Acute Infection Period Research Articles

8241 Post-Covid complications in patients with diabetes mellitus are high during 24 month after acute infection

Abstract Disclosure: A. Alieva: None. The consequences of coronavirus infection in patients with diabetes have not been fully studied. The purpose of the work was to study post-Covid complications in patients with diabetes. Materials and methods. We examined 188 patients with diabetes mellitus who had a coronavirus infection in 2020 and applied to the RSSPMCE clinic for inpatient treatment within 1-24 months after the acute period of viral infection. The criteria for inclusion in the study were: the presence of type 2 diabetes mellitus (DM), diagnosed before 2020, a history of COVID-19 infection confirmed by PCR. Exclusion criteria were pregnancy and diabetes diagnosed in 2020 and later. Results and discussion. An increase in D-dimer levels was observed at 0-3, 7-9 and 19-24 months, which was accompanied by an increase in von Willebrand factor at 4-9 months and thrombosis at 4-6 months after COVID-19. The period of 4-6 months after coronavirus infection was also characterized by an increase in inflammatory markers and the development of purulent complications. The progression of polyneuropathy was noted during the first 6 months after COVID-19; for periods of 6-12 months, the development of vasculitis was typical. In the periods of 1-3 months and 10-24 months after COVID-19, cases of the development of newly registered hypertension were observed. Conclusion. Patients with type 2 diabetes mellitus for 2 years after coronavirus infection remain at risk of developing thrombotic complications, new-onset arterial hypertension and accelerated progression of chronic complications of diabetes mellitus, which requires careful targeted monitoring of such patients. Presentation: 6/3/2024

Brain Mechanisms Involved in Post COVID Syndrome: A Narrative Review

Potentially, patients with COVID-19 can experience long-term disturbances after the acute infection period, even people with no symptoms or mild illness. Our current understanding of brain-associated post COVID-19 condition and why some people are more affected is limited. Post COVID syndrome or long COVID, with continuing symptoms of impaired brain functioning, in particular, ‘brain fog’, chronic fatigue, cognitive decline, mood disturbances, anxiety, and depression, is due to multiple molecular mechanisms. This narrative review updates most important cellular and molecular brain mechanisms as well as system mechanisms underlying post COVID syndrome.

Impact of lower-respiratory tract infections on healthcare utilization and mortality in older adults: a Swedish population-based cohort study

BackgroundLower respiratory tract infections (LRTIs) have an immediate significant impact on morbidity and mortality among older adults. However, the impact following the infectious period of LRTI remains understudied. We aimed to assess the short- to long-term impact of LRTIs on hospitalization, mortality, and healthcare utilization in older adults.MethodsData from the Swedish National Study of Aging and Care in Kungsholmen (SNAC-K) was analyzed, with data from 2001 to 2019 for mortality and 2001–2016 for healthcare utilization. LRTI-exposed participants were identified and matched with LRTI-nonexposed based on sociodemographics, lifestyle factors, and functional and clinical characteristics. Statistical models evaluated post-LRTI hospitalization risk, days of inpatient hospital admissions, healthcare visits, and mortality.Results567 LRTIs-exposed participants during the study period and were matched with 1.701 unexposed individuals. LRTI-exposed individuals exhibited increased risk of hospitalization at 1-year (HR 2.14, CI 1.74, 2.63), 3-years (HR 1.74, CI 1.46, 2.07), and 5-years (HR 1.59, CI 1.33, 1.89). They also experienced longer post-LRTI hospital stays (IRR 1.40, CI 1.18, 1.66), more healthcare visits (IRR 1.47, CI 1.26, 1.71), specialist-care visits (IRR 1.46, CI 1.24, 1.73), and hospital admissions (IRR 1.57, CI 1.34, 1.83) compared to nonexposed participants over 16-years of potential follow-up. Additionally, the 19-year risk of mortality was higher among LRTI-exposed participants (HR 1.45, CI 1.24, 1.70). Men exhibited stronger associations with these risks compared to women.ConclusionsLRTIs pose both short- and long-term risks for older adults, including increased risks of mortality, hospitalization, and healthcare visits that transpire beyond the acute infection period, although these effects diminish over time. Men exhibit higher risks across these outcomes compared to women. Given the potential preventability of LRTIs, further public health measures to mitigate infection risk are warranted.

