In this review, we discuss the role of pulmonary surfactant in the host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. In the lower respiratory system, the virus uses angiotensin-converting enzyme 2 (ACE2) receptor in conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one of the SARS-CoV-2 target cells, to enter. ATII cells are the main source of surfactant. After their infection and the resulting damage, the consequences may be severe and may include injury to the alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired lung mechanics and reduced oxygenation, which resembles acute respiratory distress syndrome (ARDS) of other etiology. The aim of this review is to highlight the key role of ATII cells and reduced surfactant in the pathogenesis of the respiratory form of COVID-19 and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS patients.
Recent molecular biology findings have shown that for the penetration of the SARS-CoV-2 coronavirus into host cells, a key role is played by protease serine 2, the activity of which is dependent on androgens. The important role of androgens is also evidenced by clinical observations that men in some age categories are infected by this novel coronavirus up to two times more frequently than women. In addition, men with androgenic alopecia tend to have more serious clinical courses, while men with androgen deprivation as a result of prostate cancer treatments tend to have milder courses. This is in line with the fact that preadolescent children are only rarely sickened with serious forms of SARS-CoV-2 infections. Even though these observations may be explained by other factors, many authors have hypothesized that lowered androgen levels and blocking their activity using anti-androgen medication may moderate the course of the viral infection in intermediately- to critically-affected cases. Clearly, it would be important for androgen deprivation to block not just gonadal androgens, but also adrenal androgens. On the other hand, low androgen levels are considered to be a risk factor for the course of SARS-CoV-2 infections, either because low androgen levels have a general effect on anaboliccatabolic equilibrium and energy metabolism, or because of the ability of testosterone to modify the immune system. It is not yet clear if infection with this novel coronavirus might induce hypogonadism, leading to undesirable side effects on male fertility.
Amiodarone seems to exhibit some antiviral activity in the disease caused by SARS-CoV-2. Here we have examined the SARS-CoV-2 disease course in the entire population of the Czech Republic and compared it with the course of the disease in patients treated with amiodarone in two major Prague’s hospitals. In the whole population of the Czech Republic SARSCoV-2 infected 1665070 persons (15.6 %) out of 10694000 (100 %) between 1 April 2020 and 30 June 2021. In the same time period only 35 patients (3.4 %) treated with amiodarone were infected with SARS-CoV-2 virus out of 1032 patients (100 %) who received amiodarone. It appears that amiodarone can prevent SARS-CoV-2 virus infection by multiple mechanisms. In in-vitro experiments it exhibits SARS-CoV-2 virus replication inhibitions. Due to its anti-inflammatory and antioxidant properties, it may have beneficial effect on the complications caused by SARS-CoV-2 as well. Additionally, inorganic iodine released from amiodarone can be converted to hypoiodite (IO- ), which has antiviral and antibacterial activity, and thus can affect the life cycle of the virus.
Increasing evidence points to host genetics as a factor in COVID19 prevalence and outcome. CCR5 is a receptor for proinflammatory chemokines that are involved in host responses, especially to viruses. The CCR5 Δ32 minor allele is an interesting variant, given the role of CCR5 in some viral infections, particularly HIV-1. Recent studies of the impact of CCR5-Δ32 on COVID-19 risk and severity have yielded contradictory results. This ecologic study shows that the CCR5-Δ32 allelic frequency in a European population was significantly negatively correlated with the number of COVID-19 cases (p=0.035) and deaths (p=0.006) during the second pandemic wave. These results suggest that CCR5-Δ32 may be protective against SARS-CoV-2 infection, as it is against HIV infection, and could be predictive of COVID-19 risk and severity. Further studies based on samples from populations of different genetic backgrounds are needed to validate these statistically obtained findings.
