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1.
Geroscience ; 43(5): 2333-2343, 2021 10.
Article in English | MEDLINE | ID: covidwho-1603920

ABSTRACT

COVID-19 is a particularly aggressive disease for the elderly as 86% of deaths related to COVID-19 occur in people over 65 years of age. Despite the urgent need for a preventive treatment, there are currently no serious leads, other than the vaccination. The aim of this retrospective case-control study is to find a pharmacological preventive treatment of COVID-19 in elderly patients. One-hundred-seventy-nine patients had been in contact with other COVID-19 patients at home or in hospital, of whom 89 had tested RT-PCR-positive (COVID-pos) for the virus and 90 had tested RT-PCR-negative (COVID-neg). Treatments within 15 days prior to RT-PCR (including antihypertensive drugs, antipsychotics, antibiotics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs), oral antidiabetics (OADs), corticosteroids, immunosuppressants), comorbidities, symptoms, laboratory values, and clinical outcome were all collected. COVID-pos patients more frequently had a history of diabetes (P = .016) and alcoholism (P = .023), a lower leukocyte count (P = .014) and a higher mortality rate - 29.2% versus 14.4% - (P = .014) when compared to COVID-neg patients. Patients on PPIs were 2.3 times less likely (odds ratio [OR] = 0.4381, 95% confidence interval [CI] [0.2331, 0.8175], P = .0053) to develop COVID-19 infection, compared to those not on PPIs. No other treatment decreased or increased this risk. COVID-pos patients on antipsychotics (P = .0013) and OADs (P = .0153), particularly metformin (P = .0237), were less likely to die. Thus, patients on treatment with PPI were less likely to develop COVID-19 infection, and those on antipsychotics or metformin had a lower risk of mortality. However, prospective studies, including clinical trials, are needed to confirm or not these findings.


Subject(s)
COVID-19 , Aged , Case-Control Studies , Humans , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
2.
Preprint in English | Other preprints | ID: ppcovidwho-294752

ABSTRACT

Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting protection against reinfection and durability of vaccine protection. Here, we longitudinally measured Spike (S) and Nucleocapsid (N)-specific antibodies in 1,309 healthcare workers (HCWs), including 916 COVID-19 negative HCWs and 393 convalescent COVID-19 for up to 422 days post-symptom. From month (M)1 to M7-9 post-infection, SARS-CoV-2 antibodies decreased moderately in convalescent HCWs in a biphasic model, with men showing a slower decay of anti-N (p=0.02), and a faster decay of anti-S (p=0.0008) than women. At M11-13, anti-N dramatically decreased (half-life: 283 days) while anti-S stabilized (half-life: 725 days) at a median of 2.39 log Arbitrary Units (AU)/mL (Interquartile Range (IQR): 2.10 -2.75). Overall, 69 SARS-CoV-2 infections developed in the COVID-19 negative group (incidence of 12.22 per 100 person-years) versus one in the COVID-19 positive group (incidence of 0.40 per 100 person-years), indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7% (p<0.0001). Correlation with live-virus neutralization assay revealed that variants D614G and B.1.1.7, but not B.1.351, were sensitive to anti-S antibodies at 2.3 log AU/mL, while IgG ≥ 3 log AU/mL neutralized all three variants. After SARS-CoV-2 vaccination, anti-S levels reached at least 3 logs regardless of pre-vaccination IgG levels, type of vaccine, and number of doses. Our study demonstrates a long-term persistence of anti-S IgG antibodies that may protect against reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against escape mutants.

