Background During the ongoing coronavirus disease COVID-19 pandemic, many individuals were infected with and have cleared the virus, developing virus-specific antibodies and effector/memory T cells. An important unanswered question is what levels of T cell and antibody responses are sufficient to protect from the infection. Methods In 5340 Moscow residents, we evaluated anti-SARS-CoV-2 IgM/IgG titers and frequencies of the T cells specific to the membrane, nucleocapsid, and spike proteins of SARS-CoV-2, using IFNγ ELISpot assay. Additionally, we evaluated the fractions of virus-specific CD4+ and CD8+ T cells using intracellular staining of IFNγ and IL2 followed by flow cytometry. We analyzed the COVID-19 rates as a function of the assessed antibody and T cell responses, using the Kaplan-Meyer estimator method, for up to 300 days post-inclusion. Results We showed that T cell and antibody responses are closely interconnected and are commonly induced concurrently. Magnitudes of both responses inversely correlated with infection probability. Individuals positive for both responses demonstrated the highest levels of protectivity against the SARS-CoV-2 infection. A comparable level of protection was found in individuals with antibody response only, while the T cell response by itself granted only intermediate protection. Conclusions We found that the contribution of the virus-specific antibodies to protection against the SARS-CoV-2 infection is more pronounced than that of the T cells. The data on the virus-specific IgG titers may be instructive for making decisions in personalized health care and public anti-COVID-19 policies.

BackgroundCoronavirus disease COVID-19 has spread worldwide extremely rapidly. Although many individuals have been infected and have cleared the virus, developing virus-specific antibodies and effector/memory T cells, an important question still to be answered is what levels of T cell and antibody responses are sufficient to protect from the infection.MethodsIn 5,340 Moscow residents, we evaluated the anti-SARS-CoV-2 IgM/IgG titers and the frequencies of the T cells specific to the nucleocapsid, membrane, and spike proteins of SARS-CoV-2, using IFNγ ELISpot, and we also evaluated the fractions of virus-specific CD4+ and CD8+ T cells using intracellular staining of IFNγ and IL2 followed by flow cytometry. Furthermore, we analyzed the post-inclusion COVID-19 rates as a function of the assessed antibody and T cell responses using the Kaplan-Meyer estimator method.ResultsWe showed that T cell and antibody responses are closely interconnected and commonly are induced concurrently. Individuals positive for both antibody and T cell immunities demonstrated the highest levels of protectivity against the SARS-CoV-2 infection, indistinguishably from individuals with antibody response only. Meanwhile, individuals with T cell response only demonstrated slightly higher protectivity than individuals without both types of immunity, as measured from N-protein–specific or CD4+IL2+ T cells. However, these individuals were characterized by higher IgG titers than individuals without any immunity, although the titers were below the seropositivity cut-off.ConclusionsThe results of the study indicated the advantage of serology testing over the analysis of T cell responses for the prediction of SARS-CoV-2 infection rates on a populational level.

Tissue autofluorescence of fixed tissue sections is a major concern of fluorescence microscopy. The adrenal cortex emits intense intrinsic fluorescence that interferes with signals from fluorescent labels, resulting in poor-quality images and complicating data analysis. We used confocal scanning laser microscopy imaging and lambda scanning to characterize the mouse adrenal cortex autofluorescence. We evaluated the efficacy of tissue treatment methods in reducing the intensity of the observed autofluorescence, such as trypan blue, copper sulfate, ammonia/ethanol, Sudan Black B, TrueVIEWTM Autofluorescence Quenching Kit, MaxBlockTM Autofluorescence Reducing Reagent Kit, and TrueBlackTM Lipofuscin Autofluorescence Quencher. Quantitative analysis demonstrated autofluorescence reduction by 12–95%, depending on the tissue treatment method and excitation wavelength. TrueBlackTM Lipofuscin Autofluorescence Quencher and MaxBlockTM Autofluorescence Reducing Reagent Kit were the most effective treatments, reducing the autofluorescence intensity by 89–93% and 90–95%, respectively. The treatment with TrueBlackTM Lipofuscin Autofluorescence Quencher preserved the specific fluorescence signals and tissue integrity, allowing reliable detection of fluorescent labels in the adrenal cortex tissue. This study demonstrates a feasible, easy-to-perform, and cost-effective method to quench tissue autofluorescence and improve the signal-to-noise ratio in adrenal tissue sections for fluorescence microscopy.

The adrenal glands are important endocrine organs that play a major role in the stress response. Some adrenal glands abnormalities are treated with hormone replacement therapy, which does not address physiological requirements. Modern technologies make it possible to develop gene therapy drugs that can completely cure diseases caused by mutations in specific genes. Congenital adrenal hyperplasia (CAH) is an example of such a potentially treatable monogenic disease. CAH is an autosomal recessive inherited disease with an overall incidence of 1:9500–1:20,000 newborns. To date, there are several promising drugs for CAH gene therapy. At the same time, it remains unclear how new approaches can be tested, as there are no models for this disease. The present review focuses on modern models for inherited adrenal gland insufficiency and their detailed characterization. In addition, the advantages and disadvantages of various pathological models are discussed, and ways of further development are suggested.