Uninfected Healthcare Workers Research Articles

SARS-CoV-2 Omicron XBB.1 variant outbreak in a defined cohort: an epidemiological investigation incorporating longitudinal assessment of humoral response

BackgroundWe describe an epidemiological investigation of a SARS-CoV-2-XBB.1 outbreak among healthcare workers (HCWs) returning from a 5-days educational tour abroad. MethodsWe prospectively followed participants for symptoms and sampled blood for neutralization assays of four SARS-CoV-2 variants (wild type, XBB, EG.5.1, and BA.2.86) at 1, 3, and 6 months after their return. When available, samples from the 3 months preceding the outbreak were also tested. We compared geometric mean titers (GMT) of neutralizing antibodies of infected versus uninfected HCWs and febrile versus afebrile infected HCWs. ResultsNineteen (10%) of 181 HCWs were infected, all had mild COVID-19, 90% (17/19) had symptoms, and 16% (3/19) reported fever. Infected individuals tended to have lower pre-exposure XBB-neutralizing antibody titers (GMT of 32 versus 107 ID50, P = 0.248). Neutralization against XBB and newer subvariants peaked at 3 months and was higher among infected individuals (GMT 702 versus 156 [P < 0.001], 558 versus 163 [P = 0.001], and 558 vs. 182 [P = 0.002], ID50 for XBB, EG.5.1., and BA.2.86, respectively). By six months, these differences were no longer observed. Fever was positively associated with XBB neutralization (GMT 3474 versus 485, ID50 P = 0.005). ConclusionsRecently infected individuals are protected from reinfection with newer subvariants. However, protection is likely short lived.

Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection.

BackgroundThe majority of those infected by ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the UK first wave (starting March 2020) did not require hospitalisation. Most had a short-lived mild or asymptomatic infection, while others had symptoms that persisted for weeks or months. We hypothesized that the plasma proteome at the time of first infection would reflect differences in the inflammatory response that linked to symptom severity and duration.MethodsWe performed a nested longitudinal case-control study and targeted analysis of the plasma proteome of 156 healthcare workers (HCW) with and without lab confirmed SARS-CoV-2 infection. Targeted proteomic multiple-reaction monitoring analysis of 91 pre-selected proteins was undertaken in uninfected healthcare workers at baseline, and in infected healthcare workers serially, from 1 week prior to 6 weeks after their first confirmed SARS-CoV-2 infection. Symptom severity and antibody responses were also tracked. Questionnaires at 6 and 12 months collected data on persistent symptoms.FindingsWithin this cohort (median age 39 years, interquartile range 30–47 years), 54 healthcare workers (44% male) had PCR or antibody confirmed infection, with the remaining 102 (38% male) serving as uninfected controls. Following the first confirmed SARS-CoV-2 infection, perturbation of the plasma proteome persisted for up to 6 weeks, tracking symptom severity and antibody responses. Differentially abundant proteins were mostly coordinated around lipid, atherosclerosis and cholesterol metabolism pathways, complement and coagulation cascades, autophagy, and lysosomal function. The proteomic profile at the time of seroconversion associated with persistent symptoms out to 12 months. Data are available via ProteomeXchange with identifier PXD036590.InterpretationOur findings show that non-severe SARS-CoV-2 infection perturbs the plasma proteome for at least 6 weeks. The plasma proteomic signature at the time of seroconversion has the potential to identify which individuals are more likely to suffer from persistent symptoms related to SARS-CoV-2 infection.Funding informationThe COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from University College London Hospitals (UCLH) Charity. This work was additionally supported by the Translational Mass Spectrometry Research Group and the Biomedical Research Center (BRC) at Great Ormond Street Hospital.

Strong SARS-CoV-2 Antibody Response After Booster Dose of BNT162b2 mRNA Vaccines in Uninfected Healthcare Workers.

