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1.
Central European Journal of Immunology ; 47(2):151-159, 2022.
Article in English | EMBASE | ID: covidwho-1988271

ABSTRACT

Introduction: The pathophysiology of multisystem inflammatory syndrome associated with SARSCoV-2 infection (MIS-C) remains poorly understood. This study aimed to define peripheral blood immune features in patients with MIS-C. Material and methods: We analyzed seven children diagnosed with MIS-C between April 1 and May 15, 2021, in St. Joseph’s Children’s Hospital in Poznan (Poland). Results: All patients had elevated inflammatory markers, IgG antibodies against SARS-CoV-2, and lymphopenia with a marked decrease in CD4+ and CD8+ T cells. The majority of CD4+ T cells were naive cells. Almost all (6/7) of the analyzed patients had a higher CD4+/CD8+ T cell ratio than average values. B cells were within the normal range – the majority were non-memory cells. Conclusions: Children with MIS-C do not resemble adults during COVID-19 recovery. The immune profile of the studied patients differs from that of children with Kawasaki disease (KD), but it is similar to that of adults with severe COVID-19. The proposed explanation is a profound lymphopenia caused by SARS-CoV-2 infection – which persists for weeks – as a result leading to uncontrolled inflammation. In COVID-19 patients the T cell level returns to normal after the second week of the disease. Our data suggest that in children prolonged lymphopenia after COVID-19 can be a practical marker for possible MIS-C alert. If there is a continuum from lymphopenia to MIS-C, there is room for screening and prevention. Further studies are needed to determine whether steroid treatment introduced in a child with prolonged lymphopenia could stop the inflammatory process.

2.
Pediatria Polska ; 97(2):81-88, 2022.
Article in English | EMBASE | ID: covidwho-1969656

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a late complication of SARS-CoV-2 infection, either symptomatic or asymptomatic. The underlying cause is immunological dysregulation, leading to severe inflammatory processes. Children with MIS-C require hospital treatment, the use of immunomodulating drugs, and often intensive care. COVID-19 vaccination is safe and highly effective in preventing not only severe COVID-19, but also MIS-C in adolescents. However, there are no explicit vaccination recommendations for children who underwent MIS-C. We present a summary of current knowledge on vaccinations against COVID-19 in the context of MIS-C. Moreover, we propose guidance concerning vaccinations for children following MIS-C.

3.
Pediatria Polska ; 97(2):71-80, 2022.
Article in English | EMBASE | ID: covidwho-1969655

ABSTRACT

Since late 2021, we have observed a significant increase in the proportion of children infected with SARS-CoV-2. The course of the disease in children is usually sparsely symptomatic or asymptomatic. However, the predominance of new virus variants makes children more likely to become symptomatically ill and require hospitalisation. This paper aims to update recommendations for managing a child with COVID-19 in out- and inpatient settings. Current options for prevention and antiviral treatment are discussed, noting the limited availability of therapy for children. In most children with COVID-19, the basis for treatment remains symptomatic and supportive therapy and measures to reduce SARS-CoV-2 infection spread.

4.
Przeglad Pediatryczny ; 49(4):18-26, 2020.
Article in Polish | Scopus | ID: covidwho-1567629

ABSTRACT

Pediatric inflammatory multisystem syndrome associated with COVID-19 (PIMS) is a new entity, occurring in children and young adults, associated with the SARS-CoV-2 infection. The first cases of PIMS were found in Poland in May 2020. Since October 2020, a significant increase in the incidence of this new disease has been observed in Poland, which reflects the increased incidence of COVID-19 in adults. PIMS development results from dysregulation of the immune system occurring after 2-4 weeks after the SARS-CoV-2 in-fection. Diagnosis is based on a set of clinical features (including fever and features of mul-tiple organ damage) and laboratory abnormalities, with the exclusion of other causes. Most common complications involve cardiovascular system: myocarditis with decreased left ven-tricular ejection fraction, shock and/or coronary artery aneurysms. Mortality is around 2%. Appropriate management, including vital functions support and immunomodulating treat-ment, allows for a quick recovery of the vast majority of patients. The following document is a proposal for diagnostic and therapeutic management of children with suspected PIMS in Poland. © 2020, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.

