Surveillance of anti-SARS-CoV-2 antibodies in plasma pools and in immunoglobulin medicinal products manufactured since 2020 has shown high neutralizing activity against SARS-CoV-2 and current variants

Background: Patients with primary and secondary immunodeficiencies have shown an impaired humoral immune response to COVID-19 vaccination. It is therefore of paramount importance to investigate anti-SARS-CoV-2 antibody levels in plasma pools and in immunoglobulin (IgG) products used to treat these patients. AIM: To assess the evolution of anti-SARS-CoV-2 antibodies (S protein) in plasma pools and IgG products and its neutralizing activity to original-type virus (Wuhan) and the variants of concern (VOC), including Omicron. Method(s): Healthy donors plasma pools collected in the US and Europe, and the subsequent intravenous (Flebogamma DIFand Gamunex-C, Grifols) and subcutaneous (Xembify, Grifols) IgG manufactured batches were followed from March 2020. Anti-SARS-CoV-2 S protein IgG titers were determined in plasma pools and in IgG batches by ELISA. Neutralization assays analyzed the capacity of IgG products to neutralize original-type virus and VOC (Alpha, Beta, Delta, Omicron BA.1 and BA.5), using pseudo viruses expressing S protein. Results were expressed as the dilution producing 50% neutralization (ID50). Result(s): In plasma pools, anti-SARS-CoV-2 S antibodies continuously increased throughout the study period regardless of the geographic origin. In the US, the first positive plasma pools were collected at the end of 2020. Since July 2021, an exponential increase over 30-fold of anti-SARS-CoV-2 S antibodies was reported. This trend continued increasing until the end of study period. Similarly, IgG products showed a similar evolution of anti-SARS-CoV-2 S antibodies. As expected, IgG batches released at the end of 2020 presented low SARS-CoV-2 neutralization activity. However, IgG products manufactured since August 2021 showed high neutralization activity against original-type virus and the rest of VOC. Regarding Omicron BA.5, a 5 to 10-fold increase was observed over time. Conclusion(s): This study reported the onset of elevated anti-SARS-CoV-2 antibody titers in plasma pools and IgG products since mid-2021, reflecting the evolution of the pandemic and vaccine campaigns. Intravenous and subcutaneous IgG products efficiently neutralized the current circulating VOC, Omicron BA.5. Further research is warranted to assess whether a clinical protective titer against SARS-CoV-2 and passive immunization is achieved in patients with immunodeficiencies treated with IgG products.Copyright © 2023 Elsevier Inc.

Detection of SARS-CoV-2 Antibodies in Matched Pregnant Women and Newborn Blood

Objective: The factors affecting the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies from mother to newborn and the duration of seropositivity rates in these infants have not yet been clearly demonstrated. The objectives of this study were (1) to assess the levels of SARS-CoV-2 spike-specific immunoglobulin G (IgG) in women infected in the pregnancy period and newborns born to these women and (2) to search the transplacental transfer ratio of spike-specific IgG. Method(s): Seventy pregnant women with symptomatic SARS-CoV-2 infection and their newborns were prospectively followed. Anti-SARS-CoV-2 immunoassay was used for the detection of the in vitro quantitative determination of total antibodies to the SARS-CoV-2 spike protein. Discussion(s): Spike-specific IgG was demonstrated in 89.1% (44 of 46) of pregnant women infected more than 14 days before delivery and in 92.6% (43 of 44) of their newborns. Median transfer ratio of spike-specific Ig was 0.87 (interquartile range [IQR], 0.34-0.90), 1.0 (IQR, 0.9-0.29), and 0.81 (IQR, 0.02-1.0) in first trimester (n = 4), second trimester (n = 14), and third trimester (n = 28) pregnant women, respectively. Antibody transfer ratio was correlated with time elapsed from infection (p < 0.001). Peak antibody transfer ratio above 1 was observed at a median 60 to 120 days after the infection from delivery. Antibody transfer ratio was high in pregnant women infected more than 60 days before delivery (p < 0.001). Transfer ratio was significantly higher in the severe-critically symptomatic women (n = 15) than the mild-moderately symptomatic women (n = 55) (p = 0.001). At 3 months, 18 of 25 infants (72%) had spike-specific IgG. Conclusion(s): Timing from infection to delivery and severity of maternal infection are critical in assessing the antibody generation and transport. Higher antibody transfer ratio can be detected in neonates when SARS-CoV-2 infection is present for more than 60 days before birth. Maternally derived antibody can persist for 3 months after birth.Copyright © 2023. The Author(s).

