Severe Coronavirus Infection Research Articles

Combination of Traditional Chinese and Western Medicine to Improve the Cure Rate of Elderly Patients with Severe Novel Coronavirus Infection

Objective: To study the curative effect of traditional Chinese and western medicine on novel coronavirus's (COVID-19) patients in Jiangmen Central Hospital. Methods: This study was a retrospective cohort study. A total of 582 cases of COVID-19 patients admitted to Jiangmen Central Hospital from January 2020 to March 31, 2023 were collected, and five indicators, such as cure rate, improvement rate, inefficiency rate, mortality rate and hospitalization time, were analyzed, and the curative effects and treatment days under different treatment methods were compared among the integrated traditional Chinese and western medicine group, the western medicine group and the Chinese medicine group. Results: There was no significant difference in the cure rate, improvement rate, inefficiency rate and mortality rate of ordinary patients of all ages and severe middle and light years (≤65 years old) after treatment with integrated traditional Chinese and western medicine, pure western medicine or pure Chinese medicine (P > 0.05). The cure rate and effective rate of severe elderly patients (> 65 years old) were significantly higher than that of pure western medicine group (P < 0.05) and the ineffective rate was significantly lower than that of western medicine group (P < 0.01). There was no significant difference in improvement rate and mortality (P > 0.05). Except severe young patients (≤40 years old), the treatment time of western medicine group was significantly shorter than that of traditional Chinese medicine group and traditional Chinese and western medicine treatment group (P < 0.05). Conclusion: The combination of traditional Chinese and western medicine can significantly improve the cure rate and effective rate of elderly patients and reduce the inefficiency of their treatment. Compared with Chinese medicine, western medicine has a better effect in shortening hospitalization time.

Increased intrapulmonary shunt and alveolar dead space post-COVID-19.

Increased intrapulmonary shunt (QS/Qt) and alveolar dead space (VD/VT) are present in early recovery from 2019 Novel Coronavirus (COVID-19). We hypothesized patients recovering from severe critical acute illness (NIH category 3-5) would have greater and longer lasting increased QS/Qt and VD/VT than patients with mild-moderate acute illness (NIH 1-2). Fifty-nine unvaccinated patients (33 males, aged 52 [38-61] yr, body mass index [BMI] 28.8 [25.3-33.6] kg/m2; median [IQR], 44 previous mild-moderate COVID-19, and 15 severe-critical disease) were studied 15-403 days postacute severe acute respiratory syndrome coronavirus infection. Breathing ambient air, steady-state mean alveolar Pco2, and Po2 were recorded simultaneously with arterial Po2/Pco2 yielding aAPco2, AaPo2, and from these, QS/Qt%, VD/VT%, and relative alveolar ventilation (40 mmHg/[Formula: see text], VArel) were calculated. Median [Formula: see text] was 39.4 [35.6-41.1] mmHg, [Formula: see text] 92.3 [87.1-98.2] mmHg; [Formula: see text] 32.8 [28.6-35.3] mmHg, [Formula: see text] 112.9 [109.4-117.0] mmHg, AaPo2 18.8 [12.6-26.8] mmHg, aAPco2 5.9 [4.3-8.0] mmHg, QS/Qt 4.3 [2.1-5.9] %, and VD/VT16.6 [12.6-24.4]%. Only 14% of patients had normal QS/Qt and VD/VT; 1% increased QS/Qt but normal VD/VT; 49% normal QS/Qt and elevated VD/VT; 36% both abnormal QS/Qt and VD/VT. Previous severe critical COVID-19 predicted increased QS/Qt (2.69 [0.82-4.57]% per category severity [95% CI], P < 0.01), but not VD/VT. Increasing age weakly predicted increased VD/VT (1.6 [0.1-3.2]% per decade, P < 0.04). Time since infection, BMI, and comorbidities were not predictors (all P > 0.11). VArel was increased in most patients. In our population, recovery from COVID-19 was associated with increased QS/Qt in 37% of patients, increased VD/VT in 86%, and increased alveolar ventilation up to ∼13 mo postinfection. NIH severity predicted QS/Qt but not elevated VD/VT. Increased VD/VT suggests pulmonary microvascular pathology persists post-COVID-19 in most patients.NEW & NOTEWORTHY Using novel methodology quantifying intrapulmonary shunt and alveolar dead space in COVID-19 patients up to 403 days after acute illness, 37% had increased intrapulmonary shunt and 86% had elevated alveolar dead space likely due to independent pathology. Elevated shunt was partially related to severe acute illness, and increased alveolar dead space was weakly related to increasing age. Ventilation was increased in the majority of patients regardless of previous disease severity. These results demonstrate persisting gas exchange abnormalities after recovery.

