scholarly journals Breakthrough Infections with Multiple Lineages of SARS-CoV-2 Variants Reveals Continued Risk of Severe Disease in Immunosuppressed Patients

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1743
Author(s):  
Xufang Deng ◽  
Monika Evdokimova ◽  
Amornrat O’Brien ◽  
Cynthia L. Rowe ◽  
Nina M. Clark ◽  
...  

The pandemic of COVID-19 caused by SARS-CoV-2 infection continues to spread around the world. Vaccines that elicit protective immunity have reduced infection and mortality, however new viral variants are arising that may evade vaccine-induced immunity or cause disease in individuals who are unable to develop robust vaccine-induced responses. Investigating the role of viral variants in causing severe disease, evading vaccine-elicited immunity, and infecting vulnerable individuals is important for developing strategies to control the pandemic. Here, we report fourteen breakthrough infections of SARS-CoV-2 in vaccinated individuals with symptoms ranging from asymptomatic/mild (6/14) to severe disease (8/14). High viral loads with a median Ct value of 19.6 were detected in the nasopharyngeal specimens from subjects regardless of disease severity. Sequence analysis revealed four distinct virus lineages, including alpha and gamma variants of concern. Immunosuppressed individuals were more likely to be hospitalized after infection (p = 0.047), however no specific variant was associated with severe disease. Our results highlight the high viral load that can occur in asymptomatic breakthrough infections and the vulnerability of immunosuppressed individuals to post-vaccination infections by diverse variants of SARS-CoV-2.

2021 ◽  
Author(s):  
Petra Mlcochova ◽  
Steven Kemp ◽  
Mahesh Shanker Dhar ◽  
Guido Papa ◽  
Bo Meng ◽  
...  

Abstract The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and has spread throughout India, displacing the B.1.1.7 (Alpha) variant and other pre-existing lineages. Mathematical modelling indicates that the growth advantage is most likely explained by a combination of increased transmissibility and immune evasion. Indeed in vitro, the delta variant is less sensitive to neutralising antibodies in sera from recovered individuals, with higher replication efficiency as compared to the Alpha variant. In an analysis of vaccine breakthrough in over 100 healthcare workers across three centres in India, the Delta variant not only dominates vaccine-breakthrough infections with higher respiratory viral loads compared to non-delta infections (Ct value of 16.5 versus 19), but also generates greater transmission between HCW as compared to B.1.1.7 or B.1.617.1 (p=0.02). In vitro, the Delta variant shows 8 fold approximately reduced sensitivity to vaccine-elicited antibodies compared to wild type Wuhan-1 bearing D614G. Serum neutralising titres against the SARS-CoV-2 Delta variant were significantly lower in participants vaccinated with ChadOx-1 as compared to BNT162b2 (GMT 3372 versus 654, p<0001). These combined epidemiological and in vitro data indicate that the dominance of the Delta variant in India has been most likely driven by a combination of evasion of neutralising antibodies in previously infected individuals and increased virus infectivity. Whilst severe disease in fully vaccinated HCW was rare, breakthrough transmission clusters in hospitals associated with the Delta variant are concerning and indicate that infection control measures need continue in the post-vaccination era.


Author(s):  
Md Ather Hussain Ansari ◽  
Md Sadique Hussain ◽  
Mohit

Many countries are engaged in making vaccine against COVID-19 as the world records more than 38 million SARS-CoV-2 infections and more than one million deaths. It has prompted nations to close the borders, halted companies, kept people inside their homes, and numerous other measures to prevent their spread. We systematically searched on Google scholar, PubMed, LitCovid, and MedRxiv using the certain search terms for published articles. The infection raging through communities is expected to have evoked some degree of immunity in many asymptomatic and recovered individuals. However, the level of protective immunity and duration of such immunity have not been studied in depth. At the same time, spanning from the conventional whole virus vaccine to recombinant vaccines using Adenovirus vectors and first-of-its kind mRNA vaccines are in human trials. Before the effectiveness and safety of such vaccines are established billions of doses have been produced and stockpiled to save time in production and distribution. Antigenic diversity and the potential role of passive surveillance in COVID-19 regulation are explored in this report.


