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1.
Viruses ; 15(5)2023 05 19.
Article in English | MEDLINE | ID: covidwho-20233031

ABSTRACT

INTRODUCTION: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. METHODS: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate-multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed. RESULTS: Overall, 331 subjects were included; their median (q1-q3) age was 71 (51-80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3-11%) and 14% (95%CI = 3-25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02-0.77) when compared with monotherapy. CONCLUSIONS: REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial.


Subject(s)
COVID-19 , Aged , Male , Humans , Aged, 80 and over , Female , Retrospective Studies , COVID-19 Drug Treatment , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing , Immunocompromised Host , Disease Progression
2.
Viruses ; 15(5)2023 05 15.
Article in English | MEDLINE | ID: covidwho-20232948

ABSTRACT

CONTEXT: We reviewed what has been studied and published during the last 3 years about the consequences, mainly respiratory, cardiac, digestive, and neurological/psychiatric (organic and functional), in patients with COVID-19 of prolonged course. OBJECTIVE: To conduct a narrative review synthesizing current clinical evidence of abnormalities of signs, symptoms, and complementary studies in COVID-19 patients who presented a prolonged and complicated course. METHODS: A review of the literature focused on the involvement of the main organic functions mentioned, based almost exclusively on the systematic search of publications written in English available on PubMed/MEDLINE. RESULTS: Long-term respiratory, cardiac, digestive, and neurological/psychiatric dysfunction are present in a significant number of patients. Lung involvement is the most common; cardiovascular involvement may happen with or without symptoms or clinical abnormalities; gastrointestinal compromise includes the loss of appetite, nausea, gastroesophageal reflux, diarrhea, etc.; and neurological/psychiatric compromise can produce a wide variety of signs and symptoms, either organic or functional. Vaccination is not associated with the emergence of long-COVID, but it may happen in vaccinated people. CONCLUSIONS: The severity of illness increases the risk of long-COVID. Pulmonary sequelae, cardiomyopathy, the detection of ribonucleic acid in the gastrointestinal tract, and headaches and cognitive impairment may become refractory in severely ill COVID-19 patients.


Subject(s)
COVID-19 , Humans , COVID-19/complications , Diarrhea , Disease Progression , Post-Acute COVID-19 Syndrome , Prognosis , SARS-CoV-2
3.
J Coll Physicians Surg Pak ; 33(6): 647-652, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-20232642

ABSTRACT

OBJECTIVE:  To evaluate the association between chronic liver disease (CLD) caused by viral hepatitis and COVID-19 hospitalisation, as well as the risk of disease progression and mortality among COVID-19 hospitalised patients in relation to their prior CLD status. STUDY DESIGN: A cohort study. Place and Duration of the study: Bahawal Victoria Hospital and Sir Sadiq Abbasi hospital, affiliated with Qauid-e-Azam Medical College, Bahawalpur, Pakistan, from July to December 2021. METHODOLOGY: In the main group analysis, the risk of hospitalisation for COVID-19 among CLD patients was determined, with the presence of CLD due to chronic viral hepatitis B and C as the exposure variable and hospitalisation for COVID-19 as the outcome measure. Patients hospitalised for a medical condition other than COVID-19 (non-COVID medical admissions) served as an external control group. In the sub-group analysis, the risk of disease severity and mortality were determined among COVID-19 admitted patients having a prior status of CLD, with disease progression to death serving as the primary outcome measure while the exposure variable remained the same as in the main analysis. RESULTS: A total of 3,976 participants [mean age 51 ±14.8 years; 54.1% men; 1616 hospitalised with COVID-19, including 27 (1.7%) exposed to CLD; and 2,360 non-COVID medical admissions, including 208 (8.8%) exposed to CLD] were evaluated. There was less likelihood of hospitalisation for COVID-19 among patients with CLD (1.7% vs. 8.8%; RR=0.270; 95% CI=0.189, 0.386; p<0.001). There was less risk of death among CLD patients admitted for COVID-19 when compared with those admitted for non-COVID CLD-related complications (14.8% vs. 35.1%; RR= 0.422; 95% CI=0.168-1.06; p=0.035). Among COVID-19 admissions, CLD was associated with a decreased risk of death compared with other comorbid conditions (14.8% vs. 36.9%; RR=0.401; 95% CI=0.162-0.994; p=0.04). CONCLUSION: CLD caused by viral hepatitis was significantly less likely to be present among COVID-19 hospitalised patients. There was a lower risk of severe COVID-19 and mortality owing to it among CLD patients compared to those with other comorbid conditions. KEY WORDS: COVID-19, Hospitalisations, Chronic liver disease, Viral hepatitis, COVID-19 severity, Death outcome.