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5-5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32-4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23-11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. UK Research and Innovation and National Institute for Health Research.

Effect of the pandemic on prehospital management of patients with mental and behavioral disorders: a retrospective cohort study.

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and the accompanying coronavirus disease (Covid-19) have shifted the priority of human and technical resources toward their handling, thus affecting the usual standards of care for populations diagnosed with other clinical entities. The phenomenon becomes even more apparent in patients with presenting symptoms of mental and behavioral disorders, a category already vulnerable and underrepresented in regard to its prehospital approach and management. For the purposes of the current retrospective cohort study, we used records of the Polish National Emergency Medical Service Command Support System for the time period between April 1, 2019 and April 30, 2021, the official register of medical interventions delivered in Poland by Emergency Medical Services (EMS). We aimed to examine the potential impact of the COVID-19 pandemic across the Masovian Voivodeship on individuals seeking medical care for mental and behavioral disorders pertaining in the "F" category of the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). We examined the individuals' baseline characteristics, prehospital vital parameters and EMS processing times in a population of 59,651 adult patients (04/2019-03/2020, 28,089 patients, 04/2020-03/2021, 31,562 patients) handled by EMS teams. Compared to pre-COVID-19, EMS personnel handled fewer patients, but more patients required mental and behavioral care. Throughout the duration of the pandemic, all prehospital time periods were significantly delayed due to the increased time needed to prepare crew, vehicles, and technical equipment to ensure COVID-19 prevention and overcrowding in Emergency Departments (EDs).

Correlation of SARS-CoV-2 RNA and nucleocapsid concentrations in samples used in INSTAND external quality assessment schemes

ObjectiveIn routine clinical laboratories, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is determined by reverse-transcription PCR (RT-PCR). In the COVID pandemic, a wide range of antigen detection tests were also in high demand. We investigated the correlation between SARS-CoV-2 NCap antigen and N gene concentration by analyzing samples from several INSTAND external quality assessment (EQA) schemes starting in March 2021. The absolute N gene concentration was measured using reverse transcriptase digital PCR (RT-dPCR) as reference value. Moreover, the performance of five commercial ELISA tests using an EQA inactivated SARS-CoV-2 sample at different concentrations was assessed on the basis of these reference values.ResultsQuantitative ELISA and RT-dPCR results showed a good correlation between SARS-CoV-2 NCap antigen and RNA concentration, but this correlation varies among SARS-CoV-2 isolates. A direct correlation between SARS-CoV-2 NCap antigen concentration and genome concentration should not be generally assumed.ConclusionFurther correlation studies between SARS-CoV-2 RNA and NCap antigen concentrations are needed, particularly in clinical samples and for emerging SARS-CoV-2 variants, to support the monitoring and improvement of antigen testing.

Клинико-эпидемиологические факторы различного исхода тяжелых форм коронавирусной инфекции (COVID-19) в инфекционном стационаре Республики Беларусь