Transplacental transfer of SARS-CoV-2 variant antibodies following COVID-19 vaccination during pregnancy

Problem: Despite being over 3 years into the pandemic, infants remain highly undervaccinated and at a high risk for hospitalization due to COVID-19. Further investigation as to how maternal health decisions for immunization can reduce morbidity from infant COVID-19 by providing passive immunity is necessary. The objective of this study was to describe the rates of SARS-CoV-2 variant antibody transfer from mother to infant cord blood by trimester ofmaternal vaccination. Methods of study: This is an observational cohort study including mother-infant dyads receiving primary or subsequent booster COVID- 19 vaccines during pregnancy.Unvaccinated, but SARS-CoV-2 infected dyads with were included as a comparison group. We quantified median titer and interquartile range (IQR) for SARS-CoV-2 receptor binding domain (RBD) IgG in infant cord blood samples at delivery using the mesoscale discovery platform (electrochemiluminescence). Primary outcome was infant cord IgG titer by trimester of vaccination for the WA1/2022 RBD IgG and current circulating, immune evasive XBB RBD IgG. Secondary outcome is the percent detectable IgG for each variant. Sensitivity analysis was performed based on known SARS-CoV-2 infection. Result(s): Eighty-three mother-infant dyads were included in this analysis. Seven were vaccinated in the first trimester, 37 in the second trimester, 33 in the third trimester, and 6 were unvaccinated and infected. Twenty-three (30%) of the vaccinated group had known SARS-CoV-2 infection. Most received monovalent mRNA COVID-19 vaccines during pregnancy, aside from two who received the viralvectored Ad26.COV2.S, and two received the bivalent mRNA vaccine during pregnancy. The median cord blood WA1/2020 RBD IgG titer was 5370 (412-7296) for first, 1225 (589-3289) for second, 2623 (664-5809) for third trimester in individuals who received aCOVID-19 vaccine dose during pregnancy, and 45 (10-187) in those unvaccinated and infected. After excluding thosewith infection, the cord blood IgG was 514 (106-4182), 1070 (518-2317), and 2477 (664-4470) for first, second, and third trimester, respectively. The rate of detectable WA1/2020 RBD IgG was 100% for all three trimesters, even when excluding infected individuals. For theXBBvariant, cord bloodRBDIgG titer was 284 (43-1296) for first, 66 (32-227) for second, 173 (45-389) for third trimester, and 10 (10-11) in the unvaccinated/infected group. Excluding infections, the cord blood XBB RBD IgG was 54 (10-128), 44 (25-181), and 152 (45-360) for first, second, and third trimester vaccination, respectively. The rate of detectable XBB IgG in those who received a vaccine during pregnancy were 83%, 91%, and 90% for first, second, and third trimester respectively, compared to 17% in the unvaccinated/infected group. Excluding infections, the rate of XBB RBD IgG detection was 66%, 89%, and 95% for first, second, and third trimester vaccination, respectively. Conclusion(s): Vaccination during pregnancy leads to high rates of detectable cord blood IgG specific to SARS-CoV-2 WA1/2020 variant and current circulating variants (XBB), regardless of trimester of vaccination. Infection history leads to higher cord blood IgG in vaccinated;however, infection alone without vaccination leads to lower titer and greater rates of undetectable cord IgG at delivery.

Immunization technologies: Time to consider new preventative solutions for respiratory syncytial virus infections.

