Serological Immunity Research Articles

High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infection

Long-term antibody responses to SARS-CoV-2 have focused on responses to full-length spike protein, specific domains within spike, or nucleoprotein. In this study, we used high-density peptide microarrays representing the complete proteome of SARS-CoV-2 to identify binding sites (epitopes) targeted by antibodies present in the blood of COVID-19 resolved cases at 5 months post-diagnosis. Compared to previous studies that evaluated epitope-specific responses early post-diagnosis (< 60 days), we found that epitope-specific responses to nucleoprotein and spike protein have contracted, and that responses to membrane protein have expanded. Although antibody titers to full-length spike and nucleoprotein remain steady over months, taken together our data suggest that the population of epitope-specific antibodies that contribute to this reactivity is dynamic and evolves over time. Further, the spike epitopes bound by polyclonal antibodies in COVID-19 convalescent serum samples aligned with known target sites that can neutralize viral activity suggesting that the maintenance of these antibodies might provide rapid serological immunity. Finally, the most dominant epitopes for membrane protein and spike showed high diagnostic accuracy providing novel biomarkers to refine blood-based antibody tests. This study provides new insights into the specific regions of SARS-CoV-2 targeted by serum antibodies long after infection.

Suboptimal Serologic Immunity Against Poliomyelitis Among New Migrant Children in Greece Calls for Organized Action.

Migration-flows pose the risk of poliovirus reintroduction from endemic countries to Greece. This study aims to evaluate serologic-immunity/vaccination against poliomyelitis in newly-arriving migrant children. Demographic-immunisation data and blood-serum were obtained from migrants 1-14years-old, referred to a hospital-clinic in Athens-Greece within three months from arrival. Immunity to polioviruses-1-3 was determined by serum-neutralizing-antibodies(WHO guidelines). Titers ≥ 1:8 were considered positive. From 9/2010 to 9/2013, 274 children(150 refugees/124 immigrants), mean age 7.1years-old, were enrolled. Only 57(20.8%) of them presented with vaccination-records. Children originated mainly from Asia(n = 198), Eastern Europe(n = 28), Middle East(n = 24) and Africa(n = 24) with 160(58.4%) from polio-endemic-countries(Afghanistan-112(40.8%), Pakistan-24(8.8%) and India-24(8.8%)). Seropositivity against polio-1-2&3 was 84.3%, 86.1% and 74.5%, respectively. Immigrants, had higher seroprotective rates against polioviruses-1-2&3 than refugees(polio-1:p = 0.002;polio-2:p = 0.004,polio-3:p < 0.001). Seronegativity to 1PVs-2PVs and all three polio serotypes was found in 37(13.5%),12 (4.4%), and 30 children(10.9%) respectively. Increasing number of vaccine-doses, and younger-age, were positively-associated with seropositivity. A remarkable fraction of newly-arrived migrant-children were seronegative to one or more polioviruses.

The efficacy of a 2,4-diaminoquinazoline compound as an intranasal vaccine adjuvant to protect against influenza A virus infection in vivo.

Adjuvants are substances added to vaccines to enhance antigen-specific immune responses or to protect antigens from rapid elimination. As pattern recognition receptors, Toll-like receptors 7 (TLR7) and 8 (TLR8) activate the innate immune system by sensing endosomal single-stranded RNA of RNA viruses. Here, we investigated if a 2,4-diaminoquinazoline-based TLR7/8 agonist, (S)-3-((2-amino-8-fluoroquinazolin-4-yl)amino)hexan-1-ol (named compound 31), could be used as an adjuvant to enhance the serological and mucosal immunity of an inactivated influenza A virus vaccine. The compound induced the production of proinflammatory cytokines in macrophages. In a dose-response analysis, intranasal administration of 1 µg compound 31 together with an inactivated vaccine (0.5 µg) to mice not only enhanced virus-specific IgG and IgA production but also neutralized influenza A virus with statistical significance. Notably, in a virus-challenge model, the combination of the vaccine and compound 31 alleviated viral infection-mediated loss of body weight and increased survival rates by 40% compared with vaccine only-treated mice. We suggest that compound 31 is a promising lead compound for developing mucosal vaccine adjuvants to protect against respiratory RNA viruses such as influenza viruses and potentially coronaviruses.

Serological Humoral Immunity Following Natural Infection of Children with High Burden Gastrointestinal Viruses.