Цель исследования. Определить влияние демографических, клинико-эпидемиологических, лабораторно-диагностических и лечебных факторов на исходы коронавирусной инфекции (COVID-19) в системе здравоохранения Республики Беларусь. Материалы и методы. Проведен анализ электронных и печатных медицинских карт при сплошной выборке пациентов с диагнозом «COVID-19, тяжелое течение, внегоспитальная 2-сторонняя интерстициальная пневмония» отделения интенсивной терапии областной инфекционной больницы г. Гродно (Республика Беларусь) в период с 1 февраля по 30 сентября 2021 года. За этот период в ретроспективное когортное исследование включены 84 пациента (мужчин – 37, женщин – 47, средний возраст – 62,1±1,59). Изучено влияние на исходы лечения демографических, клинико-эпидемиологических, лабораторно-диагностических, этиотропных, антибактериальных паттернов у выживших и умерших от COVID-19 пациентов в отделении интенсивной терапии. Результаты. Статистические различия по возрасту, коморбидной патологии в виде: ИБС, инфекции мочевыводящих путей, острого повреждения почек / хронической болезни почек (ОПП/ХБП), а также рост ферритина и С-реактивного белка от исходного уровня указывают на неблагоприятный прогноз и увеличение смертности при данном заболевании. Использование при интенсивной терапии тоцилизумабом 400 мг/сутки ассоциируется с благоприятным исходом данной инфекции. Применение парентеральных (20 видов антибиотиков) и энтеральных (4 вида антибиотиков) антибактериальных препаратов у пациентов, выживших (1-я группа) и умерших (2-я группа) при интенсивной терапии коронавирусной инфекции (COVID-19), не вызвало ни по одному виду примененного лекарственного препарата достоверного увеличения выживаемости. Заключение. Полученные статистические различия по исходам течения сепсиса при коронавирусной инфекции позволяют выявить наиболее значимые демографические, клинико-эпидемиологические, лабораторные, лечебные факторы интенсивной терапии для прогноза вирусно-бактериальной пневмонии при данном виде инфекционной патологии. Purpose. To determine the influence of demographic, clinical-epidemiological, laboratory- diagnostic and therapeutic factors on the outcomes of coronavirus infection (COVID-19) in the healthcare system of the Republic of Belarus. Materials and methods. The analysis of electronic and printed medical records was carried out with a continuous sample of patients of the intensive care unit in the period from February 01 to September 30, 2021 of the regional Infectious diseases hospital of Grodno, RB. During this period, 84 patients were included in a retrospective cohort study (husband – 37, women – 47, average age – 62.1±1.59), who are in the intensive care unit with a diagnosis of COVID-19, severe course, out-of-hospital 2-sided interstitial pneumonia. The influence of demographic, clinical-epidemiological, laboratory-diagnostic, etiotropic, and antibacterial patterns on treatment outcomes in survivors and deceased patients from COVID-19 in the intensive care unit was studied. Results. Statistical differences in age, comorbid pathology in the form of: coronary artery disease, urinary tract infection, AKI / CKD (acute kidney injury / chronic kidney disease), the growth of ferritin and C-reactive protein from the baseline level indicates an unfavorable prognosis and an increase in mortality in this disease. The use of tocilizumab 400 mg/day in intensive therapy is associated with a favorable outcome of this infection. The use of parenteral (20 types of antibiotics) and enteral (4 types of antibiotics) antibacterial drugs in patients who survived (group 1) and died (group 2) during intensive therapy of coronavirus infection (COVID-19) did not cause a significant increase in survival for any type of drug used. Conclusion. The obtained statistical differences in the outcomes of sepsis in coronavirus infection make it possible to identify the most significant demographic, clinical- epidemiological, laboratory, therapeutic factors of intensive therapy for the prognosis of viral-bacterial pneumonia in this type of infectious pathology.

Dynamics the parameters of mineral metabolism in hospitalized patients with COVID-19, the impact of etiotropic and pathogenetic therapy