Despite strict guidelines for coronavirus disease 2019 (COVID-19), South Korea is facing its fourth pandemic wave. In this study, by using an automated electrochemiluminescence immunoassay assay, we tracked anti-spike protein receptor-binding domain (anti-S-RBD) antibody titer from the second dose to 2 weeks after the booster dose vaccination. After the second dose, 234 participants had their anti-S-RBD antibody titers decrease over time. We also showed the booster dose (the third dose) increased antibody titer by average 14 (min–max, 2–255)-fold higher compared to the second dose among the 211-booster group participants, therefore, the booster dose could be recommended for low responders to the second dose. Our findings showed a distinct humoral response after booster doses of BNT162b2 mRNA vaccines and may provide further evidence of booster vaccination efficacy. These data will also be helpful in vaccination policy decisions that determine the need for the booster dose.

Comparison of immunogenicity and reactogenicity of inactivated SARS-CoV-2 vaccine (CoronaVac) in previously SARS-CoV-2 infected and uninfected health care workers

ABSTRACT The effects of inactivated SARS-CoV-2 vaccine (CoronaVac) on previously naturally infected individuals are unknown. This study compared immunogenicity and reactogenicity of CoronaVac in once naturally infected health-care workers (HCWs) and uninfected HCWs. All HCWs were immunized with two doses of CoronaVac (600 U/0.5 ml) intramuscularly at a 28-day interval. Adverse reactions were obtained by web-based questionnaires or telephone calls seven days after each vaccine dose. Detection of antibody levels against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein was done four weeks after the second dose of the vaccine. We enrolled 103 previously naturally infected and 627 uninfected HCWs. The mean time for vaccination after the first nasopharyngeal SARS-CoV-2 positivity was 64 days (range: 15–136 days) in previously naturally infected HCWs. Among the previously naturally infected HCWs, 41 (40%) were asymptomatic, 52 (50%) had mild upper respiratory tract infections, 10 (105) had pneumonia, and only 6 (5%) were hospitalized. Any reported adverse reactions, either from the first dose or the second dose of vaccine administration, did not differ between previously infected and uninfected HCWs. Anti-RBD antibody titers were obtained in 50 (51%) of 103 previously infected HCWs and 142 (23%) of 627 uninfected HCWs. Anti-RBD antibody titers were significantly higher in HCWs with a previous natural infection (median 1220 AU/ml, range: 202–10328 AU/mL) than in uninfected HCWs (median: 913 AU/ml, range: 2.8–15547 AU/mL, p = .032). CoronaVac administration was safe and may elicit higher antibody responses in previously naturally infected individuals.

SARS-CoV-2 anti-spike antibody titres after vaccination with BNT162b2 in naïve and previously infected individuals

Great expectations are placed in vaccines against COVID-19 to control the pandemic. We reviewed the antibody titres in a cohort of healthcare workers (HCWs) vaccinated with BNT162b2 to assess the influence of a previous infection on them. We stratified the results according to the individual history of nasopharyngeal swab (NPS) and symptoms. Among 3475 HCWs the highest titres were recorded among those infected more than 6 months before vaccination, independently of symptoms, followed by those infected less than 6 months before vaccination, especially in those with symptoms, and by uninfected HCWs. Vaccination with BNT162b2 can boost immunity acquired through infection, particularly in those infected more than 6 months before vaccination.

What influences the infection of COVID-19 in healthcare workers?

The outbreak of COVID-19 has spread worldwide. The evidence about risk factors of healthcare workers who infected COVID-19 is limited. This study aims to describe characteristics and influencing factors of the COVID-19 infection in healthcare workers. The study was performed among COVID-19 infected and uninfected healthcare workers in three hospitals in Wuhan. A total of 325 healthcare workers participated; among them 151 COVID-19-infected healthcare workers were included. Characteristics of infected healthcare workers, and influencing factors including exposure histories, the use of protective equipment in different risk conditions and areas, perceptions, emotions, satisfactions and educations were described and analyzed. Healthcare workers got infected clustered mostly in the physical examination center. When performing general operations on confirmed or suspected patients, the use of protective equipment including the effectiveness of masks (p < 0.001), gloves (p < 0.001); and the use of gloves (p < 0.001), suits (p < 0.001), gowns (p < 0.001), shoe covers (p < 0.001), and hats (p < 0.001) were protective factors. The use of protective equipment was a protective factor in most cases. Negative emotions and dissatisfaction to the hospital response were associated with the increased risk of infection. The use of protective equipment, emotions and satisfactions to hospital responses are key COVID-19-infected factors. The awareness, the supply and the use of protective equipment, the layout of departments and other environmental and management factors should be strictly equipped. In addition, hospitals should also pay attention to emotions and satisfaction of healthcare workers.

SARS-CoV-2 Infection in Health Care Workers: A Retrospective Analysis and Model Simulations of a Nosocomial Outbreak

Background: There had been a preliminary occurrence of human-to-human transmissions between healthcare workers (HCWs), but risk factors in the susceptibility for COVID-19, and infection patterns among HCWs have largely remained unknown. Methods: Retrospective data collection on demographics, lifestyles, contact status with infected subjects for 118 HCWs (include 12 COVID-19 HCWs) from a single-center. Sleep quality and working pressure were evaluated by Pittsburgh Sleep Quality Index (PSQI) and The Nurse Stress Index (NSI), respectively. Follow-up duration was from Dec 25, 2019, to Feb 15, 2020. Risk factors and transmission models of COVID-19 among HCWs were analyzed and constructed. Findings: A high proportion of COVID-19 HCWs had engaged in night shift-work (75.0% vs. 40.6%) and felt they were working under pressure (66.7% vs. 32.1%) than uninfected HCWs. COVID-19 HCWs had higher total scores of PSQI and NSI than uninfected HCWs. Furthermore, these scores were both positively associated with COVID-19 risk. An individual-based model (IBM) estimated the outbreak duration among HCWs in a non-typical COVID-19 ward at 62-80 days and the basic reproduction number =1.27 [1.06, 1.61]. By reducing the average contact rate per HCW by a 1.35 factor and susceptibility by a 1.40 factor, we can avoid an outbreak of the basic case among HCWs. Interpretation: Poor sleep quality and high working pressure were positively associated with high risks of COVID-19. A novel IBM of COVID-19 transmission is suitable for simulating different outbreak patterns in a hospital setting. Funding Statement: This work was supported by the Fundamental Research Funds for the Central Universities (grant 2020kfyXGYJ010 to Dr. X. Jiang). Declaration of Interests: None. Ethics Approval Statement: This study was approved by the institutional ethics board of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (No. 20200029).

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis

The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.

ST114 IL28B SNP does not predict the outcome of Hepatitis C Virus-specific cellular immune response

The CC genotype of single nucleotide polymorphism (SNP) at the rs12979860 site of interleukin (IL)28B gene has been associated with spontaneous Hepatitis C Virus (HCV) clearance and interferon-treatment response. The role of IL28B SNP in predicting HCV-specific cell mediated immune (CMI) responses has not been investigated. We recently reported HCV-specific CMI responses in exposed uninfected healthcare workers (HCW) at high risk of infection without detecting viremia or seroconversion. The HCW at the National Liver Institute serve a patient cohort with ∼90% HCV prevalence. We investigated the HCV-specific CMI response in seronegative, aviremic HCW (n=102) and their chronic (n=36) and resolved (n=20) counterparts. We used an enzyme-linked immunospot (ELISPOT) assay to quantify interferon gamma production in response to a set of genotype 4a overlapping 15mer peptide pools covering the whole HCV genome. Also, we examined IL28B genotype of these HCW by real-time PCR. We confirmed our previous findings of HCV-specific CMI without viremia or seroconversion in more than 20% of these HCW suggesting clearance of low levels of HCV exposures. The percentage of IL28B CC allele in chronic, resolved and seronegative aviremic subjects were 31%, 45%, and 46%, while that of the TT allele was 31%, 0% and 8%, respectively. Although IL28B SNP predicted the outcome of HCV infection, we did not find any correlation between the different IL28B genotypes and the outcome of HCV-specific CMI responses in the three groups tested (p>0.05). Taken together, these data support the notion that a protective HCV vaccine targeting CMI is feasible regardless of IL28B genotype. Also, IL28B does not predict the outcome of HCV-specific CMI responses.