Post-COVID syndrome: Clinical pattern and impact on health related quality of life

Background COVID-19 management has changed from just dealing with a novel respiratory viral illness to unraveling the mystery of a systemic disease. This study aimed to assess clinical pattern for post-COVID survivors and impact on quality of life. Methods 115 Patients suffering from COVID-19 affection were recruited in this study. The assessment included clinical history with special attention to symptoms attributable to post-COVID manifestations. Evaluation for presence of insomnia, anxiety and depression were done using insomnia severity index (ISI), Hamilton’s anxiety (HAM-A) and depression rating scales (HAM-D), respectively. Laboratory investigations included complete blood count (CBC), kidney function test, liver function test, C-reactive protein (CRP), and inflammatory markers including ESR, CRP and Ferritin level. EQ-5D-5L and EQ visual analogue scale (EQ-VAS) were used to assess participants’ overall health status and quality of life. Results COVID-19 patients suffered from cough (76%), fever (72.9%), fatigue (72.9%), dyspnea (69.8%) and muscle/joint pain (66.1%) as the most distressing symptoms during period of acute infection. Regarding post-COVID syndrome (PCS); Dyspnea (32.2%), fatigue (26.1%), muscle/joint pain (22.6%), loss of taste (16.5%) and loss of smell (15.7%) were the most prevalent at 3 month evaluation. 46.9% patients developed manifestations attributable to post-COVID syndrome. Fever, cough, loss of smell and taste, fatigue, anxiety and insomnia persisted significantly for longer periods among severe cases (Group 2). EQ-5D-5L domains were significantly impaired among severe COVID patients. Significant positive correlation noticed between age and increased duration of dyspnea, muscle/joint pains and depression. Also, CT chest severity scores showed significant correlation with dyspnea, fatigue, muscle/joint pains (P=0.023, 0.012 and <0.001; respectively). Conclusion High prevalence of Post-COVID syndrome is a challenge to health care resources. PCS directly impacts mobility, self-care, usual activities, pain perception and anxiety and therefore is associated with lower quality of life among post-COVID patients.

New insights into swine dysentery: faecal shedding, macro and microscopic lesions and biomarkers in early and acute stages of Brachyspira hyodysenteriae infection

BackgroundSwine dysentery (SD) is a severe mucohaemorrhagic colitis in pigs caused classically by Brachyspira hyodysenteriae. Although several aspects of B. hyodysenteriae infection dynamic are already described, further research in the early stage of this infection is required. In this study, 7-week-old pigs were orally challenged with B. hyodysenteriae to obtain information about faecal shedding, macro and microscopic intestinal lesions and serum acute phase proteins in pigs at the onset of B. hyodysenteriae shedding (early infection group, n = 8), in pigs with mucohaemorrhagic diarrhoea (acute infection group, n = 8) and in non-infected controls (n = 16).ResultsFirst B. hyodysenteriae detection by q-PCR and first loose stools with blood and mucus occurred both at 8 days post-inoculation. The lapse between a positive q-PCR and observation of mucohaemorrhagic diarrhoea ranged from 0 to 3 days, except in a single pig in which this period lasted 5 days. Macroscopic lesions were observed in the large intestine from both infected groups although more frequent and severe in acute infection group. Microscopic observation of the apex mucosa revealed that in early infection only higher ulceration values were observed compared to healthy controls. In contrast, the acute infection group exhibited higher ulceration, neutrophils infiltration and increased mucosal thickness compared to the other two groups. Among the serum biomarkers tested, only haptoglobin, C-reactive protein, and creatine kinase showed a significant increase in pigs in the acute infection period compared to controls, whereas haptoglobin was the only factor with a significant increase at the early infection compared to non-infected animals.ConclusionsThis study provides new insights about SD and remarks the complex and limited options to perform an early detection of infected animals beyond PCR diagnosis.

Enhanced diabetic wound healing with injectable hydrogel containing self-assembling nanozymes

To build a smart system in response to the variable microenvironment in infected diabetic wounds, a multifunctional wound dressing was constructed by co-incorporating glucose oxidase (GOx) and a pH-responsive self-assembly Cu2−xSe-BSA nanozyme into a dual-dynamic bond cross-linked hydrogel (OBG). This composite hydrogel (OBG@CG) can adhere to the wound site and respond to the acidic inflammatory environment, initiating the GOx-catalyzed generation of H2O2 and the self-assembly activated peroxidase-like property of Cu2−xSe-BSA nanozymes, resulting in significant hydroxyl radical production to attack the biofilm during the acute infection period and alleviate the high-glucose microenvironment for better wound healing. During the wound recovery phase, Cu2−xSe-BSA aggregates disassembled owing to the elevated pH, terminating catalytic reactive oxygen species generation. Simultaneously, Cu2+ released from the Cu2−xSe-BSA not only promotes the production of mature collagen but also enhances the migration and proliferation of endothelial cells. RNA-seq analysis demonstrated that OBG@CG exerted its antibacterial property by damaging the integrity of the biofilm by inducing radicals and interfering with the energy supply, along with destroying the defense system by disturbing thiol metabolism and reducing transporter activities. This work proposes an innovative glucose consumption strategy for infected diabetic wound management, which may inspire new ideas in the exploration of smart wound dressing.

