ABSTRACT
Neutrophilic granulocytes (NG) are the main drivers of pathological inflammation in COVID-19. Objective. To specify the mechanisms of immunopathogenesis of COVID-19 based on a comparative immunological study of the number and phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets with an assessment of their effector functions against changing profile of NG-associated cytokines IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma. Patients and methods. In patients with moderate-to-severe and severe COVID-19, we determined IL-1beta, TNFalpha, IL-6, IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma (ELISA), the phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets, NF-kappaB-NG (CYTOMICS FC500), phagocytically active NG (%), neutrophil extracellular traps (NETs), NG in apoptosis, and the activity of NADPH oxidase. Results. In COVID-19 against the background of IFNalpha and IFNgamma production blockade and high levels of NG-associated IL-8, IL-18, IL-17A, VEGF-A, a reduction in the number of mature and functionally active CD16brightSD62LbrightCD11bbrightCD63-NG subsets was revealed, as well as an increase in the number of CD16dimSD62LdimSD11bbrightCD63-NG subsets with an immunosuppressive phenotype and CD16brightSD62LbrightSD11bbrightCD63bright-NG subsets with high cytotoxic activity and ability to form NETs, a decrease in the percentage of phagocytically active NG and an increase in the activity of NADPH oxidase, NETs, and NG in apoptosis. Conclusion. IFNalpha deficiency provokes a hyperergic response of NG-associated cytokines, which leads to the formation of uncontrolled immune inflammation involving NG subsets with an immunosuppressive and cytotoxic phenotype, exacerbating the course of COVID-19. The use of recombinant IFNalpha-2b with antioxidants (Viferon) in the early stages of the disease can help to restore immune homeostasis, normalize the level of NG-associated cytokines, reduce NERTs, and achieve good clinical efficacy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Neutrophilic granulocytes (NG) are the main drivers of pathological inflammation in COVID-19. Objective. To specify the mechanisms of immunopathogenesis of COVID-19 based on a comparative immunological study of the number and phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets with an assessment of their effector functions against changing profile of NG-associated cytokines IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma. Patients and methods. In patients with moderate-to-severe and severe COVID-19, we determined IL-1beta, TNFalpha, IL-6, IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma (ELISA), the phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets, NF-kappaB-NG (CYTOMICS FC500), phagocytically active NG (%), neutrophil extracellular traps (NETs), NG in apoptosis, and the activity of NADPH oxidase. Results. In COVID-19 against the background of IFNalpha and IFNgamma production blockade and high levels of NG-associated IL-8, IL-18, IL-17A, VEGF-A, a reduction in the number of mature and functionally active CD16brightSD62LbrightCD11bbrightCD63-NG subsets was revealed, as well as an increase in the number of CD16dimSD62LdimSD11bbrightCD63-NG subsets with an immunosuppressive phenotype and CD16brightSD62LbrightSD11bbrightCD63bright-NG subsets with high cytotoxic activity and ability to form NETs, a decrease in the percentage of phagocytically active NG and an increase in the activity of NADPH oxidase, NETs, and NG in apoptosis. Conclusion. IFNalpha deficiency provokes a hyperergic response of NG-associated cytokines, which leads to the formation of uncontrolled immune inflammation involving NG subsets with an immunosuppressive and cytotoxic phenotype, exacerbating the course of COVID-19. The use of recombinant IFNalpha-2b with antioxidants (Viferon) in the early stages of the disease can help to restore immune homeostasis, normalize the level of NG-associated cytokines, reduce NERTs, and achieve good clinical efficacy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Background: The hyperactivated subsets of neutrophilic granulocytes (NG) play a negative role on the development, course and outcome of