Acute gastroenteritis (AGE) is a major cause of morbidity and mortality worldwide, resulting in an estimated 440,571 deaths of children under age 5 annually. Rotavirus, norovirus, and sapovirus are leading causes of childhood AGE. A successful rotavirus vaccine has reduced rotavirus hospitalizations by more than 50%. Using rotavirus as a guide, elucidating the determinants, breath, and duration of serological antibody immunity to AGE viruses, as well as host genetic factors that define susceptibility is essential for informing development of future vaccines and improving current vaccine candidates. Here, we summarize the current knowledge of disease burden and serological antibody immunity following natural infection to inform further vaccine development for these three high-burden viruses.

SARS‐CoV‐2 neutralizing antibodies decline over one year and patients with severe COVID‐19 pneumonia display a unique cytokine profile

ObjectivesAs coronavirus disease 2019 (COVID-19) rages on worldwide, there is an urgent need to characterize immune correlates of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify immune determinants of COVID-19 severity. MethodsThis study examined the longitudinal profiles of neutralizing antibody (NAb) titers in hospitalized COVID-19 patients clinically diagnosed with mild symptoms, pneumonia, or severe pneumonia, up to 12 months after illness onset, using live-virus neutralization. Multiplex, correlation, and network analyses were used to characterize serum-derived inflammatory cytokine profiles in all severity groups. ResultsPeak NAb titers correlated with disease severity, and NAb titers declined over the course of 12 months regardless of severity. Multiplex analyses revealed that IP-10, IL-6, IL-7, and VEGF-α were significantly elevated in severe pneumonia cases compared to those with mild symptoms and pneumonia cases. Correlation and network analyses further suggested that cytokine network formation was distinct in different COVID-19 severity groups. ConclusionsThe study findings inform on the long-term kinetics of naturally acquired serological immunity against SARS-CoV-2 and highlight the importance of identifying key cytokine networks for potential therapeutic immunomodulation.

Serologic response to mRNA COVID‐19 vaccination in lymphoma patients

Serologic response to <scp>mRNA COVID</scp>‐19 vaccination in lymphoma patients

SARS-CoV-2-specific serological and functional T cell immune responses during acute and early COVID-19 convalescence in solid organ transplant patients

The description of protective humoral and T cell immune responses specific against SARS‐CoV‐2 has been reported among immunocompetent (IC) individuals developing COVID‐19 infection. However, its characterization and determinants of poorer outcomes among the at‐risk solid organ transplant (SOT) patient population have not been thoroughly investigated. Cytokine‐producing T cell responses, such as IFN‐γ, IL‐2, IFN‐γ/IL‐2, IL‐6, IL‐21, and IL‐5, against main immunogenic SARS‐CoV‐2 antigens and IgM/IgG serological immunity were tracked in SOT (n = 28) during acute infection and at two consecutive time points over the following 40 days of convalescence and were compared to matched IC (n = 16) patients admitted with similar moderate/severe COVID‐19. We describe the development of a robust serological and functional T cell immune responses against SARS‐CoV‐2 among SOT patients, similar to IC patients during early convalescence. However, at the infection onset, SOT displayed lower IgG seroconversion rates (77% vs. 100%; p = .044), despite no differences on IgG titers, and a trend toward decreased SARS‐CoV‐2‐reactive T cell frequencies, especially against the membrane protein (7 [0–34] vs. 113 [15–245], p = .011, 2 [0–9] vs. 45 [5–74], p = .009, and 0 [0–2] vs. 13 [1–24], p = .020, IFN‐γ, IL‐2, and IFN‐γ/IL‐2 spots, respectively). In summary, our data suggest that despite a certain initial delay, SOT population achieve comparable functional immune responses than the general population after moderate/severe COVID‐19.

Two Dose Series of High-Dose Influenza Vaccine Is Associated with Longer Duration of Serologic Immunity in Patients with Plasma Cell Disorders

Background:Patients with plasma cell disorders (PCDs) are highly susceptible to infections, including influenza, which are a major source of morbidity. Seasonal influenza vaccination is routinely administered to patients with PCDs, yet influenza infections remain common. Combining the use of higher antigen dose and a booster strategy, we recently reported a randomized study of a two dose series of high-dose influenza vaccine, which was associated with fewer influenza infections than standard influenza vaccination in patients with PCDs (Branagan, et al, ASH 2016). However, the immunologic effects following this vaccination strategy remains unknown. Few studies have focused on serologic responses to influenza vaccination in PCD patients and there are none to the authors' knowledge which have measured longitudinal serologic responses over a single flu season.Methods:We conducted a double-blind, randomized clinical trial over the 2015-16 flu season, comparing two doses of Fluzone® High-Dose influenza vaccination (separated by 30 days) to standard of care influenza vaccination. Patients were allocated to the experimental arm in 2:1 ratio. Standard of care influenza vaccination was considered single age-based vaccination (standard dose <65 years and high-dose ≥ 65 years) and patients in this arm received a saline placebo injection at 30 days to assist in blinding. Eligibility criteria allowed any patient with a plasma cell disorder and no contraindication to trivalent inactivated influenza vaccine. HAI titers were analyzed by standardized procedure at four time points, baseline, 30 days following the initial vaccine, 30 days following the second vaccine, and at the end of the flu season (April 30).Results:122 total plasma cell disorder patients were enrolled (97 with disease requiring therapy and 25 with asymptomatic gammopathy). Forty-eight patients received a single standard of care influenza vaccination and 74 patients received two doses of Fluzone High-Dose vaccine. Median age was 67 years (range 42-90). Following the second vaccine / placebo, rates of total seroprotection (against all 3 influenza vaccine strains) were 86.3% for patients who received two high dose vaccines and 63.9% for standard vaccination patients. At the end of the flu season, rates of total seroprotection were 58.5% for patients who received two high dose vaccines and 33.3% for standard vaccination patients. Chi-square testing revealed that patients receiving the two dose vaccine strategy experienced significantly higher rates of total seroprotection following second vaccine (p<0.05). At the end of the flu season rates of seroprotection trended toward significance at the end of the flu season against all 3 vaccine strains (p=0.07), against the H3N2 strain (p=0.05) and were significantly higher against the H1N1 strain (p<0.05).Conclusions:We previously reported that a two dose strategy of Fluzone® High-Dose influenza vaccine is safely tolerated in patients with plasma cell disorders and associated with fewer laboratory-confirmed influenza infections. Unexpectedly, the current analysis revealed that protective HAI antibody titers rapidly fall in PCD patients. Typically, HAI titers slowly decrease following a peak protective response, but do not drop below protective levels until after 6 months. However, PCD patients in this study began to lose HAI seroprotection within 4 months and even as little as 30 days. Interestingly, patients who received the two dose series of high-dose influenza vaccine maintained higher rates of seroprotection at the end of the influenza season compared to those who received standard vaccination. The maintenance of seroprotection was greatest against the seasonal H1N1 strain (which was the predominate circulating strain during that particular 2015-2016 flu season). Importantly, these results suggest that a two dose series of high-dose vaccine provides may mitigate loss of vaccine-induced HAI titers and allow more durable serologic protection throughout the flu season. Studies are ongoing to further explore immune function following influenza vaccination, including cell-mediated responses. More studies are warranted to help determine the optimal dose and timing of influenza vaccination in PCD patients. Understanding the unique kinetics of serologic responses in PCD patients may have practice changing implications for other vaccines and therapies in this population. DisclosuresNo relevant conflicts of interest to declare.

Reduced Resistance of SARS-CoV-2 Variants Toward Affinity-Matured Serological Immunity

SARS-CoV-2 variants have raised concerns regarding resistance to neutralizing antibodies elicited by the parental virus. In the present study, we monitored multiple parameters of neutralizing antibodies in convalescent plasma up to 10 months after the symptom onset. In contrast to marked decline of neutralizing antibody titers, the neutralization potency per antibody increased with time. The antigenic drift of B.1.351 (501Y.V2) and P.1 (501Y.V3) variants conferred resistance to neutralization by convalescent plasma in the early phase; however, the resistance of these variants was attenuated by progressive increase of neutralization potency and breadth over time. Furthermore, this increase in the neutralization potency/breadth were highly correlated with the affinity maturation of IgG antibodies that target virus conserved sites with extended half-lives. Despite a quantitative decline in the neutralizing antibody titers, the serological immunity shapes the neutralization potency and breadth with time, thereby acquiring persistent neutralizing activity toward SARS-CoV-2 variants. Declaration of Interest: All authors declare that they have no competing interests. Ethical Approval: All studies were approved by the Institutional Review Board of the National Institute of Infectious Diseases (#1127, #1132, and #1197). This study was performed in accordance with the Declaration of Helsinki. All volunteers provided written informed consent prior to enrollment.

To the question of the reasons for the activation of the epidemic process of Мeasles at the stage of elimination of infection and the forecast of the situation in the near and long term

Introduction. Measles infection in recent years has become particularly relevant in connection with the registration of outbreaks of this disease in various territoriesof the Russian Federation and abroad.The aim of the study is to characterize the epidemic process of measles in a large industrial city in the near and long term with the use of modern mathematical modeling technologies for making new management decisions on infection control at the elimination stage.Materials and methods. The research materials were data from statistical reports of measles incidence in Yekaterinburg from 1950 to 2019 (70 years of follow-up), medical documentation of measles cases, population vaccination data (form No. 6 for 2000—2018 and outpatient maps of children under two years of age vaccinated against measles), results of screening for measles IgG ofmedical organizations, data of planned serological monitoringof population immunity to measles in «indicator» groups in the period from 2013 to 2017 and the results of mathematical modeling of measles incidence in different scenarios of its prevention.Results. Under the influence of vaccination, the epidemic process of measles in Yekaterinburg — a city with a population of 1.5million inhabitants-has undergone significant changes. During the observation period, the incidence decreased to sporadic levels, there was no indigenous measles, drifts from endemic areas had no consequences, the epidemic process was under control. However, outbreaks of 72 cases in 2016 and 90 cases in 2019 have changed our view of measles as a eradicated infection.Of the factors that led to the spread of infection in the foci, the most significant were the presence of measles-susceptible children and adults, including those previously vaccinated, mainly in the periods remote from vaccination and revaccination, defects in the clinical diagnosis of measlesin the first and subsequent cases, and violations in the organization and conduct of anti-epidemic measures. Conclusion. Based on the data of mathematical modeling of the epidemic process of measles with different combinations of its determinants, for the elimination of infection, it is necessary to ensure vaccination against measles at the age of 1 year and 6 years in 95—97.5%. In vulnerable groups for infection to discuss the introduction of routine revaccination among people up to 50 years of age with an interval of 10 years.

Reemergence of Human Monkeypox and Declining Population Immunity in the Context of Urbanization, Nigeria, 2017-2020.

A monkeypox outbreak in Nigeria during 2017–2020 provides an illustrative case study for emerging zoonoses. We built a statistical model to simulate declining immunity from monkeypox at 2 levels: At the individual level, we used a constant rate of decline in immunity of 1.29% per year as smallpox vaccination rates fell. At the population level, the cohort of vaccinated residents decreased over time because of deaths and births. By 2016, only 10.1% of the total population in Nigeria was vaccinated against smallpox; the serologic immunity level was 25.7% among vaccinated persons and 2.6% in the overall population. The substantial resurgence of monkeypox in Nigeria in 2017 appears to have been driven by a combination of population growth, accumulation of unvaccinated cohorts, and decline in smallpox vaccine immunity. The expanding unvaccinated population means that entire households, not just children, are now more susceptible to monkeypox, increasing risk of human-to-human transmission.

Tandem high-dose influenza vaccination is associated with more durable serologic immunity in patients with plasma cell dyscrasias

Patients with plasma cell dyscrasias (PCDs) experience an increased burden of influenza, and current practice of single-dose annual influenza vaccination yields suboptimal protective immunity in these patients. Strategies to improve immunity to influenza in these patients are clearly needed. We performed a randomized, double-blind, placebo-controlled clinical trial comparing tandem Fluzone High-Dose influenza vaccination with standard-of-care influenza vaccination. Standard-of-care vaccination was single-dose age-based vaccination (standard dose, <65 years; high dose, ≥65 years), and patients in this arm received a saline placebo injection at 30 days. A total of 122 PCD patients were enrolled; 47 received single-dose standard-of-care vaccination, and 75 received 2 doses of Fluzone High-Dose vaccine. Rates of hemagglutinin inhibition (HAI) titer seroprotection against all 3 strains (H1N1, H3N2, and influenza B) were significantly higher for patients after tandem high-dose vaccination vs control (87.3% vs 63.2%; P = .003) and led to higher seroprotection at the end of flu season (60.0% vs 31.6%; P = .04). These data demonstrate that tandem high-dose influenza vaccination separated by 30 days leads to higher serologic HAI titer responses and more durable influenza-specific immunity in PCD patients. Similar vaccine strategies may also be essential to achieve protective immunity against other emerging pathogens such as novel coronavirus in these patients. This trial was registered at www.clinicaltrials.gov as #NCT02566265.

