Use of Convalesant Plasma in CoOVID-19 Infection

Coronavirus 2 (SARS-CoV-2), which started in December 2019 in Wuhan province in China and caused serious respiratory infections in humans, was accepted as a pandemic on March 11, 2020. The disease from SARS-CoV-2 is called COVID-19. In a short period of five months, approximately 4 million people were infected and 300 thousand people died from this disease. To date, no specific therapeutic agents or prophylaxis for COVID-19 are available, so it is among the passive immunization treatment options with the plasma of patients who recover from the disease. Convalescent plasma therapy has been used in epidemic periods in the past and has been shown to be effective. Neutralizing antibodies in plasma contributes to recovery by inactivating the virus. In the literature, there are 4 publications presenting a total of 21 patients receiving convalescent plasma. They reported that the patients benefited from the treatment of convalescent plasma and that there were no complications. Studies have been initiated about convalescent plasma all over the world and their results are interestedly awaited.

Neutralising antibody titers and COVID outcomes in cancer patients

Background: Cancer patients are at high risk of severe COVID infection and recommended at least three doses of SARS-CoV2 mRNA vaccines. Various anti-neoplastic treatments may affect long-term vaccine immunogenicity. Methods: Patients with solid or haematological cancer were recruited from two Singapore hospitals between July 2021 and March 2022. GenScript cPASS surrogate virus neutralisation assays measured antibody responses, which were correlated with clinical outcomes obtained from medical records and national mandatory-reporting databases. Results: In total, 273 patients were recruited (40 with haematological malignancies and the rest solid tumours). Two-hundred and four patients (74.7%) were receiving active cancer therapy: 98 (35.9%) receiving systemic chemotherapy and the rest targeted or immunotherapy. All patients were seronegative at baseline. After receiving one, two and three doses of SARS-CoV-2-mRNA vaccination, seroconversion rate was 35.2%, 79.4% and 92.4% respectively. After three doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) as compared to patients on immunotherapy (94.1%±9.56, p<0.05) and chemotherapy (92.8%±18.1, p<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients of which 18 were severe. Conclusion: This study demonstrates high immunogenicity of three doses of vaccines and protection against severe infection in cancer patients.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.

Immunogenicity evaluation of Gam-COVID-Vac (Sputnik V)

In November 2020, the Armed Forces of the Russian Federation began mass immunisation of the personnel with Gam-COVID-Vac (Sputnik V), the first Russia vaccine against the new coronavirus infection (COVID-19). Thus, it became necessary to assess post-vaccination antibody levels and the duration and intensity of humoral immunity to COVID-19. The aim of the study was to investigate the immunogenicity and efficacy of Gam-COVID-Vac in military medical staff after vaccination. Materials and methods: the authors determined the presence of specific antibodies in the serum of individuals immunised with Gam-COVID-Vac (477 volunteers) and COVID-19 convalescents (73 patients), using virus neutralisation (VN), enzyme-linked immunosorbent assay (ELISA) with reagent kits by several manufacturers, and immunoblotting. The results of the study were evaluated using analysis of variance. Results: VN detected virus neutralising antibodies in 90.7% of vaccinated subjects;ELISA, in 95.4%. Both VN and ELISA showed lower antibody levels in the vaccinated over 50 years of age. ELISA demonstrated a significantly higher concentration of anti-SARS-CoV-2 spike IgG in the Gam-COVID-Vac group than in the COVID-19 convalescent group. The correlation between antibody detection results by VN and ELISA was the strongest when the authors used their experimental reagent kit for quantitative detection of virus neutralising antibodies by competitive ELISA with the recombinant human ACE2 receptor. Having analysed the time course of neutralising antibody titres, the authors noted a significant, more than two-fold decrease in geometric means of the titres three months after administration of the second vaccine component. Conclusions: the subjects vaccinated with Gam-COVID-Vac gain effective humoral immunity to COVID-19. The decrease in titres indicates the need for revaccination in 6 months.

