• Pandemic; COVID-19; Surgery; Mental Health; Guidelines

Seghatchian J (2021) A viewpoint commentary on the host inflammatory responses to two faces of Coronavirus variants: infectivity causing thrombotic events & cytokine storms leading to organ failure with fatal outcome. Arch Emerg Med Crit Care 5(1): 1048.

SARS-CoV-2 variant strains are amongst current pandemic of corona virus diseases, spreading fast all over the world, often with severe acute respiratory syndrome, often leading to inflammatory thromboembolic event, major organ injury with fatal outcome, particularly in the aged and immune compromised groups. The objective of this commentary is to provide a personal overview on some of the insights on three interrelated areas of current interest namely: i] Current Status of global deployment new generation of vaccines, as the essential mode of the immunotherapy, to induced neutralizing antibodies and to regulate T cells to provide some durable defense response against the Cov-2 variants, from 2-3 weeks after vaccination, upon a second booster injection; ii] The use of an alternative interventional proposal namely to directly infused some specific polyclonal neutralizing antibodies, free from infection induced the harmful circulatory cytokines such as IL-6; activated complements; and other variables in the early phase of the inflammation, coagulation and fibrinolysis processes , that can lead to organ failures and signifying that death is coming [DIC], if appropriate action is not taken in the early stages of infection; and iii]The current status of where we are now and where are we going, in terms of dealing with the 3 most relevant fast spreading CoV-2 variants namely the mutated Kent-UK; South African and the P1 &P 2 Brazilian hot spot variants. With a cautionary note that the behavior of the vaccines might not be the same and will depend upon the populations that have already exposed earlier to virus so be it being asymptomatic or mild and severe but recovered from infection, as we have experienced with the Chinese vaccine in Brazil that score poorly [ 50.3% efficacy ] while the same vaccine scored highly well[ over 92% in Trials performed in Middle Eastern countries and these results are suggestive that some potentially geographical influence of the efficacy of all available vaccines on some normal strains and their mutated variants.

Moreover there is also increasing evidence that in the acute autoimmune episodes, both monocytes and macrophages, as the essential parts of the autoimmune syndrome, do play major roles in severe Covid-19 complications by inducing inflammatory and cytokine storm responses. Hence drug therapy has also became the standard conventional therapy to reduce the clinical impacts the IL-6; activated complements; and other anti- inflammatory phenomena to improve status of the COVID therapy and to save some lives.

More recently some newer tools put in place to investigate the processes that control the patient to patient variability in T cells activation, or their killing power and exhaustion, using newer tools such as the advanced flowcytometery platform that provide not only a rapid, high throughput solution to the study or monitoring of T cell function and phenotype, but in addition helps to identify early biomarkers or perform serological characterizations that are highly relevant to the current states of newer generation of vaccines, in order to clear up the bound antibody to the infective agent from the circulation.

Moreover, some in- depth blood proteome profiling analysis of some infected cases revealed distinct functional characteristics of plasma proteins between severe and non-severe CoV-2 patients, indicate that almost a total of 76 unreported proteins, as novel prognostic biomarker candidates, have been identified as plasma proteome signatures. This supports the view that activation of neutrophil, complement, and T cell suppression as well as, the activation of pro-inflammatory factors upstream and downstream of interleukin-6, interleukin-1B, and tumor necrosis factor might occurred. These events are amongst important issues to be borne in mind in any therapeutic modalities used for the immunotherapy, including the proposed alternative therapy, using a small pool of the neutralizing antibodies as a hyper concentrate [P- NAB-H]- derived from convalescent plasmas, or cadaveric serum, that conceptually would cover comprehensively all variants.

In fact such a new bioproduct is easily obtainable by on- line affinity column adsorption from of the Coronavirus convalescent patient or vaccinated good responders individuals, having some equivalent amounts of circulating neutralizing antibodies than the convalescent patients who recovered from infection. This alternative strategy is believed to be most comprehensive move of therapeutic modality against CoV-2 strains and variants in time as it could be also prepared from the small pool of convalescent plasma [CCP] from male in the real time or the cadaveric serum of patients, using an external affinity column adsorption technology.

Both the affinity column adsorption and blood purification systems for removal of cytokines and the production of antibody hyper -concentrates are already in practice in small scale but in view of enormous demand for pure polyclonal neutralizing bioproducts in pandemic it should be carried out in collaboration with the interested manufacturers, and in full compliance with the GMP requirements.

Needless to highlight that such a polyclonal specific antibodies hyper-concentrates obtainable from the mini pool of CCP or vaccinated high responders would be effective on all types viral strains, in the real times, including the most fearful fast spreading CoV-2 variants from the mutated Kent-UK, South African and, Brazilian origins, if the vaccinations processes appears to be less effective. Evidence is accumulating that potentially 10 times more neutralizing antibody is required to neutralize such variants.