New technologies for the prevention of infectious diseases are emerging to address unmet medical needs, in particular, the use of long-acting monoclonal antibodies (mAb) to prevent Respiratory Syncytial Virus (RSV) lower respiratory tract disease in infants during their first RSV season. The lack of precedent for mAbs for broad population protection creates challenges in the assessment of upcoming prophylactic long-acting mAbs for RSV, with associated consequences in legislative and registration categorization, as well as in recommendation, funding, and implementation pathways. We suggest that the legislative and regulatory categorization of preventative solutions should be decided by the effect of the product in terms of its impact on the population and health-care systems rather than by the technology used or its mechanism of action. Immunization can be passive and active, both having the same objective of prevention of infectious diseases. Long-acting prophylactic mAbs work as passive immunization, as such, their recommendations for use should fall under the remit of National Immunization Technical Advisory Groups or other relevant recommending bodies for inclusion into National Immunization Programs. Current regulations, policy, and legislative frameworks need to evolve to embrace such innovative preventative technologies and acknowledge them as one of key immunization and public health tools.

Broad-spectrum pan-genus and pan-family virus vaccines.

Although the development and clinical application of SARS-CoV-2 vaccines during the COVID-19 pandemic demonstrated unprecedented vaccine success in a short time frame, it also revealed a limitation of current vaccines in their inability to provide broad-spectrum or universal protection against emerging variants. Broad-spectrum vaccines, therefore, remain a dream and challenge for vaccinology. This review will focus on current and future efforts in developing universal vaccines targeting different viruses at the genus and/or family levels, with a special focus on henipaviruses, influenza viruses, and coronaviruses. It is evident that strategies for developing broad-spectrum vaccines will be virus-genus or family specific, and it is almost impossible to adopt a universal approach for different viruses. On the other hand, efforts in developing broad-spectrum neutralizing monoclonal antibodies have been more successful and it is worth considering broad-spectrum antibody-mediated immunization, or "universal antibody vaccine," as an alternative approach for early intervention for future disease X outbreaks.

[Efficacy and safety of patients immunization with chronic obstructive pulmonary disease with monoclonal antibodies].

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by a high level of morbidity and mortality and is associated with significant social and economic damage to the health system and society. COPD and COVID-19 have many potentially negative relationships that can lead to worse outcomes of COVID-19, including impaired lung function, old age and the presence of concomitant diseases Aim. To assess efficacy and safety of the drug Tixagevimab + Cilgavimab for the pre-contact prevention of COVID-19 infection in patients with COPD. MATERIAL AND METHODS: A total of 324 male patients were included in the study, who were treated or monitored at the Regional Clinic Hospital №3 and the Regional Pulmonological Center of Chelyabinsk in April-May 2022. The main endpoints of observation, for 3 and 6 months, to assess the effectiveness were the dynamics of shortness of breath according to The Modified Medical Research Council Dyspnea Scale - mMRC, the The forced expiratory volume in 1 second, the number of exacerbations, emergency calls, hospitalizations, polymerase chain reaction for SARS-CoV-2. Local and general reactions after immunization were evaluated. The drug Evusheld (150 mg Tixsagevimab +150 mg Cilgavimab, AstraZeneca) was used for immunization. RESULTS AND CONCLUSION: The effectiveness of pre-contact prevention of COVID-19 was 88.8%. The administration of the drug does not provoke an exacerbation of the underlying disease. The main clinical and functional indicators have positive dynamics by the 6th month of follow-up. The drug is well tolerated and has no significant both early and late complications.

Special Issue: Understanding the impact of aging on the susceptibility and response to COVID-19 infection. (Special Issue: Understanding the impact of aging on the susceptibility and response to COVID-19 infection.)

This journal issue includes 15 articles that discuss continent-wide evolutionary trends of emerging SARS-CoV-2 variants;use of convalescent plasma therapy in hospitalised adult patients with non-critical COVID-19;evidence for preserved insulin responsiveness in the aging rat brain;SARS-CoV-2 infection in HIV-infected patients;different patterns of excess all-cause mortality by age and sex in Hungary during the 2nd and 3rd waves of the COVID-19 pandemic;mutational landscape of the newly emerging Omicron (B.1.1.529) variant and comparison of mutations with VOCs and VOIs.

Rituximab and Covid-19 Vaccines, Are They Fit for Purpose?