A Computational Framework for Determining the Breadth of Antibodies Against Highly Mutable Pathogens

Highly mutable pathogens pose daunting challenges for antibody design. The usual criteria of high potency and specificity are often insufficient to design antibodies that provide long-lasting protection. This is due, in part, to the ability of the pathogen to rapidly acquire mutations that permit them to evade the designed antibodies. To overcome these limitations, design of antibodies with a larger neutralizing breadth can be pursued. Such broadly neutralizing antibodies (bnAbs) should remain targeted to a specific epitope, yet show robustness against pathogen mutability, thereby neutralizing a higher number of antigens. This is particularly important for highly mutable pathogens, like the influenza virus and the human immunodeficiency virus (HIV). The protocol describes a method for computing the "breadth” of a given antibody, an essential aspect of antibody design. © 2023, Springer Science+Business Media, LLC, part of Springer Nature.

Preserved SARS-CoV-2 neutralizing IgG activity of in-house manufactured COVID-19 convalescent plasma.

PURPOSE: In the current study, we aimed to evaluate the neutralizing IgG activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the coagulation factors of convalescent plasmas which we manufactured in-house without a fast-freezing technique. METHODS: We collected plasmas from eligible participants who had confirmed certain titers of neutralizing antibodies. The plasmas were frozen and stored in the ordinary biofreezer without a fast-freezing function. The purified-IgG neutralizing activity of 20 samples from 19 participants and the coagulation factors of 49 samples from 40 participants were evaluated before and after freezing. RESULTS: Purified-IgG maintained its neutralizing activities, with the median 50 % inhibitory concentration (IC50) of 10.11 mg/ml (IQR 6.53-18.19) before freezing and 8.90 m g/ml (IQR 6.92-28.27) after thawing (p = 0.956). On the contrary, fibrinogen and factor Ⅷ decreased significantly after freezing and thawing in our environment. No significant temperature deviation was observed during the storage period. CONCLUSION: Neutralizing IgG activity, which largely contributes to the antiviral activity of convalescent plasma, did not change through our in-house manufacturing, without fastfreezing and storage conditions for more than 200 days. Ordinary freezers without the fast-freezing function are suitable enough to manufacture and store convalescent plasmas. Hospitals or facilities without specified resources could easily collect and store convalescent plasmas in case of upcoming emerging or re-emerging infectious diseases on-demand with appropriate neutralizing antibody levels measurements.

Neutralizing Antibodies as Predictors of Vaccine Breakthrough Infection in Healthcare Workers Vaccinated with or without a Heterologous Booster Dose: A Cohort Study during the Third COVID-19 Wave in Peru.

We evaluated neutralizing antibody (NAbs) levels as a protective factor against vaccine breakthrough infection (VBI) in healthcare workers (HCWs) during the third COVID-19 wave in Peru. This retrospective cohort study employed the information from a private laboratory in Lima (Peru) of HCW who received only two BBIBP-CorV vaccines or (additionally) a heterologous booster with BNT162b2. We evaluated the association between the VBI and the levels of NAbs at 21, 90, 180, and 210 days after the BBIBP-CorV second dose. NAbs were calculated with the cPass™ SARS-CoV-2 Neutralization Antibody Detection kit (surrogate virus neutralization test (sVNT)) and the Elecsys® anti-SARS-CoV-2 S Test. Of the 435 HCW evaluated, 31.72% had an infection previous to vaccination, 68.28% received a booster dose, and 23.21% had a VBI during the third wave. The variables associated with a lower risk of VBI were male sex (aRR: 0.43) and those who had (180 days after BBIBP-CorV inoculation) NAbs levels ≥ 60% (aRR: 0.58) and ≥90% (aRR: 0.59) on cPass™, and ≥500 with Elecsys® (aRR: 0.58). HCW whose NAbs persisted at higher levels six months after the BBIBP-CorV showed a lower risk of suffering from a VBI during the third COVID-19 wave.