Moreover there are plenty of the low and /or nonresponders, making the viral neutralizing of some fast spreading virus through vaccinotherapy alone without the use of such of hyper concentrate neutralizing antibodies even as a booster an impossible task.

Interestingly AstraZenika is developing an antibody bioproduct, based on the same principle, to deliver directly antibody to those individual who fail to develop antibody through vaccination [poor responders], though this interventional modality, [without the removal of toxic circulating substances such as cytokines and altered components anti-inflammatory parameters and potential circulating autoantibodies such as lupus anticoagulant], does not overcome some of the toxic effects of viral infection- induced in severely infected individual. Hence our proposed affinity column purification system and followed up by plasma exchange therapy in the most standardized way by using fixed concentration of P-NAB-H, and suspended it in cryosupernatant or FFP to provide in addition a balanced antiinflammatory factors and albumin in view of deficiency that usually created by severe infection.

The lack of high efficacy response to vaccination and the variability in results spark some intriguing questions if the reported efficacy for various vaccines might be related to the population under investigation and the presence of some new variants in real time. Currently the’ Drug’s-Induced Instant Immunity is becoming accepted in concept and the use pooled NAB- Concentrate in the populations that fail vaccination [i.e. non- responders] might fully resolved. Such a short coming this will clearly be right in time, as evidence is accumulating that while the Oxford vaccine is highly effective against the UK variant but less effective against South African variants requiring potentially 10 times more antibodies, begging for designing a new targeted vaccine against South African local variant. This also reflected, as highlighted before in the variability observed in the vaccine efficacy that is influenced geographically, as we have witnessed with Chinese vaccine in Brazil [ranging from 50.3% to over 90%] as compared to other countries. This is further substantiated by the effectiveness of the Oxford vaccine in the local trial in South Africa on limited numbers of young asymptomatic individual, showing a limited effectiveness for some mild diseases and failing to stopping transmission but only protecting against sever diseases and death. This also support the notion that the mass vaccination to be repeated 6 monthly or yearly reviewed in view of appearance of new viral variants. Moreover the new concept of the “mixed- matched’ vaccination strategy for phase one and phase two to be tried for the improved effectiveness on mild and more severe viral infection to survive infection, as new generation of approved vaccines like Novovacs and Johnson Johnson appeared to be effective on South African variants and a joint venture for mixed matched combination vaccines has already agreed to perused urgently by two relevant manufacturers.

To conclude, the Coronavirus virus has challenged human ingenuity, as the infection associated deaths reaching now to millions and still rising with the appearance of some newer fast transmissible variants on the scene, and in addition this upward trend is supported by the colder months, traveling season and the participation in various social events, hence it is not the time to dropping our guard early as the consequence will be enormous.

On the other hands, however, with the ongoing highly effective mass distribution of multiple vaccines and the targeted use of newly proven pharmaceuticals bioproducts and advanced technologies to mitigate infections and to prevent deaths there are some hope that both mixed – matched vaccination protocols that becoming the next step to tame these newer and emerging variants and the rush in development of newer targeted vaccines targeting these newer variants in the early stage before being firmly established is warranted . In fact evidences are accumulating that the immune response to infection follow a pyramid pattern, consisting from no symptoms, through midasymptomatic events, to extremely severe cases with fatal outcome. These patterns are also reflected to the efficacy and specificity of some vaccine as recently put in evidence that the Oxford vaccine does neutralizing extremely well the UK variant and reducing severe hospitalization but fail to be effective in South African mild and medium cases as recently highlighted when performed on a small numbers of cases. In fact so far there is only 150 cases of South African variant in the UK as identified by genetic finger printing analyses and hopefully with the current restriction in place one should be able to tame this variant to spread fast in the UK and the same analogy is applicable to the deadly Brazilian Variants a unfinished journey in the race between excellent speed of the vaccination and rate of developments of harmful variants in the UK. It is nevertheless worthy to highlight extra vaccine being under development well in advanced to survive and timely outwit the South African strain that is consistently evolving to beat human defense similar to mutated UK variants causing enormous death so far.

Meanwhile considerable progress are made in removing and eliminating the influence others toxic effects of CoV-2 infection such as the removal of autoantibodies and inhibiting or removal of the cytokines appearing in the early phase of severe the CoV-2 infection. In fact proteomics beguins to emerge from genomics shadow, as the cutting edge technologies answering critical changes by functionally defining each T cell, Monocytes and NK cells and altered functions and heterogeneous responders triggered by complement & alloantibody- activated endothelial cells that play a key drivers of alloimmune immunisation.

As for the future trends in vaccine approvals the European Medicine Agency Committee for human medicinal products recommended AstraZeneca’s COVID-19 vaccine be granted conditional marketing authorization alongside 12 other approvals and the UK Government has given £7 million of funding for a clinical trial which will investigate whether patients can be given different COVID-19 vaccines for each dose and the UK is now in the lead for the mass vaccination and the only countries involved in genetic fingerprinting all variants emerging internationally.