Background/Aims Since the COVID-19 outbreak the rheumatology community have been concerned about the risk of SARS-CoV-2 infection in patients prescribed immunosuppressing medications. Data suggests that patients receiving Rrtuximab are at increased risk of developing severe outcomes from COVID-19 (1). In our unit all patients receiving rituximab were selected to receive a targeted vaccination and booster programme with all patients receiving at least 2 vaccinations and up to 3 booster vaccinations. We studied the efficacy of the COVID-19 vaccines in rituximab patients, by checking the the Roche Elecsys Anti-SARS-CoV-2-S (Spike) IgG/IgM total antibody levels post vaccination. Our aim was to assess the vaccination response in patients receiving rituximab and to offer advice on continued shielding or alternatively passive immunization with tixagevimab/cilgavimab in those patients who did not mount a response. Methods Taking 39 patients currently on rituximab therapy, we measured Anti- SARS-CoV-2-S (Spike) antibody levels post vaccination. We recorded whether the test was positive or negative, and the numerical result. We recorded rituximab dates of administration and dates of vaccines. We also recorded diagnosis, co-prescribed DMARDs, immunoglobulin levels, white cell and lymphocyte counts. We took record of whether or not the patient subsequently contracted COVID-19, required a hospital admission, ICU or died. Results Of our 39 patients, 21 had Anti-SARS-CoV-2-S (Spike) antibody levels checked. Of these patients, 7 (33%) had a negative spike protein result. Of the patients with a positive result, 8 (38%) had an antibody level between 0-250U/ML, and only 6 (28.6%) had a level >250U/ML (The manufacturer advises that a level above 0.8U/ML is a positive result). Of patients with a negative result, 1 patient had received 3 vaccines, 5 patients had received 4, and 1 patient had 5. All of the patients had received a vaccine >4 weeks prior to receiving the drug. Two patients were co-prescribed Belimumab, 3 were co-prescribed low-dose methotrexate and 2 were not on additional disease modifying agents. The diagnoses of these patients were, 2 patients with SLE, 4 with SPRA, and 1 MPO Vasculitis. There were no significant findings in lymphocyte count, white cell count or immunoglobulin levels. Conclusion These findings suggest that our current COVID-19 vaccination and booster programme may not provide adequate response in patients receiving rituximab therapy. Despite this being a small cohort, these results show that 33% of patients have not mounted a vaccine response and this is concerning. We suggest that vaccine response should be checked in all patients receiving rituximab therapy and those patients who do not mount a vaccine response should be offered passive immunity and advised of possible additional risks regarding COVID-19 exposure.

Cross-Sectional Survey of Views on COVID-19 and Its Vaccines among Pregnant Women

Objective The objective of this study is to evaluate the acceptance of pregnant women with regards to coronavirus disease 2019 (COVID-19) vaccination during pregnancy and to identify any significant changes in their anxiety and knowledge on COVID-19 compared to our previous study. Methods This cross-sectional survey was performed in the antenatal clinics of United Christian Hospital and Tseung Kwan O Hospital of Hong Kong, China. Questionnaires were distributed to pregnant women for self-completion when attending follow-up from August to October 2021. Apart from basic demographic data, the questionnaire comprised of questions including knowledge on COVID-19 and its vaccines in pregnancy as well as attitudes and behaviors of pregnant women and their partners toward COVID-19. Continuous variables were analyzed by Student's test and Levene's test was used to confirm normal distribution and homogeneity of variance for continuous variables, whereas categorical variables were analyzed by the Chi-squared test or Fisher's exact test as appropriate. A P value of <0.05 was considered to be statistically significant. Results A total of 816 completed questionnaires were included for analysis. Pregnant women were less worried about COVID-19 in the current survey as compared to the last survey (393/816, 48.2% vs. 518/623, 83.1%, P?<?0.001). Fewer pregnant women believed that pregnancy were more susceptible to contract SARS-CoV-2 as compared to the last survey (265/816, 32.5% vs. 261/623, 41.9%, P?<?0.001). They have significant knowledge gap and concerns about COVID-19 vaccines. Nearly half of the participants believed that pregnant women cannot have COVID-19 vaccination (402/816, 49.3%) and it is unsafe to fetus (365/816, 44.7%). Around a third of women perceived that they were more prone to the side effects and complications of COVID-19 vaccines than the general population (312/816, 38.2%) and did not recognize that maternal COVID-19 vaccination could effect transferral of antibodies to the fetus to promote postnatal passive immunity (295/816, 36.2%). Most of them had not been vaccinated (715/816, 87.6%) and only (12/715) 1.7% of them would consider vaccination during pregnancy. Conclusion Despite the local and international recommendations for pregnant women to be vaccinated, the uptake of COVID-19 vaccines during pregnancy remained extremely low. Efforts should be made to effectively provide information about the safety and benefits of COVID-19 vaccines during pregnancy. There is an urgent need to booster vaccination rates in pregnant women to avoid excessive adverse pregnancy outcomes related to COVID-19.Copyright © the Author(s). Published by Wolters Kluwer Health, Inc.