Refocus on Immunogenic Characteristics of Convalescent COVID-19 Challenged by Prototype SARS-CoV-2.

Background: Mass basic and booster immunization programs effectively contained the spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, also known as COVID-19. However, the emerging Variants of Concern (VOCs) of COVID-19 evade the immune protection of the vaccine and increase the risk of reinfection. Methods: Serum antibodies of 384 COVID-19 cases recovered from SARS-CoV-2 infection were examined. Correlations between clinical symptoms and antibodies against VOCs were analyzed. Result: All 384 cases (aged 43, range 1−90) were from 15 cities of Guangdong, China. The specific IgA, IgG, and IgM antibodies could be detected within 4−6 weeks after infection. A broad cross-reaction between SARS-CoV-2 and Severe Acute Respiratory Syndrome Coronavirus, but not with Middle East Respiratory Syndrome Coronavirus was found. The titers of neutralization antibodies (NAbs) were significantly correlated with IgG (r = 0.667, p < 0.001), but showed poor neutralizing effects against VOCs. Age, fever, and hormone therapy were independent risk factors for NAbs titers reduction against VOCs. Conclusion: Humoral immunity antibodies from the original strain of COVID-19 showed weak neutralization effects against VOCs, and decreased neutralizing ability was associated with initial age, fever, and hormone therapy, which hindered the effects of the COVID-19 vaccine developed from the SARS-CoV-2 prototype virus.

SARS-CoV-2 breakthrough infections during the second wave of COVID-19 at Pune, India.

Breakthrough infections following SARS-CoV-2 vaccination remain the global concern. The current study was conducted during the second wave of COVID-19 (1st March-7th July 2021) in Pune, India, at two tertiary care hospitals. Of the 6,159 patients diagnosed as COVID-19, 372/2,210 (16.8%) were breakthrough infections. Of these, 81.1 and 18.8% received one or two doses of Covishield or Covaxin, respectively. Of note, 30.7% patients were with comorbidities, hypertension being the commonest (12.44%). The majority of infections were mild (81.2%). Forty-three patients with breakthrough infections were hospitalized with severe (n = 27, 62.8%) or moderate (n = 16, 37.2%) disease. The receptor binding domain (RBD) sequences from vaccinated (n = 126) and non-vaccinated (n = 168) samples were used for variant analysis. The delta variant was predominant followed by kappa in both vaccinated and non-vaccinated groups. Viral load (qRT-PCR) was not different among these categories. Full-genome comparisons of sequences in relation to vaccination status did not identify any mutation characteristic of the vaccinated group. Irrespective of the number of doses, neutralizing antibody titers (PRNT50) during the first week of clinical disease were higher in the vaccinated patients than the unvaccinated category. In conclusion, though not completely, SARS-CoV-2 vaccines used for country-wide immunization did reduce disease severity among the individuals without any comorbidity by inducing rapid immune response against distinctly different delta and kappa variants. The utility against emerging variants with further mutations need to be carefully examined.

Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients.

The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25−82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.

The efficacy of neutralizing monoclonal antibodies in transplant recipients with mild-to-moderate COVID-19.

