A prospective observational cohort study of covid-19 epidemiology and vaccine seroconversion in South Western Sydney, Australia, during the 2021-2022 pandemic period.

BACKGROUND: It is known that COVID-19 disproportionally adversely affects the immunocompromised, including kidney transplant recipients (KTR), as compared to the general population. Risk factors for adverse outcomes and vaccine seroconversion patterns are not fully understood. Australia was uniquely positioned to reduce initial case numbers during the 2021-2022 pandemic period due to its relative isolation and several significant public health interventions. South-Western Sydney Local Heath District was one of the predominant regions affected. METHODS: A single centre, prospective cohort study of prevalent renal transplant recipients was conducted between 25th July 2021 and 1st May 2022. Baseline characteristics, COVID-19 vaccination status, COVID-19 diagnosis and outcomes were determined from the electronic medical record, Australian vaccination register and Australian and New Zealand Dialysis and Transplant Registry. Assessment of vaccine-induced seroconversion was assessed with ELISA in a subpopulation. Analysis was performed using SPSS v.28. RESULTS: We identified 444 prevalent transplant recipients (60% male, 50% diabetic, median age 58 years (Interquartile range (IQR)21.0) and eGFR 56 ml/min/1.73m2 (IQR 21.9). COVID-19 was identified in 32% (n = 142) of patients, of which 38% (n = 54) required hospitalisation and 7% (n = 10) died. At least one COVID-19 vaccination was received by 95% (n = 423) with 17 (4%) patients remaining unvaccinated throughout the study period. Seroconversion after 2 and 3 doses of vaccine was 22% and 48% respectively. Increased COVID-19 related deaths were associated with older age (aOR 1.1, 95% CI 1.004-1.192, p = 0.040), smoking exposure (aOR 8.2, 05% CI 1.020-65.649, p = 0.048) and respiratory disease (aOR 14.2, 95%CI:1.825-110.930, p = 0.011) on multi-variable regression analysis. Receipt of three doses of vaccination was protective against acquiring COVID-19 (aOR 0.48, 95% CI 0.287-0.796, p = 0.005) and death (aOR 0.6, 95% CI: 0.007-0.523, p = 0.011), but not against hospitalisation (p = 0.32). Seroconversion was protective for acquiring COVID-19 on multi-variable regression independent of vaccination dose (aOR 0.1, 95%CI: 0.0025-0.523, p = 0.011). CONCLUSIONS: COVID-19 was associated with a high mortality rate. Older age, respiratory disease and prior smoking exposure may be risk factors for increased mortality. Vaccination of 3 doses is protective against acquiring COVID-19 and death, however not hospitalisation. Antibody response is protective for acquiring COVID-19, however seroconversion rates are low.

CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during antiviral treatment with TDF.

The serum chemokine C-X-C motif ligand-10 (CXCL10) and its unique receptor (CXCR3) may predict the prognosis of patients with chronic hepatitis B (CHB) treated with tenofovir disoproxil fumarate (TDF). Nevertheless, there are few reports on the profile of CXCL10 and CXCR3 and their clinical application in HBeAg (+) CHB patients during TDF antiviral therapy. CXCL10 and CXCR3 were determined in 118 CHB patients naively treated with TDF for at least 96 weeks at baseline and at treatment weeks 12 and 24. In addition, gene set enrichment analysis was used to examine the associated dataset from Gene Expression Omnibus and explore the gene sets associated with HBeAg seroconversion (SC). The change of CXCL10 (ΔCXCL10, baseline to 48-week TDF treatment) and CXCR3 (ΔCXCR3) is closely related to the possibility of HBeAg SC of CHB patients under TDF treatment. Immunohistochemical analysis of CXCL10/CXCR3 protein in liver tissue shows that there is a significant difference between paired liver biopsy samples taken before and after 96 weeks of successful TDF treatment of CHB patients (11 pairs) but no significance for unsuccessful TDF treatment (14 pairs). Multivariate Cox analysis suggests that the ΔCXCL10 is an independent predictive indicator of HBeAg SC, and the area under the receiver operating characteristic curve of the ΔCXCL10 in CHB patients is 0.8867 (p < 0.0001). Our results suggest that a lower descending CXCL10 level is associated with an increased probability of HBeAg SC of CHB patients during TDF therapy. Moreover, liver tissue CXCL10 might be involved in the immunological process of HBeAg SC.