3.
Preprint in English | EuropePMC | ID: ppcovidwho-293037

ABSTRACT

INTRODUCTION The objectives of this study were to assess the dynamics of the SARS-CoV-2 anti-RBD IgG response over time among older people after COVID-19 infection or vaccination and its comparison with speculative levels of protection assumed by current data. METHODS From November 2020 to October 2021, we included geriatric patients with serological test results for COVID-19. We considered antibody titre thresholds thought to be high enough to protect against SARS-CoV-2 infection: 141 BAU/ml for protection/vaccine efficacy > 89.3%. Three cohorts are presented. A vaccine group (n=34) that received two BNT162b2/Comirnaty injections 21 days apart, a group of natural COVID-19 infection (n=32) and a third group who contracted COVID-19 less than 15 days after the first BNT162b2/Comirnaty injection (n=17). RESULTS 83 patients were included, the median age was 87 (81-91) years. In the vaccine group at 1 month since the first vaccination, the median BAU/ml with IQR was 620 (217-1874) with 87% of patients above the threshold of 141 BAU/ml. Seven months after the first vaccination the BAU/ml was 30 (19-58) with 9.5% of patients above the threshold of 141 BAU/ml. In the natural COVID-19 infection group, at 1 month since the date of first symptom onset, the median BAU/ml was 798 (325-1320) with 86.7% of patients above the threshold of 141 BAU/ml and fell to 88 (37-385) with 42.9% of patients above the threshold of 141 BAU/ml at 2 months. The natural infection group was vaccinated three months after the infection. Five months after the end of the vaccination cycle the BAU/ml was 2048 (471-4386) with 83.3% of patients above the threshold of 141 BAU/ml. DISCUSSION On the humoral level, this supports the clinical results describing the decrease in vaccine protection over time.

4.
Preprint in English | EuropePMC | ID: ppcovidwho-292852

ABSTRACT

In immunocompetent subjects, the effectiveness of SARS-CoV-2 vaccines against the delta variant appears three-to five-fold lower than that observed against the alpha variant. Additionally, three doses of SARS-CoV-2 mRNA-based vaccines might be unable to elicit a sufficient immune response against any variant in immunocompromised kidney transplant recipients. This study describes the kinetics of the neutralizing antibody (NAbs) response against the delta strain before and after a fourth dose of a mRNA vaccine in 67 kidney transplant recipients who had experienced a weak antibody response after three doses. While only 16% of patients harbored NAbs against the delta strain prior to the fourth injection – this percentage raised to 66% afterwards. We also found that, after the fourth dose, the NAbs titer increased significantly (p=0.0001) from <7.5 (IQR : <7.5 –15.1) to 47.1 (IQR <7.5–284.2). Collectively, our data indicate that a fourth dose of the mRNA-1273 vaccine in kidney transplant recipients with a weak antibody response after three previous doses improves serum neutralization against the delta variant.

5.
J Infect Dis ; 224(9): 1489-1499, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522216

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. METHODS: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. RESULTS: One year after symptoms, we estimate that 36% (95% range, 11%-94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%-89%) anti-RBD IgG remains, and 7% (1%-31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0-3 months, 3-6 months, and 6-12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. CONCLUSIONS: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics.

7.
Infect Dis Now ; 2021 Nov 11.
Article in English | MEDLINE | ID: covidwho-1509833

ABSTRACT

OBJECTIVES: Strasbourg University Hospital faced an important COVID-19 first wave from early March 2020. We performed a longitudinal prospective cohort study to describe clinical and virological data, exposure history to COVID-19, and adherence to strict hygiene standards during the first pandemic wave in 1497 workers undergoing a SARS-CoV-2 serological test at our hospital, with a follow up of serology result three months later. PATIENTS AND METHODS: A total of 1497 patients were enrolled from April 6 to May 7, 2020. Antibody response to SARS-CoV-2 was measured, and COVID-19 exposure routes were analyzed according to SARS-CoV-2 serological status. RESULTS: A total of 515 patients (34.4%) were seropositive, mainly medical students (13.2%) and assistant nurses (12.0%). A history of COVID-19 exposure in a professional and/or private setting was mentioned by 83.1% of seropositive subjects (P<0.05; odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.8-3.4). COVID-19 exposure factors associated with seropositive status were non-professional exposure (OR: 1.9, 95% CI: 1.3-2.7), especially outside the immediate family circle (OR: 2.2, 95% CI: 1.2-3.9) and contact with a COVID-19 patient (OR: 1.6; 95% CI: 1.1-2.2). Among professionally exposed workers, systematic adherence to strict hygiene standards was well observed, except for the use of a surgical mask (P<0.05, OR: 1.9, 95% CI: 1.3-2.8). Of those who reported occasionally or never wearing a surgical mask, nurses (25.7%), assistant nurses (16.2%), and medical students (11.7%) were predominant. CONCLUSION: Infection of staff members during the first pandemic wave in our hospital occurred after both professional and private COVID-19 exposure, underlining the importance of continuous training in strict hygiene standards.