Zidovudine toxicity in uninfected health care workers

Zidovudine toxicity in uninfected health care workers

Discussion: Zidovudine toxicity in uninfected healthcare workers

Discussion: Zidovudine toxicity in uninfected healthcare workers

Zidovudine toxicity in uninfected healthcare workers

To evaluate the toxicity of zidovudine (ZDV) prophylaxis in human immunodeficiency virus (HIV)-exposed healthcare workers (HCWs) in Italy, a national protocol for postexposure prophylaxis has been implemented and a national registry has been established. All Italian clinical centers licensed to dispense ZDV participate. As of December 1995, data from 674 individuals who received ZDV prophylaxis have been collected. In three cases ZDV was used in combination with either didanosine (DDI) or dideoxycytidine (DDC). In 556 cases (82%), the daily dose of ZDV was 1,000 mg/day; 21 HCWs (3%) were treated with 300-800 mg/day, and in 72 persons (11%) the dose was 1,200-3,000 mg/day. A total of 332 (49%) HCWs reported at least one adverse effect; 132 (20%) discontinued prophylaxis because of side effects (40% of those reporting side effects). Nausea was reported in 243 cases; other side effects included vomiting, gastric pain, diarrhea, asthenia, and headache. Most constitutional adverse effects were reported during the first week of prophylaxis. Grade 1 anemia (hemoglobin 9.5-11 g/dL) occurred in 10 cases (3%); in 2 cases, the neutrophil count decreased to <1,000 cells/mm3. A transient increase of serum alanine aminotransferase to three times the upper limit of normal was observed in 7 persons. All side effects were reversible after the prophylaxis was stopped. Among those reporting at least one side effect the mean duration of treatment was 22 days; for HCWs reporting hematologic or liver adverse effects the mean length of treatment was 34 days. A total of 351 HCWs (54.6%) ceased the treatment before the scheduled 1-month period. In the 132 persons who discontinued treatment because of side effects, the mean length of prophylaxis was 8 days. One HCW seroconverted after conjunctival exposure to blood. The short-term toxicity of ZDV prophylaxis is frequent, mild, dose related, and reversible. Further studies are needed to assess the risk of long-term sequelae of this treatment as well as of prophylaxis with combinations of antiretroviral drugs.

Zidovudine safety and tolerance among uninfected healthcare workers: A brief update

e W initiated a collaborative study of the safety and tolerance of zidovudine treatment for postexposure prophylaxis of occupational exposures in >14 institutions soon after the drug was licensed. Our study was not designed to evaluate treatment efficacy, since the number of expected exposures was too small to provide sufficient power for an assessment of this outcome. However, we were interested in addressing several questions relevant to exposed workers and their treating clinicians: (1) what is the prevalence, severity, and temporal sequence of adverse events associated with drug treatment; (2) what is the effect of zidovudine treatment on the temporal sequence of markers of human immunodeficiency virus (HIV) infection, should it occur; (3) what is the epidemiology of HIV exposures for which postexposure treatment was elected; and (4) what is the feasibility of implementing a postexposure treatment program. Updates on the progress of this study have been presented.‘-’ As of March 1996, >250 healthcare workers have been enrolled. Preliminary findings to date include the following: 1. Initiation of postexposure treatment within 4 hours of exposure appears to be a feasible goal, even for exposures occurring at night and on weekends; 2. Symptoms of drug intolerance (nausea, fatigue, headache, etc.) occurred in a substantial number of subjects and in some, contributed to the decision to stop treatment. No unexpected symptoms attributable to zidovudine developed; 3. No laboratory toxicities requiring dose adjustment or discontinuation have been observed to date.