Impact of the COVID-19 pandemic on the manifestation and course of mental illness in elderly

IntroductionCOVID-19 is a multisystem disease affecting not only the respiratory, gastroenterstitial and vascular systems, but also the central nervous system, which leads to a wide range of neurological and mental complications. 3 years of experience in combating the pandemic has shown that elderly people burdened with chronic somatic diseases are the most vulnerable risk group for the development of severe course and complications of COVID-19.ObjectivesTo study the impact of COVID-19 on the onset and course of mental illness in elderly inpatientsMethodsWe examined 67 inpatients aged 50 to 95 years with various mental pathologies, who underwent COVID-19 from February 2020 to December 2021. 46 people had previous history of mentall disease (PHMD), in 21 cases the disease developed for the first time. Statistical analysis was performed.ResultsIn the manifest group of patients, depressive episodes predominated (42.9%), including psychotic episodes (9.5%). In 28.6% of cases, organic disorders were diagnosed in the form of emotional lability, organic depression, mild cognitive impairment and delirium. In 23.8% of patients, neurotic disorders were observed in the form of depressive reactions, panic and generalized anxiety disorder. In one case (4.8%), acute polymorphic psychosis with symptoms of schizophrenia was diagnosed. The PHMD group includes affective disorders - 45.7%; organic disorders, including dementia 26.1%; schizophrenic spectrum disorders -19.6% and neurotic somatoform disorders - 8.7%. In the acute and subacute periods of COVID-19, acute psychotic states (APS) developed in both groups of patients (in 23.3% and 30.4%, respectively) in the form of delirium, psychotic depression, or polymorphic psychosis. APS were more common in PHMD patients with organic (50%) and schizophrenic spectrum disorders (33.3%) with a predominance of delirium. In the long-term period of COVID-19, PHMD patients more often than non-PHMD (60.9% and 38.1%) developed cognitive impairment (CI), especially in schizophrenia-like (77.8%) and organic (83.3%) disorders. CI developed twice as often after APS (89.5% and 39.6%, p<0.001), reaching the degree of dementia in 15.8% of cases. APS were significantly associated (p<0.05) with the development of CI (0.567733), the age of patients (0.410696) and the presence of previous cerebrovascular insufficiency (0.404916).ConclusionsThe age-related features of the mental consequences of COVID-19 are the occurrence of APS in the acute period of infection and the deterioration of cognitive activity at a remote stage. The PHMD patients, especially with disorders of organic and schizophrenic spectrum, were found to be more vulnerable to the effects of COVID-19. In them, the occurrence of APS was a risk factor for the development of dementia, while in primary diseased, and patients with affective and neurotic disorders, CI was reversible or had the character of a mild cognitive disorder.Disclosure of InterestNone Declared

Clinical features of coronavirus infection with impaired sense of smell

Previously, olfactory disturbances were not considered as a possible single symptom of an acute period of coronavirus infection.
 Aim: to identify the clinical features of low-symptomatic forms of COVID-19 coronavirus infection occurring with olfactory dysfunction.
 Materials and methods: the study was conducted on the basis of the Federal State Budgetary Institution of the Central Research Institute of Epidemiology of Rospotrebnadzor by questioning people who have suffered a coronavirus infection. A total of 39,676 people were interviewed, of whom 24,086 (60.70%) had suffered some form of new coronavirus infection COVID-19. Methods of descriptive statistics were used for statistical analysis of the research results.
 Results: olfactory dysfunction may be the only symptom of the acute period of COVID-19 coronavirus infection in 4%. The occurrence of this symptom depends on the dominant circulating genovariant (maximum at Alpha is 7.8%), the basic reproductive number (inverse relationship, Pearson correlation coefficient -0.9) and the age of the patient (more often in persons under 44 years of age). The occurrence of the symptom does not depend on the patient's gender. Patients with olfactory dysfunction with COVID-19 coronavirus infection are significantly less likely (4.2% vs. 12.6%, P = 0.04) to require hospitalization and oxygen therapy (2.5% vs. 32.2%, P 0.001).
 Conclusion: olfactory dysfunction may be the only symptom of the acute period of COVID-19 coronavirus infection, which allows us to suggest its isolation into a separate form. The occurrence of this form depends on the dominant circulating genovariant, the basic reproductive number of the virus and the age of the patient. Patients with this form of coronavirus infection are less likely to require hospitalization and oxygen therapy.