2020 ◽  
Vol 8 (35) ◽  
pp. 7-16 ◽  
Author(s):  
Albin John ◽  
Freedom Ha ◽  
Mimi Zumwalt

The COVID-19 pandemic has taken a great toll on many families. From its rapid spread to debilitating outcomes, the virus has wreaked havoc on healthcare systems around the world. As researchers study this novel virus, the public continues to seek more information on who is the most susceptible and which population will be affected by the more severe manifestations of the disease. As a result, scientists have started analyzing the variable effects of COVID-19 infection in different age groups. While the information is still nascent, these studies demonstrate that no one is immune, that all are susceptible to infection by this virus, and that certain demographics of the general population have more severe disease than others. This literature review examines how COVID-19 has affected different age groups, from neonates to older adults, by exploring statistics, mechanisms, and possible risk factors. This article will also investigate the role of comorbidities in increasing the severity of this viral infection. Key words: COVID-19, SARS-CoV-2, coronavirus, age, neonates, pregnancy, older adults, mechanism, comorbidities, angiotensin converting enzyme 2


Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1815
Author(s):  
Magdalena Komiazyk ◽  
Jaroslaw Walory ◽  
Jan Gawor ◽  
Iza Ksiazek ◽  
Robert Gromadka ◽  
...  

The introduction of effective vaccines against SARS-CoV-2 is expected to prevent COVID-19. However, sporadic cases of infection in vaccinated persons have been reported. We describe a case of a double-dose vaccinated woman with COVID-19. All stages of infection were observed, from no identification of virus, then the start of the infection, a high viral load, coming out of viraemia, and finally no detection of the virus. Despite the high viral load, the woman demonstrated mild COVID-19 symptoms, manifested only by a sore throat. The antibody results showed that she produced both post-infectious and post-vaccination immune responses. Phylogenetic analysis of the obtained viral genome sequence indicated that the virus belonged to the UK SARS-CoV-2 lineage B.1.1.7 (GR 501Y.V1; 20I/S:501Y.V1; Alpha variant).


2007 ◽  
Vol 75 (7) ◽  
pp. 3539-3547 ◽  
Author(s):  
James P. Hewitson ◽  
Paul A. Hamblin ◽  
Adrian P. Mountford

ABSTRACT The cytokine interplay during the development of protective immunity to the radiation-attenuated (RA) schistosome vaccine has been extensively characterized over recent years, yet the role of costimulatory molecules in the development of cell-mediated immunity is much less well understood. Here we demonstrate the importance of CD40/CD154 in vaccine-induced immunity, as CD154−/− mice exposed to RA schistosomes develop no protection to challenge infection. We showed that vaccinated CD154−/− mice have defective Th1-associated immune responses in the skin-draining lymph nodes and the lungs, with reduced or absent levels of interleukin-12p40 (IL-12p40), gamma interferon, and nitric oxide, but elevated levels of lung IL-4 and IL-5. The expression of major histocompatibility complex II (MHC-II) on antigen-presenting cells recovered from the lungs of vaccinated CD154−/− mice was also severely compromised. The administration of anti-CD40 monoclonal antibody (MAb) to CD154−/− mice did not reconstitute sustained Th1 responses in the lymph nodes or the lungs, nor did the MAb restore anti-parasite immunoglobulin G production or protective immunity. On the other hand, the administration of recombinant IL-12 (rIL-12) to CD154−/− mice shortly after vaccination caused elevated and sustained levels of Th1-associated cytokines, rescued MHC-II expression by lung CD11c+ cells, and restored the appearance of inflammatory effector foci in the lungs. However, the treatment of CD154−/− mice with rIL-12 did not restore protection. We conclude that protective immunity to the RA schistosome vaccine is CD154 dependent but is independent of IL-12-orchestrated cellular immune mechanisms in the lungs.


2005 ◽  
Vol 73 (10) ◽  
pp. 7011-7013 ◽  
Author(s):  
D. Mitchell Magee ◽  
Rhonda L. Friedberg ◽  
Melanie D. Woitaske ◽  
Stephen Albert Johnston ◽  
Rebecca A. Cox

ABSTRACT We investigated secondary immunity against coccidioidomycosis by using gene expression microarrays. Surprisingly, a high percentage of B-cell-related genes were associated with protective immunity. A functional confirmation of the importance of B cells against coccidioidomycosis was achieved by demonstrating that vaccination was not fully protective in B-cell-deficient MuMT mice.