INTRODUCTION: Transplant recipients (TRs) are at high risk for severe coronavirus disease 2019 (COVID-19). Neutralizing monoclonal antibodies (mAbs) are used for treating mild-to-moderate COVID-19. However, reports comparing the efficacy of COVID-19 treatment without/with mAbs in TRs are limited. We assessed the efficacy of casirivimab/imdevimab against mild-to-moderate COVID-19 in TRs. METHODS: Forty-one patients were retrospectively evaluated. The duration until defervescence, oxygen (O2) requirement ≥5 L, and neutralizing antibody levels were compared in TRs with COVID-19 without/with casirivimab/imdevimab. RESULTS: Casirivimab/imdevimab was correlated with shorter duration until defervescence and non-requirement of O2 ≥ 5 L in TRs with COVID-19 [mean: without/with: 6 vs. 2; P = 0.0002, hazard ratio (HR) = 0.3333, 95% confidence interval (CI) = 0.1763-0.6301; 15 vs. 8; P < 0.0001, HR = 0.5333, 95% CI = 0.2878-0.9883; P = 0.0377, HR = 0.1502, 95% CI = 0.02511-0.8980]. Casirivimab/imdevimab was associated with early defervescence after adjusting for sex and age (P = 0.013, HR = 0.412, 95% CI = 0.205-0.826). The antibody levels between patients without/with casirivimab/imdevimab on the day of hospitalization were not significantly different (P = 0.1055), including 13 TRs with vaccination. Antibody levels were higher in patients with casirivimab/imdevimab at 3-5 days after hospitalization than in those without, at 7-9 days after hospitalization (P < 0.0001, mean, without/with: 414.9/40000 AU/mL). CONCLUSION: Casirivimab/imdevimab was effective and increased the neutralizing antibody in TRs with mild-to-moderate COVID-19, it may contribute toward preventing the progression.

Protective roles and protective mechanisms of neutralizing antibodies against SARS-CoV-2 infection and their potential clinical implications.

Neutralizing antibodies (NAbs) are central players in the humoral immunity that defends the body from SARS-CoV-2 infection by blocking viral entry into host cells and neutralizing their biological effects. Even though NAbs primarily work by neutralizing viral antigens, on some occasions, they may also combat the SARS-CoV-2 virus escaping neutralization by employing several effector mechanisms in collaboration with immune cells like natural killer (NK) cells and phagocytes. Besides their prophylactic and therapeutic roles, antibodies can be used for COVID-19 diagnosis, severity evaluation, and prognosis assessment in clinical practice. Furthermore, the measurement of NAbs could have key implications in determining individual or herd immunity against SARS-CoV-2, vaccine effectiveness, and duration of the humoral protective response, as well as aiding in the selection of suitable individuals who can donate convalescent plasma to treat infected people. Despite all these clinical applications of NAbs, using them in clinical settings can present some challenges. This review discusses the protective functions, possible protective mechanisms against SARS-CoV-2, and potential clinical applications of NAbs in COVID-19. This article also highlights the possible challenges and solutions associated with COVID-19 antibody-based prophylaxis, therapy, and vaccination.

Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease.

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.

High-Throughput Neutralization and Serology Assays Reveal Correlated but Highly Variable Humoral Immune Responses in a Large Population of Individuals Infected with SARS-CoV-2 in the US between March and August 2020.

The ability to measure neutralizing antibodies on large scale can be important for understanding features of the natural history and epidemiology of infection, as well as an aid in determining the efficacy of interventions, particularly in outbreaks such as the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Because of the assay's rapid scalability and high efficiency, serology measurements that quantify the presence rather than function of serum antibodies often serve as proxies of immune protection. Here, we report the development of a high-throughput, automated fluorescence-based neutralization assay using SARS-CoV-2 virus to quantify neutralizing antibody activity in patient specimens. We performed large-scale testing of over 19,000 COVID-19 convalescent plasma (CCP) samples from patients who had been infected with SARS-CoV-2 between March and August 2020 across the United States. The neutralization capacity of the samples was moderately correlated with serological measurements of anti-receptor-binding domain (RBD) IgG levels. The neutralizing antibody levels within these convalescent-phase serum samples were highly variable against the original USA-WA1/2020 strain with almost 10% of individuals who had had PCR-confirmed SARS-CoV-2 infection having no detectable antibodies either by serology or neutralization, and ~1/3 having no or low neutralizing activity. Discordance between neutralization and serology measurements was mainly due to the presence of non-IgG RBD isotypes. Meanwhile, natural infection with the earliest SARS-CoV-2 strain USA-WA1/2020 resulted in weaker neutralization of subsequent B.1.1.7 (alpha) and the B.1.351 (beta) variants, with 88% of samples having no activity against the BA.1 (omicron) variant. IMPORTANCE The ability to directly measure neutralizing antibodies on live SARS-CoV-2 virus in individuals can play an important role in understanding the efficacy of therapeutic interventions or vaccines. In contrast to functional neutralization assays, serological assays only quantify the presence of antibodies as a proxy of immune protection. Here, we have developed a high-throughput, automated neutralization assay for SARS-CoV-2 and measured the neutralizing activity of ~19,000 COVID-19 convalescent plasma (CCP) samples collected across the United States between March and August of 2020. These data were used to support the FDA's interpretation of CCP efficacy in patients with SARS-CoV-2 infection and their issuance of emergency use authorization of CCP in 2020.