5.
Przeglad Pediatryczny ; 50(2):6-16, 2021.
Article in Polish | Scopus | ID: covidwho-1567628

ABSTRACT

Pediatric inflammatory multisystem syndrome associated with COVID-19 (PIMS) is a new entity, occurring in children and young adults, associated with the SARS-CoV-2 infection. The first cases of PIMS were found in Poland in May 2020. Since October 2020, a signi-ficant increase in this new disease incidence has been observed in Poland, reflecting the increased incidence of COVID-19 in the pediatric population. PIMS development results from dysregulation of the immune system occurring after ca. 4 weeks after the SARS-CoV-2 infection. Diagnosis is based on criteria: a set of clinical features (including fever and features of multiple organ damage) and elevated inflammatory markers, excluding other cau-ses. The most common complications involve the cardiovascular system: heart damage with decreased left ventricular ejection fraction, shock, and coronary artery abnormalities. Mortality is around 2%. Appropriate management, including vital functions support and immunomodulating treatment, allows for a quick recovery of the vast majority of patients. The following document is a guideline for the diagnostic and therapeutic management of children with suspected PIMS in Poland. © 2021, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.

6.
Przeglad Pediatryczny ; 49(4):10-16, 2020.
Article in Polish | EMBASE | ID: covidwho-1567582

ABSTRACT

Recently, a significant increase in the number of patients infected with SARS-CoV-2 has been observed, including children. The available data indicate, that children are less sus-ceptible to SARS-CoV-2 infection compared to adults and may play a lesser role in the transmission of the infection. Children get infected much less frequently than adults, most of them do not have comorbidities, and in 80-90% of cases in children, the clinical course of COVID-19 is mild (oligo-or asymptomatic). The aim of this paper is to discuss the management of a child with COVID-19 in outpatient and inpatient settings. The current options and indications for antiviral therapy (including remdesivir), tociliziumab, and convalescent plasma, were discussed, indicating the limited availability of therapies in children. The mainstay of COVID-19 treatment in most pediatric patients is symptomatic and supportive treatment as well as measures aimed at reducing the spread of SARS-CoV-2 infection.

7.
Journal of the American Society of Nephrology ; 32:58, 2021.
Article in English | EMBASE | ID: covidwho-1489670

ABSTRACT

Background: We have previously shown that in the ischemia reperfusion model of AKI kidney ACE2 activity decreases and that the administration of a shorter soluble ACE2 variant markedly attenuates AKI in terms of GFR and kidney histology (Shirazi et al, ASN 2019). Here, we report the effect of a novel ACE2 variant designed to prevent/ treat SARS-CoV-2 in transgenic k18-hACE2 mice infected with a lethal viral dose. Methods: In a BSL-3 facility, transgenic k18-hACE2 mice were infected intranasally with 2×104 PFU SARS-CoV-2. ACE2 1-618-DDC-ABD was administered intranasally and intra-peritoneally 1 hour prior to viral challenge as well as 24 and 48 hours afterwards for a total of 3 doses. Infected control animals received PBS at the same time-points. Kidneys were removed from all animals and examined by light microscopy (LM) histologically and for apoptosis, using PAS and TUNEL staining, respectively. Results: In mice infected with SARS-CoV-2, variable degrees of AKI were found by LM with the following features seen in the few most severe cases: proximal tubule brush border loss (black arrows, figure 1A and B), cytolysis (red arrow, figure 1A), tubular basement membrane disruption (blue arrows, figure 1A and B) and apoptosis (white arrows, figure 1A, B, D and E). In animals treated with ACE2 1-618-DDC-ABD, survival was near 100% and proximal tubular kidney injury was absent or markedly attenuated with less proximal tubule injury (figure 1C) and minimal apoptosis (figure 1F). Glomeruli appeared ischemic (figure 1B, green arrow) but otherwise normal without evidence of thrombosis. Conclusions: Kidneys from a transgenic mouse susceptible to SARS-CoV-2 infection, like patients with COVID-19, displays variable degrees of proximal tubular injury suggesting that this model can be useful to study AKI in COVID-19. Mice that received soluble ACE2 1-618-DDC-ABD protein were essentially protected from AKI suggesting a potential preventative/therapeutic role for soluble ACE2 in this otherwise pharmacologically untreatable devastating disease.