Covid-19 Vaccinated Maternal/Cord Blood Dont Have Neutralization for Omicron Variants

Background: Maternally derived antibodies are crucial for neonatal immunity. Understanding the binding and -cross neutralization capacity of maternal/ cord antibody responses to COVID-19 vaccination during pregnancy can inform neonatal immunity. Method(s): Here we characterized binding and neutralizing antibody profile at delivery in 24 pregnant individuals following two doses of Moderna mRNA-1273 or Pfizer BNT162b2 vaccination. We evaluated the transplacental antibody transfer by profiling maternal and umbilical cord blood. We analyzed for SARS-CoV-2 multivariant cross-neutralizing antibody levels for wildtype Wuhan, Delta, Omicron BA1, BA2, and BA4/BA5 variants by enzyme-linked immunosorbent assay Results: Our results reveal that current vaccination induced significantly higher (p=0.003) RBD-specific binding IgG titers in cord blood compared to maternal blood for both Wuhan and Omicron BA1 strain. Interestingly, binding IgG antibody levels for the Omicron BA1 strain were significantly lower (P< 0.0001) when compared to the Wuhan strain in both maternal and cord blood. In contrast to the binding, the Omicron BA1, BA2, BA4/5 specific neutralizing antibody levels were significantly lower (P< 0.0001) compared to the Wuhan and Delta variants. It is interesting to note that the BA4/5 neutralizing capacity was not at all detected in both maternal and cord blood. Conclusion(s): Our data suggest that the initial series of COVID-19 mRNA vaccines were immunogenic in pregnant women, and vaccine-elicited binding antibodies were detectable in cord blood at significantly higher levels for Wuhan and Delta variants but not for Omicron variants. Interestingly, the vaccination did not induce neutralizing antibodies for Omicron variants. These results provide novel insight into the impact of vaccination on maternal humoral immune response and transplacental antibody transfer for SARS-CoV-2 variants and support the need for boosters as new variants emerge.

Covid-19 vaccination uptake by Hapu Mama - How are we progressing?

The Covid-19 vaccine has been recommended for pregnant people (hapu mama) in Aotearoa New Zealand since June 2021. We surveyed people birthing in a tertiary hospital regarding their vaccination status and reasons for this. There were 74% (142/191) of pregnant people who were fully vaccinated. Motivators for vaccination included protection against Covid-19 and antibody transfer to the baby (pepe). Unvaccinated participants worried about vaccine safety. Concerns were raised about the change in official advice without well-communicated reasons for the change. Future vaccine and booster rollouts must be delivered equitably and hapu mama must be a priority group.Copyright © 2022 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists. © 2022 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Egg Yolk Antibody for Passive Immunization: Status, Challenges, and Prospects.

The immunoglobulin Y (IgY) derived from hyperimmune egg yolk is a promising passive immune agent to combat microbial infections in humans and livestock. Numerous studies have been performed to develop specific egg yolk IgY for pathogen control, but with limited success. To date, the efficacy of commercial IgY products, which are all delivered through an oral route, has not been approved or endorsed by any regulatory authorities. Several challenging issues of the IgY-based passive immunization, which were not fully recognized and holistically discussed in previous publications, have impeded the development of effective egg yolk IgY products for humans and animals. This review summarizes major challenges of this technology, including in vivo stability, purification, heterologous immunogenicity, and repertoire diversity of egg yolk IgY. To tackle these challenges, potential solutions, such as encapsulation technologies to stabilize IgY, are discussed. Exploration of this technology to combat the COVID-19 pandemic is also updated in this review.

rAAV expressing recombinant antibody for emergency prevention and long-term prophylaxis of COVID-19.