Subject(s)
COVID-19 , Hepatitis B, Chronic , Male , Humans , Adult , Middle Aged , Aged , Female , COVID-19/epidemiology , COVID-19/therapy , COVID-19/complications , Cohort Studies , Hospitalization , Disease Progression , Chronic Disease
4.
BMJ Open ; 13(6): e073300, 2023 06 01.
Article in English | MEDLINE | ID: covidwho-20240200

ABSTRACT

INTRODUCTION: Rheumatic heart disease (RHD) is responsible for a significant burden of cardiovascular morbidity and mortality, and remains the most common cause of acquired heart disease among children and young adults in low-income and middle-income countries. Additionally, the global COVID-19 pandemic has forced the emergency restructuring of many health systems, which has had a broad impact on health in general, including cardiovascular disease. Despite significant cost to the health system and estimates from 2015 indicating both high incidence and prevalence of RHD in South Africa, no cohesive national strategy exists. An updated review of national burden of disease estimates, as well as literature on barriers to care for patients with RHD, will provide crucial information to assist in the development of a national RHD programme. METHODS AND ANALYSIS: Using predefined search terms that capture relevant disease processes from Group A Streptococcal (GAS) infection through to the sequelae of RHD, a search of PubMed, Scopus, ISI Web of Science, Sabinet African Journals, SA Heart and Current and Completed Research databases will be performed. All eligible studies on RHD, acute rheumatic fever and GAS infection published from April 2014 to December 2022 will be included. Vital registration data for the same period from Statistics South Africa will also be collected. A standardised data extraction form will be used to capture results for both quantitative and qualitative analyses. All studies included in burden of disease estimates will undergo quality assessment using standardised tools. Updated estimates on mortality and morbidity as well as a synthesis of work on primary, secondary and tertiary prevention of RHD will be reported. ETHICS AND DISSEMINATION: No ethics clearance is required for this study. Findings will be disseminated in a peer-reviewed journal and submitted to national stakeholders in RHD. PROSPERO REGISTRATION NUMBER: CRD42023392782.


Subject(s)
COVID-19 , Rheumatic Heart Disease , Streptococcal Infections , Child , Young Adult , Humans , Rheumatic Heart Disease/therapy , Rheumatic Heart Disease/prevention & control , South Africa/epidemiology , Pandemics , COVID-19/epidemiology , Streptococcal Infections/epidemiology , Disease Progression , Cost of Illness , Review Literature as Topic
5.
J Med Virol ; 95(6): e28831, 2023 06.
Article in English | MEDLINE | ID: covidwho-20239959

ABSTRACT

Despite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS-CoV-2. This study, enrolling all COVID-19 adults admitted to a reference hospital who underwent both the S-gene-target-failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in-hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid-February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid-March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10-day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28-day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID-19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , Hospitals , Disease Progression
6.
Viruses ; 15(5)2023 05 17.
Article in English | MEDLINE | ID: covidwho-20237711