8.
Journal of the American Society of Nephrology ; 32:39-40, 2021.
Article in English | EMBASE | ID: covidwho-1489669

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) uses full-length angiotensin converting enzyme 2 (ACE2) as the main receptor to enter the target cells. A novel soluble ACE2 protein with increased duration of action and binding capacity to exert a decoy effect as a way to intercept SARS-CoV-2 from binding to membrane-bound ACE2 was generated. The protein was administered to a lethal mouse model of COVID-19 to examine its efficacy. Methods: A human soluble ACE2 variant fused with a 5kD albumin binding domain (ABD) was linked via a dimerization motif hinge-like 4-cysteine dodecapeptide to improve binding capacity to the SARS-CoV-2. This novel protein (ACE2 1-618-DDCABD) was administered intranasally and intraperitoneally prior to viral inoculation and on the two following consecutive days. Infected animals were observed for weight, clinical score and mortality in a BSL-3 facility. Upon sacrifice, lung histopathology was evaluated, and viral loads were measured by plaque assay. Results: Infected mice that received ACE2-1-618-DDC-ABD developed only moderate disease assessed by a clinical score, modest weight loss and lung histology. At 6 days, mortality was totally prevented in the treated group (figure), lung histopathology was markedly improved and viral lung and brain titers reduced or non-detectable. By contrast, in untreated animals, lung histology revealed extensive pulmonary alveolar hemorrhage and mononuclear infiltrates, and they all became severely ill and had to be euthanized by day 6/7 (figure). Conclusions: This study demonstrates for the first time in vivo the preventative/ therapeutic efficacy of a soluble ACE2 protein in a preclinical animal model.

9.
Journal of the American Society of Nephrology ; 32:59, 2021.
Article in English | EMBASE | ID: covidwho-1489562

ABSTRACT

Background: Studies at the single cell level have revealed that the localization of TMPRSS2 is in the distal nephron whereas ACE2 is in the proximal tubule. Since TMPRSS2 is a serine protease necessary for activation of the SARS-CoV-2 S spike protein after it binds to ACE2, this spatial separation would make it difficult to explain how SARS-CoV-2 can infect the kidney. The purpose of this study was to examine the localization of these proteins by immunofluorescence in the kidneys of patients who died from COVID-19. Methods: Human kidney slides from a Northwestern COVID-19 repository were used after IRB approval. Slides from paraffin-embedded blocks were probed with different antibodies (ACE2, TMPRSS2, ACE, NBC-1, Aquaporin 2) for immunofluorescence studies. Mouse kidneys were also examined as additional controls. Results: In mouse kidneys, TMPRSS2 was found in the brush border of proximal tubules and co-localized strongly with ACE2. Similarly, in human kidneys from patients who died from COVID-19, with or without AKI and from non-COVID-19 subjects, ACE2 and TMPRSS2 co-localized in the proximal tubule. TMPRSS2 and ACE2 also co-localized with ACE, a marker of the apical proximal tubule and to a lesser extent with NBC-1, a marker of the basolateral proximal tubule membrane. By contrast, TMPRSS2 and ACE2 did not co-localize with Aquaporin 2, a marker of principal cells in the collecting tubule. Conclusions: In both mouse and human kidneys, ACE2 and TMPRSS2 co-localize in the proximal tubule. In kidneys from patients with COVID-19 with or without AKI obtained at autopsy, both proteins co-localized in the proximal tubule but not in the collecting tubule. Contrary to what was suggested from single-cell mRNA analysis?, the co-localization of both proteins in the proximal tubule would make it possible for the SARS-CoV-2-ACE2 complex to be activated when coronavirus reaches the kidney.

