Mucosal immunity in health care workers' respiratory tracts in the post-COVID-19 period.

Coronavirus disease (COVID-19) has generated interest in the assessment of systemic immune status, but existing knowledge about mucosal immunity is clearly insufficient to understand the full pathogenetic mechanisms of the disease. The aim of this study was to evaluate the long-term effects of novel coronavirus infection on mucosal immunity in the postinfection period among health care workers (HCWs). A total of 180 health care workers with and without a history of COVID-19 who ranged in age from 18 to 65 years were enrolled in this one-stage, cross-sectional study. The study subjects completed the 36-Item Short Form (36) Health Survey (SF-36) and the Fatigue Assessment Scale. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, and nasopharyngeal and oropharyngeal scrapings by an enzyme-linked immunosorbent assay. Specific anti-SARS-CoV-2 IgG antibodies were quantified in serum samples by chemiluminescence immunoassay. Analysis of the questionnaire data showed that all HCWs with a history of COVID-19 reported health problems that limited their daily activities and negative changes in their emotional health three months after the disease, regardless of its severity. The following shifts were detected in the adaptive arm of the immune response in different mucosal compartments. Among subjects who had severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p < 0.05 and p < 0.005, respectively). Compared to the subjects in the control group, all subjects with prior COVID-19 had significantly higher levels of total IgG in induced sputum. In the group of patients who had had severe infection, total IgG in saliva was also higher (p < 0.05). A direct statistically significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum. A significant correlation was observed between total IgG levels and the parameters of physical and social activities, mental health, and fatigue levels. Our study demonstrated long-term changes in the humoral mucosal immune response, which were most pronounced in health care workers with a history of severe or moderate-to-severe COVID-19, and an association of these changes with certain clinical signs of post-COVID-19 syndrome.

Thermal Helium-Oxygen Mixture as Part of a Treatment Protocol for Patients with COVID-19