9.
J Infect Dis ; 224(6): 983-988, 2021 09 17.
Article in English | MEDLINE | ID: covidwho-1455308

ABSTRACT

We measured anti-spike (S), nucleoprotein (N), and neutralizing antibodies in sera from 308 healthcare workers with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 and with mild disease, collected at 2 timepoints up to 6 months after symptom onset. At month 1, anti-S and -N antibody levels were higher in male participants aged >50 years and participants with a body mass index (BMI) >25 kg/m2. At months 3-6, anti-S and anti-N antibodies were detected in 99% and 59% of individuals, respectively. Anti-S antibodies and neutralizing antibodies declined faster in men than in women, independent of age and BMI, suggesting an association of sex with evolution of the humoral response.


Subject(s)
Antibodies, Neutralizing/blood , COVID-19/immunology , Sex Characteristics , Adult , Antibodies, Viral/blood , Female , HEK293 Cells , Health Personnel , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
10.
Clin Infect Dis ; 73(7): e1762-e1765, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455264

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma.


Subject(s)
COVID-19 , RNA-Dependent RNA Polymerase , Adenosine Monophosphate/analogs & derivatives , Aged , Alanine/analogs & derivatives , B-Lymphocytes , COVID-19/drug therapy , COVID-19/therapy , Female , Humans , Immunization, Passive , Mutation , SARS-CoV-2
11.
Transplantation ; 105(10): 2165-2169, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1447690

ABSTRACT

BACKGROUND: Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in kidney transplant recipients (KTRs) remain rare. We sought to shed further light on this issue by conducting a single-center study in a kidney transplant center located in one of the France's highest risk zone (Grand Est) for coronavirus disease 2019 (Covid-19) during the initial disease outbreak. METHODS: To this aim, we used a survey approach coupled with systematic investigation of SARS-CoV-2 serology in a cohort of 1390 KTRs. RESULTS: SARS-CoV-2 serologies were available for 780 survey respondents, among whom 48 had anti-SARS-CoV-2 antibodies (total seroprevalence: 6.2%). Thirty-five of the 48 seropositive KTRs had previously received a diagnosis of Covid-19, whereas the remaining 13 patients were not known to be infected (8 asymptomatic cases). Specifically, 18.7% of seropositive KTRs and 1.1% of the entire cohort were asymptomatic. Household exposure was found to markedly increase the risk of SARS-CoV-2 transmission. CONCLUSIONS: Our findings demonstrate that the overall SARS-CoV-2 seroprevalence in KTRs living in one of the France's highest risk zone for Covid-19 during the first French lockdown was as low as 6.3%. Rapid and strict implementation of protective measures could have significantly mitigated virus spread even in an area of high virus circulation.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , Kidney Transplantation , SARS-CoV-2/immunology , France/epidemiology , Humans , Seroepidemiologic Studies
14.
EBioMedicine ; 71: 103561, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1372964

ABSTRACT

BACKGROUND: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. METHODS: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. FINDINGS: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11-13 of 283 days (95% CI 231-349) for anti-N and 725 days (95% CI 623-921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42-1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. INTERPRETATION: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. FUN1DING: None.


Subject(s)
COVID-19/pathology , Immunity, Humoral , Reinfection/pathology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibodies, Viral/metabolism , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Kinetics , Longitudinal Studies , Male , Middle Aged , Phosphoproteins/immunology , Prospective Studies , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Time Factors
15.
J Clin Med ; 10(16)2021 Aug 04.
Article in English | MEDLINE | ID: covidwho-1341697

ABSTRACT

OBJECTIVE: Correct and timely identification of SARS-CoV-2-positive patients is critical in the emergency department (ED) prior to admission to medical wards. Antigen-detecting rapid diagnostic tests (Ag-RDTs) are a rapid alternative to Reverse-transcriptase polymerase chain reaction (RT-PCR) for the diagnosis of COVID-19 but have lower sensitivity. METHODS: We evaluated the performance in real-life conditions of a strategy combining Ag-RDT and chest computed tomography (CT) to rule out COVID-19 infection in 1015 patients presenting in the ED between 16 November 2020 and 18 January 2021 in order to allow non-COVID-19 patients to be hospitalized in dedicated units directly. The combined strategy performed in the ED for patients with COVID-19 symptoms was assessed and compared with RT-PCR. RESULTS: Compared with RT-PCR, the negative predictive value was 96.7% for Ag-RDT alone, 98.5% for Ag-RDT/CT combined, and increased to 100% for patients with low viral load. CONCLUSION: A strategy combining Ag-RDT and chest CT is effective in ruling out COVID-19 in ED patients with high precision.

