Determining SARS-CoV-2 non-infectivity state–A brief overview

Publisher Copyright: Copyright © 2022 Brynjolfsson, Sigurgrimsdottir, Gudlaugsson, Kristjansson, Kristinsson and Ludviksson.From the beginning of the COVID-19 pandemic, it has claimed over 6 million lives, and globally the pandemic rages with detrimental consequences, with the emergence of new more infectious and possibly virulent variants. A clinical obstacle in this battle has been to determine when an infected individual has reached a non-infectious state. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can be transmitted under diverse circumstances, and various rules and regulations, along with different testing methods, have been applied in an attempt to confine the transmission. However, that has proven to be a difficult task. In this review, we take together recently published data on infectivity and transmission of SARS-CoV-2 and have combined it with the clinical experience that physicians in Iceland have accumulated from the pandemic. In addition, we suggest guidelines for determining when patients with COVID-19 reach a non-infectious state based on a combination of clinical experience, scientific data, and proficient use of available tests. This review has addressed some of the questions regarding contagiousness and immunity against SARS-CoV-2.Peer reviewe

Long-Lived Plasma Cells in Mice and Men

Even though more than 30 years have passed since the eradication of smallpox, high titers of smallpox-specific antibodies are still detected in the blood of subjects vaccinated in childhood. In fact, smallpox-specific antibody levels are maintained in serum for more than 70 years. The generation of life-long immunity against infectious diseases such as smallpox and measles has been thoroughly documented. Although the mechanisms behind high persisting antibody titers in the absence of the causative agent are still unclear, long lived plasma cells (LLPCs) play an important role. Most of the current knowledge on LLPCs is based on experiments performed in mouse models, although the amount of data derived from human studies is increasing. As the results from mouse models are often directly extrapolated to humans, it is important to keep in mind that there are differences. These are not only the obvious such as the life span but there are also anatomical differences, for instance the adiposity of the bone marrow (BM) where LLPCs reside. Whether these differences have an effect on the function of the immune system, and in particular on LLPCs, are still unknown. In this review, we will briefly discuss current knowledge of LLPCs, comparing mice and humans

Detailed Multiplex Analysis of SARS-CoV-2 Specific Antibodies in COVID-19 Disease.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadA detailed understanding of the antibody response against SARS-CoV-2 is of high importance, especially with the emergence of novel vaccines. A multiplex-based assay, analyzing IgG, IgM, and IgA antibodies against the receptor binding domain (RBD), spike 1 (S1), and nucleocapsid proteins of the SARS-CoV-2 virus was set up. The multiplex-based analysis was calibrated against the Elecsys® Anti-SARS-CoV-2 assay on a Roche Cobas® instrument, using positive and negative samples. The calibration of the multiplex based assay yielded a sensitivity of 100% and a specificity of 97.7%. SARS-CoV-2 specific antibody levels were analyzed by multiplex in 251 samples from 221 patients. A significant increase in all antibody types (IgM, IgG, and IgA) against RBD was observed between the first and the third weeks of disease. Additionally, the S1 IgG antibody response increased significantly between weeks 1, 2, and 3 of disease. Class switching appeared to occur earlier for IgA than for IgG. Patients requiring hospital admission and intensive care had higher levels of SARS-CoV-2 specific IgA levels than outpatients. These findings describe the initial antibody response during the first weeks of disease and demonstrate the importance of analyzing different antibody isotypes against multiple antigens and include IgA when examining the immunological response to COVID-19.Student Innovation Fun