ABSTRACT

OBJECTIVE: The main goal of this study was to assess the potential clinical impact of an outpatient administration of available antivirals including SOT, N/R, and MOL to COVID-19 patients at high risk for disease progression. METHODS: We conducted a retrospective analysis on 2606 outpatient individuals with mild to moderate COVID-19 at risk for disease progression, hospitalization, or death. After receiving either SOT (420/2606), MOL (1788/2606), or N/R (398/2606), patients were followed-up with regarding primary (hospitalization rate) and secondary (treatment and side effects) outcomes by phone. RESULT: A total of 2606 patients were treated at the outpatient clinic (SOT: 420; N/R: 398; MOL: 1788). 3.2% of the SOT patients (1 ICU admission), 0.8% of the MOL patients (2 ICU admissions), and none of the N/R patients were hospitalized. 14.3% of the N/R patients reported strong to severe side effects, exceeding SOT (2.6%) and MOL (5%) patients. A reduction in COVID symptoms after the treatment was experienced by 43% of patients in both the SOT and MOL groups and by 67% of patients in the N/R group, respectively. Women had a higher chance of symptom improvement with MOL (OR 1.2, 95%CI 1.0-1.5). CONCLUSION: All antiviral treatment options effectively prevented hospitalization in high-risk COVID-19 patients and were well tolerated. Side effects were pronounced in patients with N/R.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Humans , Female , Outpatients , Retrospective Studies , Antiviral Agents/adverse effects , Disease Progression , Lactams , Leucine
7.
Nat Commun ; 14(1): 3267, 2023 06 05.
Article in English | MEDLINE | ID: covidwho-20236776

ABSTRACT

COVID-19 survivors often suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Current evidence suggests dysregulated alveolar regeneration as a possible explanation for respiratory PASC, which deserves further investigation in a suitable animal model. This study investigates morphological, phenotypical and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+ alveolar differentiation intermediate (ADI) cells occur following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of TP53 at 6- and 14-days post infection (dpi), indicating a prolonged arrest in the ADI state. Transcriptome data show high module scores for pathways involved in cell senescence, epithelial-mesenchymal transition, and angiogenesis in cell clusters with high ADI gene expression. Moreover, we show that multipotent CK14+ airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, ADI cells, peribronchiolar proliferates, M2-macrophages, and sub-pleural fibrosis are observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The results provide important information on a translational COVID-19 model, which is crucial for its application in future research addressing pathomechanisms of PASC and in testing of prophylactic and therapeutic approaches for this syndrome.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cricetinae , Humans , Post-Acute COVID-19 Syndrome , Cell Differentiation , Alveolar Epithelial Cells , Disease Progression , Mesocricetus
8.
J Med Virol ; 95(6): e28819, 2023 06.
Article in English | MEDLINE | ID: covidwho-20235863

ABSTRACT

An understanding of the midterm sequelae in COVID-19 and their association with corticosteroids use are needed. Between March and July 2020, we evaluated 1227 survivors of COVID-19, 3 months posthospitalization, of whom 213 had received corticosteroids within 7 days of admission. Main outcome was any midterm sequelae (oxygen therapy, shortness of breath, one major clinical sign, two minor clinical signs or three minor symptoms). Association between corticosteroids use and midterm sequelae was assessed using inverse propensity-score weighting models. Our sample included 753 (61%) male patients, and 512 (42%) were older than 65 years. We found a higher rate of sequelae among users than nonusers of corticosteroids (42% vs. 35%, odds ratio [OR] 1.40 [1.16-1.69]). Midterm sequelae were more frequent in users of low-dose corticosteroids than nonusers (64% vs. 51%, OR 1.60 [1.10-2.32]), whereas no association between higher doses (≥20 mg/day equivalent of dexamethasone) and sequelae was evidenced (OR 0.95 [0.56-1.61]). Higher risk of sequelae with corticosteroids use was observed among subjects with propensity score below the 90th percentile. Our study suggest that corticosteroids use during hospitalization for COVID-19 is associated with higher risk of midterm sequelae.