10.
Polish Otorhinolaryngology Review ; 10(2):18-24, 2021.
Article in English | Scopus | ID: covidwho-1328228

ABSTRACT

COVID-19 manifests itself in a wide spectrum of clinical symptoms, both in terms of their variety and severity. It can be asymptomatic or abortive, mild, moderate, severe and fulminant, i.e. having a septic course with multiple organ failure and shock. Typical leading symptoms of COVID-19 include: high fever poorly responding to drugs, severe loss of strength, chest pain, dyspnoea, headaches, bone and joint pain and muscle pain, and finally the onset of acute respiratory distress syndrome (ARDS). However, other symptoms not related to the lower respiratory tract involvement are also mentioned as possible in numerous publications. These include gastrointestinal disorders, damage to the central and peripheral nervous system, catarrh of the upper respiratory tract, and dysfunctions of the sensory organs. The aim of this literature review was to determine the frequency of various head and neck dysfunctions that are part of COVID-19. Symptoms of conjunctivitis, nasal mucostis, pharyngits and laryngitis are reported by about 3/4 of patients, albeit they do not always occur at the same time, as in infections caused, for example, by rhinoviruses. Anosmia/hyposmia or ageusia/hypogeusia occur with a similar frequency. Symptoms of damage to the equilibrium system, such as dizziness, are reported by approx. 1/3 of patients, vertigo and hearing loss by approx. 5-6%, of patients, tinnitus by approx. 10% of patients. To date, reports of peripheral paresis of the facial nerve coexisting with COVID-19 are relatively scarce and the symptom is often included in the category of neurological symptoms, the frequency of which also corresponds to about 1/3 of COVID-19 cases. Importantly, both catarrhal and other symptoms listed herein may precede, co-occur or follow the onset of the leading symptoms of COVID-19. They can also be the only symptoms of this disease. This should prompt otorhinolaryngologists to be particularly vigilant in this regard. © 2021 Index Copernicus International. All right reserved.

11.
Pediatria Polska ; 96(2):121-128, 2021.
Article in English | EMBASE | ID: covidwho-1325916

ABSTRACT

Multisystem Inflammatory Syndrome in Children (MIS-C) is a new clinical entity occurring in children and young adults, which is associated with the SARS-CoV-2 infection. The first cases of MIS-C were diagnosed in Poland in May 2020. Since October 2020, a significant increase in the incidence of this new disease has been observed in Poland, reflecting the increased incidence of COVID-19 in the paediatric population. MIS-C develops as a result of dysregulation of the immune system occurring 4 weeks after the SARS-CoV-2 infection. Diagnosis is based on the following criteria: a set of clinical features (including fever and signs of multiple organ damage) and elevated inflammatory markers, with exclusion of other causes. The most common complications involve the cardiovascular system: acute myocardial damage with reduced left ventricular ejection fraction, shock, and coronary artery abnormalities and arrhythmias. Mortality in Western Europe and the United States is around 1-2%. Appropriate management, including vital function support and immunomodulatory treatment, allows for a quick recovery in the vast majority of patients. This document is an updated guideline for the diagnostic and therapeutic management of children with suspected MIS-C in Poland. The most important changes concern treatment, steroid therapy, and antiplatelet therapy in particular.