Immunogenicity of 2 or 3 Doses of 9vHPV Vaccine in U.S. Female Individuals 15 to 26 Years of Age.

Immunogenicity of Two or Three Doses of 9vHPV VaccineThis noninferiority trial examined two versus three doses of 9-valent human papillomavirus (9vHPV) vaccine in individuals 15 to 26 years of age in the United States. In an unplanned interim analysis of female participants, two doses of 9vHPV vaccine appeared to elicit similar rates of seroconversion and antibody titers for each of the nine HPV genotypes to three doses at 1 month postvaccination.

A hidden burden of disease in a specific group: Evaluation of COVID-19 seroconversion rates in pediatric patients with leukemia.

BACKGROUND: SARS-CoV-2, a respiratory viral disease, is thought to have a more severe course in patients with malignancy and low immune systems. METHODS: This prospective single-center study was conducted at the University of Health Sciences Dr Behçet Uz Children's Hospital from September 22 to December 31, 2021. Asymptomatic COVID-19 transmission rates were assessed using SARS-CoV-2 serology in patients with leukemia who had no history of COVID-19 infection. RESULTS: Among the 54 patients, 19 (35.2%) were females and 35 (64.8%) were males. The median age was 5.5 years (min 6 months, max 17 years). Forty-nine (90.5%) of the leukemia patients had acute lymphoblastic leukemia, while 5 (9.5%) had acute myeloid leukemia. Five of the 54 patients had a history of COVID-19 or contact with a positive person. SARS-CoV-2 IgG positivity was detected in 18 (36.7%) of 49 patients with no history of COVID-19 infection. DISCUSSION: Leukemia patients have a high seroconversion for SARS-CoV-2 without showing any symptoms supporting the asymptomatic course of COVID-19 infection in this risk group. CONCLUSION: As a result, patients with leukemia may have a high rate of COVID-19 seroconversion without showing symptoms.

Rates of John Cunningham virus seroconversion greatly reduced in natalizumab-treated patients during COVID-19-related lockdowns.

BACKGROUND AND PURPOSE: This study was undertaken to retrospectively compare rates of John Cunningham virus (JCV) seroconversion in natalizumab-treated patients before and during COVID-19-related community restrictions. Natalizumab is highly effective therapy for relapsing-remitting multiple sclerosis. Prolonged exposure to natalizumab in JCV-positive patients can cause progressive multifocal leukoencephalopathy, a potentially fatal brain infection. Serial assessment of JCV status is required for patients receiving natalizumab. METHODS: Patients receiving natalizumab at the Royal Melbourne Hospital were assessed for change in JCV serostatus and duration of exposure to natalizumab in two discrete time periods: from 1 February 2012 until 1 February 2017 ("pre-COVID"; n = 128) and from 1 April 2020 until 12 October 2022 ("COVID"; n = 214). A Poisson regression model adjusted for age at natalizumab commencement and sex was used to model seroconversion rate between the two time periods. RESULTS: The pre-COVID JCV seroconversion rate among natalizumab-treated patients at the Royal Melbourne Hospital was 9.08%. Conversely, we found a precipitous decline in JCV seroconversion during COVID lockdown. Annualized seroconversion during COVID-19-related restrictions was 2.01%. The annualized seroconversion rate was 4.7 times higher during the pre-COVID-19 period (95% confidence interval = 2.96-7.45, p < 0.0001) compared to the annualized seroconversion rate during COVID lockdown. Males had a 2× higher rate of seroconversion compared to females. CONCLUSIONS: JCV seroconversion among natalizumab-treated patients was markedly lower during COVID-19-related community restrictions. Restrictions observed in Melbourne were among the longest and most comprehensive implemented worldwide. This suggests the presence of modifiable risk factors that could lower rates of JCV seroconversion among natalizumab-treated patients.

Higher pro-inflammatory cytokines IL-6 and IFN-γ are associated with anti-SARS-CoV-2 spike protein-specific seroconversion in renal allograft recipients.