Severity of Postcovid Syndrome: A Systematic Review

Postcovid syndrome includes many conditions and symptoms, both those that arose directly during the acute period of infection and the appearance of new ones. The purpose of the systematic review is to determine the criteria for the severity of postcovid syndrome. Materials and methods. The following keywords were used to search for literary sources: “postcovid syndrome”, “severity of postcovid syndrome”, “severity of postcovid syndrome” and “symptoms of postcovid syndrome” in Russian and English. We used the search engines “eLibrary.RU — Scientific Electronic Library” and PubMed.gov. Articles were included that presented a study of patients with laboratory-confirmed coronavirus infection at least a month after recovery from COVID-19 with residual clinical signs and/or biochemical changes. The analysis included only publications from the last 3 years (2020– 2023). Results. A total of 2,913 publications were found by two search engines. After removing duplicates, literature reviews, clinical studies of medicines, studies conducted on animals, studies unsatisfactory for time after acute COVID-19, and studies performed on persons under the age of 18, 69 articles were selected for analysis that meet the criteria for inclusion in the analysis. Conclusion. An analysis of the literature of the last 3 years has allowed us to determine that the presence and severity of postcovid syndrome can probably be determined by the presence in a patient of at least one of the signs presented in the review that developed during or after a laboratory-verified COVID-19 infection and persisted for more than 4 weeks from the onset of the disease and that cannot be explained by other reasons.

Клиническое наблюдение обонятельной дисфункции у больных коронавирусной инфекцией

The olfactory dysfunction is one of the clinical manifestations of coronavirus infection. Unlike a decrease in the sense of smell, which can be observed with mucosal edema in influenza and other acute respiratory infections, with coronavirus infection, there is often a complete shutdown of the sense of smell – anosmia. This condition can be observed in patients not only in the acute period of infection, but also persist for a long time during the period of convalescence, which significantly reduces the quality of life of such patients. The presented clinical analysis shows, using examples from clinical practice, various variants of the influence of olfactory dysfunction disorders on the quality of life of patients and emphasizes the importance of the problem for the healthcare provider. Key words: coronavirus infection, anosmia, parosmia

Клинико-микробиологические признаки и метаболическая активность микроорганизмов фекальных масс при реабилитации детей с постковидным синдромом

The significant occurrence of a cohort of children who do not achieve complete recovery after the acute period of coronavirus infection has drawn the attention of researchers to elucidate the etiopathogenetic reasons for the lack of process termination. Objective. To study clinical-anamnestic and microbiologic parameters of fecal samples as possible predictors of the prolongation of the post-COVID state on the basis of laboratory tests performed at admission to the sanatorium at different time periods after COVID-19 infection. Patients and methods. In 61 children aged 4 to 17 years, a comprehensive clinical and laboratory investigation was performed in the rehabilitation of the post-COVID-19 condition. Results. The main complaints on admission: rapid fatigability, decreased appetite, decreased tolerance of habitual physical and mental exertion, tendency to constipation, increased frequency of episodes of acute respiratory diseases. In the microbiota of fecal excretions the reduced level of high-grade Escherichia coli, bifido- and lactobacilli was established. Inhibition of functional activity of microbiota was noted. Abnormal amount of fatty components was detected at scatoscopy. General health-improving measures promoted clinical and laboratory recovery processes. Conclusion. Commonly accepted recreational sanatorium activities contribute to the rehabilitation of children with post-COVID condition and can be recommended as a mandatory program. Key words: children, microbiota, post-COVID-19 syndrome, rehabilitation

Elevated Interleukin-6 (IL-6) Levels with Ig (G & M) Antibodies in the Recovery Phase of Patients with COVID-19: Indication of Cytokine Storm and Re-infection

