О роли эозинофилов

Основная роль в иммунном ответе, как считается, это борьба против паразитов; так же могут принимать участие в борьбе против бактерий, грибков, вирусов. Это клетки не столько фагоциты, сколько "огнеметы".
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В случае с ковидом (итп легочными заболеваниями), активного участия эозинофилов в процессе, желательно избежать, на мой взгляд. Я в этом мнении не одинока- нашлась статья, где  хорошо разобрано вовлечение эозинофилов в патологию ковида и сложности создания в прошлом вакцин к коронавирусам,  из-за перекоса ответа организма в сторону активации эозинофилов и формирования АУЗИ после прививок (на моделях животных).
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There are a number of diseases associated with eosinophil expansion in which eosinophils are causally related to the disease pathology, such as subsets of moderate and severe asthma.
..eosinophil depletion occurs in response to multiple triggers of acute inflammation,⁸ including during sepsis, and multiple studies have consistently shown that low eosinophil levels correlate with poor outcome in critically ill patients.⁹
..do patients with eosinopenia have unique COVID-19 disease features? This is a particularly relevant question because eosinopenia has already been reported in patients with acute respiratory deterioration during infection with severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS-CoV-2), the causative agent of COVID-19.

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Third, do eosinophils contribute to the lung pathology induced during COVID-19 and will they contribute to adverse events associated with emerging COVID-19 vaccines? Indeed, eosinophil-associated lung pathology is known to occur following certain viral infections (eg, respiratory syncytial virus [RSV]) and importantly is a known complication in previous severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) vaccination studies (see Table I).^{11,12,13,14,15,16,17} On the basis of previous experience with SARS-CoV vaccines, it is expected that COVID-19 vaccines will need careful safety evaluations for immunopotentiation that might increase infectivity and/or eosinophilic infiltration.¹⁸
The role of eosinophils in mucosal immune responses in the respiratory tract has largely focused on the detrimental impact that these cells can have in inflammatory responses due to their potent proinflammatory function. However, preclinical studies (mainly in mice) have shown that eosinophils are equipped with an assortment of molecular tools that enable them to recognize, respond, and orchestrate antiviral responses to respiratory viruses.¹⁹ Human eosinophils express several endosomal Toll-like receptors (TLRs), including TLR3, TLR7, and TLR9, that detect viral microbe–associated molecular patterns.^{20,21 22} TLR7 enables eosinophils to recognize single-stranded RNA viruses such as coronavirus, and stimulating this receptor in human eosinophils triggers eosinophil cytokine production, degranulation, superoxide and nitric oxide (NO) generation, and prolonged cellular survival.^21,22,23 Eosinophil-derived neurotoxin (EDN/RNAse2) and eosinophil cationic protein (ECP/RNAse3) from human eosinophils reduce infectivity of RSV by a ribonuclease-dependent mechanism.

²⁴,²⁵ Both human and murine eosinophils produce NO via inducible NO synthase, which can have direct antiviral effects on parainfluenza virus and RSV. ²³ ,²⁶ ,²⁷

Eosinophils are able to produce extracellular traps composed of eosinophilic granule proteins bound to genomic and mitochondrial DNA, and murine eosinophils can release these DNA traps in response to RSV infection in vitro,²⁸ especially in oxidative lung tissue environments.²⁹ Eosinophils are also capable of quickly mobilizing preformed granule pools of T_H1 cytokines, including IL-12 and IFN-γ, which are important for mounting effective antiviral immune responses.³⁰ In a murine model of allergic asthma, pulmonary eosinophils upregulate MHC-I and CD86 in response to influenza virus infection, where they can directly interact with CD8⁺ T cells and promote the recruitment of virus-specific CD8⁺ T cells into the lungs to enhance antiviral immunity.³¹ Activated murine and human eosinophils also express MHC-II molecules and costimulatory molecules and can function as antigen-presenting cells for viral antigens, leading to T-cell activation and cytokine secretion.^32,33
Although these data substantiate the antiviral potential of eosinophils, the clinical significance of eosinophils in antiviral responses in human disease continues to remain debatable. Patients with eosinophilic asthma have an increased risk for viral-induced asthma exacerbations, and there is mounting evidence that patients with eosinophilic asthma may actually have reduced innate responses against respiratory viruses.^35,36,37 Importantly, biologic agents that decrease pulmonary eosinophil levels reduce asthma exacerbations, and patients with asthma treated with these agents have not been reported to have increased viral infections.^{36,38,39,40,41,42,43} Rosenberg et al

⁴⁴ suggested that eosinophils in the respiratory tract might represent a “double-edged sword,” promoting antiviral responses against some respiratory viruses that could become dysregulated during allergic disease given their increased numbers and/or activation status, ultimately resulting in an exaggerated host response that can lead to host tissue damage. The growing number of biologic agents that target eosinophils may be useful tools to help clarify the role eosinophils have in different antiviral responses. Taken together, although preclinical studies have demonstrated antiviral activity for eosinophils, their clinical relevance in immune responses to different respiratory viruses remains unclear and needs further investigation.