To study the dynamics of mineral metabolism parameters in patients with a confirmed COVID-19 at the time of hospitalization and after discharge, including the impact of etiotropic and pathogenetic therapy on them. A single-center study of 106 patients (aged ≥18 years) with clinically or laboratory confirmed diagnosis of COVID-19 was carried out at the Endocrinology Research Centre, Moscow. Baseline biochemical parameters, including serum calcium, phosphorus, albumin, 25(OH)D, parathyroid hormone (PTH), inflammatory markers, and instrumental assessment of COVID-19 severity were performed before specific immunotherapy, as well as on 3rd and 7th days of hospitalization and before discharge. Statistical analysis was performed with Statistica 13 software (StatSoft, USA). On the first day, hypocalcemia (low albumin-adjusted calcium level) was detected in 40.6% of cases, the prevalence of vitamin D deficiency/insufficiency amounted to 95.3% of cases. At the same time, secondary hyperparathyroidism was identified only in 14.2% of patients. A comparative analysis of mineral metabolism during hospitalization (between 1, 3, 7 days of hospitalization and before discharge) during baricitinib treatment revealed a statistically significant increase in albumin-adjusted calcium by the end of hospitalization (p&lt;0.001, Friedman criterion, Bonferroni correction p0=0.01). A pairwise comparison of subgroups, depending on the therapy, revealed a statistically significantly lower level of albumin-adjusted calcium on 3rd day among patients on baricitinib monotherapy or combined with tocilizumab compared with a subgroup of patients undergoing etiotropic treatment (2.16 [2.13; 2.18] mmol/l vs 2.23 [2.19; 2.28] mmol/l, p=0.002, U-test, Bonferroni correction p0=0.012). Patients with severe coronavirus infection are characterized by a high prevalence of vitamin D deficiency and hypocalcemia. Associations between calcium and saturation as well as the severity of lung lesion characterizes hypocalcemia as an important predictor of severe course and poor outcome in COVID-19. Pathogenetic therapy with baricitinib, including in combination with tocilizumab, contributes to achieve normocalcemia, but further studies are required.

Effects of Severe Acute Respiratory Syndrome Coronavirus Vaccination on Reinfection: A Community-Based Retrospective Cohort Study.

Coronavirus disease 2019 (COVID-19) is a disease that is characterized by frequent reinfection. However, the factors influencing reinfection remain poorly elucidated, particularly regarding the effect of COVID-19 vaccination on preventing reinfection and its effects on symptomatology and the interval until reinfection. This retrospective cohort study examined patients with severe acute respiratory syndrome coronavirus reinfection between January 2020 and February 2022. This study included patients aged >17 years who were reinfected at least 90 days between two infections with severe acute respiratory syndrome coronavirus. The main outcome measure was a reduction in symptoms during reinfection, and reinfection interval. Overall, 712 patients (average age: 40.52 ± 16.41 years; 312 males) were included. The reduction rate of symptoms at reinfection than that at first infection was significantly higher in the vaccinated group than in the unvaccinated group (p < 0.001). The average reinfection interval was 265.81 days. The interval between the first and second infection was 63.47 days longer in the vaccinated group than in the unvaccinated group. The interval was also 57.23 days, significantly longer in the asymptomatic group than in the symptomatic group (p < 0.001). Besides its role in preventing severe acute respiratory syndrome coronavirus infection, vaccination reduces the rate of symptomatic reinfection and increases the reinfection interval; thus, it is necessary to be vaccinated even after a previous infection. The findings may inform the decision to avail COVID-19 vaccination.

COVID-19: An opportunity to engage African Americans and women in research on cardiovascular disease

IntroductionAfrican Americans (AA) have been disproportionately affected with the COVID-19 disease experiencing 30%-60% of the deaths, while only making up 13% of the US population. Early data suggest that pregnant women and those with cardiovascular disease (CVD) may experience worse outcomes with severe coronavirus infection. There is an urgent need to incorporate AA and female perspectives into the design of research on the CVD complications related to COVID-19. ObjectivesThe goal of this project was to incorporate perspectives of AA and female patients in developing research priorities and AN agenda related to COVID-19. Objectives included: (a) develop a strong, research-ready partnership capable of executing PCOR, (b) creation of a research agenda and a set of priorities on racial/sex-specific CVD disparities in COVID-19 which reflects the perspectives of AA's and women; (c) long-term objective is creation of a set of research questions suitable for clinical research using the AHA Registry. MethodsThe project used principles of active and adult learning within the framework of capacity building to build a strong, patient-centered vision of research needs. Different methods of obtaining patient input were used to identify questions suitable for research using the America Heart Association COVID-19 CVD Quality Improvement Registry: focus groups and town halls to identify concerns and interests vis-à-vis CVD and COVID research; narrative medicine methods collected compelling real-life, COVID-19 health stories; a research advisory council reviewed and prioritized research questions. ResultsOutcomes include a replicable method of obtaining patient-oriented input into the creation of a research agenda and a set of research priorities for COVID-19. Outputs include the establishment of a research advisory council and stakeholder training using the PCORI funded, PORTAL program resources; a catalogue of patient generated narratives on COVID-19 experiences in the voice of AAs and women, and a set of research questions suitable for research using the AHA Registry. ConclusionThe project created a research ready stakeholder network, ready to develop a research agenda about COVID-19.