Introduction: Numerous agents for prophylaxis of SARS-CoV-2-induced diseases are currently registered for the clinical use. Formation of the immunity happens within several weeks following vaccine administration which is their key disadvantage. In contrast, drugs based on monoclonal antibodies, enable rapid passive immunization and therefore can be used for emergency pre- and post-exposure prophylaxis of COVID-19. However rapid elimination of antibody-based drugs from the circulation limits their usage for prolonged pre-exposure prophylaxis. Methods: In current work we developed a recombinant adeno-associated viral vector (rAAV), expressing a SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibody P2C5 fused with a human IgG1 Fc fragment (P2C5-Fc) using methods of molecular biotechnology and bioprocessing. Results and discussions: A P2C5-Fc antibody expressed by a proposed rAAV (rAAV-P2C5-Fc) was shown to circulate within more than 300 days in blood of transduced mice and protect animals from lethal SARS-CoV-2 virus (B.1.1.1 and Omicron BA.5 variants) lethal dose of 105 TCID50. In addition, rAAV-P2C5-Fc demonstrated 100% protective activity as emergency prevention and long-term prophylaxis, respectively. It was also demonstrated that high titers of neutralizing antibodies to the SARS-CoV-2 virus were detected in the blood serum of animals that received rAAV-P2C5-Fc for more than 10 months from the moment of administration.Our data therefore indicate applicability of an rAAV for passive immunization and induction of a rapid long-term protection against various SARS-CoV-2 variants.

Treatment and Outcome of COVID-19 after Heart Transplantation: Update from a German Transplant Center

Background: The SARS-CoV-2 pandemic is leading to hospitalizations and increased mortality worldwide. With potentially high prevalence and severity of COVID-19 in cardiac transplantation, there is a great need to generate data in this at-risk cohort. We report here our experience on outcome and treatment of heart transplant recipients infected with SARS-CoV-2 at a German transplant center longitudinally over the previous pandemic waves. Method(s): All adult patients who had received a heart transplant at our center and had confirmed COVID-19 infection between December 2020 and July 2022 (n = 48) were included and retrospectively characterized. Result(s): The median age was 60.5 (46.3-63.8) years, and the majority were male (83%). The hospitalization rate was 83%. Comorbidities included diabetes (31%), arterial hypertension (73%), and chronic renal failure (90%). The percentage of SARS-CoV-2 positive patients since the beginning of our vaccination campaign (03/2021) was 90%, while from those 43 patients, 88% were fully vaccinated at the time of infection (vaccine breakthrough). The median time from vaccination to infection within those patients was 138 (85-225) days. Antiviral therapy was given in 83% of all cases, and passive immunization (convalescent plasma/monoclonal antibodies) was performed in 98% of all cases. Oxygen administration was required in 10% of patients;only one patient required noninvasive ventilation (2%), and no patient required invasive ventilation or mechanical cardiovascular support (ECMO). No new cardiovascular or thromboembolic events were found, and we observed no COVID-19-associated mortality. Conclusion(s): Under increasing numbers of vaccinated patients and treatment options, we could not detect severe courses or increased mortality of COVID-19 in heart transplanted patients. Prospective studies are needed to make better prognostic estimates of COVID-19 in (heart) transplanted patients in the future.

COVID-19 Pandemic: An Overview of its Origin, Current Status, and Ongoing Clinical Trials

The COVID-19 pandemic is raging across the globe, with the total active cases increas-ing each day. Globally over 63 million COVID-19cases and more than 1.4 million deaths have been reported to WHO. Throughout the world, academicians, clinicians and scientists are working tirelessly on developing a treatment to combat this pandemic. The origin of novel SARS-CoV-2 virus still remains foggy but is believed to have originated from a bat coronavirus RaTG13 with which it shares approximately 96% sequence similarity. In the present review, the authors have pro-vided an overview of the COVID-19 pandemic, epidemiology, transmission, developments related to diagnosis, drugs and vaccines, along with the genetic diversity and lifecycle of the SARS-CoV-2 based on the current studies and information available.Copyright © 2022 Bentham Science Publishers.