The innate immune response to coronavirus disease (COVID-19) by inflammatory cytokines, such as interleukin 6 (IL-6), has been described as an early response, followed by an adaptive immune response with the production of antibodies. IL-6 is produced in response to viral infections and is crucial for the activation of T cells and the differentiation of B cells, which produce antibodies. Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies are produced during the initial acute period of infection and the recovery period from the period of onset of symptoms. There has been some relationship between the innate response of the cytokine and the adaptive response of the antibodies in patients with COVID-19 infection. There has been a positive correlation between IL-6 levels and the presence of COVID-19 antibodies, suggesting that higher IL-6 levels may be associated with a stronger immune response and studies have confirmed that patients with higher IL-6 levels have a higher antibody response. High IL-6 levels on admission observed within 2 weeks after onset of symptoms were positively correlated with high concentrations of IgG seen 5 weeks after onset of symptoms. We have previously described elevated IL-6 levels in the sera of 68% of COVID-19 convalescent patients (40–93 days) post-onset of symptoms (recovery phase). In this study we decided to investigate whether there was some relationship between the IL-6 levels in patients 40–93 days post-onset of symptom in the recovery phase and their antibody response using a wide range of antibody assays (iCHROMA IgG, GOLD IgG & IgM, Abbott SARS-CoV-2 IgG II Quant-test (Abbott S IgG), Diasorin Liaison SARS-CoV-2 S1/2 (Diasorin S1/2 IgG). The patients were divided into two groups, those with normal IL-6 levels (<7 pg/ml) and those with elevated IL-6 levels (>7 pg/ml). All patients (100%) had positive IgG antibodies, only 8 out the 28 patients (29%) were positive for IgM antibodies. The mean antibodies concentrations of the patients (n = 9) with normal IL-6 levels (<7 pg/ml) for iCHROMA IgG (20.0 Units), GOLD IgG (34.4 AU/mL), Abbott IgG (4175 AU/mL), Diasorin Liaison IgG (75.8 AU/mL) and GOLD IgM (4.7 AU/mL), respectively. The mean antibodies concentrations of the patients (n = 19) with elevated IL-6 levels (>7 pg/ml) for iCHROMA IgG (20.9 Units), GOLD IgG, (34.9 AU/mL), Abbott IgG (2287 AU/mL), Diasorin Liaison IgG (121.7 AU/mL) and GOLD IgM (11.2 AU/mL), respectively. The antibodies of the patients with the elevated IL-6 levels were significantly higher for Diasorin Liaison IgG (p = 0.02) and GOLD IgM (p = 0.003) but lower for Abbott IgG (p = 0.02). In conclusion, this study using a panel of antibody assays highlights that increased levels of IL-6 in the convalescent phase (recovery phase) indicate an active immune response leading to higher concentrations of antibodies especially IgM, suggesting that cytokine storms and re-infection occur in the recovery phase.

Duration of systemic alteration in vasomotor function of microvascular endothelium caused by the influenza A(H1N1)pdm09 virus

Introduction. The influenza A virus (IAV) can infect vascular endothelial cells and cause activation and/or dysfunction of the endothelium. Previously, we have shown that the influenza A(H1N1)pdm09 virus leads to alteration in functional activity of blood vessels in different vascular beds, and also causes various histopathological changes in pulmonary blood vessels of Wistar rats in the acute period of infection. Aim – to study the duration of systemic alteration in vasomotor function of microvascular endothelium caused by the influenza A(H1N1)pdm09 virus. Materials and methods. The Wistar rats were intranasally infected with the influenza A/St. Petersburg/48/16 (H1N1)pdm09 virus and at 1, 4, 7, 14, 21, 30, 60 and 90 days post infection (dpi) they were anesthetized and necropsied. The expression level of endothelial nitric oxide synthase (eNOS) was determined in mesenteric vascular endothelium by immunohistochemistry. The vasomotor activity of the mesenteric arteries was studied using wire myography. Results. The influenza A(H1N1)pdm09 virus causes a decrease in eNOS expression by 13–39 % within 60 dpi (p<0.05). In addition, the influenza virus also reduces the maximal response of mesenteric arteries to the vasodilator by 74–108 % within 21 days (p<0.0001) and reduces the response by 16–26 % within 30 and 60 dpi (p<0.0001), respectively, and also increases the maximum response of the arteries to the vasoconstrictor by 26–57 % within 30 dpi (p<0.05). It should be noted that such long-term changes are observed while virus is eliminated by the 7th dpi. Conclusion. The influenza A(H1N1) pdm09 virus causes long-term endothelial dysfunction in the Wistar rats which is characterized by the reduced expression of eNOS in mesenteric microvascular endothelium within 60 dpi, decrease of the maximal response of mesenteric microvessels to vasodilator within 60 dpi and increase of the maximal response to vasoconstrictor within 30 dpi. Alterations of systemic functional activity of mesenteric microvessels in rats infected with influenza A(H1N1)pdm09 virus are registered in absence of the reproduction of virus in mesenteric blood vessels while virus is eliminated from pulmonary tissues by the 7th dpi.