Clinical Course and Outcomes of COVID-19 Infection in Patients Treated with Rituximab: A Tertiary Care Center Experience.

Patients receiving rituximab (RTX) may be at increased risk for severe Coronavirus infections and worse outcomes compared with the general population. Because of the conflicting results concerning the effect of RTX on the clinical course and outcomes of COVID-19 infection, we aimed to share our experience with 35 patients infected with COVID-19 while treated with RTX for a variety of clinical indications. This was a single-centre retrospective cohort study that included 35 patients. All patients aged ≥14 years who were treated with RTX for various conditions and were found to have COVID-19 infection were included. Patients with poor outcomes or patients with suspected COVID-19 infection were excluded. The patients' mean age was 42.8 ± 16.3 years with an average BMI of 29.9 ± 11.4 kg/m2. Over half (51.4%, n = 18) of the patients received RTX at a dose of 375 mg/m2 with a median frequency of 4 doses. More than a third (37.1%, n = 13) of the patients had hypogammaglobulinemia and 25.7% had low CD19. Over a third (42.9%, n= 15) of the patients required hospitalization and almost a third (25.7%, n = 9) required treatment in the intensive care unit. There was a statistically significant association between intensive care unit admission and age, steroid use, and low CD19. The mortality rate was 25.7%, and it was significantly higher in elderly, diabetics, corticosteroid users, patients who were hospitalized, treated in the intensive care unit, and had low immunoglobin or CD19. Treatment with RTX seems to be a potential risk factor for unfavorable outcomes in COVID-19 patients. RTX should be used with caution or avoided unless the benefit clearly outweighs the risk.

Coronavirus infection (COVID-19): clinical case of a severe disease in a newborn

The article presents a single clinical case of a severe coronavirus infection (COVID-19) in a newborn. Clinical and laboratory examination and treatment of the patient were carried out in accordance with the guidelines for the treatment of coronavirus infection in children. On the third day of hospitalization neonatal death occurred due to the development of multiple organ failure despite the medical therapy. An autopsy revealed diffuse alveolar damage (DAD) of the type of adult respiratory distress syndrome (ARDS) accompanied by bilateral polysegmental pneumonia and systemic inflammatory response syndrome.

Pulmonary hypertension and right ventricular dysfunction as predictors of severe coronavirus infection

Coronavirus disease 2019 (COVID-19) is a disease characterized by diverse clinical manifestations, the severity of which can vary from asymptomatic to extremely severe. At this stage, the urgent task is the early detection of reliable markers of its severity in the acute period of infection and possible changes that cause symptoms in the post-COVID period. The severe COVID-19 is associated with extensive damage to the lungs, pulmonary vessels, and cardiovascular system. In this regard, it seems natural to study the problem of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in patients with COVID-19, and their significance for assessing the severity of the condition and prognosis. Also important is the availability of reliable non-invasive diagnostics. This review presents data on the incidence of PH and RVD and their potential significance in patients with COVID-19. We have analyzed literature sources in the eLIBRARY, PubMed/MEDLINE, ScienceDirect and ProQuest databases.