12.
Vaccines (Basel) ; 9(4):14, 2021.
Article in English | MEDLINE | ID: covidwho-1209722

ABSTRACT

Vaccine hesitancy is a major threat to the success of COVID-19 vaccination programs. The present cross-sectional online survey of adult Poles (n = 1020) expressing a willingness to receive the COVID-19 vaccine was conducted between February and March 2021 and aimed to assess (i) the general trust in different types of vaccines, (ii) the level of acceptance of the COVID-19 vaccines already in use in Poland (BNT162b2 by BioNTech/Pfizer, mRNA-1273 by Moderna and AZD1222 by Oxford/AstraZeneca) as well as eight vaccines approved outside European Union (EU) or in advanced stages of clinical trials, (iii) level of fear of vaccination against COVID-19, and (iv) main sources of information on COVID-19 vaccination. Among all major vaccine technology, the highest level of trust was observed for the mRNA platform, with a considerable number of surveyed (>20%) not aware of the existence of vaccines produced using the traditional approach (inactivated and live attenuated vaccines). The age of participants was the main factor differentiating the level of trust in a particular vaccine type. Both BNT162b and mRNA-1273 received a high level of acceptance, contrary to AZD1222. From eight vaccines unauthorized in the EU at the moment of study, the CVnCoV (mRNA;CureVac) was met with the highest level of trust, followed by Ad26.COV2.S (vector;Janssen/Johnson&Johnson) and NVX-CoV2373 (protein;Novavax). Sputnik V (vector;Gamaleya Research Institute) was decidedly the least trusted vaccine. The median level of fear (measured by the 10-point Likert-type scale) in the studied group was 4.0, mostly related to the risk of serious allergic reactions, other severe adverse events and unknown long-term effects of vaccination. Female, individuals with a lower level of education and those not seeking any information on the COVID-19 vaccines revealed a higher fear of vaccination. Experts' materials were the major source of information on COVID-19 vaccines in the studied group. The study shows the level of trust in COVID-19 vaccines can vary much across the producers while the mRNA vaccines are received with a high level of acceptance. It also emphasizes the need for effective and continuous science communication when fighting the pandemic as it may be an ideal time to increase the general awareness of vaccines.

13.
Journal of the American Society of Nephrology ; 31:296-297, 2020.
Article in English | EMBASE | ID: covidwho-984533

ABSTRACT

Background: There have been concerns that ACE inhibitors and Ang II receptor blockers may cause an increase in full length (FL) membrane bound ACE2, the main receptor for SARs-CoV-2, that could enhance the risk and worsen the clinical course of COVID -19. Information on the impact of ACE deficiency and AT1 blockade on ACE2 expression at target sites is required to understand this issue. Methods: Kidneys from two genetic models of kidney ACE ablation and mice treated with captopril or telmisartan were used to examine ACE2 in isolated kidney and lung membranes. Results: In global ACE KO mice, ACE2 protein abundance in kidney membranes was reduced to 42 % of wild type, p < 0.05. In ACE 8/8 mice that over-express cardiac ACE protein but has no kidney ACE expression, ACE2 protein in kidney membranes wasalso decreased (38 % of the WT, p<0.01). In kidney membranes from mice that received captopril or telmisartan for 2 weeks there was a reduction in ACE2 protein to the level of 37%, p<0.01 and 76%, p <0.05 of that of vehicle control mice, respectively. In lung membranes the expression of ACE2 was very low and not detected by western blotting but no significant differences in terms of ACE2 activity could be detected in mice treated with captopril (118% of control) or telmisartan (93% of control). Conclusions: Genetic kidney ACE deficiency, suppressed ACE enzyme activity by Captopril or blockade of the AT1 receptor with telmisartan are all associated with a decrease in ACE2 expression in kidney membranes. These findings altogether suggest that ACE2 protein abundance at two potential target sites for SARS-CoV-2 infection is decreased or unaffected by RAS blockers. Since these medications do not increase ACE2 expression in lung or kidney epithelia, we conclude that they likely would not pose a risk for increased susceptibility to COVID -19.

14.
Hypertension (Dallas, Tex. : 1979). 2020 Aug 27|: 10.1161/HYPERTENSIONAHA.120.15256 ; 2020.
Article in English | PMC | ID: covidwho-843603
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