Influenza Hemagglutinin Antibody Levels in the Elderly: Impact of Sex, Age, and Influenza/COVID-19 Vaccination Status During the 2021/2022 Epidemic Season in Warsaw, Poland.

BACKGROUND The purpose of the study was to determine the level of antihemagglutinin antibodies in the serum of patients in the geriatric population in Doctor's Surgery NZOZ Nucleus Warsaw, Poland, during the epidemic season 2021/2022 using the hemagglutination inhibition assay (HAI), according to anti-influenza and anti-COVID-19 vaccination, age, and sex. MATERIAL AND METHODS Serum samples taken from 256 patients aged 65 to 99 years were examined for anti-hemagglutinin antibodies and protective levels of antibodies against antigens: A/Victoria/2570/2019 (H1N1)pdm09, A/Cambodia/e0826360/2020(H3N2), B/Washington/02/2019 (B/Victoria lineage), and B/Phuket/3073/2013 (B/Yamagata lineage) of the quadrivalent influenza vaccine for epidemic season 2021/2022. RESULTS The highest protective level, ie, the percentage of people with antibody titers ≥40 was 87.5% and was recorded for subtype A/Cambodia/e0826360/2020(H3N2), the dominant type causing infections in the epidemic season 2021/2022 confirmed by molecular biology methods. Geometric mean titer (GMT) values and protective levels for B/Washington/02/2019 (B/Victoria lineage) antigen were higher for men than women (respectively 38.4 vs 67.6; P<0.001 and 58.0% vs 74.6%; P<0.001). The protective levels of antibodies among patients vaccinated vs unvaccinated against COVID-19 were higher for B/Washington/02/2019 (B/Victoria lineage) and B/Phuket/3073/2013 (B/Yamagata lineage) antigens (64.2% vs 44.4%; P=0.023 and 78.6% vs 55.6%; P=0.004). GMT values for vaccinated against COVID-19 were also higher. There were no significant differences between younger (65-79 years) and older (≥80 years) seniors. CONCLUSIONS The analysis shows differences in the level of individual antibodies, GMT and the protective level depending on subtypes of influenza A or B virus, B/Victoria or B/Yamagata lineage, sex, and previous vaccination history against influenza and COVID-19.

In vitro immune evaluation of adenoviral vector-based platform for infectious diseases.

New prophylactic vaccine platforms are imperative to combat respiratory infections. The efficacy of T and B memory cell-mediated protection, generated through the adenoviral vector, was tested to assess the effectiveness of the new adenoviral-based platforms for infectious diseases. A combination of adenovirus AdV1 (adjuvant), armed with costimulatory ligands (ICOSL and CD40L), and rRBD (antigen: recombinant nonglycosylated spike protein rRBD) was used to promote the differentiation of T and B lymphocytes. Adenovirus AdV2 (adjuvant), without ligands, in combination with rRBD, served as a control. In vitro T-cell responses to the AdV1+rRBD combination revealed that CD8+ platform-specific T-cells increased (37.2 ± 0.7% vs. 23.1 ± 2.1%), and T-cells acted against SARS-CoV-2 via CD8+TEMRA (50.0 ± 1.3% vs. 36.0 ± 3.2%). Memory B cells were induced after treatment with either AdV1+rRBD (84.1 ± 0.8% vs. 82.3 ± 0.4%) or rRBD (94.6 ± 0.3% vs. 82.3 ± 0.4%). Class-switching from IgM and IgD to isotype IgG following induction with rRBD+Ab was observed. RNA-seq profiling identified gene expression patterns related to T helper cell differentiation that protect against pathogens. The analysis determined signaling pathways controlling the induction of protective immunity, including the MAPK cascade, adipocytokine, cAMP, TNF, and Toll-like receptor signaling pathway. The AdV1+rRBD formulation induced IL-6, IL-8, and TNF. RNA-seq of the VERO E6 cell line showed differences in the apoptosis gene expression stimulated with the platforms vs. mock. In conclusion, AdV1+rRBD effectively generates T and B memory cell-mediated protection, presenting promising results in producing CD8+ platform-specific T cells and isotype-switched IgG memory B cells. The platform induces protective immunity by controlling the Th1, Th2, and Th17 cell differentiation gene expression patterns. Further studies are required to confirm its effectiveness.