Efficacy, Safety and Immunogenicity of Anti-SARS-CoV-2 Vaccines in Patients with Cirrhosis: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), has led to a pandemic with more than 6.5 million deaths worldwide. Patients with liver cirrhosis (PWLC) are regarded as prone to severe COVID-19. Vaccination against SARS-CoV-2 has been proven to be the most effective measure against COVID-19 and a variety of different vaccines have been approved for use; namely mRNA and vector-based, inactivated, whole virion, and protein subunit vaccines. Unfortunately, only a small number of PWLC were included in phase I-III vaccine trials, raising concerns regarding their efficacy and safety in this population. The authors, in this review, present available data regarding safety and efficacy of anti-SARS-CoV-2 vaccination in PWLC and discuss post-vaccination antibody responses. Overall, all vaccines seem to be extremely safe, with only a few and insignificant adverse events, and efficient, leading to lower rates of hospitalization and COVID-19-related mortality. T- and B-cell responses, on the other hand, remain an enigma, especially in patients with decompensated disease, since these patients show lower titers of anti-SARS-CoV-2 antibodies in some studies, with a more rapid waning. However, this finding is not consistent, and its clinical impact is still undetermined.

Immune profiling of SARS-CoV-2 epitopes in asymptomatic and symptomatic pediatric and adult patients.

BACKGROUND: The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unpredictable manifestations of coronavirus disease (COVID-19) and variable clinical course with some patients being asymptomatic whereas others experiencing severe respiratory distress, or even death. We aimed to evaluate the immunoglobulin G (IgG) response towards linear peptides on a peptide array containing sequences from SARS-CoV-2, Middle East respiratory syndrome-related coronavirus (MERS) and common-cold coronaviruses 229E, OC43, NL63 and HKU1 antigens, in order to identify immunological indicators of disease outcome in SARS-CoV-2 infected patients. METHODS: We included in the study 79 subjects, comprising 19 pediatric and 30 adult SARS-CoV-2 infected patients with increasing disease severity, from mild to critical illness, and 30 uninfected subjects who were vaccinated with one dose of SARS-CoV-2 spike mRNA BNT162b2 vaccine. Serum samples were analyzed by a peptide microarray containing 5828 overlapping 15-mer synthetic peptides corresponding to the full SARS-CoV-2 proteome and selected linear epitopes of spike (S), envelope (E) and membrane (M) glycoproteins as well as nucleoprotein (N) of MERS, SARS and coronaviruses 229E, OC43, NL63 and HKU1 (isolates 1, 2 and 5). RESULTS: All patients exhibited high IgG reactivity against the central region and C-terminus peptides of both SARS-CoV-2 N and S proteins. Setting the threshold value for serum reactivity above 25,000 units, 100% and 81% of patients with severe disease, 36% and 29% of subjects with mild symptoms, and 8% and 17% of children younger than 8-years reacted against N and S proteins, respectively. Overall, the total number of peptides in the SARS-CoV-2 proteome targeted by serum samples was much higher in children compared to adults. Notably, we revealed a differential antibody response to SARS-CoV-2 peptides of M protein between adults, mainly reacting against the C-terminus epitopes, and children, who were highly responsive to the N-terminus of M protein. In addition, IgG signals against NS7B, NS8 and ORF10 peptides were found elevated mainly among adults with mild (63%) symptoms. Antibodies towards S and N proteins of other coronaviruses (MERS, 229E, OC43, NL63 and HKU1) were detected in all groups without a significant correlation with SARS-CoV-2 antibody levels. CONCLUSIONS: Overall, our results showed that antibodies elicited by specific linear epitopes of SARS-CoV-2 proteome are age dependent and related to COVID-19 clinical severity. Cross-reaction of antibodies to epitopes of other human coronaviruses was evident in all patients with distinct profiles between children and adult patients. Several SARS-CoV-2 peptides identified in this study are of particular interest for the development of vaccines and diagnostic tests to predict the clinical outcome of SARS-CoV-2 infection.

Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease.

Background & Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among CLD patients of different etiologies and disease stages. Methods: 357 patients were recruited in clinical centers from 6 European countries. 132 healthy volunteers served as controls. Serum IgG, IgM (nM) and neutralizing antibodies (NAb; %) against the Wuhan-Hu-1, B.1.617 and B.1.1.529 SARS-CoV-2 spike proteins were determined prior to vaccination (T0), 14 days (T2) and 6 months (T3) after second dose vaccination. Patients fulfilling inclusion criteria at T2 (n=212) were stratified into "low" or "high" responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM and neutralization levels significantly increased from T0 to T2 in patients vaccinated with either BNT162b2 (70.3%), mRNA-1273 (18.9%) or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted "low" humoral response, while viral hepatitis and antiviral therapy predicted "high" humoral response. Comparing with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, CLD patients presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-COV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease etiology. The type of vaccine leads to different antibody responses, that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Lay summary: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a "lower" humoral response, while viral hepatitis etiology and prior antiviral therapy predict a "higher" humoral response. This differential response appears not to associate with SARS-COV-2 infection incidence or vaccine efficacy. Still, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritized for receiving booster doses and/or recently approved adapted vaccines.

Pilot Study for Immunogenicity of SARS-CoV-2 Vaccine with Seasonal Influenza and Pertussis Vaccines in Pregnant Women.

Background: It is well known that the implementation of routine immunizations to prevent vaccine-preventable diseases has a significant impact on the health and well-being of infants, children, and pregnant women. We aimed to evaluate the influence of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine on the immunogenicity of SARS-CoV-2 vaccine among pregnant women, the priority population recommended for vaccination. Methods: We conducted a prospective study among pregnant women without previous SARS-CoV-2 infection in Taiwan. Maternal and umbilical cord blood samples at delivery were analyzed for the percentage of inhibition of neutralizing antibodies (NAbs) against the original strain, Delta, and Omicron variants of SARS-CoV-2 as well as the total antibody to the SARS-CoV-2 spike protein. We examined the association between different doses of SARS-CoV-2 vaccine in combination with influenza and Tdap vaccination, and two-dose SARS-CoV-2 vaccination with or without influenza and Tdap vaccines via a two-sample t-test. Results of p < 0.05 were considered to be statistically significant. Results: 98 pregnant women were enrolled in our study, with 32 receiving two doses of SARS-CoV-2 mRNA-1273 vaccine, 60 receiving three-dose of mRNA-1273, and 6 receiving one-dose of ChAdOx1 and two-dose of mRNA-1273. Twenty-one participants were immunized with SARS-CoV-2, influenza, and Tdap vaccines. Of these 21 individuals, there were no significant NAbs levels in maternal and cord blood samples against the Omicron variant, regardless of doses or type of SARS-CoV-2 vaccine. However, antibody responses against the wild-type and Delta variant were significantly lower in all maternal sera in the two-dose SARS-CoV-2 vaccine group. Among 32 women receiving two-dose mRNA-1273, significantly lower levels of NAbs in maternal sera were observed against the Delta variant and total antibody both in maternal sera and cord blood were observed in individuals receiving SARS-CoV-2 and influenza vaccine. Conclusion: This is the pilot study to demonstrate the effects of influenza and the Tdap vaccine on the immunogenicity of the SARS-CoV-2 vaccine among pregnant women. These results suggest that combination vaccination during pregnancy may result in immunogenic interactions.