The occurrence of age-related macular degeneration in the presence of a transferred, confirmed COVID-19

BACKGROUND: COVID-19 can affect the eyes and both the anterior and posterior segments of the eye. Retinal complications associated with COVID-19 have been reported.
 CLINICAL CASE DESCRIPTION: We present a clinical case of age-related macular degeneration that developed during the acute period of coronavirus infection. A patient with COVID-19 and pneumonia (CT-1) experienced sudden decrease in visual acuity within 1 month. A dark spot appeared in front of the left eye, which did not disappear despite eye movements, and distortion of objects was observed. The disease was manifested acutely. A complete ophthalmological examination revealed a sharp decrease in visual acuity and a positive Amsler test (distortion of lines at a distance of 30 cm). In the field of view, scotomas were noted in the center. Ophthalmoscopy revealed light and dark foci in the central macular zone of the retina. Cptical coherence tomography with an angiographic mode detected severe changes at the level of the neuroepithelium and retinal pigment epithelium with the formation of gray tissue. Aflibercept (approved for use in the Russian Federation, No. LP-003544) was intravitreally prescribed according to the clinical guidelines for treating age-related macular degeneration. After treatment with positive dynamics, visual acuity increased to 1.0, and the thickness of the retina decreased by 102 microns.
 CONCLUSION: The key objective in making a correct diagnosis was the use of optical coherence tomography with an angiographic mode. This method allows the visualization of the retinal layers without invasion The angiography mode allows the assessment of the state of the foveolar avascular zone and the density and perfusion of blood vessels, which enable the diagnosis of age-related macular degeneration and choroidal neovascularization. Timely antiangiogenic treatment, that is, a single intraocular injection, completely restored the visual acuity and visual field and normalized the state of the retina according to objective data of optical coherence tomography with angiography mode.

Cerebral Blood Flow and Arterial Transit Time Variations in Elders with Long COVID

AbstractBackgroundMany COVID‐19 patients experience persistant neurological symptoms that often extend beyond the period of acute infection, referred to as “Long COVID”, where most patients reported brain fog and cognitive dysfunction. While elderly individuals are more vulnerable to possible enduring cognitive impairments after acute COVID‐19 requiring hospitalization, there is increasing concern that older patients with Long COVID will be at high risk for developing Alzheimer’s disease (AD) and dementia. Although there is emerging recognition of Long COVID, its underlying neuropathology remains unknown. This study aimed to investigate neurovascular function using advanced MRI perfusion in elder patients with Long COVID.MethodWell‐matched elderly Long COVID patients (n = 14, mean age = 60.1±4.3 years, 12F, 2M) and control subjects (n = 25, mean age = 60.4±7.2 years, 19F, 6M) underwent neurocognitive testing as well as neuroimaging. Patients were seen 711.57 ± 165.02 days after the initial mild non‐hospitalized COVID‐19 infection. Clinical cognitive complaints of Long COVID patients included memory changes (n = 12, 85.7%), attention (n = 12, 85.7%), speech/writing (n = 9, 64.3%), and multitasking (n = 9, 64.3%). Brain perfusion was evaluated using an advanced 3D pseudo‐continuous arterial spin labeling (pCASL) sequence with Hadamard encoded multiple post‐labeling delays (PLDs), enabling estimation of Cerebral Blood Flow (CBF) and Arterial Transit Time (ATT) ATT and ATT corrected CBF.ResultConventional MRI scans (T1, T2, and FlAIR) appear normal in all subjects. Voxelwise comparisons between Long‐COVID and control subjects showed a significant global decrease in the ATT (p < 0.05, cluster corrected at a < 0.05), along default mode and other key networks, where there is a trend of decreased CBF (p<0.05, uncorrected) specifically in the frontal lobe in those with Long COVID.ConclusionThese preliminary results in an aging group indicate that neurocognitive effects of Long COVID could be attributed to neurovascular dysfunction, even in those cases with initial non‐hospitalized mild COVID‐19 of more than 500 days. The novel finding of diffusely decreased ATT could be something attributable to the unique neurovascular mechanism of Long COVID. Future longitudinal research following the progression of those elderly Long COVID patients with known abnormal neurovascular function to fully evaluate their risk for developing AD and dementia.

Cerebral Blood Flow and Arterial Transit Time Variations in Elders with Long COVID