16.
ESC Heart Fail ; 8(5): 4307-4312, 2021 10.
Article in English | MEDLINE | ID: covidwho-1332963

ABSTRACT

Here, we present the case of an 81-year-old male patient, who was hospitalized for a severe form of COVID-19. Transthoracic echocardiogram (TTE) performed 1 month after symptom onset was normal. Respiratory evolution was favourable, and the patient was discharged at Day 78. At 6 months, despite a good functional recovery, he presented pulmonary sequelae, and the TTE revealed a clear reduction of left ventricular ejection fraction (LVEF) and mild LV dilatation without cardiac symptoms. The cardiac magnetic resonance (CMR) using Lake Louise Criteria (LLC), T1 and T2 mapping showed focal infero-basal LV wall oedema, elevated T1 and T2 myocardial relaxation times especially in basal inferior and infero-lateral LV walls, and sub-epicardial late gadolinium enhancement in those LV walls. The diagnosis of active myocarditis was raised especially based on TTE abnormalities and CMR LLC, T1 and T2 mapping. Currently, we are not aware of published reports of a 6 month post-COVID-19 active myocarditis.


Subject(s)
COVID-19 , Myocarditis , Aged, 80 and over , Contrast Media , Follow-Up Studies , Gadolinium , Humans , Male , Myocarditis/diagnosis , SARS-CoV-2 , Stroke Volume , Ventricular Function, Left
18.
J Infect Dis ; 224(9): 1489-1499, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1317919

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. METHODS: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. RESULTS: One year after symptoms, we estimate that 36% (95% range, 11%-94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%-89%) anti-RBD IgG remains, and 7% (1%-31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0-3 months, 3-6 months, and 6-12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. CONCLUSIONS: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics.

19.
Geroscience ; 43(5): 2333-2343, 2021 10.
Article in English | MEDLINE | ID: covidwho-1316315

ABSTRACT

COVID-19 is a particularly aggressive disease for the elderly as 86% of deaths related to COVID-19 occur in people over 65 years of age. Despite the urgent need for a preventive treatment, there are currently no serious leads, other than the vaccination. The aim of this retrospective case-control study is to find a pharmacological preventive treatment of COVID-19 in elderly patients. One-hundred-seventy-nine patients had been in contact with other COVID-19 patients at home or in hospital, of whom 89 had tested RT-PCR-positive (COVID-pos) for the virus and 90 had tested RT-PCR-negative (COVID-neg). Treatments within 15 days prior to RT-PCR (including antihypertensive drugs, antipsychotics, antibiotics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs), oral antidiabetics (OADs), corticosteroids, immunosuppressants), comorbidities, symptoms, laboratory values, and clinical outcome were all collected. COVID-pos patients more frequently had a history of diabetes (P = .016) and alcoholism (P = .023), a lower leukocyte count (P = .014) and a higher mortality rate - 29.2% versus 14.4% - (P = .014) when compared to COVID-neg patients. Patients on PPIs were 2.3 times less likely (odds ratio [OR] = 0.4381, 95% confidence interval [CI] [0.2331, 0.8175], P = .0053) to develop COVID-19 infection, compared to those not on PPIs. No other treatment decreased or increased this risk. COVID-pos patients on antipsychotics (P = .0013) and OADs (P = .0153), particularly metformin (P = .0237), were less likely to die. Thus, patients on treatment with PPI were less likely to develop COVID-19 infection, and those on antipsychotics or metformin had a lower risk of mortality. However, prospective studies, including clinical trials, are needed to confirm or not these findings.


Subject(s)
COVID-19 , Aged , Case-Control Studies , Humans , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
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