Seroprevalence of anti-SARS-CoV-2 antibodies and cross-variant neutralization capacity after the Omicron BA.2 wave in Geneva, Switzerland: A population-based study.

Background: More than two years into the COVID-19 pandemic, most of the population has developed anti-SARS-CoV-2 antibodies from infection and/or vaccination. However, public health decision-making is hindered by the lack of up-to-date and precise characterization of the immune landscape in the population. Here, we estimated anti-SARS-CoV-2 antibodies seroprevalence and cross-variant neutralization capacity after Omicron became dominant in Geneva, Switzerland. Methods: We conducted a population-based serosurvey between April 29 and June 9, 2022, recruiting children and adults of all ages from age-stratified random samples of the general population of Geneva, Switzerland. We tested for anti-SARS-CoV-2 antibodies using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein, and for antibody neutralization capacity against different SARS-CoV-2 variants using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. We estimated seroprevalence and neutralization capacity using a Bayesian modeling framework accounting for the demographics, vaccination, and infection statuses of the Geneva population. Findings: Among the 2521 individuals included in the analysis, the estimated total antibodies seroprevalence was 93.8% (95% CrI 93.1-94.5), including 72.4% (70.0-74.7) for infection-induced antibodies. Estimates of neutralizing antibodies in a representative subsample (N = 1160) ranged from 79.5% (77.1-81.8) against the Alpha variant to 46.7% (43.0-50.4) against the Omicron BA.4/BA.5 subvariants. Despite having high seroprevalence of infection-induced antibodies (76.7% [69.7-83.0] for ages 0-5 years, 90.5% [86.5-94.1] for ages 6-11 years), children aged <12 years had substantially lower neutralizing activity than older participants, particularly against Omicron subvariants. Overall, vaccination was associated with higher neutralizing activity against pre-Omicron variants. Vaccine booster alongside recent infection was associated with higher neutralizing activity against Omicron subvariants. Interpretation: While most of the Geneva population has developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, less than half has neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection confers the greatest neutralization capacity, including against Omicron. Funding: General Directorate of Health in Geneva canton, Private Foundation of the Geneva University Hospitals, European Commission ("CoVICIS" grant), and a private foundation advised by CARIGEST SA.

Neutralizing antibodies and T-cell responses to inactivated SARS-CoV-2 vaccine in COVID-19 convalescents one and a half years after infection.

Vaccines have been considered the most promising solution for ending the coronavirus disease 2019 (COVID-19) pandemic. Information regarding neutralizing antibodies (NAbs) and T-cell immune response in inactivated SARS-CoV-2 vaccine-immunized COVID-19 convalescent patients were either only available for a short time after illness recovered or not available at all (T-cell immunity). We evaluated SARS-CoV-2 NAbs and cellular immune responses to the SARS-CoV-2 inactivated vaccine in convalescent patients who recovered from infection for about one and a half years. We found that compared to before vaccination, SARS-CoV-2 NAbs and specific T-cell responses were significantly boosted by the inactivated vaccine in convalescent patients, which confirmed the pre-existing adaptive immunity in SARS-CoV-2 infected people. We observed that NAbs and IFN-γ-secreting T-cell response elicited by a single vaccine dose in subjects with prior COVID-19 infection were higher than after two doses of vaccine in SARS-CoV-2 naïve subjects. Both humoral and cellular immune responses elicited by one and two doses of inactivated vaccine were comparable in COVID-19-recovered persons. In conclusion, inactivated COVID-19 vaccine induced robust NAbs and T-cell responses to SARS-CoV-2 in COVID-19 convalescent patients and immune responses after one dose were equal to that after receiving two doses, which highlighted that robust humoral and cellular immune response can be reactivated by the inactivated vaccine in SARS-CoV-2 convalescent patients.