The SARS-CoV-2 pandemic has indeed been one of the most significant problems facing the world in the last decade. It has affected (directly or indirectly) the entire population and all age groups. Children have accounted for 1.7 % to 2 % of the diagnosed cases of COVID-19. COVID-19 in children is usually associated with a mild course of the disease and a better survival rate than in adults. In this review, we investigate the different mechanisms which underlie this observation. Generally, we can say that the innate immune response of children is strong because they have a trained immunity, allowing the early control of infection at the site of entry. Suppressed adaptive immunity and a dysfunctional innate immune response is seen in adult patients with severe infections but not in children. This may relate to immunosenescence in the elderly. Another proposed factor is the different receptors for SARS-CoV-2 and their differences in expression between these age groups. In infants and toddlers, effective immune response to viral particles can be modulated by the pre-existing non-specific effect of live attenuated vaccines on innate immunity and vitamin D prophylaxis. However, all the proposed mechanisms require verification in larger cohorts of patients. Our knowledge about SARS-CoV-2 is still developing.
A close interaction between the virus SARS-CoV-2 and the
immune system of an individual results in a diverse clinical
manifestation of the COVID-19 disease. While adaptive immune
responses are essential for SARS-CoV-2 virus clearance, the
innate immune cells, such as macrophages, may contribute, in
some cases, to the disease progression. Macrophages have
shown a significant production of IL-6, suggesting they may
contribute to the excessive inflammation in COVID-19 disease.
Macrophage Activation Syndrome may further explain the high
serum levels of CRP, which are normally lacking in viral
infections. In adaptive immune responses, it has been revealed
that cytotoxic CD8+ T cells exhibit functional exhaustion patterns,
such as the expression of NKG2A, PD-1, and TIM-3. Since SARSCoV-2 restrains antigen presentation by downregulating
MHC class I and II molecules and, therefore, inhibits the T cellmediated immune responses, humoral immune responses also
play a substantial role. Specific IgA response appears to be
stronger and more persistent than the IgM response. Moreover,
IgM and IgG antibodies show similar dynamics in COVID-19
disease.
Few peculiarities have been observed in the etiology of coronavirus disease 2019 (COVID-19), one such being its greater prevalence in men than women partly due to the higher expressions of angiotensin-converting enzyme-2 (ACE2) in the male reproductive tissues. Recent scientific reports are in line with some of the evidence-based hypotheses in the initial phase of the COVID-19 pandemic, regarding the involvement of oxidative stress (OS) and oxidant-sensitive pathways in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-mediated male reproductive disruptions. The seminal dissemination of SARS-CoV-2 or its components, testicular disruptions due to viral infection and oxidative damage in the testis have all been evidenced recently. High-dose of antioxidants, such as vitamin C, have been shown to be a useful treatment for COVID-19 patients, to alleviate systemic inflammation and OS. In addition, vitamin C is a major testicular antioxidant that neutralizes excess reactive oxygen species (ROS), prevents sperm agglutination, prevents lipid peroxidation, recycles vitamin E, and protects against DNA damage. Thus, the present review aims to discuss the mechanism of COVID-19- mediated male reproductive dysfunctions, based on the evidence available so far, and explore the possibility of using vitamin C in alleviating testicular OS and associated damage caused by COVID-19.