To Minister of State for Defence

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldNeonates have a poorly developed immune system. Therefore it is important to develop vaccination strategies that induce protective immunity and immunological memory against pathogens early in life. The immunogenicity of a meningococcal serogroup C polysaccharide conjugate (MenC-CRM(197)) was assessed in neonatal mice, and effects of LT-K63 and CpG2006 and immunisation routes were compared. Neonatal mice were primed subcutaneously (s.c.) or intranasally (i.n.) with MenC-CRM(197) with or without LT-K63 or CpG2006 and re-immunised 16 and 30 days later by the same route and formulation. Antibody levels were measured and generation of immunological memory assessed by affinity maturation and kinetics of the Ab response. Serum bactericidal activity (SBA) was measured to evaluate protective efficacy. The second and third dose of MenC-CRM(197) mixed with either LT-K63 or CpG2006 induced a rapid increase in MenC-specific IgG antibodies, to levels higher than elicited by MenC-CRM(197) alone (P<0.01) and in unimmunised mice (P<0.001), indicating efficient generation of memory by priming through both s.c. and i.n. routes. SBA was detected after three s.c. immunisations with MenC-CRM(197) s.c. alone. However, only two doses of MenC-CRM(197)+LT-K63 or MenC-CRM(197)+CpG2006 were needed to induce SBA levels>16. LT-K63 and CpG2006 enhanced neonatal antibody responses, affinity maturation, immunological memory to the conjugate MenC-CRM(197) and protective immunity. These results encourage the development of neonatal vaccination strategies to induce protective immunity and immunological memory against meningococcal disease

Hyporesponsiveness following booster immunization with bacterial polysaccharides is caused by apoptosis of memory B cells.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Repeated immunizations with polysaccharide (PS) vaccines cause hyporesponsiveness through undefined mechanisms. We assessed the effects of a PS booster on immune responses, frequency, and survival of PS-specific B-cell subpopulations in spleen and bone marrow. Neonatal mice were primed with meningococcus serotype C (MenC) conjugate MenC-CRM(197)+CpG1826, boosted with MenC-CRM(197), MenC-PS, or saline; subsequently, bromodeoxyuridine (BrdU) was injected daily intraperitoneally. MenC-PS-specific cells were labeled with fluorescent MenC-PS and phenotyped by flow cytometry. After MenC-PS booster, proliferating (BrdU(+)) MenC-PS-specific naive B cells (CD138(-)/B220(+); P = .0003) and plasma cells (CD138(+)/B220(-); P = .0002) in spleen were fewer than after saline booster. BrdU(+) MenC-PS-specific plasma cells were also reduced in bone marrow (P = .0308). Compared to saline, MenC-PS booster reduced BrdU(+) IgG(+) MenC-PS-specific B cells in spleen (P = .0002). Twelve hours after the MenC-PS booster, an increased frequency of apoptotic (AnnexinV(+)) MenC-PS-specific B cells in spleen was observed compared with MenC-CRM(197) (P = .0286) or saline (P = .001) boosters. We demonstrated that the MenC-PS booster significantly reduced the frequency of newly activated MenC-PS-specific B cells-mostly switched IgG(+) memory cells-by driving them into apoptosis. It shows directly that apoptosis of PS-specific memory cells is the cause of PS-induced hyporesponsiveness. These results should be taken into account prior to consideration of the use of PS vaccines.University of Iceland, Landspitali University Hospital

Detailed Multiplex Analysis of SARS-CoV-2 Specific Antibodies in COVID-19 Disease

A detailed understanding of the antibody response against SARS-CoV-2 is of high importance, especially with the emergence of novel vaccines. A multiplex-based assay, analyzing IgG, IgM, and IgA antibodies against the receptor binding domain (RBD), spike 1 (S1), and nucleocapsid proteins of the SARS-CoV-2 virus was set up. The multiplex-based analysis was calibrated against the Elecsys® Anti-SARS-CoV-2 assay on a Roche Cobas® instrument, using positive and negative samples. The calibration of the multiplex based assay yielded a sensitivity of 100% and a specificity of 97.7%. SARS-CoV-2 specific antibody levels were analyzed by multiplex in 251 samples from 221 patients. A significant increase in all antibody types (IgM, IgG, and IgA) against RBD was observed between the first and the third weeks of disease. Additionally, the S1 IgG antibody response increased significantly between weeks 1, 2, and 3 of disease. Class switching appeared to occur earlier for IgA than for IgG. Patients requiring hospital admission and intensive care had higher levels of SARS-CoV-2 specific IgA levels than outpatients. These findings describe the initial antibody response during the first weeks of disease and demonstrate the importance of analyzing different antibody isotypes against multiple antigens and include IgA when examining the immunological response to COVID-19