Subject(s)
COVID-19 , Humans , Male , Female , SARS-CoV-2 , Prospective Studies , Adrenal Cortex Hormones/adverse effects , Hospitalization , Hospitals , Disease Progression , Survivors
9.
J Int Med Res ; 51(5): 3000605231174303, 2023 May.
Article in English | MEDLINE | ID: covidwho-20245366

ABSTRACT

OBJECTIVE: To explore the transmission patterns and clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in Wuhan, China in December 2019 as clustered and non-clustered cases of coronavirus disease (COVID-19) emerged in Shenzhen, China. METHODS: This retrospective study included the patients that were confirmed by laboratory detection of SARS-CoV-2 in Shenzen between 19 January 2020 and 21 February 2020. Data on the epidemiological and clinical characteristics were analysed. The patients were divided into non-clustered and clustered groups. The time course, intervals between first and second COVID-19 cases and other transmission patterns were compared between the groups. RESULTS: The 417 patients were divided into clustered (n = 235) and non-clustered groups (n = 182). Compared with the non-clustered group, the clustered group had significantly more young (≤20 years) and old (>60 years) patients. The clustered group had significantly more severe cases (nine of 235; 3.83%) compared with the non-clustered group (three of 182; 1.65%). Patients with severe disease spent 4-5 more days of hospitalization than patients with moderate and mild disease. CONCLUSION: This retrospective study analysed the transmission patterns and clinical course of the first wave of COVID-19 infection in Shenzhen, China.


Subject(s)
COVID-19 , Humans , Retrospective Studies , COVID-19/epidemiology , SARS-CoV-2 , China/epidemiology , Disease Progression
10.
JAAPA ; 36(7): 11-15, 2023 Jul 01.
Article in English | MEDLINE | ID: covidwho-20244696

ABSTRACT

ABSTRACT: An estimated 21.5% of patients in the United States who have had COVID-19 report development of a prolonged postviral syndrome that has been called postacute sequelae of COVID-19 (PASC). Symptoms can range from very mild to debilitating damage to organ systems caused directly by the virus and indirectly by the body's inflammatory response. Research into defining PASC and discovering effective treatments is ongoing. This article discusses the common presentations of PASC in patients who have had COVID-19; describes specific effects on the pulmonary, cardiovascular, and central nervous systems; and identifies potential treatments based on current literature.


Subject(s)
COVID-19 , Humans , COVID-19/complications , Central Nervous System , Disease Progression , Post-Acute COVID-19 Syndrome
11.
Sci Rep ; 13(1): 9035, 2023 06 03.
Article in English | MEDLINE | ID: covidwho-20244246

ABSTRACT

In respiratory infections, anemia is both a consequence of acute inflammation and a predictor of poor clinical outcomes. There are few studies investigating the role of anemia in COVID-19, suggesting a potential role in predicting disease severity. In this study, we aimed to assess the association between the presence of anemia at admission and incidence of severe disease and death in patients hospitalized for COVID-19. Data from all adult patients admitted for COVID-19 in University Hospital "P. Giaccone" Palermo, and University Hospital of Bari, Italy, were retrospectively collected from 1st of September 2020 to 31 August 2022. The association between anemia (defined as Hb < 13 g/dl and < 12 g/dl in males and females, respectively), in-hospital mortality and severe COVID-19 was tested using a Cox's regression analysis. Severe COVID-19 forms were defined as admission to intensive or sub-intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. p values were calculated using the Student's t test for continuous variables and the Mantel-Haenszel Chi-square test for categorical ones. The association between anemia and the mortality was made using a Cox's regression analysis, adjusted, in two models, for the potential confounders and using a propensity score. Among the 1562 patients included in the analysis, prevalence of anemia was 45.1% (95% CI 43-48%). Patients with anemia were significantly older (p < 0.0001), reported more co-morbidities, and presented higher baseline levels of procalcitonin, CRP, ferritin and IL-6. Overall, the crude incidence of mortality was about four times higher in patients with anemia compared to those without. After adjusting for 17 potential confounders, the presence of anemia significantly increased the risk of death (HR = 2.68; 95% CI: 1.59-4.52) and of risk of severe COVID-19 (OR = 2.31; 95% CI: 1.65-3.24). The propensity score analysis substantially confirmed these analyses. Our study provides evidence that, in patients hospitalized for COVID-19, anemia is both associated with a more pronounced baseline pro-inflammatory profile and higher incidence of in-hospital mortality and severe disease.