AbstractBackgroundMany COVID‐19 patients experience persistant neurological symptoms that often extend beyond the period of acute infection, referred to as “Long COVID”, where most patients reported brain fog and cognitive dysfunction. While elderly individuals are more vulnerable to possible enduring cognitive impairments after acute COVID‐19 requiring hospitalization, there is increasing concern that older patients with Long COVID will be at high risk for developing Alzheimer’s disease (AD) and dementia. Although there is emerging recognition of Long COVID, its underlying neuropathology remains unknown. This study aimed to investigate neurovascular function using advanced MRI perfusion in elder patients with Long COVID.MethodWell‐matched elderly Long COVID patients (n = 14, mean age = 60.1±4.3 years, 12F, 2M) and control subjects (n = 25, mean age = 60.4±7.2 years, 19F, 6M) underwent neurocognitive testing as well as neuroimaging. Patients were seen 711.57 ± 165.02 days after the initial mild non‐hospitalized COVID‐19 infection. Clinical cognitive complaints of Long COVID patients included memory changes (n = 12, 85.7%), attention (n = 12, 85.7%), speech/writing (n = 9, 64.3%), and multitasking (n = 9, 64.3%). Brain perfusion was evaluated using an advanced 3D pseudo‐continuous arterial spin labeling (pCASL) sequence with Hadamard encoded multiple post‐labeling delays (PLDs), enabling estimation of Cerebral Blood Flow (CBF) and Arterial Transit Time (ATT) ATT and ATT corrected CBF.ResultConventional MRI scans (T1, T2, and FlAIR) appear normal in all subjects. Voxelwise comparisons between Long‐COVID and control subjects showed a significant global decrease in the ATT (p < 0.05, cluster corrected at α < 0.05), along default mode and other key networks, where there is a trend of decreased CBF (p<0.05, uncorrected) specifically in the frontal lobe in those with Long COVID.ConclusionThese preliminary results in an aging group indicate that neurocognitive effects of Long COVID could be attributed to neurovascular dysfunction, even in those cases with initial non‐hospitalized mild COVID‐19 of more than 500 days. The novel finding of diffusely decreased ATT could be something attributable to the unique neurovascular mechanism of Long COVID. Future longitudinal research following the progression of those elderly Long COVID patients with known abnormal neurovascular function to fully evaluate their risk for developing AD and dementia.

Features of the course of bronchial asthma in patients who have suffered a new coronavirus infection

Objective: to evaluate the clinical status of patients with bronchial asthma in the post-Covid period depending on the severity of the acute period of COVID-19. Materials and methods: a case-control study was conducted of patients diagnosed with asthma who had suffered a coronavirus infection, who turned to the Nizhny Novgorod Regional Pulmonology Center for consultation about asthma. The analysis included 56 patients. The survey methods included two stages: retrospective and prospective. The following scales were assessed: the severity of asthma, the level of asthma therapy, asthma control according to the Global Initiative for Asthma (GINA), and the severity of shortness of breath (mMRC test). Results: the analysis revealed statistically significant differences on all scales, regardless of the severity of the acute course of COVID-19, p <0.005. In the process of data analysis, depending on the severity of the acute period of infection, statistically significant differences in the clinical status before and after COVID-19 were found in patients with mild and moderate coronavirus infection. In patients who had mild COVID-19, clinical status indicators worsened on all scales: asthma severity before COVID-19 ─ 2.00 [2.00–2.00], after COVID-19 ─ 2.00 [2.00–3.00], р<0.005; control according to GINA before COVID-19 ─ 2.00 [2.00–2.00] after COVID-19 ─ 3.00 [2.00–3.00]; step therapy before COVID-19 ─ 3.00 [2.25–3.00], after ─ 4.00 [4.00–5.00], р<0.005; severity of shortness of breath before COVID-19 ─ 1.00 [0.25–1.00], after COVID-19 ─ 2.00 [1.00–2.00], р<0.005. Patients who had moderate COVID-19 also worsened all indicators of clinical status on all scales: severity of asthma before COVID-19 ─ 2.00 [2.00–2.00], after COVID-19 ─ 2.00 [2,00–3.00], p<0.005; control according to GINA before COVID-19 ─ 2.00 [2.00–2.00], after COVID-19 ─ 3.00 [2.00–3.00]; level of therapy before COVID-19 ─ 3.00 [3.00–3.00], after COVID-19 ─ 4.00 [4.00–5.00], p<0.005; severity of shortness of breath before COVID-19 ─ 1,00 [1.00–1.00], after COVID-19 ─ 2.00 [1.00–2.00], p<0.005. Conclusion. еhe results of our study demonstrate the negative impact of SARS-CoV-2 on the clinical status of patients with asthma who have suffered a new coronavirus infection.

Peculiarities of clinical signs, course and treatment of musculoskeletal system lesions in post-COVID syndrome.