Inflammation and Immune Reactions in the Fetus as a Response to COVID-19 in the Mother

Background: Contracting COVID-19 during pregnancy can harm both the mother and the unborn child. Pregnant women are highly likely to develop respiratory viral infection complications with critical conditions caused by physiological changes in the immune and cardiopulmonary systems. Asymptomatic COVID-19 in pregnant women may be accompanied by fetal inflammatory response syndrome, which has adverse consequences for the newborn’s life and health. Purpose: To conduct an inflammatory response assessment of the fetus due to the effects of COVID-19 on the mother during pregnancy by determining pro-inflammatory cytokines, cell markers, T regulatory cells, T cell response, evaluation of cardiac function, and thymus size. Materials and methods: A prospective study included pregnant women (n = 92). The main group consisted of 62 pregnant women with COVID-19 infection: subgroup 1—SARS-CoV-2 PCR-positive pregnant women 4–6 weeks before delivery (n = 30); subgroup 2—SARS-CoV-2 PCR-positive earlier during pregnancy (n = 32). The control group consisted of 30 healthy pregnant women. In all pregnant women, the levels of circulating cytokines and chemokines (IL-1α, IL-6, IL-8, IL-10, GM-CSF, TNF-α, IFN-γ, MIP-1β, and CXCL-10) were determined in the peripheral blood and after delivery in the umbilical cord blood, and an analysis was performed of the cell markers on dendritic cells, quantitative and functional characteristics of T regulatory cells, and specific T cell responses. The levels of thyroxine and thyroid-stimulating hormone were determined in the newborns of the studied groups, and ultrasound examinations of the thymus and echocardiography of the heart were also performed. Results: The cord blood dendritic cells of newborns born to mothers who suffered from COVID-19 4–6 weeks before delivery (subgroup 1) showed a significant increase in CD80 and CD86 expression compared to the control group (p = 0.023). In the umbilical cord blood samples of children whose mothers tested positive for COVID-19 4–6 weeks before delivery (subgroup 1), the CD4+CCR7+ T cells increased with a concomitant decrease in the proportion of naive CD4+ T cells compared with the control group (p = 0.016). Significantly higher levels of pro-inflammatory cytokines and chemokines were detected in the newborns of subgroup 1 compared to the control group. In the newborns of subgroup 1, the functional activity of T regulatory cells was suppressed, compared with the newborns of the control group (p &lt; 0.001). In all pregnant women with a severe coronavirus infection, a weak T cell response was detected in them as well as in their newborns. In newborns whose mothers suffered a coronavirus infection, a decrease in thymus size, transient hypothyroxinemia, and changes in functional parameters according to echocardiography were revealed compared with the newborns of the control group. Conclusions: Fetal inflammatory response syndrome can occur in infants whose mothers suffered from a COVID-19 infection during pregnancy and is characterized by the activation of the fetal immune system and increased production of pro-inflammatory cytokines. The disease severity in a pregnant woman does not correlate with SIRS severity in the neonatal period. It can vary from minimal laboratory parameter changes to the development of complications in the organs and systems of the fetus and newborn.

The unfolded protein response components IRE1α and XBP1 promote human coronavirus infection.

The cellular processes that support human coronavirus replication and contribute to the pathogenesis of severe disease remain incompletely understood. Many viruses, including coronaviruses, cause endoplasmic reticulum (ER) stress during infection. IRE1α is a component of the cellular response to ER stress that initiates non-conventional splicing of XBP1 mRNA. Spliced XBP1 encodes a transcription factor that induces the expression of ER-related targets. Activation of the IRE1α-XBP1 pathway occurs in association with risk factors for severe human coronavirus infection. In this study, we found that the human coronaviruses HCoV-OC43 (human coronavirus OC43) and SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) both robustly activate the IRE1α-XBP1 branch of the unfolded protein response in cultured cells. Using IRE1α nuclease inhibitors and genetic knockdown of IRE1α and XBP1, we found that these host factors are required for optimal replication of both viruses. Our data suggest that IRE1α supports infection downstream of initial viral attachment and entry. In addition, we found that ER stress-inducing conditions are sufficient to enhance human coronavirus replication. Furthermore, we found markedly increased XBP1 in circulation in human patients with severe coronavirus disease 2019 (COVID-19). Together, these results demonstrate the importance of IRE1α and XBP1 for human coronavirus infection. IMPORTANCE There is a critical need to understand the cellular processes co-opted during human coronavirus replication, with an emphasis on identifying mechanisms underlying severe disease and potential therapeutic targets. Here, we demonstrate that the host proteins IRE1α and XBP1 are required for robust infection by the human coronaviruses, SARS-CoV-2 and HCoV-OC43. IRE1α and XBP1 participate in the cellular response to ER stress and are activated during conditions that predispose to severe COVID-19. We found enhanced viral replication with exogenous IRE1α activation, and evidence that this pathway is activated in humans during severe COVID-19. Together, these results demonstrate the importance of IRE1α and XBP1 for human coronavirus infection.