the COVID-19. With this position, NG are interesting target for creation of new therapeutic approaches. Method(s): The study group (SG) included 31 patients with moderate COVID-19, aged 61(57;71)years. Before and after incubation of whole blood with HP (106 g/l, 60 min., 37degreeC) 2 NG subsets were tested: major -CD64- CD16+CD32+CD11b+, minor -CD64+ CD16+CD32+CD11b+ with detection of their phenotypes using MFI (FC 500, Beckman Coulter, USA). Phagocytic activity of NG against S. aureus was studied. Comparison group(CG) consisted 22 healthy volunteers 58 (57;70) years old. Result(s): In patients with COVID-19 the minor subset of NG CD64+CD16+CD32+CD11b+(% ) was significantly increased in 5-fold versus the CG (p <= 0.005) and had transformed phenotype: CD64dimCD16brightCD32midCD11bbright versus CD64midCD16dimCD32midCD11b brightin the CG (p <= 0.005). This transformed phenotype had high expression levels of receptors of activation: CD16 and CD11b, that suggested its negative hyperactivation. The % of the major subset NG did not change (p > 0.05), but an altered phenotype of CD64-CD16brightCD32midCD11bdimNG was determine against CD64-CD16dimCD32midCD11boNG in the CG. Defects of phagocytic activities of NG were found: the decrease of % an active phagocytic NG, absorbing and digesting abilities (p1 <= 0.005;p2 <= 0.005;p3 <= 0.005).The effects of HP in vitro were shown: the significant decreasing of NG minor subset (%) in comparison with it's level before HP influences (p <= 0.005) reached to the values of the CG (p > 0.05). In parallel, the phenotype of minor subset changed to CD64brightCD16dimCD32midCD11bo, with decreasing level of CD16 to normal (p > 0.05). The transformed phenotype of the major subset was changed to CD64-CD16midCD32brightCD11 bmidNG: a decrease in MFI CD16, an increase in MFI CD32 and MFI CD11b (p1 <= 0.005;p2 <= 0.005;p3 <= 0.005). The restoration of defective phagocytic function of NG was received. Conclusion(s): Immunomodulating effects of HP in vitro on NG in moderate COVID-19 were shown: positive remodeling of the phenotype of minor aggressive NG subset from hyperactivated to normal and the restoration of defective NG phagocytic function.
ABSTRACT
The Advisory Board chaired by the chief specialist in infectious diseases of the Ministry of Health of Russian Federation, Professor V.P. Chulanov was held on June 18, 2022 in Saint Petersburg. Aim. The main purpose of the Board was following discussion: the analysis of the real-world data of levilimab as an anticipatory therapy for COVID-19 in hospitalized patients; the review of the experience and perspectives of levilimab as an anticipatory anti-inflammatory option for outpatient patients who meet defined clinical and laboratory criteria. Results. The analyzed data on clinical efficacy and safety formed the basis of recommendations proposed by experts for the use of levilimab in the inpatient and outpatient medical care for COVID-19.
Subject(s)
COVID-19 Drug Treatment , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Anti-Inflammatory Agents , Receptors, Interleukin-6ABSTRACT
This article aims to give an up-to-date review and summary of existing literature on the long-term cardiovascular effects of COVID-19. It details clinical manifestations, diagnostics, and treatment options. The ongoing COVID-19 pandemic caused by SARS-CoV-2 has resulted in a growing number of patients with the so called post-COVID-19 syndrome that often affects the cardiovascular system. Both instrumental (magnetic resonance imaging, echocardiography, electrocardiography) and laboratory (measurement of cardiac troponin, N-terminal pro-brain natriuretic peptide) examinations demonstrated that many patients develop myocarditis, arterial hypertension, or cardiac arrhythmias after COVID-19 or have aggravation of preexisting cardiovascular disorders. The mechanisms underlying the post-COVID-19 syndrome pathogenesis are diverse, while the effect of each of these mechanisms is not fully understood. The current strategy of follow-up is often suboptimal due to the high prevalence and severity of cardiovascular lesions in patients after COVID-19. Treatment options are often limited to symptomatic care.