Studie představuje výsledky výzkumu zaměřeného na psychologické dopady spojené s epidemií covid-19 v České republice v průběhu měsíců březen–květen 2020. Cílem studie je sledovat a popsat dynamiku psychologických ukazatelů v čase, s ohledem na vývoj situace v ČR – od prvního nárůstu počtu nakažených a výrazných restrikcí, přes kulminaci a ústup první vlny epidemie, až k pomalému návratu do stavu uvolněných restrikcí. Výzkum pracuje se souborem 2716 respondentů ve věku 18–89 let, kteří se zúčastnili on-line dotazníkového šetření, případně byli dotazováni trénovanými výzkumnými asistenty (zejm. v případě seniorů a dalších osob, kteří neměli přístup k internetu). Výzkumná data zahrnovala deskriptivy účastníků a výsledky psychologických testů zaměřených na emoční stavy respondentů, jejich psychický nepokoj (distres) a přítomnost úzkosti a deprese. Tyto psychologické ukazatele byly sledovány jak v celém souboru, tak ve skupinách podle pohlaví a věku. Výsledky dokládají, že nastalá epidemická situace souvisela s výrazným nárůstem negativního emočního prožívání, se symptomatikou psychického nepokoje, úzkostí a depresí, a to až do období kulminace. Poté bylo zaznamenáno postupné zlepšování psychického stavu dotazovaných osob. Negativní dopady byly výraznější v populaci mladších dospělých a v populaci žen. Výsledky poukazují také na rozdílnosti v míře reportovaného stresu u izolovaných osob, které byly dotazovány zprostředkovaně (asistenty), oproti osobám, které reportovaly svůj stav přímo do dotazníku. V případě nezprostředkovaného dotazování byly hodnoty negativních psychických ukazatelů vyšší, oproti osobám, které byly dotazovány asistenty. and The study presents the results of a screening focused on the psychological impact associated with the outbreak and further development of COVID-19 pandemic in the Czech population during March – May 2020. The aim of the study was to investigate temporal dynamics of psychological impact covering the first wave of the epidemic, i.e., first phases of the epidemic growth, culmination, decrease, and slow return to a normal lifestyle. The sample of 2716 respondents aged between 18 and 89 years participated in an online survey from March 18th to May 25th, 2020; part of them (typically seniors and others, who had not access to the internet) were assisted in entering the data by trained interviewers. The survey comprised questionnaires capturing emotional states, psychological disturbance, anxiety, and depression. The changes in the scores by pandemic phase (time frame) were studied for the whole sample and for gender and age groups. The results show that the threat of COVID-19 caused a significant increase in negative emotional experience and in the symptoms of psychological disturbance, anxiety, and depression in the Czech population in time of infection culmination, even when the spread of the pandemic was well controlled, and then a gradual decline over time. The data indicated that the pandemic situation had a more pronounced impact on women and younger adults. The study also showed that in situations of pandemic stress associated with isolation, when isolated people are interviewed about their mental state, their reports on negative experiencing might be significantly reduced compared to direct anonymous selfreports data entry.
Genetic predispositions may influence geographical and interethnic differences in COVID-19 prevalence and mortality in affected populations. Of the many genes implicated in COVID-19 progression, a substantial number have no direct functional link on virus transfer/viability or on the host immune system. To address this knowledge deficit, a large number of in silico studies have recently been published. However, the results of these studies often contradict the findings of studies involving real patients. For example, the ACE2 has been shown to play an important role in regulating coronavirus entry into cells, but none of its variations have been directly associated with COVID19 susceptibility or severity. Consistently was reported that increased risk of COVID-19 is associated with blood group A and with the APOE4 allele. Among other genes with potential impacts are the genes for CCR5, IL-10, CD14, TMPRSS2 and angiotensinconverting enzyme. Variants within the protein-coding genes OAS1 and LZTFL1 (transferred to the human genome from Neanderthals) are understood to be among the strongest predictors of disease severity. The intensive research efforts have helped to identify the genes and polymorphisms that contribute to SARS-CoV-2 infection and COVID-19 severity.
Aged people are the most susceptible group to COVID-19 infection. Immunosenescence characterized by impairment of immune function with inflamm-aging contributes to pathophysiological alterations, among which endocrine and metabolic diseases are not exception. Diabetes, obesity along with impairment of disorders of thyroid functions are the most frequent ones, the common feature of which is failure of immune system including autoimmune processes. In the minireview we discussed how COVID-19 and aging impact innate and adaptive immunity, diabetes and selected neuroendocrine processes. Mentioned is also beneficial effect of vitamin D for attenuation of these diseases and related epigenetic issues. Particular attention is devoted to the role of ACE2 protein in the light of its intimate link with renin-angiotensin regulating system.