Seroprevalence of Measles Antibodies in Healthcare Professionals in a Central Hospital in Portugal

Immunity against measles may result from previous contact with the virus or vaccination. In this study we aimed to evaluate the prevalence of immunity to measles in healthcare professionals of a central hospital. Retrospective study, with description of the results of measles-specific IgG assay in healthcare professionals, between May 2010 and March 2018. The results of 1339 healthcare professionals were analyzed. The average age was 39.3 ± 10.11 years, 71.1% female. The prevalence of positive IgG was 81.5%, higher among professionals in the age groups 40 - 49 and over 50 years (91.9% and 94.6% respectively). Healthcare professionals who presented negative or equivocal IgG were mostly under 40 years old (83.1%) (p < 0.05). The prevalence of serological immunity to measles in healthcare professionals was found to be lower than in other studies. That may be due to differences between the characteristics of the studied samples. Susceptibility to measles was higher in lower age groups. These results may reflect low vaccination coverage in this age group, an incomplete vaccination schedule, or the possibility of older healthcare professionals having the disease, which may confer an immune response with higher IgG levels. Knowing the prevalence of susceptibility to measles in healthcare professionals enabled the establishment of prevention strategies for outbreaks that may occur. Vaccination remains the best preventative measure, but a third dose of vaccine may be considered in certain epidemiological contexts, particularly in the youngest exposed healthcare professionals.

Decline of serologic immunity to diphtheria, tetanus and pertussis with age suggested a full life vaccination in mainland China

ABSTRACT Background: Diphtheria-tetanus-pertussis (DTP) vaccine has already been involved in national vaccination program for several decades in China. The immunity against these diseases in the people of all ages is not well investigated. Materials and methods: Serum samples were tested for IgG antibodies to diphtheria toxoid (DT), tetanus toxoid (TT) and pertussis toxin (PT) by using commercial ELISA kits. Results: A total of 666 sera of patients from 1 day to 89 years of age was collected from 2018 to 2019. The protective rates of diphtheria, tetanus and pertussis were 45.5%, 54.4% and 4.7%, respectively. Only 4.7% of the study population had seropositivity against three of the diseases. Young infant (<3 m) and adult (>18y) were generally lack of protective antibody against diphtheria (81.7% and 58.3%) and tetanus (91.5% and 86.2%). An obvious increase in immunity level of diphtheria and tetanus was observed at 3 m-3y, but there was no significant increase of immunity to pertussis at any age group. All age groups showed low immunity to pertussis. Conclusions: The present results revealed the susceptibility to diphtheria and tetanus in young infants and adults, and the susceptibility to pertussis over the ages, which highlight the need to improve the current vaccination program.

Gaps in Serologic Immunity against Contemporary Swine-Origin Influenza A Viruses among Healthy Individuals in the United States.

Influenza A Viruses (IAV) in domestic swine (IAV-S) are associated with sporadic zoonotic transmission at the human–animal interface. Previous pandemic IAVs originated from animals, which emphasizes the importance of characterizing human immunity against the increasingly diverse IAV-S. We analyzed serum samples from healthy human donors (n = 153) using hemagglutination-inhibition (HAI) assay to assess existing serologic protection against a panel of contemporary IAV-S isolated from swine in the United States (n = 11). Age-specific seroprotection rates (SPR), which are the proportion of individuals with HAI ≥ 1:40, corresponded with lower or moderate pandemic risk classifications for the multiple IAV-S examined (one H1-δ1, one H1-δ2, three H3-IVA, one H3-IVB, one H3-IVF). Individuals born between 2004 and 2013 had SPRs of 0% for the five classified H3 subtype IAV-S, indicating youth may be particularly predisposed to infection with these viruses. Expansion of existing immunologic gaps over time could increase likelihood of future IAV-S spillover to humans and facilitate subsequent sustained human-to-human transmission resulting in disease outbreaks with pandemic potential.

