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Id Subject Object Predicate Lexical cue
T1 0-74 Sentence denotes Can an effective SARS-CoV-2 vaccine be developed for the older population?
T2 76-84 Sentence denotes Abstract
T3 85-268 Sentence denotes The emergence of SARS-CoV-2 and its inordinately rapid spread is posing severe challenges to the wellbeing of millions of people worldwide, health care systems and the global economy.
T4 269-554 Sentence denotes While many younger people experience no or mild symptoms on infection, older adults are highly susceptible to life-threatening respiratory and systemic conditions which demand a full understanding and leveraging of knowledge of the differences between immunity in young and old people.
T5 555-716 Sentence denotes Consequently, we welcome papers addressing any issues relevant to immunity and ageing in the context of SARS-CoV-2, and will endeavour to fast-track peer-review.
T6 717-952 Sentence denotes We aim to provide a platform exclusively for discussions of individual and age differences in susceptibility and immune responses to COVID caused by SARS-CoV-2 infection and how to prevent or reduce severity of disease in older adults.
T7 954-966 Sentence denotes Introduction
T8 967-1177 Sentence denotes The newly-emerged Coronavirus SARS-CoV-2 is highly infectious and has rapidly spread throughout the world with a case fatality rate (CFR) highly dependent on age and pre-existing conditions associated with age.
T9 1178-1454 Sentence denotes As more data become available, average CFRs in children appear negligible, in young adults perhaps up to 1%, but in people over 60 rising to 4%, over 70 up to 9% and over 80 even up to 18% (see, for example, https://www.cebm.net/covid-19/global-covid-19-case-fatality-rates/).
T10 1455-1738 Sentence denotes Clearly, these figures can vary tremendously from country to country, and depend on the state of health of the patients and the state of the health care system, but it is likely that this sort of age stratification reflects the general characteristics of Coronavirus disease (COVID).
T11 1739-1858 Sentence denotes Obviously, there is vigorous debate as to why this may be, but a common denominator is the waning of immunity with age.
T12 1859-2101 Sentence denotes Although much effort is currently directed at repurposing licensed drugs as anti-virals, particularly those with anti-inflammatory effects [1] this is usually viewed as a stop-gap measure and hopes are pinned on developing effective vaccines.
T13 2102-2247 Sentence denotes An unprecedented world-wide effort is channelling academic and industrial resources into the rapid production and testing of SARS-CoV-2 vaccines.
T14 2248-2529 Sentence denotes Quite apart from the potential dangers of accelerated vaccine development [2], and remembering the additional danger of immune enhancement [3], even were this successful the question remains whether the most susceptible members of the population (say, those over 60) would benefit.
T15 2531-2580 Sentence denotes COVID immunopathology and potential interventions
T16 2581-2762 Sentence denotes There is no pre-existing immunity to a virus not previously encountered except via cross-reactivity or shared viral antigen, as is sometimes the case for seasonal influenza strains.
T17 2763-2992 Sentence denotes As SARS-CoV-2 is almost certainly completely novel for at least the vast majority of people, the virus enjoys unrestrained entry into host cells which then rely on intracellular (cell-intrinsic) anti-viral defence mechanisms [4].
T18 2993-3118 Sentence denotes If these fail, cell death releases damage-associated molecules (DAMPs) and viral particles triggering inflammatory reactions.
T19 3119-3418 Sentence denotes Severe acute respiratory syndrome is caused by dysregulated over-exuberant inflammatory responses that can progress to a systemic sepsis-like “cytokine storm” [5], which together with effects of the virus also directly infecting other organs, not just the lung, can result in multiple organ failure.
T20 3419-3648 Sentence denotes The aim of prophylactic vaccination of course is to induce sufficient neutralising antibody to prevent infection and sufficient numbers of virus-specific resident memory cytotoxic T cells in the lung to prevent viral replication.
T21 3649-3812 Sentence denotes This requires the presence and efficient cooperation of antigen-presenting cells, T cells and B cells within a correctly functioning microenvironment (lymph node).
T22 3813-3998 Sentence denotes When vaccination is unable to elicit qualitatively or quantitatively sufficient protective antibody, host cell infection will still take place, and may trigger sequelae described above.
T23 3999-4255 Sentence denotes Given the rapidity and degree with which SARS-CoV-2 can cause immunopathology in the lung, vaccines would have to be highly efficient in generating neutralising antibody as well as protective cell mediated local immunity to prevent this sequence of events.
T24 4256-4471 Sentence denotes Achieving such immune protection by a vaccine is quite feasible in the young, but it may prove to be challenging in old populations as evidenced by the low efficacy of seasonal influenza vaccine in such populations.
T25 4472-4637 Sentence denotes Alternatively, adoptive immunotherapy with neutralising monoclonal antibody, as in cancer treatment, may be a possibility, and several companies are working on this.
T26 4638-4736 Sentence denotes However, repeated i.v. infusion of sufficient antibody does not seem a priori an optimal approach.
T27 4737-4900 Sentence denotes Clearly, traditional vaccination to stimulate the patient’s own response would be preferable, but how likely is it that that could be accomplished in older people?
T28 4902-4948 Sentence denotes Immunosenescence and its underlying mechanisms
T29 4949-5103 Sentence denotes Altered immune competence with increasing age, so-called immunosenescence [6], is the result of changes at multiple levels of the immune system over time.
T30 5104-5302 Sentence denotes It includes the altered balance of immune cell production in the bone marrow resulting in reduced lymphopoiesis and increased output of myeloid lineage cells which are also functionally compromised.
T31 5303-5414 Sentence denotes Thymic involution substantially reduces the output of naïve T cells and the TCR repertoire contracts over time.
T32 5415-5561 Sentence denotes Although loss of circulating naïve B cells is less profound than naïve T cells, reduced BCR repertoire diversity with age is also well recognized.
T33 5562-5794 Sentence denotes Furthermore, aging is associated with the dysfunction of innate immune cells like neutrophils at sites of infection possibly due to the poorer capacity of the adaptive immune system to reign in over-exuberant inflammatory responses.
T34 5795-5957 Sentence denotes The ability to generate adaptive immune responses is compromised by dysfunction of antigen-presenting cells and disorganised and fibrotic lymph node architecture.
T35 5958-6220 Sentence denotes Collectively, these changes prevent appropriate control of the initial inflammatory response and decrease the generation of an efficient and robust adaptive immune response which requires the production of large number of functional effector T cells and B cells.
T36 6221-6510 Sentence denotes For all these reasons, protective responses to infection or vaccination tend to be on average lower in many older adults than in the young, but there is enormous inter-individual variation in people owing to the individual variations of genetics and the history of environmental exposures.
T37 6511-6575 Sentence denotes Hence, two crucial questions are raised by these considerations:
T38 6576-6800 Sentence denotes 1) how can we measure immune and physiological status in an individual in a clinically meaningful manner and 2) how can we intervene at the crucial checkpoints thus identified in order to restore appropriate immune function?
T39 6801-7058 Sentence denotes Identification of biomarkers of protective or detrimental responses to a SARS-CoV-2 infection or vaccine and determination of the kinetic pattern of these biomarkers during the course of infection or vaccine response are critical to address these questions.
T40 7060-7094 Sentence denotes Biomarkers and vaccine requirement
T41 7095-7138 Sentence denotes There are few precedents to assist us here.
T42 7139-7243 Sentence denotes Efforts to develop a prophylactic vaccine or SARS-CoV-1 were shelved when the infection faded by itself.
T43 7244-7367 Sentence denotes There are surprisingly few data available concerning the status of immune responsiveness to truly novel antigens in humans.
T44 7368-7588 Sentence denotes A study on Yellow Fever vaccination of the elderly pointed to dysfunctional antigen-presenting cells and a dearth of antigen-specific CD4+ Th helper cells as culprits in the low antibody responses of older vaccinees [7].
T45 7589-7681 Sentence denotes Otherwise, we have to rely mostly on the large literature on seasonal influenza vaccination.
T46 7682-7857 Sentence denotes However, the problem here is that everyone has already been exposed to some strains of influenza and even newly-emerging strains such as the avian H7N1 are not entirely novel.
T47 7858-8032 Sentence denotes Nonetheless, knowledge garnered on immunity and responses to vaccination against this virus may tell us something about the capacity of older adults to respond to SARS-CoV-2.
T48 8033-8141 Sentence denotes Primate models featuring the responses of older monkeys to SARS-CoV-1 infection may also be informative [8].
T49 8142-8391 Sentence denotes A systems biology approach will be needed to identify the protective antigen/epitopes of SARS-CoV-2 for both antibody/B cell responses and T cell responses and to classify them as protective or non-protective responses to serve as useful biomarkers.
T50 8392-8565 Sentence denotes Importantly, vaccine design for the older adult should aim to stimulate a broad T and B cell response potentially overcoming reduced immune function in the older population.
T51 8567-8660 Sentence denotes How can current immunological knowledge be leveraged to protect the oldest old against COVID?
T52 8661-8958 Sentence denotes According to the above arguments, we consider it unlikely that a conventional vaccine based on young adult responses will be highly effective in COVID prophylaxis for older adults, but should be rigorously applied to everyone else to achieve herd immunity that will indirectly protect the elderly.
T53 8959-9089 Sentence denotes The ability to prevent infection by adoptive immunotherapy remains a possibility, albeit logistically and financially challenging.
T54 9090-9269 Sentence denotes Pharmacological prevention of infection by other means, for example, by blocking the interactions between viral proteins and host cell molecules acting as receptors may be useful.
T55 9270-9461 Sentence denotes Finally, various ways to improve the general immune functions in the older population should be considered and developed to strengthen the immune response to infection and vaccine in general.
T56 9462-9961 Sentence denotes These approaches could include interventions at the level of hematopoiesis to correct the skewing of output towards dysfunctional myeloid cells responsible for acute inflammatory responses in the lung, normalisation of T cell progenitor output and reconstitution of the thymus for correct selection of T cells, especially regulatory T cells to keep inflammation in check, reconstitution of antigen presentation function in the lymph nodes and re-alignment of T-B cell interactions and functionality.
T57 9962-10067 Sentence denotes In the meantime, the major benefit of vaccination will be seen at the population level in younger people.
T58 10068-10397 Sentence denotes Once herd immunity is established, the well-known effect of diluting out new hosts for acute viruses should result in the virus disappearing, with the proviso that protective immunity is retained for long enough (this is not yet established) and reinfection is not introduced from a location where new hosts were still available.
T59 10398-10512 Sentence denotes And with the linked proviso that the virus does not mutate into a form against which immune memory is not present.
T60 10513-10829 Sentence denotes We welcome papers addressing any of the issues discussed above and will endeavour to fast-track peer-review to provide a platform exclusively for discussions of individual and age differences in immune responses SARS-CoV-2 and susceptibility to COVID and how to prevent or reduce severity of disease in older adults.
T61 10831-10847 Sentence denotes Publisher’s Note
T62 10848-10966 Sentence denotes Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
T63 10968-10984 Sentence denotes Acknowledgements
T64 10985-10990 Sentence denotes None.
T65 10992-11014 Sentence denotes Authors’ contributions
T66 11015-11061 Sentence denotes Both authors wrote and revised the manuscript.
T67 11062-11115 Sentence denotes The author(s) read and approved the final manuscript.
T68 11117-11137 Sentence denotes Authors’ information
T69 11138-11161 Sentence denotes No further information.
T70 11163-11170 Sentence denotes Funding
T71 11171-11191 Sentence denotes No specific funding.
T72 11193-11227 Sentence denotes Availability of data and materials
T73 11228-11243 Sentence denotes Not applicable.
T74 11245-11287 Sentence denotes Ethics approval and consent to participate
T75 11288-11303 Sentence denotes Not applicable.
T76 11305-11328 Sentence denotes Consent for publication
T77 11329-11377 Sentence denotes Both Co-Editors-in-Chief consent to publication.
T78 11379-11398 Sentence denotes Competing interests
T79 11399-11443 Sentence denotes Both authors declare no competing interests.