2021 ◽  
Vol 14 (11) ◽  
pp. e246308
Author(s):  
Oluwafeyi Adedoyin ◽  
Sharmela Brijmohan ◽  
Ross Lavine ◽  
Fausto Gabriel Lisung

Since the beginning of COVID-19 vaccination in New Jersey in December 2020, we have observed multiple cases of undetectable adaptive immunity, post-vaccination or post-COVID-19 infection, in patients using immunosuppressants. Here, we present three cases of patients using immunosuppressants: mycophenolate and tacrolimus for renal transplant; ocrelizumab for multiple sclerosis and rituximab for peripheral ulcerative keratitis. All three patients were admitted for acute respiratory distress syndrome (ARDS) from COVID-19 pneumonia; two patients reported having received full COVID-19 vaccination prior to admission and one unvaccinated patient required readmission. Our findings showed that these patients tested negative for SARS-CoV-2 IgM spike and CoV-2 IgG nucleocapsid antibodies. All three patients were treated with standard-of-care remdesivir, dexamethasone and convalescent plasma; two recovered successfully and one patient died from respiratory failure secondary to worsening ARDS from COVID-19 pneumonia. We highlight the challenges of treating immunosuppressed patients with COVID-19 pneumonia, in an era where dissemination of such information is paramount to helping doctors standardise and improve the quality of care for these patients.


2021 ◽  
Vol 4 (4) ◽  
pp. e202000886 ◽  
Author(s):  
Prabhuanand Selvaraj ◽  
Christopher Z Lien ◽  
Shufeng Liu ◽  
Charles B Stauft ◽  
Ivette A Nunez ◽  
...  

A critical question in understanding the immunity to SARS-COV-2 is whether recovered patients are protected against re-challenge and transmission upon second exposure. We developed a Syrian hamster model in which intranasal inoculation of just 100 TCID50 virus caused viral pneumonia. Aged hamsters developed more severe disease and even succumbed to SARS-CoV-2 infection, representing the first lethal model using genetically unmodified laboratory animals. After initial viral clearance, the hamsters were re-challenged with 105 TCID50 SARS-CoV-2 and displayed more than 4 log reduction in median viral loads in both nasal washes and lungs in comparison to primary infections. Most importantly, re-challenged hamsters were unable to transmit virus to naïve hamsters, and this was accompanied by the presence of neutralizing antibodies. Altogether, these results show that SARS-CoV-2 infection induces protective immunity that not only prevents re-exposure but also limits transmission in hamsters. These findings may help guide public health policies and vaccine development and aid evaluation of effective vaccines against SARS-CoV-2.


2021 ◽  
Author(s):  
Ivette A Nunez ◽  
Christopher Z Lien ◽  
Prabhuanand Selvaraj ◽  
Charles B Stauft ◽  
Shufeng Liu ◽  
...  

Epidemiological studies have revealed the emergence of multiple SARS-CoV-2 variants of concern (VOC), including the lineage B.1.1.7 that is rapidly replacing old variants. The B.1.1.7 variant has been linked to increased morbidity rates, transmissibility, and potentially mortality. To assess viral fitness in vivo and to address whether the B.1.1.7 variant is capable of immune escape, we conducted infection and re-infection studies in naive and convalescent Syrian hamsters (>10 months old). Hamsters infected by either a B.1.1.7 variant or a B.1 (G614) variant exhibited comparable viral loads and pathology. Convalescent hamsters that were previously infected by the original D614 variant were protected from disease following B.1.1.7 challenge with no observable clinical signs or lung pathology. Altogether, our study did not find that the B.1.1.7 variant significantly differs from the B.1 variant in pathogenicity in hamsters and that natural infection-induced immunity confers protection against a secondary challenge by the B1.1.7 variant.


Author(s):  
O. E. Bradfute

Maize mosaic virus (MMV) causes a severe disease of Zea mays in many tropical and subtropical regions of the world, including the southern U.S. (1-3). Fig. 1 shows internal cross striations of helical nucleoprotein and bounding membrane with surface projections typical of many plant rhabdovirus particles including MMV (3). Immunoelectron microscopy (IEM) was investigated as a method for identifying MMV. Antiserum to MMV was supplied by Ramon Lastra (Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela).


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