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We highlighted in this current paper similar prolonged respiratory presentation with COVID-19 pneumonia in four severely immunocompromised patients currently being treated with anti-CD20 monoclonal antibodies (mAbs), such as ocrelizumab and rituximab, for multiple sclerosis or rheumatoid polyarthritis. Real-time reverse transcription-polymerase chain reaction on a nasopharyngeal swab specimen was negative in all patients. SARS-CoV-2 infection was confirmed from bronchoalveolar lavage fluid. A high titer of post-vaccine COVID-19 convalescent plasma was administered with complete recovery in all patients. [ABSTRACT FROM AUTHOR]

Currently, SARS-CoV-2 spike receptor-binding-domain (RBD)-based vaccines are considered one of the most effective weapons against COVID-19. During the first step of assessing vaccine immunogenicity, a mouse model is often used. In this paper, we tested the use of five experimental animals (mice, hamsters, rabbits, ferrets, and chickens) for RBD immunogenicity assessments. The humoral immune response was evaluated by ELISA and virus-neutralization assays. The data obtained show hamsters to be the least suitable candidates for RBD immunogenicity testing and, hence, assessing the protective efficacy of RBD-based vaccines. [ABSTRACT FROM AUTHOR]

As solid organ transplant (SOT) recipients remain at risk of severe outcomes after SARS-CoV-2 infections, vaccination continues to be an important preventive measure. In SOT recipients previously vaccinated with at least three doses of BNT162b2, we investigated humoral responses to BNT162b2 booster doses. Anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G (IgG) was measured using an in-house ELISA. Linear mixed models were fitted to investigate the change in the geometric mean concentration (GMC) of anti-SARS-CoV-2 RBD IgG after vaccination in participants with intervals of more or less than six months between the last two doses of vaccine. We included 107 SOT recipients vaccinated with a BNT162b2 vaccine. In participants with an interval of more than six months between the last two vaccine doses, we found a 1.34-fold change in GMC per month (95% CI 1.25–1.44), while we found a 1.09-fold change in GMC per month (95% CI 0.89–1.34) in participants with an interval of less than six months between the last two vaccine doses, resulting in a rate ratio of 0.82 (95% CI 0.66 to 1.01, p = 0.063). In conclusion, the administration of identical COVID-19 mRNA vaccine boosters within six months to SOT recipients may result in limited humoral immunogenicity of the last dose. [ABSTRACT FROM AUTHOR]

Cellular and humoral immunity exhibit dynamic adaptation to the mutating SARS-CoV-2 virus. It is noteworthy that immune responses differ significantly, influenced by whether a patient has received vaccination or whether there is co-occurrence of naturally acquired and vaccine-induced immunity, known as hybrid immunity. The different immune reactions, conditional on vaccination status and the viral variant involved, bear implications for inflammatory responses, patient outcomes, pathogen transmission rates, and lingering post-COVID conditions. Considering these developments, we have performed a review of recently published literature, aiming to disentangle the intricate relationships among immunological profiles, transmission, the long-term health effects post-COVID infection poses, and the resultant clinical manifestations. This investigation is directed toward understanding the variability in the longevity and potency of cellular and humoral immune responses elicited by immunization and hybrid infection. [ABSTRACT FROM AUTHOR]

Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population. [ABSTRACT FROM AUTHOR]

Cellular and humoral immunity are both required for SARS-CoV-2 infection recovery and vaccine efficacy. The factors affecting mRNA vaccination-induced immune responses, in healthy and fragile subjects, are still under investigation. Thus, we monitored the vaccine-induced cellular and humoral immunity in healthy subjects and cancer patients after vaccination to define whether a different antibody titer reflected similar rates of cellular immune responses and if cancer has an impact on vaccination efficacy. We found that higher titers of antibodies were associated with a higher probability of positive cellular immunity and that this greater immune response was correlated with an increased number of vaccination side effects. Moreover, active T-cell immunity after vaccination was associated with reduced antibody decay. The vaccine-induced cellular immunity appeared more likely in healthy subjects rather than in cancer patients. Lastly, after boosting, we observed a cellular immune conversion in 20% of subjects, and a strong correlation between pre- and post-boosting IFN-γ levels, while antibody levels did not display a similar association. Finally, our data suggested that integrating humoral and cellular immune responses could allow the identification of SARS-CoV-2 vaccine responders and that T-cell responses seem more stable over time compared to antibodies, especially in cancer patients. [ABSTRACT FROM AUTHOR]