Tracheal stenosis and diaphragm relaxation of post-COVID origin

Pandemic of the new coronavirus infection has presented the medical community with challenges that call for immediate action. An increase in the number of severe cases of COVID-19 requiring mechanical ventilation inevitably leads not only to an increase in the complication rates, but also to combined complications. A clinical case of a combined tracheal stenosis and diaphragm after severe COVID-19 is presented here.The aim of this publication was to improve treatment outcomes of patients with multiorgan complications of post-COVID origin.Conclusion. Combined complications of a severe coronavirus infection worsen the rehabilitation prognosis, and require surgical treatment.

Drug target of natural products and COVID-19: how far has science progressed?

The new coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] that caused a viral disease with a high risk of mortality (coronavirus disease 2019) was found toward the end of 2019. This was a significant acute respiratory syndrome. In a brief period, this virus spread throughout the entire planet, causing tremendous loss of life and economic damage. The process of developing new treatments takes time, and there are presently no recognized specific treatments to treat this infection. The most promising participants, who subsequently developed into prospective leads, were dropped from the clinical research in their latter phases. Medication that has previously acquired permission may only be repurposed for use for various medical reasons following a thorough investigation for safety and effectiveness. Because there are now no effective treatments available, natural products are being used haphazardly as antiviral medications and immunity boosters. The fundamental statement that most natural compounds have powerful antiviral action does not apply to SARS-CoV-2. Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus infections are inhibited by natural treatments. According to an in silico study, the virus' nonstructural proteins, including PLpro, Mpro, and RdRp, as well as structural proteins like the spike (S) protein, have been shown to have a strong affinity for several natural products and to be inhibited by them. The virus also suggests that it is a valid candidate for therapeutic research since it utilizes the intracellular angiotensin-converting enzyme 2 receptor of the host cell. In this study, interesting targets for SARS-CoV-2 medication development are explored, as well as the antiviral properties of some well-known natural compounds.

Successful Kidney Transplantation of Two Patients with Donors Positive for Severe Acute Respiratory Syndrome Coronavirus Infection

Despite preventative measures, including vaccination, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection may result in severe illness, particularly in immunosuppressed transplant recipients. This has had a negative impact on organ donation and transplantation rates. However, the risk of transmission from SARS-CoV-2 positive donors to kidney transplant recipients is unknown. We describe 2 cases of successful kidney transplantation from SARS-CoV-2 positive donors. Case 1: 38-year old unvaccinated female, established on haemodialysis for 1 year, with underlying reflux nephropathy. Donor tested SARS-CoV-2 positive on polymerase chain reaction testing with a cycle threshold (CT) value of 29 initially. Sequential testing demonstrated a rise in CT value (37.8), aiding the decision to proceed. The recipient was high immunological risk and received a controlled category 3 donation after circulatory death (DCD) kidney transplant. She had immediate graft function and did not develop SARS-CoV-2 infection. Case 2: 63-year old female, with diabetes mellitus and hypertension. She was low immunological risk and for pre-emptive transplantation. The donor was SARS-CoV-2 positive with a CT value of 41.5 and was subsequently negative. Decision was made to proceed with a donation after brainstem death (DBD) transplant. The recipient had immediate graft function and did not develop SARS-CoV-2 infection. We report 2 cases of successful transplantation from SARS-CoV-2 positive donors, without severe infection, with no transmission seen in the recipients post-operatively. Decisions to proceed were primarily made on clinical grounds with assistance from RT-PCR CT values, making this a useful additional tool in determining suitability of organ donation in people who are SARS-CoV-2 positive.