Rhinovirus, RSV, and influenza virus are common triggers of viral-induced asthma exacerbations, whereas coronaviruses are far less common triggers for acute asthma exacerbations.^{36,45, 46,47, 48} Asthma has not yet been identified as a major risk factor for severity of SARS-CoV-1 infections.⁴⁹
The pathophysiology for eosinopenia in COVID-19 remains unclear but is likely multifactorial, involving inhibition of eosinophil egress from the bone marrow, blockade of eosinophilopoiesis, reduced expression of chemokine receptors/adhesion factors,^8,58 and/or direct eosinophil apoptosis induced by type 1 IFNs released during the acute infection.⁵⁹ Importantly, no eosinophil enrichment into the pulmonary tissue has been observed in samples from patients with COVID-19 at early stages of disease⁶⁰ or in postmortem analyses.⁶¹ Moreover, postmortem analysis of lung tissue from a patient who died from COVID-19 demonstrated signs of acute respiratory distress syndrome that was dominated by mononuclear inflammatory infiltrates, mostly lymphocytes.⁶²
..Eosinopenia, however, may serve as a prognostic indicator for more severe COVID. Following the outbreak of the SARS epidemic in late 2002, investigators raced to develop candidate SARS-CoV-1 vaccines. Diverse strategies were tested, including the use of attenuated or inactivated whole CoV particles, DNA-based vaccines, recombinant viral particles, and recombinant subunit vaccines.⁶⁴ Sera from patients convalescing from SARS revealed robust antibody titers against the spike protein (S protein) and the nucleocapsid protein.⁶⁵ Vaccine candidates that induced neutralizing antibodies targeting the S protein demonstrated efficacy in blocking viral replication,⁶⁶ a concept later confirmed by passive antibody transfer studies.^67,68 Unfortunately, anti–SARS vaccine–associated pathology emerged in early ferret (hepatitis⁶⁹ and pulmonary eosinophilia^15,69), cynomolgus monkey (T_H2-type immunopathology with eosinophils^15,70), and mouse (pulmonary eosinophilia)¹¹ studies. SARS-CoV-1–driven, eosinophil-associated T_H2 immunopotentiation also occurred with reinfection (green monkey model), suggesting that immune enhancement of CoV-associated disease may be relevant in future outbreaks of heterologous CoVs.⁷¹ Eosinophil-associated disease enhancement following exposure after vaccination is unfortunately not a new phenomenon. Historical reports from the 1960s link administration of a candidate formalin-inactivated RSV vaccine to severe, eosinophil-associated pulmonary disease following natural infection. This severe eosinophilic pulmonary disease hospitalized most study participants and led to at least 2 deaths.^72,73,74 Memories of such disease enhancement postvaccination strongly influenced subsequent RSV F protein subunit vaccine development and trial design.⁷⁵ The development of a safe and efficacious SARS-CoV-2 vaccine will require the development of vaccine candidates that take into account the risk of similar vaccine-associated immunopathology.
In the decade following these early observations, a series of mouse studies (see Table I) evaluated the factors driving the observed T_H2-skewed vaccine immunopathology. Two independent studies using recombinant viral particles (Venezuelan equine encephalitis virus or vaccinia) used isolated SARS structural proteins to investigate the source of immunopathology.^11,13 Nucleocapsid protein vaccination was implicated as a major driver of vaccine-associated pulmonary eosinophilia, although passive transfer of anti– nucleocapsid protein antibody was not sufficient to drive enhanced T_H2 disease, suggesting a possible role for anti–nucleocapsid protein–specific T cells.¹¹ T_H2-mediated disease enhancement was also linked to age, as vaccination of aged mice (>12 months old) with double-inactivated SARS-CoV-1 led to increased morbidity/mortality and accentuated eosinophilic pulmonary disease.¹⁴ Follow-up studies comparing vaccination strategies, vaccine preparations (whole virus/virus-like particles vs subunits vs subunit fragments), boosting strategies and timing, and the inclusion of alum versus other adjuvants (TLR agonists) have yielded variable results. In early studies, chimeric recombinant virus–like particle vaccines displaying only the SARS S protein did not induce eosinophilia.^11,13 In contrast, isolated S protein subunit vaccines (Spike^ΔTM [S^ΔTM]) appeared capable of T_H2 immunopotentiation.^15,16,17 S protein–derived fragments containing just the receptor-binding domain have also been proposed as vaccine antigens, but these vaccine formulations have required more aggressive use of adjuvants and more boosters (3-4 times more) than other approaches.⁶⁴ Investigations into the T_H2 immunopotentiation capacity of these compounds have been limited but reassuring, with 1 study showing no evidence of pulmonary eosinophilia in postchallenge animals¹² and a follow-up study showing balanced T_H1/T_H2 cytokine induction following vaccination.⁷⁶ Some investigators have implicated the inclusion of the T_H2-skewing adjuvant alum in causing the immunopotentiation, and subsequent studies have shown that the inclusion of T_H1-skewing adjuvants with both whole virus and subunit vaccine candidates has attenuated or blocked the development of pulmonary eosinophilia with SARS-CoV-1 challenge.^16,17 Alternatively, contaminating exogenous proteins from serum-containing media (ie, BSA) in vaccine preparation or viral stocks may explain the observed T_H2 skewing in certain experiments; however, the absence of eosinophilic infiltrates in mock-vaccinated control animals makes this possibility less likely. Overall, the SARS-CoV-1 vaccination literature documents recurrent, postvaccination disease enhancement in diverse vaccine preparations and across multiple animal models; however, this side effect declines with the use of more tightly defined antigens (S protein receptor-binding domain peptide) and the use of T_H1-skewing adjuvants
Finally, and likely most importantly, there is considerable concern about whether SARS-CoV-2 exposure postvaccination would cause eosinophil-associated lung pathology through immunopotentiation (see Fig 1). Although these concerns mainly have been derived from murine studies using vaccine candidates from the original SARS-CoV-1 virus, similar responses have also been seen in other species (eg, ferrets and monkey studies); it is also notable that SARS-CoV-1 and SARS-CoV-2 share more than 80% identity. Although the ongoing COVID-19 outbreak places new emphasis on the critical need for an effective SARS-CoV-2 vaccine, safety must be a central focus for any vaccine designed for general use. Current clinical reports show that most (up to 81%) patients with COVID-19 have mild disease,⁷⁷and therefore, trials of vaccine candidates must rigorously demonstrate the absence of eosinophil-associated disease enhancement before widespread deployment.