Endogenous antibody response to SARS-CoV-2 in patients who received monoclonal antibodies against COVID-19: A systematic review

Passive immunization with mAbs has been employed in COVID-19. We performed a systematic review of the literature assessing the endogenous humoral immune response against SARS-CoV-2 in patients treated with mAbs. Administration of mAbs in seronegative patients led to a reduction in both antibody titres and neutralizing activity against the virus.Copyright © 2022

Presence of SARS-CoV-2 neutralizing and vaccine spike antibodies in amniotic fluid during the second trimester of pregnancy, detected by amniocentesis (Winner of the SIMP Award, in memory of Professor Giorgio Pardi)

Objective. Thanks to the SARS-CoV-2 vaccination, pregnant women are protected from the complications of COVID-19 infection, but the benefits of this vaccination in preventing morbidity and mortality in the fetus are not yet clear: it is not well understood if and how these antibodies cross the placenta. Indeed antibodies made after a pregnant person has received an mRNA COVID-19 vaccine have been found in amniotic fluid and umbilical cord blood at term and represent a safer method of enhancing neonatal antibody levels than administration of immunoglobulin preparation to the infant. The aim of the study is to test the presence of neutralizing SARS-CoV-2 antibodies and spike antibodies in the amniotic fluid in the second trimester of pregnancy, and then to compare the antibodies level in maternal serum and amniotic fluid to evaluate their correlation. Materials and Methods. This cohort study took place at the Department of Obstetrics and Gynecology of Messina at the AOU Policlinico G. Martino from September 2021 to February 2022;the study consisted of 22 pregnant women who had amniocentesis in the gestational period between 15 weeks plus 6 days and 18 weeks: we analyzed serum and amniotic fluid samples of women who contracted the SARS-CoV-2 infection, or who were vaccinated against the same virus, within one year, or never infected by SARS-CoV-2 or vaccinated against it. During the amniocentesis, all patients underwent a single sample of maternal serum and of amniotic fluid to evaluate SARS-CoV-2 neutralizing antibody and S1 receptor binding domain IgG antibody levels. Inclusion criteria were pregnant women with the need to undergo amniocentesis. Results. 22 pregnant women were enrolled in the study:10 of them were vaccinated with a mRNA COVID-19 vaccine;12 women were not vaccinated, 4 of them had developed COVID-19 infection within one year before the collection and 2 of them developed the infection during pregnancy;the other 6 never developed the infection and have not been vaccinated, enrolled as comparators. Mann-Whitney test showed that vaccinated patients had significantly higher S1 receptor binding domain antibody levels both in amniotic fluid (p < 0.006) and maternal blood (p < 0.005) than not vaccinated women;also SARS-CoV-2 neutralizing antibody levels were higher in pregnant women who developed COVID-19 infection both in amniotic fluid (p < 0.007) and maternal blood (p < 0.004) than not vaccinated women. There was a significantly high correlation between the concentrations of spikes antibody levels in vaccinated pregnant women's serum and amniotic fluid (p = 0.000), and of neutralizing antibody levels in serum and amniotic fluid of women who developed COVID-19 infection (p = 0.000). Conclusions. To the best of our knowledge, the analysis of amniotic fluid and serum showed for the first time that all the vaccinated pregnant women samples had SARS-CoV-2 spikes immunoglobulins both in maternal blood and amniotic fluid. There is a very high correlation between maternal blood and amniotic fluid S1 receptor binding domain antibody levels in vaccinated women: this demonstrates that there is an early transplacental antibody transfer. Also neutralizing antibodies were found in the amniotic fluid of infected pregnant women, with high correlation between concentrations.