Subject(s)
Anemia , COVID-19 , Male , Adult , Female , Humans , COVID-19/complications , Retrospective Studies , Anemia/epidemiology , Risk Factors , Disease Progression
12.
Arch Virol ; 168(7): 178, 2023 Jun 13.
Article in English | MEDLINE | ID: covidwho-20244122

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a high mortality rate. The clinical course is attributed to the severity of pneumonia and systemic complications. In COVID-19 patients and murine models of SARS-CoV-2 infection, the disease may be accompanied by excessive production of cytokines, leading to an accumulation of immune cells in affected organs such as lungs. Previous reports have shown that SARS-CoV-2 infection antagonizes interferon (IFN)-dependent antiviral response, thereby preventing the expression of IFN-stimulated genes (ISGs). Lower IFN levels have been linked to more-severe COVID-19. Interleukin 27 (IL27) is a heterodimeric cytokine composed of IL27p28 and EBI3 subunits, which induce both pro- and anti-inflammatory responses. Recently, we and others have reported that IL27 also induces a strong antiviral response in an IFN-independent manner. Here, we investigated transcription levels of both IL27 subunits in COVID-19 patients. The results show that SARS-CoV-2 infection modulates TLR1/2-MyD88 signaling in PBMCs and monocytes and induces NF-κB activation and expression of NF-κB-target genes that are dependent on a robust pro-inflammatory response, including EBI3; and activates IRF1 signaling which induces IL27p28 mRNA expression. The results suggest that IL27 induces a robust STAT1-dependent pro-inflammatory and antiviral response in an IFN-independent manner in COVID-derived PBMCs and monocytes as a function of a severe clinical course of COVID-19. Similar results were observed in macrophages stimulated with the SARS-CoV-2 spike protein. Thus, IL27 can trigger an antiviral response in the host, suggesting the possibility of novel therapeutics against SARS-CoV-2 infection in humans.


Subject(s)
COVID-19 , Interleukin-27 , Humans , Antiviral Agents/therapeutic use , COVID-19/immunology , Cytokines , Disease Progression , Interleukin-27/immunology , NF-kappa B , SARS-CoV-2
13.
JAMA ; 329(22): 1934-1946, 2023 06 13.
Article in English | MEDLINE | ID: covidwho-20243721

ABSTRACT

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.


Subject(s)
COVID-19 , SARS-CoV-2 , Female , Adult , Humans , Middle Aged , Male , COVID-19/complications , Prospective Studies , Post-Acute COVID-19 Syndrome , Cohort Studies , Disease Progression , Fatigue
14.
Nat Commun ; 14(1): 3417, 2023 Jun 09.
Article in English | MEDLINE | ID: covidwho-20243574

ABSTRACT

Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months following acute SARS-CoV-2 infection. The aetiologies may include persistent inflammation, unresolved tissue damage or delayed clearance of viral protein or RNA, but the biological differences they represent are not fully understood. Here we evaluate the serum proteome in samples, longitudinally collected from 55 PASC individuals with symptoms lasting ≥60 days after onset of acute infection, in comparison to samples from symptomatically recovered SARS-CoV-2 infected and uninfected individuals. Our analysis indicates heterogeneity in PASC and identified subsets with distinct signatures of persistent inflammation. Type II interferon signaling and canonical NF-κB signaling (particularly associated with TNF), appear to be the most differentially enriched signaling pathways, distinguishing a group of patients characterized also by a persistent neutrophil activation signature. These findings help to clarify biological diversity within PASC, identify participants with molecular evidence of persistent inflammation, and highlight dominant pathways that may have diagnostic or therapeutic relevance, including a protein panel that we propose as having diagnostic utility for differentiating inflammatory and non-inflammatory PASC.


Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Humans , SARS-CoV-2 , Blood Proteins , Disease Progression , Inflammation
15.
Ter Arkh ; 95(3): 217-222, 2023 Apr 26.
Article in Russian | MEDLINE | ID: covidwho-20242903

ABSTRACT

AIM: To establish symptoms, lung function and to evaluate subsequent exacerbations of chronic obstructive pulmonary disease (COPD) during a year after virus-induced COPD exacerbations. MATERIALS AND METHODS: Patients hospitalized with viral (n=60), bacterial (n=60) and viral-bacterial (n=60) COPD exacerbations were enrolled to single-center prospective observational study. COPD was diagnosed according spirography criteria. Viral infection was established in bronchoalveolar lavage fluid or sputum by real-time reverse transcription-polymerase chain reaction for RNA of influenza A and B virus, rhinovirus, respiratory syncytial virus and SARS-CoV-2. Symptoms, lung function, COPD exacerbations were assessed. Patients were investigated at the hospitalization onset and then 4 and 52 weeks following the discharge from the hospital. RESULTS: After 52 weeks in viral and viral-bacterial COPD exacerbations groups the rate of forced expiratory volume in one second (FEV1) decline were maximal - 71 (68; 73) ml/year and 69 (67; 72) ml/year versus 59 (55; 62) ml/year after bacterial exacerbations. Low levels of diffusion lung capacity for carbon monoxide (DLco/Va) - 52.5% (45.1%; 55.8%), 50.2% (44.9%; 56.0%) and 75.3% (72.2%; 80.1%) respectively, of 6-minute walk distance; p<0.001 in relation to bacterial exacerbations. In Cox proportional hazards regression analyses viral and viral-bacterial exacerbations were associated with increased risk of subsequent COPD exacerbations by 2.4 times independent of exacerbations rate before index event and FEV1. In linear regression models the relationships between airflow limitation and respiratory syncytial virus, rhinovirus and influenza virus infection, between low DLco/Va and rhinovirus, influenza virus and SARS-CoV-2 infection. CONCLUSION: COPD after virus-induced exacerbations were characterized by progression of airflow limitation, low DLco/Va, low 6-minute walking test distance, subsequent COPD exacerbations risk.


Subject(s)
COVID-19 , Influenza, Human , Pulmonary Disease, Chronic Obstructive , Humans , Influenza, Human/complications , Influenza, Human/diagnosis , COVID-19/complications , COVID-19/diagnosis , SARS-CoV-2 , Pulmonary Disease, Chronic Obstructive/complications , Lung , Disease Progression
16.
PLoS One ; 18(5): e0286014, 2023.
Article in English | MEDLINE | ID: covidwho-20242574

ABSTRACT

BACKGROUND/AIMS: The COVID-19 pandemic situation poses new challenges for research. Ethical issues might arise if especially vulnerable individuals for severe COVID-19 course expose themselves because of participation in studies to a higher risk of infection for study purposes. How is the feasibility and acceptance of self-organized blood sample collections to measure anti-SARS-CoV-2 Spike IgG antibodies in persons with a high risk for a severe COVID-19 disease progression? METHODS: Persons with a high risk for a severe COVID-19 disease progression (immunocompromised, oncology patients or over 80 years old) were recruited between January and September 2021 to send in blood samples (at least 500 µl) 1 month and 6 months after second COVID-19 vaccination. Participants were given the choice of drawing capillary or venous blood themselves or having blood drawn by health professionals belonging to either the study's own research team or the personnel found in local practices or clinics. Participants were surveyed via a telephone interview in December 2021 and January 2022 about their choice of blood sampling methods and influence of blood collection choice upon study participation. RESULTS: Data from 360 participants was collected via telephone follow-up. First blood samples were collected by the participants themselves (35.8%), local practices or clinics (31.9%) and the research team (22.5%). Second blood samples were mostly collected in local practices or clinics (35.6%) followed by participants themselves (25.9%) and the research team (11.5%). Blood samples were not collected in 2.5% and 19.1% of persons during first and second blood draw, respectively. Only 2% of blood samples did not reach the laboratory or were not analyzable. About one-fourth (26%) of participants stated that they would not have participated in the study if it would have been required to travel to the university hospital to give their blood sample. CONCLUSIONS: Participants were able to self-organize blood collection, making use of several different blood sample methods. Nearly all blood samples were analyzable when self-collected and sent in by post. One-fourth of the participants would not have participated in the study if required to give their blood sample in the study location. TRIAL REGISTRATION: German Clinical Trial Registry, DRKS00021152.