BACKGROUND: Maintenance immunosuppressive regimens are speculated to hamper immunogenic response against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in renal transplant recipients (RTRs) compared to the healthy population. Healthy people with SARS-CoV-2 infection often develop neutralizing antibodies and secret copious quantities of cytokines, leading to virus clearance and sometimes more severe immune-related complications. METHODS: RTRs, either acquired SARS-CoV-2 infection (infection group, n = 132) or were vaccinated with two vaccine doses (vaccination group, n = 78) against SARS-CoV-2, were recruited in the study. Thirty-five unvaccinated RTRs, without anti-SARS-CoV-2 spike protein-specific antibodies, were also included as control. Cytokines interleukine-6 (IL-6), interferon-γ (IFN-γ), TGF-ß, and IL-10 were measured using ELISA. The SARS-CoV-2 spike protein-specific IgG-titer was measured by chemiluminescent microparticle immunoassay methods. RESULTS: The seroconversion rate in the infection group was 115/132 (87.12%), with a median antibody titer 706.40 au/mL (IQR, 215.45-1844.42), and in the vaccination group was 63/78 (80.76%) with antibody titer 1454.20 au/mL (IQR, 80.52-3838.75). The IL-6, IFN-γ, TGF-ß, and IL-10 levels were significantly higher in both the infection and vaccination group compared to healthy control. In the infection group, pro-inflammatory cytokines IL-6 (55.41 ± 24.30 vs. 31.64 ± 16.98 pg/mL, p < .001) and IFN-γ (91.21 ± 33.09 vs. 61.69 ± 33.28 pg/mL, p = .001) were significantly higher in the seroconverter group as compared to non-seroconverter. Similarly, in the vaccination group, pro-inflammatory cytokines IL-6 (50.31 ± 25.67 vs. 30.00 ± 11.19 pg/mL; p = .002) and IFN-γ (65.70 ± 39.78 vs. 32.14 ± 17.48 pg/mL; p = .001) were significantly higher in the seroconverter group compared to non-seroconverter. In contrast, TGF-ß (820.96 ± 415.78 vs. 1045.57 ± 204.66; p = .046) was higher in non-seroconverter. CONCLUSIONS: Pro-inflammatory cytokines IL-6 and IFN-γ were significantly associated with seroconversion after SARS-CoV-2 infection and vaccination in RTRs.

Effects of Maternal HIV Infection on Early Kaposi Sarcoma-Associated Herpesvirus Seroconversion in a Kenyan Mother-Infant Cohort.

BACKGROUND: We identified whether maternal human immunodeficiency virus (HIV) infection during pregnancy affects transplacental transfer of Kaposi sarcoma-associated herpesvirus (KSHV)-specific antibodies and subsequent infant infection. METHODS: We followed pregnant Kenyan women through delivery and their infants until age 2 years. Children were classified as HIV-exposed uninfected (HEU) or HIV-unexposed uninfected (HUU) based on maternal HIV status. Maternal venous and cord blood at delivery and child venous blood every 6 months were tested for antibodies to 20 KSHV antigens by multiplex bead-based immunoassay. Multiple comparisons were adjusted using false discovery rate (FDR). RESULTS: Maternal HIV infection was significantly associated with decreased transplacental transfer of antibodies against all KSHV antigens and lower cord blood levels for 8 antigens at FDR P < .10. Neither birth to 6-month antibody level changes nor 6-month levels differed in HEU and HUU, except for ORF50. By age 24 months, 74% of children KSHV seroconverted but HEU and HUU did not differ in time to seroconversion nor 2-year seropositivity after adjustment for child malaria infection. CONCLUSIONS: Maternal HIV infection reduced a child's initial KSHV antibody levels but did not affect age of infection. Regardless of HIV exposure in utero, KSHV seroconversion in Kenyan children occurred early; associated factors must be identified.

Seroconversion following empiric praziquantel treatment as confirmatory diagnostic tool for chronic schistosomiasis.

We report on six patients with suspected chronic schistosomiasis and negative microbiological findings at baseline. All patients were treated empirically with praziquantel and all seroconverted 20 days to two months after treatment. We suggest that seroconversion after praziquantel treatment may be used as a confirmatory diagnostic tool for chronic schistosomiasis.

Impaired Seroconversion After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA Vaccine in Patients With Thymic Epithelial Tumors.