Influenza Vaccination Coverage Among Polish Patients with Chronic Diseases.

Patients at a high-risk of severe influenza, because of their underlying health disorders, are recommended to receive a seasonal influenza vaccination. In Poland, influenza coverage rate in the general population is very low (3.4 %). However, there is little known about the coverage rate among high-risk patients. The aim of this study was to describe a general knowledge, perception, and influenza vaccination coverage rate among Polish patients with enhanced risk for influenza. We conducted a self-reported survey among 500 patients with chronic disorders: 120 pulmonary, 80 hemodialyzed, 100 thyroid cancer, and 200 cardiovascular patients. We found the following influenza vaccination coverage in the respective groups of patients: 58 % in pulmonary, 34 % in hemodialyzed, 32 % in cardiovascular, and 9 % in thyroid cancer patients. The difference between the coverage rate in pulmonary patients compared with the other risk groups was significant (p < 0.05). In pulmonary patients, the most important barrier for influenza vaccination was a lack of recommendations from healthcare workers, while a high awareness of influenza was the most powerful driver for vaccination (p < 0.05). We conclude that although the influenza vaccination coverage in Polish patients with chronic diseases is higher than that reported in the general population, this rate remains much below the recommended level and should be improved.

[Influenza in Poland in 2005]. / Grypa w 2005 roku.

A total number of 773,234 cases of influenza and influenza-like illness registered in Poland in 2004 (incidence 1921.4 per 100,000 population). Regionally the incidence ranged from 3391.8 per 100,000 population in Mazowieckie to 364.0 in Swietokrzyskie. Children and adolescents under 15 years of age accounted for 34.5% of all cases (age specific incidence 4045.3 per 100,000). In this age group the incidence varied regionally from 6381.1 in Mazowieckie to 797.6 in Swietokrzyskie. 1469 patients (0.20% of all cases) required hospital admission. There were 52 deaths due to influenza, in 82.7% these were persons over 70 years of age. In the epidemic season 2004/05 forty nine strains of influenza virus were isolated in Poland, including 2 strains of subtype A/H1, 23 strains of subtype A/H3 and 24 strains of type B. Antigenic analysis showed that they were similar to A/New Caledonia/20/99 (H1N1), A/Wyoming/3/2003 (H3N2), B/Hong Kong/330/2001 and B/Jiangsu/10/2003. Besides, RT-PCR method and immunofluorescence test allowed to confirm influenza in other 26 cases and infections with respiratory viruses as RSV, parainfluenza or adenovirus in other 25 cases.

Immunogenicity of influenza vaccination in patients with non-Hodgkin lymphoma.

PURPOSE: The purpose of this study was to assess humoral response to influenza vaccine in patients (pts) with non-Hodgkin lymphoma (NHL) as compared to healthy subjects (ctrl). PATIENTS AND METHODS: In two epidemic seasons, 2003/2004 and 2004/2005, 163 pts and 92 ctrl were vaccinated. Antibody titers to hemagglutinin (HA) and neuraminidase (NA) were measured in serum samples collected before vaccination, and 1 and 6 months apart. Changes in antibody titers were assessed by comparing geometric mean titers (GMT), mean fold increases (MFI), and seroprotection and seroresponse rates to baseline values. RESULTS: Pts vaccinated in 2003/2004 had, after 1 month, increase in GMT by a factor of 8.64-26.60 for antihemagglutinin antibodies (HI) and 6.93-12.66 for antineuraminidase antibodies (NI), as compared to factor of 9.12-24.41 for HI and 4.83-10.31 for NI in ctrl. At 1 month after vaccination, seroprotection and seroresponse rates were similar in both groups, ranging from 68.42 to 84.21% and 71.93 to 94.74% in NHL, and 66.67-82.22% and 62.22-86.67% in ctrl, respectively. Pts vaccinated in 2004/2005 had increase in the GMT by a factor of 38.76-41.49 for HI and 26.59-30.31 for NI, as compared to factor of 81.19-104.32 for HI and 52.16-54.52 for NI in ctrl. Seroprotection and seroresponse rates were lower in the former group, ranging from 62.11 to 65.26% and 74.47 to 77.66%, respectively. In both seasons, pts achieved titres of antibodies greater than the protective threshold, irrespective of the previous chemotherapy administration. CONCLUSIONS: The results indicate that influenza vaccination induces sufficient immune response in pts with NHL, irrespective of previous chemotherapy.