Post-COVID syndrome (PCS) is a frequent phenomenon of patients who have suffered from an acute attack of COVID-19 infection, and it is characterized by a wide range of symptoms from different organs and systems including the musculoskeletal system (MSS). However, peculiarities of MSS lesions have not been sufficiently studied to date, in particular, in the aspect of the therapeutic process. We aimed to investigate peculiarities of MSS lesions in patients with PCS. Observations were carried out in 142 patients with PCS and MSS lesions. The age of patients was 36-67 years. Up-to-date methods of disease verification were used. An acute period of COVID-19 in all the patients was of moderate severity without oxygen support. Musculoskeletal system lesions in patients with PCS were found to appear 1-4 weeks after the experienced acute period of COVID-19 infection. Against the background of significant arthralgia (100%) in 93 (65.5%) patients manifestations of acute arthritis were detected, the frequency of which increased with age. Musculoskeletal system lesions were found against the background of dominating PCS manifestations from the cardiovascular and digestive systems. Deterioration of the course and results of treatment of diseases caused by an age-related polymorbid background was determined. Certain difficulties in the treatment of MSS lesions by means of non-steroidal anti-inflammatory drugs and limitation in the use of glucocorticosteroids are caused by severe gastroduodenopathy and arterial hypertension. Long-term, up to 6 months, administration of L-arginine, L-carnitine and quercetin in the rehabilitation complex improved the overall results of treatment of PCS manifestations including arthropathy. Musculoskeletal system lesions in patients with PCS are not the main constituent of this syndrome. Difficulties in the treatment of arthropathy are due to the signs of gastroduodenopathy and arterial hypertension. Additional administration of L-arginine, L-carnitine and quercetin is reasonable.

The impact of overall obesity on serotonin level in the acute phase of coronavirus infection and post-coronavirus sequelae: aspects of neuropsychological and cognitive impairments

Aim: to study the relationship between neurotransmitter support and the degree of cognitive and psycho-emotional impairments in patients in the post-coronavirus period depending on the presence of overall obesity. Materials and methods. 44 patients aged 19 to 76 years (17 women and 27 men) with a history of moderate-to-severe COVID-19 were examined. 2 groups were allocated depending on body mass index (BMI): Group 1 – 20 non-obese patients (BMI <30 kg/m2; male / female 10/10); Group 2 – 24 obese people (BMI ≥30 kg/m2; male / female 17/7). The groups of subjects were comparable in age, length of hospital stay, severity of COVID-19, hematological and biochemical parameters, C-reactive protein, D-dimer. Parameters of quality of life (QL), psycho-emotional state, and cognitive function were studied by a questionnaire method 6 months after recovery. Results. It has been found that the serotonin level was significantly lower in the acute period of infection in the group of obese patients compared to that in the non-obese group. However, after treatment, serum serotonin returned to reference values. No significant differences were detected between the two groups of patients regarding the values of neurocognitive and social parameters in the post-COVID period. Correlation analysis has shown that QL scores in Group 1 were positively correlated with cognitive function (r from 0.54 to 0.73) and negatively – with anxiety and depression (r from -0.60 to -0.80). In Group 2, the serotonin level was positively correlated with self-assessments of the QL (r from 0.42 to 0.53) and negatively – with cognitive abilities and anxiety (r from -0.51 to -0.60). Conclusions. The presence of obesity (BMI ≥30 kg/m2) in patients with COVID-19 was accompanied by reduced serum serotonin levels during the acute phase of COVID-19. In the post-COVID period, the initial level of serotonin in obese patients was correlated with the deterioration of quality of life and worsening cognitive function assessments.

Predictive models of long COVID

The cause and symptoms of long COVID are poorly understood. It is challenging to predict whether a given COVID-19 patient will develop long COVID in the future. We used electronic health record (EHR) data from the National COVID Cohort Collaborative to predict the incidence of long COVID. We trained two machine learning (ML) models - logistic regression (LR) and random forest (RF). Features used to train predictors included symptoms and drugs ordered during acute infection, measures of COVID-19 treatment, pre-COVID comorbidities, and demographic information. We assigned the 'long COVID' label to patients diagnosed with the U09.9 ICD10-CM code. The cohorts included patients with (a) EHRs reported from data partners using U09.9 ICD10-CM code and (b) at least one EHR in each feature category. We analysed three cohorts: all patients (n=2,190,579; diagnosed with long COVID=17,036), inpatients (149,319; 3,295), and outpatients (2,041,260; 13,741). LR and RF models yielded median AUROC of 0.76 and 0.75, respectively. Ablation study revealed that drugs had the highest influence on the prediction task. The SHAP method identified age, gender, cough, fatigue, albuterol, obesity, diabetes, and chronic lung disease as explanatory features. Models trained on data from one N3C partner and tested on data from the other partners had average AUROC of 0.75. ML-based classification using EHR information from the acute infection period is effective in predicting long COVID. SHAP methods identified important features for prediction. Cross-site analysis demonstrated the generalizability of the proposed methodology. NCATS U24 TR002306, NCATS UL1 TR003015, Axle Informatics Subcontract: NCATS-P00438-B, NIH/NIDDK/OD, PSR2015-1720GVALE_01, G43C22001320007, and Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy Contract No. DE-AC02-05CH11231.