INTRODUCTION: Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system and humoral- and cell-mediated immunity abnormalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine is effective in preventing coronavirus disease 2019 morbidity and mortality. The aim of this study was to evaluate the seroconversion in patients with TET after two doses of mRNA vaccine. METHODS: This is a prospective study in which consecutive patients with TET were enrolled before receiving the first dose of SARS-CoV-2 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding immunoglobulin (Ig)G antibody serologic levels were analyzed at different time points, including before first vaccine dose (T0), 1 month after the second dose (T2), and 3 months after the second dose (T3). RESULTS: Overall, 39 patients were included in the analysis. All patients had negative antibody titer results at T0. There were 19 patients (48.7%) in the follow-up with no residual tumor lesion/s (referred as no evidence of disease), and 20 (51.3%) had evidence of disease (ED) and were receiving systemic treatment. Dysregulations of the immune system were diagnosed in 29 patients (74.4%) with Good syndrome (GS) being the most frequent immune disorder (48.7%). At univariate analysis, lack of seroconversion at T2 was significantly associated with ED (p < 0.001) and with GS (p = 0.043). A significant association with impaired seroconversion was confirmed at multivariate analysis for ED (p = 0.00101) but not for GS (p = 0.625). CONCLUSIONS: Our data revealed that patients with TET with ED had substantially higher probability of impaired seroconversion after SARS-CoV-2 mRNA vaccine as compared with patients with no evidence of disease.

To study the pattern of seroconversion for SARS-CoV-2 IgG antibodies in COVID-infected cancer patients and to correlate it clinically - A cross-sectional study.

Background: Though as per literature cancer is also consider an associated risk factor for morbidity and mortality for covid infection but practically most of the cancer patients showed no symptoms with less mortality in second wave of pandemic. So this cross sectional comparative analysis study was designed to see the prevalence of sero-conversion for SARS -coV for IgG in covid infected cancer patients and to compare the IgG antibodies level between covid infected cancer patients and covid infected healthy persons. Material and Method: Covid-19 antibody screening of covid recovered cancer patients as well as covid recovered healthy persons was done in department of Transfusion Medicine.IgG antibody for COVID-19 was detected using microtiter plate with whole-cell antigen coating, an in-house validated kit by NIV ICMR3. Prevalence of sero-conversion was noted down in both the groups and compared. Result: There was more infectivity rate in second covid wave. Case fatality rate was much lesser as compared to 1st wave in cancer patients. In cancer patients maximum seroconversion was seen in younger group i.e. 21-30 yrs. of age, this was in contrast to finding in general population, where minimum seroconversion was seen in younger age group. It was observed that more prevalence of sero conversion was seen in general population as compared to cancer patients, but difference was non-significant. Conclusion: Though cancer patients showed less rate of seroconversion as compared to normal healthy person, but none of them showed any moderate or severe symptoms inspite of being a risk factor for severity of covid. Though larger study are required to comment on statistical conclusion.

Early warning signs of thyroid autoantibodies seroconversion: A retrospective cohort study.

BACKGROUND: Serum anti-thyroid peroxidase antibody (anti-TPO) and anti-thyroglobulin antibody (anti-Tg) levels are key indicators for the diagnosis of autoimmune diseases, especially autoimmune thyroiditis. Before the thyroid autoantibodies turn from negative to positive, it is unknown whether any clinical indicators in the body play a warning role. PURPOSE: To establish an early prediction model of seroconversion to positive thyroid autoantibodies. METHODS: This retrospective cohort study collected information based on clinical laboratory data. A logistic regression model was used to analyse the risk factors associated with a change in thyroid autoantibodies to an abnormal status. A machine-learning approach was employed to establish an early warning model, and a nomogram was used for model performance assessment and visualisation. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses were used for internal and external validation. RESULTS: Logistic regression analysis revealed that albumin to globulin ratio, triglyceride levels, and Glutamic acid levels among liver function and some metabolism-related indicators, high density lipoprotein C among metabolism-related indicators, and cystatin C among renal function indicators were all risk factors for thyroid antibody conversion (P < 0.05). In addition, several indicators in the blood count correlated with thyroid conversion (P < 0.05). Changes in the ratio of free thyroxine to free triiodothyronine were a risk factor for positive thyroid antibody conversion (ORfT4/fT3 = 1.763; 95% confidence interval 1.554-2.000). The area under the curve (AUC) of the early warning model based on the positive impact of clinical laboratory indicators, age, and sex was 0.85, which was validated by both internal (AUC 0.8515) and external (AUC 0.8378) validation. CONCLUSIONS: The early warning model of anti-TPO and anti-Tg conversion combined with some clinical laboratory indicators in routine physical examination has a stable warning efficiency.