Humoral response to hemagglutinin components of influenza vaccine in patients with non-Hodgkin malignant lymphoma.

Lymphoma disease and immunosuppressive drugs used in this case cause immunity disorders increasing the risk of severe infections, including influenza. There are opinions that patients from high-risk group are not able to respond to vaccination effectively and vaccination may contribute to exacerbation of the chronic disease. The aim was to assess humoral response to influenza vaccine in 32 patients with non-Hodgkin malignant lymphoma (mean age 57.2) and 32 healthy subjects (mean age 44.3). Sixteen patients were treated with immunosupressive drugs (group A) and 11 were not subjected to this therapy (group B). Levels of antihemagglutinin (anti-HA) antibodies were assessed in sera before vaccination and after 1 month by hemagglutination inhibition test. Nasal and throat swabs were collected from persons with influenza symptoms during the study to detect the etiological agent of the infection. Post-vaccination anti-HA antibody levels were significantly higher than pre-vaccination values and mean fold increases (MFI) ranged from 9.3 to 12.2 in patients and from 27.6 to 44.3 in healthy subjects. The percentage of patients with the protective anti-HA antibody titers > or =1:40 (protection rate) ranged after vaccination from 59.4% to 68.8%. The percentage of patients with at least a four-fold increase of anti-HA antibody titers (response rate) after vaccination ranged from 46.9% to 68.8%. There were no significant differences in antibody levels between patients treated with immunosuppressive drugs and those not treated. No respiratory infections were laboratory confirmed. This study showed that influenza vaccine is less immunogenic in patients with non-Hodgkin malignant lymphoma, because it induces antibody production in lower titers in comparison to the production in healthy people. Despite this, influenza vaccine should be offered to this group, considering high MFI values and response rates as well as the protective effect for individual patients.

[Influenza diagnostics in patient with leukemia suspicion]. / Diagnostyka grypy u pacjenta z podejrzeniem bialaczki.

Influenza is a seasonal viral disease, with the peak of morbidity occurring in Poland between January and March. It is estimated that up to 70% of respiratory infections during the season is caused by this virus. Influenza virus infection poses an ultimate threat to the elderly > or = 65 years old and chronically ill, in whom postinfluenzal complications--including viral pneumonia and secondary bacterial pneumonia--cause from 0.1% to 0.4% deaths annually. Influenza also triggers off from 5% to 7% cases of nosocomial infections in these patients. Among three influenza types being human pathogens only influenza A and B have clinical and diagnostic significance. Type C causes mild respiratory infections, usually in children. Out of the viruses circulating in our region the most pathogenic is A/H3N2 subtype that causes more severe infections, an increased number of hospitalizations and higher mortality than A/ H1N1 or B viruses. Lack of pathognomonic symptoms makes difficult a case definition-based diagnosis and draws an attention to key role of laboratory diagnostics for respiratory infections. It has an essential significance in high-risk patients not vaccinated against influenza giving an opportunity to use antiviral drugs of the new generation as oseltamivir.

[Diagnostics of viral respiratory infections in hospitalized patients and ambulatory patients from SENTINEL program during 2004/05 season in Poland]. / Diagnostyka wirusowych infekcji oddechowych u pacjentów hospitalizowanych i pacjentów leczonych ambulatoryjnie objetych programem SENTINEL w sezonie 2004/05 w Polsce.