Background. The paper discusses the use of a thermal helium-oxygen mixture (t-Не/О2 ), a novel technology, in treating patients with the 2019-nCoV acute respiratory disease (COVID-19) who develop life-threatening respiratory failure. Aim - to evaluate the safety and efficacy of t-Не/О2 inhalation combined with standard therapy in the treatment of acute respiratory failure in patients with COVID-19. Materials and Methods. This was a single-center, randomized, prospective study of 70 patients with COVID-19. All patients were divided into two groups: in Group 1 (n = 38) patients received t-He/О2 in addition to the standard COVID-19 treatment;and in Group 2 (n = 32) patients were given the standard treatment in accordance with the Clinical Treatment Guidelines for patients with COVID-19, developed by the Ministry of Health of the Russian Federation. The male/female ratio was 18/20 in Group 1 and 18/14 in Group 2. The mean age of the patients in the study was 53.5 years (43;62): 56 years (42;64) in Group 1 and 52 years (43;66) in Group 2. All patients had computed tomography (CT) signs of lung injury: ground-glass opacities and areas of consolidation. SARS-CoV-2 RNA was detected in 30 Group 1 patients and 28 Group 2 patients. The patients were matched by sex, age, body mass index (BMI), area of pulmonary involvement, and laboratory findings. All patients provided voluntary informed consent to participate in the study and signed a consent form. Results. Inhalation of thermal helium-oxygen mixture combined with standard therapy did not cause any procedure-related side effects in any of the patients. The following changes were observed in all patients: pO2 /FiO2 , SpO2 , and lymphocyte counts increased, C-reactive protein (CRP) levels decreased, and D-dimer and ferritin levels returned to normal. In Group 1 statistically significant changes in the above-mentioned parameters were seen within three days, while in Group 2 the same changes were observed between Days 7 and 10 of treatment. In Group 1 patients cleared SARS-CoV-2 within 48-72 hours after initiation of inhalation, which was confirmed by polymerase chain reaction (PCR), and in Group 2 virus elimination was achieved within 72-168 hours. Conclusion. The addition of inhalation of a thermal gas mixture of helium and oxygen (t-He/О2 ) to the standard therapy for patients with SARS-CoV-2 infection, CT signs of pneumonia (grades СT2 or CT3), and acute respiratory failure improves gas exchange, contributes to a more rapid virus elimination, and indirectly reduces inflammation. Обоснование. В представленной работе речь пойдет о новой технологии применения термического гелия и кислорода (t-Не/О2 ) в лечении больных с вирусным заболеванием СOVID-19 на этапе развития жизнеугрожающего синдрома дыхательной недостаточности. Цель - изучить безопасность и эффективность ингаляционной терапии t-Не/О2 в лечении острой дыхательной недостаточности пациентов с СOVID-19 на фоне стандартной терапии. Материалы и методы. В одноцентровое рандомизированное проспективное исследование было включено 70 пациентов с COVID-19. Пациенты были разделены на две группы: в первой (n = 38) в стандартный протокол лечения COVID-19 была включена терапия t-Не/О2 ;во второй (n = 32) проводилась стандартная терапия в соответствии с клиническими рекомендациями Минздрава России для больных с COVID. В первой группе соотношение мужчины/женщины - 18/20, а во второй - 18/14. Средний возраст пациентов в исследовании составлял 53,5 года (43 года - мужчины;62 года - женщины), в первой группе - 56 лет (42 и 64 года соответственно), во второй - 52 года (43 и 66 лет). У всех пациентов имелись КТ-признаки поражения легких по типу «матового стекла», участки консолидации. Тест РНК коронавируса SARS-CoV-2 положительный в первой группе у 30 пациентов, во второй - у 28. Пациенты сопоставимы по полу, возрасту, индексу массы тела (ИМТ), площади поражения легочной паренхимы, лабораторным данным. Всеми пациентами было подписано информированное добровольное согласие на участие в исследовании. Результаты. Вследствие применения термической гелий-кислородной смеси на фоне стандартной терапии ни у одного пациента объективных побочных эффектов, связанных с процедурой, не выявлено. У всех пациентов обнаружены следующие изменения: повышение pО2 /FiO2, SpO2 и уровня лимфоцитов, снижение концентрации С-реактивного белка, восстановление уровней Д-димера, ферритина. Эти признаки статистически значимо изменились в первой группе в течение 3 сут, тогда как во второй группе - на 7-10-е сут терапии. Элиминация вируса SARS-CoV-2 в первой группе происходила в течение 48-72 ч от момента начала ингаляции, что подтверждалось методом ПЦР, а во второй - в течение 72-168 ч. Заключение. Включение ингаляций термической газовой смеси гелия с кислородом (t-Не/О2 ) в стандартную терапию пациентов, переносящих инфекционное заболевание, вызванное SARS-CоV-2, c КТ-признаками пневмонии (КТ2, КТ3), с острой дыхательной недостаточностью улучшает газообмен, способствует ускорению элиминации вируса и опосредованно повышает противовоспалительный эффект.

Thermovaccination - thermoheliox as a stimulator of the immune response. Kinetics of the synthesis of antibodies and C-reactive protein in coronavirus infection.

Clinical trials of thermoheliox application (inhalation with a high-temperature mixture of oxygen and helium, 90 °C) in the treatment of the acute phase of coronavirus infection were conducted. Dynamics of disease development in infected patients (PCR test for the virus) and, dynamics of changes in blood concentration of C-reactive protein, immunoglobulin M, specific immunoglobulin G were studied. High efficiency of thermoheliox in releasing the organism from the virus and stimulating the immune response (thermovaccination effect) was shown. The kinetic model of the process is proposed and analyzed.

Chemical kinetics of the development of coronaviral infection in the human body: Critical conditions, toxicity mechanisms, "thermoheliox", and "thermovaccination".

Kinetic modeling of the behavior of complex chemical and biochemical systems is an effective approach to study of the mechanisms of the process. A kinetic model of coronaviral infection development with a description of the dynamic behavior of the main variables, including the concentration of viral particles, affected cells, and pathogenic microflora, is proposed. Changes in the concentration of hydrogen ions in the lungs and the pH -dependence of carbonic anhydrase activity (a key breathing enzyme) are critical. A significant result is the demonstration of an acute bifurcation transition that determines life or system collapse. This transition is connected with exponential growth of concentrations of the process participants and with functioning of the key enzyme carbonic anhydrase in development of toxic effects. Physical and chemical interpretations of the therapeutic effects of the body temperature rise and the potential therapeutic effect of "thermoheliox" (respiration with a thermolized mixture of helium and oxygen) are given. The phenomenon of "thermovaccination" is predicted, which involves stimulation of the immune response by "thermoheliox".