ABSTRACT
Objective. To clarify the features of the defect in the function of NK cells, T lymphocytes, the interferon system in patients with moderate and severe COVID-19. Patients and methods. Tests of the peripheral blood of 50 COVID-19 patients aged 61(57–71) and having the moderate and severe disease were performed. The following parameters were measured: the quantity of CD3+CD19–, CD3+CD4+, CD3+CD8+ T lymphocytes, NK – (CD3–CD16+CD56+), and TNK – CD3+CD16+CD56+ with expression density considered membrane receptors (MFI) (FC 500 Beckman Coulter, USA), the levels of IFN-α, IFN-γ, IL-6, TNF-α cytokines (IFA). Results. Combined immunodeficiency associated with quantitative and functional defects in NK, T lymphocytes and their subsets was revealed in moderate and severe COVID-19. An imbalance of cytokines has been established: blockade of the production of IFN-α and IFN-γ against the background of a significant increase in IL-6 and TNF-α, which negatively affects both the number and functionality of the participants in the immune response and is associated with a severe course and poor prognosis of COVID-19. Conclusion. The data obtained demonstrate the need to develop new strategies and tactics for the treatment of COVID-19, including replacement systemic therapy with recombinant IFN-α2b in combination with antioxidants (Viferon®) in adequate therapeutic doses, aimed at restoring the normal functioning of T lymphocytes, NK and the interferon system.
ABSTRACT
Investigation of molecular mechanisms associated with interferon (IFN) production and receptor function of neutrophil granulocytes (NGs) in COVID-19 is highly relevant because it can be promising in the search for new therapeutic strategies targeting NGs and their reactivity to restore and strengthen the innate immune response against SARS-CoV-2. Objective. To assess the effects of recombinant IFN-α2b on the phenotype of CD16+IFNα/βR1–CD119+, CD16+IFNα/βR1+CD119–, and CD16+IFNα/βR1+CD119+ NGs from peripheral blood of patients with COVID-19 in an in vitro experiment. Patients and methods. We analyzed blood samples from 31 patients with a mean age of 61 years (range: 57;71 years) with moderate COVID-19. We assessed the number of CD16+IFNα/βR1–CD119+, CD16+IFNα/βR1+CD119–, and CD16+IFNα/βR1+CD119+ NGs, receptor density (FC 500, ‘Beckman Coulter,’ USA), phagocytic activity of NGs before and after incubation with recombinant IFN-α2b. We also measured serum levels of several cytokines, including IFNα, IFNγ, IL-6, IL-8 (ELISA, ‘Vektor-Best’ LLC). The control group comprised 22 adult healthy individuals with a mean age of 58 years (range: 57;70 years). Results. Patients with moderate COVID-19 demonstrated low serum levels of IFNα and IFNγ along with elevated levels of IL-6 and IL-8. We observed transformation of 3 phenotypes among NG subpopulations: CD16+IFNα/βR1–CD119+, CD16+IFNα/βR1+CD119-, and CD16+IFNα/βR1+CD119+. We observed positive remodulating effects of recombinant IFN-α2b on the number and phenotype of NG subpopulations and their phagocytic activity in our in vitro experiment. Conclusion. Recombinant IFN-α2b demonstrated positive effects in in vitro experiments;therefore, it can be considered in the future as a potential therapeutic tool for moderate COVID-19. Restoration of type I IFN might be an effective treatment option for COVID-19, because it can promote faster virus elimination, restore normal functioning of the IFN system, and have positive regulatory effects on the phenotype of NG subpopulations.
ABSTRACT
Objective. To assess the dynamics of seroprevalence of anti-SARS-CoV-2 antibodies in the population of non-vaccinated people. Materials and methods. During two months of the last quarter of 2020 (before the start of mass vaccination against the coronavirus infection), we analyzed the dynamics of the level of total anti-SARS-CoV-2 IgG and level of virus-neutralizing IgG (anti-RBD/S1) in 806 unvaccinated people without clinical signs of the disease Results. Upon first examination, 16.0% of participants were found to have positive total anti-SARS-CoV-2 IgG, while 82.6% were negative and 1.4% had indeterminate result. During two months of the pandemic, seroprevalence increased by 23.7% (from 16.0% to 39.7%). The proportion of people with an indeterminate result remained the same (1.4%). The proportion of patients with asymptomatic COVID-19 who were initially IgG-positive but became negative in two months was 5.4%. Some individuals with positive total anti-SARS-CoV-2 IgG were found to have non-reactive anti-RBD antibodies that did not ensure neutralization of coronavirus (17.8% upon first and 10.6% upon second examination). © 2021, Dynasty Publishing House. All rights reserved.