Kidney transplanted recipients (KTR) are at high risk of severe SARS-CoV-2 infection due to immunosuppressive therapy. Although several studies reported antibody production in KTR after vaccination, data related to immunity to the Omicron (B.1.1.529) variant are sparse. Herein, we analyzed anti-SARS-CoV-2 immune response in seven KTR and eight healthy controls after the second and third dose of the mRNA vaccine (BNT162b2). A significant increase in neutralizing antibody (nAb) titers were detected against pseudoviruses expressing the Wuhan-Hu-1 spike (S) protein after the third dose in both groups, although nAbs in KTR were lower than controls. nAbs against pseudoviruses expressing the Omicron S protein were low in both groups, with no increase after the 3rd dose in KTR. Reactivity of CD4+ T cells after boosting was observed when cells were challenged with Wuhan-Hu-1 S peptides, while Omicron S peptides were less effective in both groups. IFN-γ production was detected in KTR in response to ancestral S peptides, confirming antigen-specific T cell activation. Our study demonstrates that the 3rd mRNA dose induces T cell response against Wuhan-Hu-1 spike peptides in KTR, and an increment in the humoral immunity. Instead, humoral and cellular immunity to Omicron variant immunogenic peptides were low in both KTR and healthy vaccinated subjects. [ABSTRACT FROM AUTHOR]

Several reports demonstrated the susceptibility of domestic cats to SARS-CoV-2 infection. Here, we describe a thorough investigation of the immune responses in cats after experimental SARS-CoV-2 inoculation, along with the characterization of infection kinetics and pathological lesions. Specific pathogen-free domestic cats (n = 12) were intranasally inoculated with SARS-CoV-2 and subsequently sacrificed on DPI (days post-inoculation) 2, 4, 7 and 14. None of the infected cats developed clinical signs. Only mild histopathologic lung changes associated with virus antigen expression were observed mainly on DPI 4 and 7. Viral RNA was present until DPI 7, predominantly in nasal and throat swabs. The infectious virus could be isolated from the nose, trachea and lungs until DPI 7. In the swab samples, no biologically relevant SARS-CoV-2 mutations were observed over time. From DPI 7 onwards, all cats developed a humoral immune response. The cellular immune responses were limited to DPI 7. Cats showed an increase in CD8+ cells, and the subsequent RNA sequence analysis of CD4+ and CD8+ subsets revealed a prominent upregulation of antiviral and inflammatory genes on DPI 2. In conclusion, infected domestic cats developed a strong antiviral response and cleared the virus within the first week after infection without overt clinical signs and relevant virus mutations. [ABSTRACT FROM AUTHOR]

The implementation of vaccination among healthcare workers (HCWs) allowed the management of the pandemic in a manner that differed from that in the first waves. It has been demonstrated that the mRNA vaccines elicit good humoral responses but that there are still breakthrough infections. In summer 2021, a fifth wave emerged, despite the good coverage of HCWs in Spain. We aimed to study the SARS-CoV-2 IgG antibody levels as a marker to predict the possibility of Delta variant infections after vaccination after a seroepidemiological campaign. Of the 5000 participants, a total of 4902 (98.04%) showed a positive result in the serological anti-S test and only 98 (1.96%) were negative. Among the 4368 fully vaccinated participants, only in five cases was the serology negative. Of the total number of participants that received antibody results during the study, 162 were PCR positive in the subsequent two months. Among these, 151 were fully vaccinated (two doses). Significant differences between antibody BAU/mL levels were found between PCR positive and non-PCR positive participants (p < 0.01). The median of BAU/mL was higher in those vaccinated patients with no infection (1260 BAU/mL; 465–2080) versus infected patients (661 BAU/mL; 361–2080). These data support the idea that vaccines play an important role in the control of the pandemic, especially among HCWs at the time of the Delta variant circulation. More studies with other variants of concern must be performed in order to establish a correlation between the levels of IgG and the new infections. [ABSTRACT FROM AUTHOR]

Background and Aims: Elderly nursing home residents are especially prone to a severe course of SARS-CoV-2 infection. In this study, we aimed to investigate the complex immune response after vaccination depending on the convalescence status and vaccine. Methods: Sampling took place in September–October 2021. IgG antibodies against spike protein and nucleocapsid protein, the titer of virus neutralization antibodies against delta and (on a subset of patients) omicron, and cellular immunity (interferon-gamma release assay) were tested in nursing home residents vaccinated with Pfizer, Moderna (both 30–31 weeks after the completion of vaccination), or AstraZeneca (23 weeks) vaccines. The prevalence with 95% confidence intervals (CI) was evaluated in Stata version 17. Results: 95.2% (95% CI: 92.5–97.1%) of the 375 participants had positive results of anti-S IgG, 92.8% (95% CI: 89.7–95.2%) were positive in virus neutralization assay against delta, and 89.0% (95% CI: 84.5–92.5%) in the interferon-gamma-releasing assay detecting cellular immunity. Results of the virus neutralization assay against omicron correlated with those against delta but the neutralization capacity was reduced by about half. As expected, the worst results were found for the AstraZeneca vaccine, although the vaccination-to-test period was the shortest for this vaccine. All immune parameters were significantly higher in convalescent residents than in naive residents after vaccination. No case of COVID-19 occurred during the vaccination-to-test period. Conclusions: A high immune response, especially among vaccinated convalescents (i.e., residents with hybrid immunity), was found in elderly nursing home residents 5–7 months after vaccination against SARS-CoV-2. In view of this, it appears that such residents are much better protected from COVID-19 than those who are only vaccinated and the matter of individual approach to the booster dose in such individuals should be further discussed. [ABSTRACT FROM AUTHOR]

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults. [ABSTRACT FROM AUTHOR]