Human Immunodeficiency Virus Seroconversion Among Men Who Have Sex With Men Who Use Event-Driven or Daily Oral Pre-Exposure Prophylaxis (CohMSM-PrEP): A Multi-Country Demonstration Study From West Africa.

BACKGROUND: Data on human immunodeficiency virus (HIV) seroconversion among men who have sex with men (MSM) using pre-exposure prophylaxis (PrEP) in West Africa are needed. This study aimed to document HIV seroconversion and associated determinants, PrEP adherence, plasma drug concentrations, and HIV drug resistance in MSM using event-driven or daily PrEP in Burkina Faso, Côte d'Ivoire, Mali, and Togo. METHODS: A prospective cohort study was conducted in 2017-2021 among HIV-seronegative MSM aged 18 or over who were at high risk of HIV infection. Participants could choose between event-driven and daily PrEP, switch regimens, and discontinue or restart PrEP. The determinants of HIV incidence were investigated using a multivariate mixed-effects Poisson regression analysis. RESULTS: A total of 647 participants were followed for a total time of 1229.3 person-years. Of 5371 visits, event-driven PrEP was chosen in 3873 (72.1%), and daily PrEP in 1400 (26.1%). HIV incidence was 2.4 per 100 person-years (95% confidence interval [CI] 1.5-3.6) for event-driven PrEP, and 0.6 per 100 person-years (95% CI .1-2.3) for daily PrEP (adjusted incidence rate ratio 4.40, 95% CI 1.00-19.36, P = .050). Adequate adherence was lower with event-driven than daily PrEP (44.3% vs 74.9%, P < .001). Plasma drug concentrations were undetectable in 92 (97.9%) of the 94 measures taken for 23 participants who seroconverted. Only 1 participant had resistance to PrEP drugs. CONCLUSIONS: HIV seroconversions mainly occurred in participants who chose event-driven PrEP. The study's data highlighted major difficulties with adherence to this regimen. Improving adherence to event-driven PrEP constitutes a major research and public health priority in this context.

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV.

Introduction: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals. Methods: A total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis. Results: At 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron. Discussion: This study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges. Clinical trial registration: https://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.

Longitudinal Associations Between TPO Gene Variants and Thyroid Peroxidase Antibody Seroconversion in a Population-Based Study: Tehran Thyroid Study.

Introduction: Autoimmune thyroid diseases (AITD) are usually accompanied by anti-thyroid antibodies which can serve as early predictive markers. This study was designed to investigate the relationship between thyroid peroxidase (TPO) gene variants and the presence of TPOAb and to evaluate the effect of environmental factors associated with seroconversion from TPOAb-negative to TPOAb-positive. Methods: Participants from phases 1 and 2 of the Tehran Thyroid Study in (n = 5327, ≥20 years) were evaluated in terms of TPOAb positivity, and its relationship with 53 single nucleotide polymorphisms (SNPs) from within the TPO gene (cross-sectional approach). TPOAb-negative participants (n = 4815) were followed up for seroconversion for 5.5 years. The relationship between the TPO gene variants and the TPOAb seroconversion was evaluated (longitudinal approach). Results: There were 521 TPOAb-positive participants in the cross-sectional phase and 266 new TPOAb-positive cases observed during the follow-up period. After quality control (Hardy-Weinberg equilibrium (p < 1 × 10-5) and minor allele frequency < 0.05), 49 SNPs were qualified for association analyses. From this set fourteen SNPs were identified that were associated with TPOAb positivity. rs6605278, located in the 3'UTR TPO gene, was the most highly significantly associated of the variant and remained associated after adjustment for age, gender, body mass index (BMI), smoking, number of parity, and oral contraceptive consumption in both cross-sectional and longitudinal analyses (p < 0.05). Conclusions: TPOAb-positivity can be partially explained by variants in the TPO gene. New TPOAb-associated SNPs were observed in Iranians as an ethnically diverse population.

Epidemiology of occupational exposure to blood-borne viruses, postexposure prophylaxis and seroconversion over 10 years among healthcare workers.

BACKGROUND: Healthcare workers (HCWs) are at increased risk of infection with blood-borne pathogens due to occupational blood exposures (OBEs). Early reporting, detection and postexposure prophylaxis (PEP) help to prevent infections. AIM: To investigate the incidence of OBEs, related epidemiological characteristics, PEP completion rate, time and reason for PEP discontinuation, and seroconversion rate reported over 10 years. METHODS: This retrospective study analysed 1086 cases of OBE and PEP management from January 2012 to December 2021 among staff in a South Korean tertiary hospital. FINDINGS: The mean incidence of OBE was 7.82 per 100 beds and 3.0 per 100 HCWs. Of 1086 cases of OBE, 633 (58.3%) HCWs required PEP and 453 (41.7%) did not. After OBE, 70.1% (444/633) of HCWs subject to PEP completed tracking, and 29.9% (189/633) stopped PEP tracking (P<0.001). The PEP completion rate showed a significant difference by gender (P=0.024), occupation (P<0.001) and exposure frequency (P<0.001). None of the 444 HCWs who completed PEP seroconverted to hepatitis B virus, hepatitis C virus, human immunodeficiency virus or Treponema pallidum (syphilis). CONCLUSION: The study findings demonstrate the need to improve follow-up care among HCWs following OBE. There is a need for education in healthcare facilities; moreover, establishing a national surveillance system is necessary to ensure that HCWs undergo PEP proactively and complete their follow-up visits.

No seroconversion among healthcare workers exposed to SARS-CoV-2 during the early phase of the pandemic / Ausencia de seroconversión en trabajadores de la salud expuestos a SARS-CoV-2 durante la primera fase de la pandemia

BACKGROUND: The SARS-CoV-2 pandemic is associated with morbidity, hospitalizations, absenteeism, and mortality among healthcare workers (HCW). AIM: To evaluate the seroconversion rate in HCW exposed to SARS-CoV-2 in the early pandemic phase in 2020 at a regional reference hospital. MATERIAL AND METHODS: One hundred seventy-nine HCW working at a regional hospital were invited to a longitudinal study performed between April-July 2020. A serological analysis by ELISA IgG for viral nucleoprotein and protein S with a secondary analysis by ELISA IgG protein S1/S2 for samples with positive or doubtful result was carried out together with a complementary online survey to inquire about occupational or community exposures to SARS-CoV-2. RESULTS: Two cases with baseline infection were detected (1.1%, one symptomatic and one asymptomatic) and no cases of seroconversion were detected. During the study period, there were 136 patients hospitalized with COVID-19, and regional weekly COVID-19 incidence ranged from 2.7 to 24.4 per 100,000 inhabitants. No SARS-CoV-2 cases were detected by PCR among 27 HCW who consulted for respiratory symptoms in the period. Online surveys confirmed direct care of COVID-19 patients and also detected a high degree of unprotected social interaction at work. CONCLUSIONS: There was no evidence of seroconversion in this group of HCW exposed to the risk of infection by SARS-CoV-2 during the onset of the COVID-19 pandemic. Personal protective equipment and other measures used by the HCW were extremely useful for their protection in the initial phase of the pandemic.

ANTECEDENTES: La pandemia de SARS-CoV-2 está asociada a morbilidad, hospitalizaciones, ausentismo y mortalidad entre el personal de salud (PS). OBJETIVO: Evaluar la tasa de seroconversión en el PS expuesto al SARS-CoV-2 en la fase pandémica inicial el 2020 en un hospital regional de referencia. MATERIAL Y MÉTODOS: Ciento setenta y nueve trabajadores de la salud fueron invitados a un estudio longitudinal realizado entre abril-julio de 2020. Se efectuó un análisis serológico por ELISA IgG para nucleoproteína viral y proteína S con un análisis secundario por ELISA IgG proteína S1 / S2 para muestras con resultado positivo o dudoso junto a encuestas complementarias en línea para preguntar sobre exposiciones ocupacionales o comunitarias al SARS-CoV-2. RESULTADOS: Se detectaron dos casos con infección basal (1,1%, uno sintomático y uno asintomático) sin casos de seroconversión. Durante el período de estudio, hubo 136 pacientes hospitalizados con COVID-19, y la incidencia semanal regional de COVID-19 osciló entre 2,7 y 24,4 por 100.000 habitantes. No se detectaron casos de SARS-CoV-2 por PCR entre los 27 funcionarios que consultaron por síntomas respiratorios en este período. Las encuestas en línea confirmaron la atención directa de los pacientes con COVID-19 y también detectaron un alto grado de interacción social desprotegida en el trabajo. CONCLUSIONES: No hubo evidencia de seroconversión en un grupo de funcionarios expuestos al riesgo de infección por SARS-CoV-2 durante el inicio de la pandemia de COVID-19. Los equipos de protección personal y otras medidas utilizadas por el PS fueron de suma utilidad para su protección en la fase inicial de la pandemia.

Cervical and systemic innate immunity predictors of HIV risk linked to genital herpes acquisition and time from HSV-2 seroconversion.

OBJECTIVES: To examine innate immunity predictors of HIV-1 acquisition as biomarkers of HSV-2 risk and biological basis for epidemiologically established HIV-1 predisposition in HSV-2 infected women. METHODS: We analysed longitudinal samples from HIV-1 negative visits of 1019 women before and after HSV-2 acquisition. We measured cervical and serum biomarkers of inflammation and immune activation previously linked to HIV-1 risk. Protein levels were Box-Cox transformed and ORs for HSV-2 acquisition were calculated based on top quartile or below/above median levels for all HSV-2 negative visits. Bivariate analysis determined the likelihood of HSV-2 acquisition by biomarker levels preceding infection. Linear mixed-effects models evaluated if biomarkers differed by HSV-2 status defined as negative, incident or established infections with an established infection cut-off starting at 6 months. RESULTS: In the cervical compartment, two biomarkers of HIV-1 risk (low SLPI and high BD-2) also predicted HSV-2 acquisition. In addition, HSV-2 acquisition was associated with IL-1ß, IL-6, IL-8, MIP-3α, ICAM-1 and VEGF when below median levels. Systemic immunity predictors of HSV-2 acquisition were high sCD14 and IL-6, with highest odds when concomitantly increased (OR=2.23, 1.49-3.35). Concomitant systemic and mucosal predictors of HSV-2 acquisition risk included (1) serum top quartile sCD14 with cervical low SLPI, VEGF and ICAM-1, or high BD-2; (2) serum high IL-6 with cervical low VEGF and ICAM-1, SLPI, IL-1ß and IL-6; and (3) serum low C reactive protein with cervical high BD-2 (the only combination also predictive of HIV-1 acquisition). Most cervical biomarkers were decreased after HSV-2 acquisition compared with the HSV-2 negative visits, with incident infections associated with a larger number of suppressed cervical biomarkers and lower serum IL-6 levels compared with established infections. CONCLUSIONS: A combination of systemic immunoinflammatory and cervical immunosuppressed states predicts HSV-2 acquisition. A persistently suppressed innate immunity during incident HSV-2 infection may add to the increased HIV-1 susceptibility.

Characteristics of Human Immunodeficiency Virus (HIV) Seroconversions in a Large Prospective Implementation Cohort Study of Oral HIV Preexposure Prophylaxis in Men Who Have Sex with Men (EPIC-NSW).

BACKGROUND: Most human immunodeficiency virus (HIV) seroconversions in people who have initiated preexposure prophylaxis (PrEP) occur in the context of insufficient adherence. We describe participants who seroconverted after being dispensed PrEP in a large PrEP implementation study in Australia. METHODS: Expanded PrEP Implementation in Communities in New South Wales was an implementation study of daily oral PrEP in individuals aged ≥18 years at high risk for acquiring HIV. HIV seroconversions were defined as a positive HIV test by either antigen, antibody, or detectable HIV viral load after enrollment. Insufficient adherence, measured by dispensing logs or participant self-report, was defined as <4 PrEP doses per week. RESULTS: A total of 9596 participants were enrolled and dispensed PrEP between 1 March 2016 and 30 April 2018; 30 were diagnosed with HIV by 31 March 2019. The median (interquartile range [IQR]) age was 31 (25-38) years, all identified as male, 29 (97%) identified as gay or homosexual, and 20 (69%) lived in a postcode with a low concentration of gay male residents. The median (IQR) days from first PrEP dispensing to diagnosis was 409 (347-656). There was no evidence that participants who seroconverted had been sufficiently adherent to PrEP. Nineteen (63%) participants who seroconverted were diagnosed with chlamydia, gonorrhoea, syphilis, or new hepatitis C infection. One participant had resistance to emtricitabine (M184V mutation) at diagnosis. CONCLUSIONS: Participants who seroconverted were insufficiently adherent to PrEP despite being at high risk for acquiring HIV. Understanding the reasons for poor PrEP adherence in individuals who subsequently acquire HIV is critical to improving PrEP effectiveness.