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There have been very few studies analyzing neuropsychiatric aspects of COVID-19 and the impact of somatic aspects of infection on the development of transient or persistent deficits in higher cerebral functions. This is primarily due to the small number of specialists in neuropsychiatry who work with COVID-19 patients and also because the healthcare system is primarily focused on the diagnosis and treatment of the somatic pathology. In this review, we analyzed the studies assessing the neuropsychiatric aspects of COVID-19 with a focus on possible somatic predictors of their development. We discuss neuropsychiatric manifestations of cerebral dysfunction in patients with new coronavirus infection and provide a description of the dynamics of symptom development and regression. We also cover the issues related to stress resistance of healthcare professionals working with COVID-19 patients. Particular attention is paid to the treatment of COVID-associated cerebral dysfunction and therapeutic options of neuroprotection. © 2021, Dynasty Publishing House. All rights reserved.
ABSTRACT
Objective. To analyze the efficacy of levilimab in patients with COVID-19 to optimize proactive anti-inflammatory therapy. Patients and methods. This single-center retrospective observational controlled study included 75 COVID-19 patients with a mean age of 58.6 years who received intravenous (71%) or subcutaneous (29%) levilimab at a dose of 324 mg on day 9 of the disease [range: 7.0–12.0 days]. Ten patients (14%) additionally received tocilizumab, whereas 14 participants (19%) received only levilimab without dexamethasone. The control group (received no levilimab) included 29 matched patients. The levels of C-reactive protein (CRP), ferritin, fibrinogen, creatine phosphokinase (CPK), D-dimer, as well as lymphocyte and white blood cell (WBC) counts were measured daily. The percentage of lung damage was assessed using computed tomography (CT) at baseline and later in dynamics. The primary endpoint was patient's transfer to the intensive care unit (ICU). Statistical analysis was performed using the Statistica v. 12 software (StatSoft, USA);the risk of transfer to ICU was evaluated using the Kaplan-Meier cumulative proportional risk method and Cox proportional hazards model by calculating relative risks with a 95% confidence interval (RR [CI]). The dynamics of patients' status and its association with the route of levilimab administration was evaluated using a seven-point scale (seven-category scale) approved by the World Health Organization. Results. No lethal outcomes were registered in this study. Levilimab reduced the risk of transfer to the ICU;significant covariates included obesity (RR = 11.09 [1.29–95.72]) and percentage of lung damage on CT scans (RR = 1.06 [1.01–1.13]). The target group for levilimab therapy should include patients with moderate COVID-19 before day 10 of the disease, who have not yet received corticosteroids (CSs), with a maximum body temperature of ≤38.5°C, lung damage <40% on CT at the time of therapy initiation, and CPK <300 U/L. Levilimab therapy is more beneficial for patients with diabetes mellitus, obesity, severe arterial hypertension, and stomach and duodenal ulcers. Intravenous administration of levilimab at a dose of 324 mg is optimal for a reliable prevention of excessive cytokine release. Levilimab demonstrated equivalent positive effects both together with CSs, and when used alone. Levilimab without CSs alleviated hyperglycemia and normalized WBC count. The following laboratory parameters were found to be most important for the decision on levilimab initiation and further control of treatment efficacy: absolute lymphocyte count, CRP, fibrinogen, and CPK. Levels of lactate dehydrogenase, ferritin, platelets, D-dimer did not provide any reliable information on the mitigation of systemic inflammation.