Loss of memory B cells impairs maintenance of long-term serologic memory during HIV-1 infection

Circulating memory B cells are severely reduced in the peripheral blood of HIV-1-infected patients. We investigated whether dysfunctional serologic memory to non-HIV antigens is related to disease progression by evaluating the frequency of memory B cells, plasma IgG, plasma levels of antibodies to measles, and Streptococcus pneumoniae, and enumerating measles-specific antibody-secreting cells in patients with primary, chronic, and long-term nonprogressive HIV-1 infection. We also evaluated the in vitro production of IgM and IgG antibodies against measles and S pneumoniae antigens following polyclonal activation of peripheral blood mononuclear cells (PBMCs) from patients. The percentage of memory B cells correlated with CD4+ T-cell counts in patients, thus representing a marker of disease progression. While patients with primary and chronic infection had severe defects in serologic memory, long-term nonprogressors had memory B-cell frequency and levels of antigen-specific antibodies comparable with controls. We also evaluated the effect of antiretroviral therapy on these serologic memory defects and found that antiretroviral therapy did not restore serologic memory in primary or in chronic infection. We suggest that HIV infection impairs maintenance of long-term serologic immunity to HIV-1-unrelated antigens and this defect is initiated early in infection. This may have important consequences for the response of HIV-infected patients to immunizations.

How Australia's commitment and activities for measles control achieved rubella elimination

Background: The global measles and rubella strategic plan 2012–20 has a target for measles and rubella elimination in five WHO regions by the end of 2020. Only one region has eliminated rubella. The WHO Strategic Advisory Group of Experts on Immunization advised rubella control was lagging and recommended rubella vaccination be introduced into all country immunisation programmes as soon as possible. We describe the impact enhanced measles control activities, using measles-mumps-rubella (MMR) vaccines, had on rubella incidence in Australia and how these activities lead to the successful elimination of both viruses. Methods and materials: We reviewed rubella notifications from Australia's National Notifiable Disease Surveillance System (1991–2018) and stratified by age, sex and vaccination status. Three-year cumulative incidences were calculated by birth-cohort to assess the impact of two major measles immunisation activities in Australia; the 1998 Measles Control Campaign (MCC), targeted children 5–12 years; and the 2001 Young Adult MMR immunisation program (YA-MMR), targeted adults 18–30 years. MMR immunisation coverage estimates were extracted and compared with notification data. Aggregate national serological survey data (1999, 2002, 2007 and 2012) was assigned to birth-cohorts and the mean, median and ranges of age-group estimates were calculated. Results: The MCC attained 96% coverage, the three-year cumulative incidence of rubella declined by 90% compared with the three years preceding. This effect was also seen following the YA-MMR with a 73% decline in pre-and-post three-year periods, however vaccine coverage during this campaign was considerably lower. Serological surveys displayed a high and constant level of immune protection among females, but males were estimated to have 4–13% lower immunity. Rubella immunity significantly benefited by a direct 17% boost in serological immunity in those 6–11 years of age in the 1999 pre-and-post serological survey. Conclusion: The use of combined MMR vaccines to address measles immunity concerns in Australia demonstrated a symbiotic benefit in not only controlling and eliminating measles transmission but rubella as well. Although the coverage of the YA-MMR was considered to be “sub-optimal”, it effectively closed the rubella immunity gap in Australia, and demonstrates that utilising combination MR-containing vaccines in routine and mass vaccination programs is effective in eliminating the transmission of both viruses.

Perceptions of immunity and vaccination certificates among the general population: a nested study within a serosurvey of anti-SARS-CoV-2 antibodies (SEROCoV-POP).

At a time when COVID-19 immunity certificates are debated and vaccination certificates might potentially be made available if an effective vaccine is established, we conducted a study to elucidate public opinion on this issue. Our objective was to determine social and individual perceptions of COVID-19 immunity certificates through a population-based study. A nested survey within the SEROCoV-POP study, a population-based serosurvey of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland, was conducted with a self-administered questionnaire. The questionnaire was proposed to 1520 SEROCoV-POP participants. Measures included percentage of participants agreeing or disagreeing with statements on immunity and vaccination certificates. Stratification by age, gender, education and work status was used to examine socio-demographic variations. Of the 1520 SEROCoV-POP participants, 1425 completed the questionnaire (response rate 93%; mean age &plusmn; standard deviation 52 &plusmn; 15.1 years; 51.9% women). About 80% of participants agreed that knowing one&rsquo;s serology status would lead to a change in one&rsquo;s behaviour. In the event that the presence of antibodies correlated with immunity, 60% of participants reported that certificates should be offered to the general population. The results showed variations in perceptions of certificates depending on the context (73% agreed on certificates&rsquo; utility for travel, 72% for entering a country, and 32% for the right to work). Provided an effective vaccine was available, 55% of participants agreed that vaccination should be mandatory and 49% agreed that a vaccination certificate should be mandatory. About 68% reported a potential risk of discrimination and 28% a risk of deliberate infection. Differences were seen with age, gender and education level. This study shows that the general adult population in Geneva, Switzerland can envisage scenarios where COVID-19 immunity, and eventually vaccination, certificates would be useful. Seroprevalence estimates of anti-SARS-CoV-2 antibodies remain low to date, and the interpretability of serological testing and immunity remains undefined. However, the information from this study is important, especially the differences based on context and the socio-demographic variations, and should be taken into account if COVID-19-related certificates are to be implemented.

T cell and antibody responses to SARS-CoV-2: Experience from a French transplantation and hemodialysis center during the COVID-19 pandemic.

Immunosuppressed organ‐transplanted patients are considered at risk for severe forms of COVID‐19. Moreover, exaggerated innate and adaptive immune responses might be involved in severe progression of the disease. However, no data on the immune response to SARS‐CoV‐2 in transplanted patients are currently available. Here, we report the first assessment of antibody and T cell responses to SARS‐CoV‐2 in 11 kidney‐transplanted patients recovered from RT‐PCR–confirmed (n = 5) or initially suspected (n = 6) COVID‐19. After reduction of immunosuppressive therapy, RT‐PCR–confirmed COVID‐19 transplant patients were able to mount vigorous antiviral T cell and antibody responses, as efficiently as two nontherapeutically immunosuppressed COVID‐19 patients on hemodialysis. By contrast, six RT‐PCR–negative patients displayed no antibody response. Among them, three showed very low numbers of SARS‐CoV‐2–reactive T cells, whereas no T cell response was detected in the other three, potentially ruling out COVID‐19 diagnosis. Low levels of T cell reactivity to SARS‐CoV‐2 were also detected in seronegative healthy controls without known exposure to the virus. These results suggest that during COVID‐19, monitoring both T cell and serological immunity might be helpful for the differential diagnosis of COVID‐19 but are also needed to evaluate a potential role of antiviral T cells in the development of severe forms of the disease.

S2471 A Fatal Case of Fulminant Hepatic Failure Associated With Hepatitis A Virus

INTRODUCTION: Hepatitis A Virus (HAV) is a RNA virus that is contagious and spread by fecal-oral transmission. It is a global public health concern with 1.4 million cases each year(1) and is typically a self-limited illness. Fulminant hepatic failure, acute liver failure with encephalopathy and impaired synthetic function, occurs in less than one percent of cases(1). We present a case of unresolving HAV infection leading to fulminant liver failure and death. CASE DESCRIPTION/METHODS: An 83-year-old female with CAD presented with 3 days of lethargy. Vital were normal and exam revealed jaundice. Medications did not reveal hepatotoxic agents. Lab revealed glucose 21, lactate 6, bilirubin 4.9, AST 9291, ALT 8757, INR 13. Hepatitis panel positive for HAV IgM and negative IgG. EBV, CMV, HBV and HCV serology negative. Autoimmune work up, urine toxicology and acetaminophen levels were negative. Doppler showed mild intrahepatic ductal dilation with no thrombosis. Despite improving transaminases, she became encephalopathic for which lactulose enemas were given. She was transferred to the ICU for grade-3 hepatic encephalopathy. It was discovered the patient received food donations from multiple sources. Liver transplant centers were consulted however the patient was denied candidacy given age and comorbidities. Improvement in liver enzymes were indicative of liver exhaustion as the patient’s condition deteriorated. She eventually required vasopressor support. After discussions with palliative care, patient was transitioned to comfort care and passed. DISCUSSION: The incidence of HAV declined from 6 to 0.4 per 100,000 between 1999 and 2014(5). Introduction of HAV vaccine, measures to improve food preparation, sanitation and educational initiatives are likely explanations for decreasing incidence. Despite this, our case demonstrates a fatality as a result of fulminant HAV in an elderly female, in a developed nation, with no recent history of travel or evidence of prior immunity or coinfection. Fulminant liver failure occurs more commonly in individuals >50 years with other liver diseases such as hepatitis B and C(2). The source of infection in our patient is unclear although suspicion of foodborne illness remains and whether prior immunity would have improved her outcome. Interestingly, only 1/3 of the United States have serological immunity and additional measures are needed to avoid sporadic cases of acute HAV which have the potential to cause fulminant hepatic failure and death(4).