New characteristics of COVID-19 caused by the Omicron variant in Guangzhou

We investigated the types of novel coronavirus strains present during the Omicron epidemic from late 2022 to early 2023, COVID-19 co-infections with other pathogens, and clinical characteristics of patients with novel coronavirus infections. Adult patients hospitalized due to SARS CoV-2 infection in six hospitals in Guangzhou city were included in the study from November 2022 to February 2023. Clinical information was collected and analyzed, and bronchoalveolar lavage fluid was obtained for pathogen detection using a variety of techniques, including standard methods and mNGS, tNGS. The results showed that the main strain circulating in Guangzhou was Omicron BA.5.2, and the overall detection rate of potentially pathogenic pathogens combined with Omicron COVID-19 infection was 49.8%. In patients with severe COVID-19 infection, special attention should be paid to aspergillosis and combined Mycobacterium tuberculosis infection. In additon, Omicron strain infection could cause viral sepsis, which led to a worse prognosis for COVID-19 patients. Diabetic patients with SARS-CoV-2 infection did not benefit from glucocorticoid treatment, and caution was necessary when using glucocorticoids. These findings highlighted some new features of severe Omicron coronavirus infection that should be noted.

Structural requirements of Holothuria floridana fucosylated chondroitin sulfate oligosaccharides in anti-SARS-CoV-2 and anticoagulant activities.

Fucosylated chondroitin sulfate (FucCS) is a unique glycosaminoglycan found primarily in sea cucumbers. This marine sulfated glycan is composed of a chondroitin sulfate backbone decorated with fucosyl branches attached to the glucuronic acid. FucCS exhibits potential biological actions including inhibition of blood clotting and severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. These biological effects have been attributed to certain structural features, including molecular weight (MW), and/or those related to fucosylation, such as degrees of fucosyl branches, sulfation patterns and contents. In a previous work, we were able to generate oligosaccharides of the FucCS from Pentacta pygmaea (PpFucCS) with reduced anticoagulant effect but still retaining significant anti-SARS-CoV-2 activity against the delta strain. In this work, we extended our study to the FucCS extracted from the species Holothuria floridana (HfFucCS). The oligosaccharides were prepared by free-radical depolymerization of the HfFucCS via copper-based Fenton reaction. One-dimensional 1H nuclear magnetic resonance spectra were employed in structural analysis. Activated partial thromboplastin time and assays using protease (factors Xa and IIa) and serine protease inhibitors (antithrombin, and heparin cofactor II) in the presence of the sulfated carbohydrates were used to monitor anticoagulation. Anti-SARS-CoV-2 effects were measured using the concentration-response inhibitory curves of HEK-293T-human angiotensin-converting enzyme-2 cells infected with a baculovirus pseudotyped SARS-CoV-2 wild-type and delta variant spike (S)-proteins. Furthermore, the cytotoxicity of native HfFucCS and its oligosaccharides was also assessed. Like for PpFucCS, we were able to generate a HfFucCS oligosaccharide fraction devoid of high anticoagulant effect but still retaining considerable anti-SARS-CoV-2 actions against both variants. However, compared to the oligosaccharide fraction derived from PpFucCS, the average MW of the shortest active HfFucCS oligosaccharide fraction was significantly lower. This finding suggests that the specific structural feature in HfFucCS, the branching 3,4-di-sulfated fucoses together with the backbone 4,6-di-sulfated N-acetylgalactosamines, is relevant for the anti-SARS-CoV-2 activity of FucCS molecules.

AVASCULAR NECROSIS AS A MANIFESTATION OF POST-COVID SYNDROME IN ROUTINE PRACTICE OF RHEUMATOLOGIST

Avascular necrosis as a part of post-COVID syndrome requires increased attention of physicians due to significant misfunction of musculoskeletal system, increased disability, and frequently requires surgical intervention. It is known that hypercoagulation, thrombosis as well as systemic corticosteroid therapy during severe coronavirus infection play an important role in the development of avascular necrosis. A case report of progressive avascular necrosis in multiple loci accompanied by polyarthritis in a young man developed after severe COVID-19 is reported below