The aim of the study was to evaluate an impact of respiratory infections on the study population, type/subtype of influenza viruses circulating during 2004/05 season within the groups of hospitalised (n=35) and ambulatory patients (n=420) and to determine antigenic affinity of isolated viral strains. Laboratory diagnostics of influenza A and B type, RSV, adenovirus and parainfluenzavirus (type 1, 2 and 3) was performed using direct immunofluorescence test (DIFA), virus isolation on MDCK cell line and RT-PCR assay. Respiratory viruses were detected in about half of hospitalised patients and one fifth of ambulatory patients. Within these groups more than 80% hospitalised patients and 70% ambulatory patients were infected with influenza virus. Two influenza A subtypes (H3N2) and (H1N1) and B type were detected. Influenza ranged from 68,8% (26-45 age group) to 89,5% (15-25 age group) of all laboratory confirmed respiratory infections, only among the youngest children (0-3 years old) one fourth of infections was caused by influenza virus and in 50% samples RSV was detected. Influenza virus was also present in over 80% positive samples from hospitalised patients over 65 years old. Sensitivity of RT-PCR compared to other influenza diagnostic methods was 95% and specificity was > or = 99%. Fast and accurate influenza diagnostics using molecular biology methods enables implementing therapy with the new generation antivirals (neuraminidase inhibitors), that are effective only when administered up to 36-48 h from onset of the illness. In diagnostics of other. respiratory viruses it is necessary to apply more sensitive diagnostic methods e.g. multiplex RT-PCR. Influenza isolates were A/Wyoming/3/2003-like, B/Hong Kong/330/2001-like, A/New Caledonia/20/99-like and B/Jiangsu/10/2003-like strains that were components of influenza vaccines for 2003/04 and/or 2004/05 seasons. Annual vaccination remains the best way to prevent infection in high risk populations. Costs of influenza vaccine and oseltamivir prophylaxis in our country are on average respectively fifty and five times lower than each day of patients' stay at an intensiv care unit. Every year within the confines of global surveillance programs (e.g. SENTINEL), there are monitored circulating influenza viruses, in order to define vaccine composition for the next season and identify new and potentially pandemic strains.

Immune consequences of the spontaneous pro-inflammatory status in depressed elderly patients.

INTRODUCTION: The aim of the study was to describe the interrelationship between senescence, depression, and immunity. METHODS: We assessed 10 elderly patients with depression and 10 age- and sex-matched controls: before, at one and at six month intervals after the anti-influenza vaccination. Levels of TNFalpha, IL6, ACTH, and cortisol, titres of anti-hemagglutinins and anti-neuraminidases, lymphocytes secreting IFNgamma, IL2, IL4, and IL10, cytotoxicity of NK and CD3+ CD8+ IFNgamma+ cells, anti-CMV antibodies, and CD28- CD57+ lymphocytes known to be associated with the CMV carrier status were evaluated. RESULTS: Higher levels of anti-CMV, higher percentage of the CD28- CD57+ cells, and elevated levels of TNFalpha, IL6, and cortisol concomitant with decreased levels of ACTH and insufficient production of IL10 (which increased the IFNgamma+ /IL10+ ratio) were found in the patients suffering from depression, in comparison to healthy controls. The subjects with depression revealed a low NK cytotoxicity, while a level of CD3+ CD8+ IFNgamma+ cells was comparable between the groups. Although the levels of anti-hemagglutinins and anti-neuraminidases were low in the depressed patients, they reached the protective titres. The majority of these differences disappeared when CMV titres were entered into the analyses as a covariate. DISCUSSION: The results suggest that the elderly depressed patients were characterised by increased exposure to CMV in the past, which could have resulted in a pro-inflammatory profile demonstrated as elevated levels of TNFalpha, IL6 and deficiency of suppressive IL10+ cells. These changes negatively affect humoral and innate response in the depressed patients.