Anti-SARS-CoV-2 antibody responses in convalescent plasma donors with varying clinical manifestation severity of COVID-19

Background/Aim. Plasma containing a high titer of anti-SARS-CoV-2 antibodies, donated from individuals who re-covered from COVID-19, has the potential to be used as initial therapy for patients who have been infected (passive immunization). It is a challenge to find suitable donors. The aim of the study was to successively monitor antibody titer in donations and to investigate the correlation between an-tibody titer and the severity of the clinical manifestations. Methods. The retrospective study was conducted from May 1 to October 31, 2020, at the Blood Transfusion Insti-tute of Vojvodina. Donors had to meet certain criteria for inclusion in the study: proven SARS-CoV-2 infection, de-tected SARS-CoV-2 antibodies in the serum/plasma, ful-fillment of general criteria for performing plasmapheresis, and adequate laboratory findings. Results. During the study, 651 apheresis plasma units were collected and divided into two equal doses. Plasma was donated by 311 COVID-19 convalescents, including 208 (66.9%) men and 103 (33.1%) women. There were 15 (4.8%) plasma donors with asymptomatic infection, 235 (75. 6%) with a mild form of illness, 45 (14.5%) with a moderate form of illness, 16 (5.1%) with a severe form of illness, and none with a critical form of illness. Anti-SARS-CoV-2 IgG antibodies were pre-sent in the plasma of donors for more than 6 months after the disease. Plasma donors with a more severe clinical mani-festation of COVID-19 had stable antibody levels for a longer period. However, the Pearson correlation of clinical severity and antibody titer did not confirm a statistically sig-nificant correlation between the variables. Conclusion. An-ti-SARS-CoV-2 antibodies were present in the sample of re-covered patients, plasma donors, for more than 6 months after the disease. Even though no statistically significant correlation was found between the anti-SARS-CoV-2 anti-body titer and the clinical severity of COVID-19, in patients with a more severe clinical manifestations of the disease, stable antibody levels were maintained for a longer period.Copyright © 2022 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Therapeutic options in COVID-19

Treatment of COVID-19 can be categorized into prophylactic treatment, early-stage treatment, and late-stage treatment. Prophylactic treatment, as either pre or postexposure passive immunization with monoclonal antibodies, is currently limited to high-risk groups, with preexisting risk factors for severe disease and death in case of contracting COVID-19. Additional prophylactic treatment for hospitalized patients includes anticoagulation. In early treatment, when the infectious state is dominant, antiviral agents are used as well as passive immunization with monoclonal antibodies. Late-stage treatment in progressive and-inflammatory disease characterized by a cytokine storm and lung involvement in most severe/critical patients, includes corticosteroids, interluekin-6 inhibitors, and JAK inhibitors. Oxygen support is mandatory in severe patients and in patients with moderate to severe adult respiratory distress syndrome and refractory hypoxemia. Rescue procedures include protonation, alveolar recruitment maneuvers, neuromuscular blockade, pulmonary vasodilators, and extracorporeal membrane oxygenation. Additional potential treatments that have not been yet authorized are beyond the scope of this discussion. © 2023 Elsevier Inc. All rights reserved.

Passive pre-exposure immunization by tixagevimab/cilgavimab in patients with hematological malignancy and COVID-19: matched-paired analysis in the EPICOVIDEHA registry.

Only few studies have analyzed the efficacy of tixagevimab/cilgavimab to prevent severe Coronavirus disease 2019 (COVID-19) and related complications in hematologic malignancies (HM) patients. Here, we report cases of breakthrough COVID-19 after prophylactic tixagevimab/cilgavimab from the EPICOVIDEHA registry). We identified 47 patients that had received prophylaxis with tixagevimab/cilgavimab in the EPICOVIDEHA registry. Lymphoproliferative disorders (44/47, 93.6%) were the main underlying HM. SARS-CoV-2 strains were genotyped in 7 (14.9%) cases only, and all belonged to the omicron variant. Forty (85.1%) patients had received vaccinations prior to tixagevimab/cilgavimab, the majority of them with at least two doses. Eleven (23.4%) patients had a mild SARS-CoV-2 infection, 21 (44.7%) a moderate infection, while 8 (17.0%) had severe infection and 2 (4.3%) critical. Thirty-six (76.6%) patients were treated, either with monoclonal antibodies, antivirals, corticosteroids, or with combination schemes. Overall, 10 (21.3%) were admitted to a hospital. Among these, two (4.3%) were transferred to intensive care unit and one (2.1%) of them died. Our data seem to show that the use of tixagevimab/cilgavimab may lead to a COVID-19 severity reduction in HM patients; however, further studies should incorporate further HM patients to confirm the best drug administration strategies in immunocompromised patients.