Subject(s)
COVID-19 , Humans , Adult , Aged, 80 and over , COVID-19/epidemiology , Pandemics , COVID-19 Vaccines , Feasibility Studies , Antibodies, Viral , Disease Progression , Primary Health Care
18.
J Med Virol ; 95(6): e28852, 2023 06.
Article in English | MEDLINE | ID: covidwho-20241688

ABSTRACT

Long-term sequelae conditions of COVID-19 at least 2-year following SARS-CoV-2 infection are unclear and little is known about their prevalence, longitudinal trajectory, and potential risk factors. Therefore, we conducted a comprehensive meta-analysis of survivors' health-related consequences and sequelae at 2-year following SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to February 10, 2023. A systematic review and meta-analysis were performed to calculate the pooled effect size, expressed as event rate (ER) with corresponding 95% confidence interval (CI) of each outcome. Twelve studies involving 1 289 044 participants from 11 countries were included. A total of 41.7% of COVID-19 survivors experienced at least one unresolved symptom and 14.1% were unable to return to work at 2-year after SARS-CoV-2 infection. The most frequent symptoms and investigated findings at 2-year after SARS-CoV-2 infection were fatigue (27.4%; 95% CI 17%-40.9%), sleep difficulties (25.1%; 95% CI 22.4%-27.9%), impaired diffusion capacity for carbon monoxide (24.6%; 95% CI 10.8%-46.9%), hair loss (10.2%; 95% CI 7.3%-14.2%), and dyspnea (10.1%; 95% CI 4.3%-21.9%). Individuals with severe infection suffered more from anxiety (OR = 1.69, 95% CI 1.17-2.44) and had more impairments in forced vital capacity (OR = 9.70, 95% CI 1.94-48.41), total lung capacity (OR = 3.51, 95% CI 1.77-6.99), and residual volume (OR = 3.35, 95% CI 1.85-6.07) after recovery. Existing evidence suggest that participants with a higher risk of long-term sequelae were older, mostly female, had pre-existing medical comorbidities, with more severe status, underwent corticosteroid therapy, and higher inflammation at acute infection. Our findings suggest that 2-year after recovery from SARS-CoV-2 infection, 41.7% of survivors still suffer from either neurological, physical, and psychological sequela. These findings indicate that there is an urgent need to preclude persistent or emerging long-term sequelae and provide intervention strategies to reduce the risk of long COVID.


Subject(s)
COVID-19 , Humans , Female , Male , COVID-19/complications , COVID-19/epidemiology , Post-Acute COVID-19 Syndrome , SARS-CoV-2 , Anxiety/epidemiology , Carbon Monoxide , Disease Progression
19.
Front Immunol ; 14: 1182544, 2023.
Article in English | MEDLINE | ID: covidwho-20231008

ABSTRACT

Background: Post-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis. Methods: A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL). Results: 415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p<.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p<.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p<.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)]. Conclusions: PASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/metabolism , Cross-Sectional Studies , Lipoproteins, LDL/metabolism , C-Reactive Protein/metabolism , Disease Progression
20.
Elife ; 122023 05 26.
Article in English | MEDLINE | ID: covidwho-20230960

ABSTRACT

With a global tally of more than 500 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses are key determinants of the severity and outcomes of the initial SARS-CoV-2 infection as well as subsequent PASC. The complexity of the innate and adaptive immune responses in the acute and post-acute period requires in-depth mechanistic analyses to identify specific molecular signals as well as specific immune cell populations which promote PASC pathogenesis. In this review, we examine the current literature on mechanisms of immune dysregulation in severe COVID-19 and the limited emerging data on the immunopathology of PASC. While the acute and post-acute phases may share some parallel mechanisms of immunopathology, it is likely that PASC immunopathology is quite distinct and heterogeneous, thus requiring large-scale longitudinal analyses in patients with and without PASC after an acute SARS-CoV-2 infection. By outlining the knowledge gaps in the immunopathology of PASC, we hope to provide avenues for novel research directions that will ultimately lead to precision therapies which restore healthy immune function in PASC patients.


Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Humans , COVID-19/complications , Disease Progression , SARS-CoV-2
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