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Objective. To analyze polymorphisms of genes involved in hemostasis among patients with coronavirus disease 2019 (COVID 19) to improve the diagnosis of coagulopathy and prognosis of COVID-19 severity. Patients and methods. We have examined 52 patients with COVID-19 aged 33 to 84 years. Of them, 30 individuals (Group 1) were hospitalized with extremely severe (1A) and severe (1B) disease, whereas 22 patients with mild and asymptomatic disease were treated in outpatient departments (group 2). We assessed allelic variants of genes associated with hemostasis dysfunction (including FGB, FII, FV, FVII, F13A1, PAI-I, Gp1a, and Gp3a) using genomic DNA isolated from peripheral blood leukocytes. Polymorphisms were detected by polymerase chain reaction. Data analysis was performed using the Statistica, version 12 (StatSoft, USA). To compare independent categorical variables, we constructed contingency tables, performed Pearson chisquare test with Yates correction, Fisher exact test, and calculated relative risk (RR) [CI]. Results. COVID-induced coagulopathy (CAC) was diagnosed in 16.7% of patients;risk of CAC was identified in 30% of patients;sepsis-induced coagulopathy (SIC) was observed in 3.3% of patients;none of study participants had disseminated intravascular coagulation (DIC). Hemostasis impairments were more common in group 1A (RR = 2.28 [1.16–4.48]). Only patients from Group 1 had mutations in the gene encoding prothrombin (FII) –6.9% (RR = 1.78 [1.40–2.28]);protective polymorphisms in the FVII gene were more common in patients from Group 2 (χ2 = 3.28, р = 0.046);the rs 5985 polymorphism in the F13A1 gene was more common in patients from Group 1 (RR = 1.73 [1.06–2.82]). Patients with extremely severe COVID-19 were more likely to have polymorphisms in the Gp1a gene (ITGA2) (RR =1.64 [1.05–2.56]) and F13A1 gene (χ2 = 2.67, р = 0.05), as well as homozygous mutation in the FII gene;they had no polymorphisms in the FVII gene (10976G→A). Thrombophilia, detected in 3 patients from Group 1, was a risk factor for thrombocytopenia (RR = 13.5 [3.56–51.23]), САС (RR = 9.0 [3.1–26.16]), and death (n = 4). The 4G allele (4G/4G, 4G/5G variants) in the PAI-I gene (rs 1799889), causing impaired fibrinolysis, was more frequently registered in patients with mild COVID-19 (91%) than in those with extremely severe COVID-19 (70%). It is possible that patients with extremely severe disease develop transient hyperfibrinolysis, which results in the transformation of local pulmonary COVID-19 into sepsis. Therefore, the 4G/4G and 4G/5G polymorphisms may have a protective role. © 2021, Dynasty Publishing House. All rights reserved.
ABSTRACT
In light of the ongoing COVID-19 pandemic, it is becoming increasingly important to address the problem of resourcefulness in the healthcare personnel of COVID-19 red zones. The aim of this study was to assess hardiness and the state of vital resources in physicians continuously working in red zones and to test a hypothesis that that long-term work in a COVID-19 red zone adversely affects the resourcefulness, reducing resistance to stress. Group 1 (n = 94) consisted of physicians with a history of employment in a COVID-19 red zone between May 2020 and June 2021;group 2 (n = 77) comprised physicians who were not involved in managing COVID-19 patients. The tests showed that hardiness and its components (commitment, control and challenge) were at high levels in group 2 (59.7%;67.5%;61.0%;20.9%, respectively). The index of resourcefulness (RI;1.24) reflected the prevalence of personal gains over losses in group 1 over the past year. In this group, there were no sex differences in the results. By contrast, hardiness was significantly reduced in 31.9% of the respondents in group 1 (red zone). Working in the red zone had a devastating effect on all hardiness components: the ratio of the percentages of high to low values was 8.5/27.7 for commitment, 9/6/34.0 for control and 10.6/35.1 for challenge. RI was reduced (0.77). The most pronounced loss of resources was observed in female physicians. The study found a significant mutual impact between challenge and the state of personality resources in red zone staff, which may indicate activation of proactive coping strategies and the acceptance of new professional experience.