetics , Schools
11.
Nat Commun ; 13(1): 3840, 2022 07 04.
Article in English | MEDLINE | ID: covidwho-1991578

ABSTRACT

Emerging SARS-CoV-2 variants raise questions about escape from previous immunity. As the population immunity to SARS-CoV-2 has become more complex due to prior infections with different variants, vaccinations or the combination of both, understanding the antigenic relationship between variants is needed. Here, we have assessed neutralizing capacity of 120 blood specimens from convalescent individuals infected with ancestral SARS-CoV-2, Alpha, Beta, Gamma or Delta, double vaccinated individuals and patients after breakthrough infections with Delta or Omicron-BA.1. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta and Omicron-BA.1) determined by plaque-reduction neutralization assay allowed us to map the antigenic relationship of SARS-CoV-2 variants. Highest neutralization titers were observed against the homologous variant. Antigenic cartography identified Zeta and Omicron-BA.1 as separate antigenic clusters. Substantial immune escape in vaccinated individuals was detected for Omicron-BA.1 but not Zeta. Combined infection/vaccination derived immunity results in less Omicron-BA.1 immune escape. Last, breakthrough infections with Omicron-BA.1 lead to broadly neutralizing sera.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies , COVID-19/prevention & control , Humans , Vaccination
12.
Microbiol Spectr ; 10(4): e0085322, 2022 08 31.
Article in English | MEDLINE | ID: covidwho-1986335

ABSTRACT

The emergence of each novel SARS-CoV-2 variant of concern (VOC) requires investigation of its potential impact on the performance of diagnostic tests in use, including antigen-detecting rapid diagnostic tests (Ag-RDTs). Although anecdotal reports have been circulating that the newly emerged Omicron-BA.1 variant is in principle detectable by Ag-RDTs, few data on sensitivity are available. We have performed (i) analytical sensitivity testing with cultured virus in eight Ag-RDTs and (ii) retrospective testing in duplicates with clinical samples from vaccinated individuals with Omicron-BA.1 (n = 59) or Delta (n = 54) breakthrough infection on seven Ag-RDTs. Overall, in our analytical study we have found heterogenicity between Ag-RDTs for detecting Omicron-BA.1. When using cultured virus, we observed a trend toward lower endpoint sensitivity for Omicron-BA.1 detection than for earlier circulating SARS-CoV-2 and the other VOCs. In our retrospective study, the detection of Delta and Omicron-BA.1 was assessed in a comparable set of stored clinical samples using seven Ag-RDTs. Four hundred ninety-seven of all 826 tests (60.17%) performed on Omicron-BA.1 samples were positive, compared to 489/756 (64.68%) for Delta samples. In the analytical study, the sensitivity for both Omicron-BA.1 and Delta between the Ag-RDTs was variable. All seven Ag-RDTs showed comparable sensitivities to detect Omicron-BA.1 and Delta in the retrospective study. IMPORTANCE Sensitivity for detecting Omicron-BA.1 shows high heterogenicity between Ag-RDTs, necessitating a careful consideration when using these tests to guide infection prevention measures. Analytical and retrospective testing is a proxy and timely solution to generate rapid performance data, but it is not a replacement for clinical evaluations, which are urgently needed. Biological and technical reasons for detection failure by some Ag-RDTs need to be further investigated.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Humans , Retrospective Studies , SARS-CoV-2/genetics , Sensitivity and Specificity
13.
Prev Med Rep ; 29: 101899, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1983824

ABSTRACT

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population. The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models. Healthcare workers (n = 3083) suffered mostly from fatigue (25.5 %), headache (10.0 %), difficulty concentrating (7.9 %), exhaustion/burnout (7.1 %), insomnia (6.2 %), myalgia (6.7 %) and arthralgia (6.3 %). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n = 3556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76-2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59-5.60). Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19.

14.
Pract Lab Med ; 31: e00290, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1926839

ABSTRACT

Objectives: Serological assays for the presence of anti-SARS-CoV-2 antibodies are crucially needed for research and monitoring of the SARS-CoV-2 pandemic. Antibodies are reliability detected in capillary blood, a minimally invasive and cost-effective alternative to venous blood testing. However, there is a limited knowledge on feasibility of capillary blood self-sampling. This study compared the feasibility of capillary blood self-testing in people aged less than 65 vs. people aged 65 or more. A secondary aim was to investigate the performance of the Hem-Col® (no additive) device compared to venous blood testing. Design and methods: Data were collected in a prospective study in Switzerland (n = 106). Capillary blood was collected using the Hem-Col® (no additive) device. Feasibility was assessed using 1) collecting the recommended amount of capillary blood and 2) achieving all steps of capillary blood collection. A sample of 5 ml of venous blood was also collected. Results: For the primary objective, 86.2%/62.1% of patients aged less than 65 collected the recommended amount of capillary blood/achieved all steps vs. 62.5%/39.6% of patients aged 65 or more (p = .006/p = .022). For the secondary objective, the correlation between capillary and venous blood was r = 0.992 and kappa = 1. Conclusions: Capillary blood self-testing appeared as a feasible and reliable alternative to venous blood testing. Such alternative would improve access to serological testing and spare health care resources. However, the difference between age groups should be considered when using self-sampling devices. Help should be developed for older people, such as phone counseling or encouraging asking younger family members for help.

15.
Eur J Clin Invest ; 52(10): e13818, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1861301

ABSTRACT

BACKGROUND: SARS-CoV-2 infection triggers different auto-antibodies, including anti-apolipoprotein A-1 IgGs (AAA1), which could be of concern as mediators of persistent symptoms. We determined the kinetics of AAA1 response over after COVID-19 and the impact of AAA1 on the inflammatory response and symptoms persistence. METHODS: All serologies were assessed at one, three, six and twelve months in 193 hospital employees with COVID-19. ROC curve analyses and logistic regression models (LRM) were used to determine the prognostic accuracy of AAA1 and their association with patient-reported COVID-19 symptoms persistence at 12 months. Interferon (IFN)-α and-γ production by AAA1-stimulated human monocyte-derived macrophages (HMDM) was assessed in vitro. RESULTS: AAA1 seropositivity was 93% at one month and declined to 15% at 12 months after COVID-19. Persistent symptoms at 12 months were observed in 45.1% of participants, with a predominance of neurological (28.5%), followed by general (15%) and respiratory symptoms (9.3%). Over time, strength of correlations between AAA1 and anti-SARS-COV2 serologies decreased, but remained significant. From the 3rd month on, AAA1 levels predicted persistent respiratory symptoms (area under the curves 0.72-0.74; p < 0.001), independently of disease severity, age and gender (adjusted odds ratios 4.81-4.94; p = 0.02), while anti-SARS-CoV-2 serologies did not. AAA1 increased IFN-α production by HMDMs (p = 0.03), without affecting the IFN-γ response. CONCLUSION: COVID-19 induces a marked though transient AAA1 response, independently predicting one-year persistence of respiratory symptoms. By increasing IFN-α response, AAA1 may contribute to persistent symptoms. If and how AAA1 levels assessment could be of use for COVID-19 risk stratification remains to be determined.


Subject(s)
COVID-19 , Antibodies, Viral , Antiviral Agents , Apolipoprotein A-I , Autoantibodies , Humans , SARS-CoV-2
16.
Front Immunol ; 13: 841009, 2022.
Article in English | MEDLINE | ID: covidwho-1855352

ABSTRACT

Objective: To comprehensively evaluate SARS-CoV-2 specific B-cell and antibody responses up to one year after mild COVID-19. Methods: In 31 mildly symptomatic COVID-19 participants SARS-CoV-2-specific plasmablasts and antigen-specific memory B cells were measured by ELISpot. Binding antibodies directed against the proteins spike (S), domain S1, and nucleocapsid (N) were estimated using rIFA, ELISA, and commercially available assays, and avidity measured using thiocyanate washout. Neutralizing antibodies against variants of concern were measured using a surrogate-neutralization test. Results: Plasmablast responses were assessed in all participants who gave sequential samples during the first two weeks after infection; they preceded the rise in antibodies and correlated with antibody titers measured at one month. S1 and N protein-specific IgG memory B-cell responses remained stable during the first year, whereas S1-specific IgA memory B-cell responses declined after 6 months. Antibody titers waned over time, whilst potent affinity maturation was observed for anti-RBD antibodies. Neutralizing antibodies against wild-type (WT) and variants decayed during the first 6 months but titers significantly increased for Alpha, Gamma and Delta between 6 months and one year. Therefore, near-similar titers were observed for WT and Alpha after one year, and only slightly lower antibody levels for the Delta variant compared to WT. Anti-RBD antibody responses correlated with the neutralizing antibody titers at all time points, however the predicted titers were 3-fold lower at one year compared to one month. Conclusion: In mild COVID-19, stable levels of SARS-CoV-2 specific memory B cells and antibodies neutralizing current variants of concern are observed up to one year post infection. Care should be taken when predicting neutralizing titers using commercial assays that measure binding antibodies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Humans , Spike Glycoprotein, Coronavirus
17.
Epidemics ; 39: 100572, 2022 06.
Article in English | MEDLINE | ID: covidwho-1821233

ABSTRACT

Serosurveys are an important tool to estimate the true extent of the current SARS-CoV-2 pandemic. So far, most serosurvey data have been analyzed with cutoff-based methods, which dichotomize individual measurements into sero-positives or negatives based on a predefined cutoff. However, mixture model methods can gain additional information from the same serosurvey data. Such methods refrain from dichotomizing individual values and instead use the full distribution of the serological measurements from pre-pandemic and COVID-19 controls to estimate the cumulative incidence. This study presents an application of mixture model methods to SARS-CoV-2 serosurvey data from the SEROCoV-POP study from April and May 2020 in Geneva (2766 individuals). Besides estimating the total cumulative incidence in these data (8.1% (95% CI: 6.8%-9.9%)), we applied extended mixture model methods to estimate an indirect indicator of disease severity, which is the fraction of cases with a distribution of antibody levels similar to hospitalized COVID-19 patients. This fraction is 51.2% (95% CI: 15.2%-79.5%) across the full serosurvey, but differs between three age classes: 21.4% (95% CI: 0%-59.6%) for individuals between 5 and 40 years old, 60.2% (95% CI: 21.5%-100%) for individuals between 41 and 65 years old and 100% (95% CI: 20.1%-100%) for individuals between 66 and 90 years old. Additionally, we find a mismatch between the inferred negative distribution of the serosurvey and the validation data of pre-pandemic controls. Overall, this study illustrates that mixture model methods can provide additional insights from serosurvey data.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19/epidemiology , Humans , Pandemics , Seroepidemiologic Studies , Young Adult
18.
Nat Med ; 28(7): 1491-1500, 2022 07.
Article in English | MEDLINE | ID: covidwho-1784006

ABSTRACT

Infectious viral load (VL) expelled as droplets and aerosols by infected individuals partly determines transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RNA VL measured by qRT-PCR is only a weak proxy for infectiousness. Studies on the kinetics of infectious VL are important to understand the mechanisms behind the different transmissibility of SARS-CoV-2 variants and the effect of vaccination on transmission, which allows guidance of public health measures. In this study, we quantified infectious VL in individuals infected with SARS-CoV-2 during the first five symptomatic days by in vitro culturability assay in unvaccinated or vaccinated individuals infected with pre-variant of concern (pre-VOC) SARS-CoV-2, Delta or Omicron BA.1. Unvaccinated individuals infected with pre-VOC SARS-CoV-2 had lower infectious VL than Delta-infected unvaccinated individuals. Full vaccination (defined as >2 weeks after receipt of the second dose during the primary vaccination series) significantly reduced infectious VL for Delta breakthrough cases compared to unvaccinated individuals. For Omicron BA.1 breakthrough cases, reduced infectious VL was observed only in boosted but not in fully vaccinated individuals compared to unvaccinated individuals. In addition, infectious VL was lower in fully vaccinated Omicron BA.1-infected individuals compared to fully vaccinated Delta-infected individuals, suggesting that mechanisms other than increased infectious VL contribute to the high infectiousness of SARS-CoV-2 Omicron BA.1. Our findings indicate that vaccines may lower transmission risk and, therefore, have a public health benefit beyond the individual protection from severe disease.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Serologic Tests , Viral Load
19.
J Intern Med ; 292(1): 103-115, 2022 07.
Article in English | MEDLINE | ID: covidwho-1769735

ABSTRACT

BACKGROUND: Persistent symptoms of SARS-CoV-2 are prevalent weeks to months following the infection. To date, it is difficult to disentangle the direct from the indirect effects of SARS-CoV-2, including lockdown, social, and economic factors. OBJECTIVE: The study aims to characterize the prevalence of symptoms, functional capacity, and quality of life at 12 months in outpatient symptomatic individuals tested positive for SARS-CoV-2 compared to individuals tested negative. METHODS: From 23 April to 27 July 2021, outpatient symptomatic individuals tested for SARS-CoV-2 at the Geneva University Hospitals were followed up 12 months after their test date. RESULTS: At 12 months, out of the 1447 participants (mean age 45.2 years, 61.2% women), 33.4% reported residual mild to moderate symptoms following SARS-CoV-2 infection compared to 6.5% in the control group. Symptoms included fatigue (16% vs. 3.1%), dyspnea (8.9% vs. 1.1%), headache (9.8% vs. 1.7%), insomnia (8.9% vs. 2.7%), and difficulty concentrating (7.4% vs. 2.5%). When compared to the control group, 30.5% of SARS-CoV-2 positive individuals reported functional impairment at 12 months versus 6.6%. SARS-CoV-2 infection was associated with the persistence of symptoms (adjusted odds ratio [aOR] 4.1; 2.60-6.83) and functional impairment (aOR 3.54; 2.16-5.80) overall, and in subgroups of women, men, individuals younger than 40 years, those between 40-59 years, and in individuals with no past medical or psychiatric history. CONCLUSION: SARS-CoV-2 infection leads to persistent symptoms over several months, including in young healthy individuals, in addition to the pandemic effects, and potentially more than other common respiratory infections. Symptoms impact functional capacity up to 12 months post infection.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Communicable Disease Control , Female , Humans , Male , Middle Aged , Pandemics , Quality of Life
20.
Scand J Public Health ; 50(1): 124-135, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1724282

ABSTRACT

Aims: To assess SARS-CoV-2 seroprevalence over the first epidemic wave in the canton of Geneva, Switzerland, as well as risk factors for infection and symptoms associated with IgG seropositivity. Methods: Between April and June 2020, former participants of a representative survey of the 20-74-year-old population of canton Geneva were invited to participate in the study, along with household members aged over 5 years. Blood samples were tested for anti-SARS-CoV-2 immunoglobulin G. Questionnaires were self-administered. We estimated seroprevalence with a Bayesian model accounting for test performance and sampling design. Results: We included 8344 participants, with an overall adjusted seroprevalence of 7.8% (95% credible interval 6.8-8.9). Seroprevalence was highest among 18-49 year-olds (9.5%), and lowest in 5-9-year-old children (4.3%) and individuals >65 years (4.7-5.4%). Odds of seropositivity were significantly reduced for female retirees and unemployed men compared to employed individuals, and smokers compared to non-smokers. We found no significant association between occupation, level of education, neighborhood income and the risk of being seropositive. The symptom most strongly associated with seropositivity was anosmia/dysgeusia. Conclusions: Anti-SARS-CoV-2 population seroprevalence remained low after the first wave in Geneva. Socioeconomic factors were not associated with seropositivity in this sample. The elderly, young children and smokers were less frequently seropositive, although it is not clear how biology and behaviours shape these differences.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Aged , Bayes Theorem , Child , Child, Preschool , Female , Humans , Immunoglobulin G , Male , Middle Aged , Risk Factors , Seroepidemiologic Studies , Switzerland/epidemiology , Young Adult
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