При содании вакцин к САРС

Fig 1 SARS-CoV immunity. The structural proteins of the SARS-CoV viral particle are shown and putative T_H1- vs T_H2-mediated immune responses detailed. The Spike (S) glycoprotein mediates binding of the virus to the angiotensin-converting enzyme-2 protein and subsequent fusion/entry into host cells. Sera from convalescing patients have revealed that anti–nucleocapsid protein and anti–S protein antibodies predominate the humoral immune response to SARS-CoV-1 but that only anti–S protein antibodies (especially those targeting the receptor-binding domain region) are neutralizing and protective. Beneficial antiviral responses appear to be linked to T_H1-skewed immunity, whereas T_H2 immunopotentiation in multiple animal model systems is associated with vaccination-enhanced disease, leading to pulmonary eosinophilia. To date, these potentially adverse consequences have been observed only in animal model systems following virus challenge with certain vaccine formulations (see Table I). Various SARS-CoV-2 vaccine candidates are currently under development (see box), which should be scrutinized for safety before widespread deployment. CTL, Cytotoxic T lymphocyte; ssRNA, single-stranded RNA.

Eosinophil responses related to COVID-19

Issue	Likely significance
Atopy-related eosinophilia	Atopy does not appear to have an exacerbating role in COVID-19
Eosinophil antiviral activity	The antiviral activity of eosinophils is unlikely involved in COVID-19 because the antiviral activity of eosinophils has not yet been observed in humans
Biological drug–induced eosinopenia	There are no data to date substantiating any risk for infections following depletion of eosinophils
COVID-19–associated eosinopenia	The eosinopenia associated with COVID-19 is likely a secondary phenomenon and not directly contributing to the disease course
Lung eosinophilia associated with immunopotentiation by SARS vaccines	Vaccine candidates must demonstrate the absence of eosinophil-associated disease enhancement before widespread deployment

Обзор по долгому ковиду

О том, какие механизмы могут быть вовлечены в формирвоание постковидного синдрома.
Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms