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2.
Rev Alerg Mex ; 67(4): 350-369, 2020.
Article in Spanish | MEDLINE | ID: covidwho-2293343

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2 that has caused an unprecedented pandemic with a high rate of morbidity and mortality worldwide. Although most cases are mild, there are a considerable number of patients who develop pneumonia or even acute respiratory distress syndrome (ARDS). After having recovered from the initial disease, many patients continue with various symptoms (fatigue, dry cough, fever, dyspnea, anosmia, and chest pain, among others.), which has led to consider the possible existence of "post-COVID-19 syndrome". Although the definition and validity of this syndrome are not clear yet, several studies report that individuals who have recovered from COVID-19 may have persistent symptoms, radiological abnormalities, and compromised respiratory function. Current evidence suggests that there is a large number of pulmonary sequelae after COVID-19 pneumonia (interstitial thickening, ground glass opacities, crazy paving pattern, and bronchiectasis, among others.). Likewise, it seems that pulmonary function tests (spirometry, DLCO, 6MWT, and measurement of maximum respiratory pressures), in addition to high-resolution computed axial tomographies (CAT scan), are useful for the assessment of these post-COVID-19 pulmonary sequelae. This review aims to describe the possible pulmonary sequelae after COVID-19 pneumonia, as well as to suggest diagnostic procedures for their correct assessment and follow-up; thus, allowing proper management by a multidisciplinary medical team.


COVID-19 es la enfermedad causada por el virus SARS-CoV-2, la cual ha ocasionado una pandemia sin precedentes, con gran cantidad de infectados y muertos en el mundo. Aunque la mayoría de los casos son leves, existe una cantidad considerable de pacientes que desarrollan neumonía o, incluso, síndrome de distrés respiratorio agudo (SDRA). Luego de recuperarse del cuadro inicial, muchos pacientes continúan con diversos síntomas (fatiga, tos seca, fiebre, disnea, anosmia, dolor torácico, entre otras), lo que ha llevado a considerar la posible existencia del "síndrome pos-COVID-19". Aunque la definición y validez de este síndrome aún no son claras, varios estudios reportan que los individuos recuperados de la COVID-19 pueden tener persistencia de síntomas, anormalidades radiológicas y compromiso en la función respiratoria. La evidencia actual sugiere que existe gran cantidad de secuelas pulmonares despues de una neumonía por COVID-19 (engrosamiento intersticial, infiltrado en vidrio esmerilado, patrón en empedrado, bronquiectasias, entre otras.). De igual forma, parece ser que las pruebas de función pulmonar (espirometría, prueba de difusión pulmonar de monóxido de carbono, prueba de caminata de seis minutos y la medición de las presiones respiratorias máximas), además de la tomografía axial computarizada de alta resolución, son útiles para evaluar las secuelas pulmonares pos-COVID-19. En esta revisión se pretende describir las posibles secuelas a nivel pulmonar posteriores a neumonía por COVID-19, así como sugerir procedimientos diagnósticos para su correcta evaluación y seguimiento, que permitan el manejo adecuado por parte de un equipo médico multidisciplinario.


Subject(s)
COVID-19/complications , Convalescence , Lung Diseases/etiology , Respiratory Distress Syndrome/etiology , Bronchiectasis/diagnostic imaging , Bronchiectasis/etiology , Bronchiectasis/physiopathology , Disease Progression , Follow-Up Studies , Humans , Hypoxia/blood , Hypoxia/etiology , Hypoxia/physiopathology , Lung Diseases/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/physiopathology , Mental Disorders/etiology , Mental Disorders/physiopathology , Oxygen/blood , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/etiology , Pulmonary Embolism/physiopathology , Respiratory Distress Syndrome/physiopathology , Respiratory Function Tests , Spirometry , Tomography, X-Ray Computed
3.
Microbiol Spectr ; 11(3): e0516322, 2023 Jun 15.
Article in English | MEDLINE | ID: covidwho-2294281

ABSTRACT

Rising breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.4/5 led to the performance of various studies investigating systemic immunity and neutralizing antibodies in sera, but mucosal immunity remains understudied. In this cohort study, the humoral immune responses, including immunoglobulin levels and the presence of virus-neutralizing antibodies, of 92 vaccinated and/or BA.1/BA.2 convalescent individuals were investigated. Cohorts received two doses of ChAdOx1, BNT162b2, or mRNA-1273 and subsequent booster vaccination with either BNT162b2 or mRNA-1273, following BA.1/BA.2 infection. In addition, vaccinated and nonconvalescent or unvaccinated and BA.1 convalescent individuals were studied. Serum and saliva samples were used to determine SARS-CoV-2 spike-specific IgG and IgA titers and neutralizing activity against replication-competent SARS-CoV-2 wild-type virus and the Omicron BA.4/5 variant. Vaccinated/convalescent cohorts demonstrated strongest neutralization against BA.4/5, with 50% neutralization titer (NT50) values reaching 174.2; however, neutralization was reduced up to 11-fold, compared to wild-type virus. Both BA.1 convalescent and vaccinated nonconvalescent cohorts displayed the weakest neutralization against BA.4/5, with NT50 values being reduced to 4.6, accompanied by lower numbers of positive neutralizers. Additionally, salivary neutralization against wild-type virus was strongest in vaccinated and BA.2 convalescent subjects, but this elevated neutralization efficiency was lost when challenged with BA.4/5. Our data support the contention that current coronavirus disease 2019 (COVID-19) vaccines efficiently induce humoral immunity. However, antiviral effectiveness in serum and saliva is greatly reduced against novel variants of concern. These results suggest an adjustment of current vaccine strategies to an adapted or alternative vaccine delivery, such as mucosal booster vaccinations, which might establish enhanced or even sterilizing immunity against novel SARS-CoV-2 variants. IMPORTANCE Rising incidences of breakthrough infections caused by SARS-CoV-2 Omicron BA.4/5 have been observed. Although various studies were conducted investigating neutralizing antibodies in sera, mucosal immunity was barely evaluated. Here, we investigated mucosal immunity, since the presence of neutralizing antibodies at mucosal entry sites plays a fundamental role in disease limitation. We found strong induction of serum IgG/IgA, salivary IgA, and neutralization against SARS-CoV-2 wild-type virus in vaccinated/convalescent subjects but detected 10-fold reduced (albeit positive) serum neutralization against BA.4/5. Interestingly, vaccinated and BA.2 convalescent patients demonstrated the greatest serum neutralization against BA.4/5, but this advantageous neutralizing effect was not observed in the saliva. Our data support the contention that current COVID-19 vaccines are very efficient against severe/critical disease progression. Moreover, these results suggest an adjustment of the current vaccine strategy to adapted and alternative vaccine delivery, such as mucosal booster vaccinations, to establish robust sterilizing immunity against novel SARS-CoV-2 variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , BNT162 Vaccine , COVID-19 Vaccines , 2019-nCoV Vaccine mRNA-1273 , Cohort Studies , Convalescence , COVID-19/prevention & control , Vaccination , Antibodies, Neutralizing , Antibodies, Viral , Breakthrough Infections , Immunoglobulin A
4.
PLoS Pathog ; 19(4): e1011293, 2023 04.
Article in English | MEDLINE | ID: covidwho-2279093

ABSTRACT

The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures.


Subject(s)
COVID-19 , Animals , Cricetinae , Humans , Convalescence , Mesocricetus , SARS-CoV-2
5.
J Investig Med ; 71(5): 545-562, 2023 06.
Article in English | MEDLINE | ID: covidwho-2275018

ABSTRACT

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the global coronavirus disease 2019 (COVID-19) pandemic. Although most infections cause a self-limited syndrome comparable to other upper respiratory viral pathogens, a portion of individuals develop severe illness leading to substantial morbidity and mortality. Furthermore, an estimated 10%-20% of SARS-CoV-2 infections are followed by post-acute sequelae of COVID-19 (PASC), or long COVID. Long COVID is associated with a wide variety of clinical manifestations including cardiopulmonary complications, persistent fatigue, and neurocognitive dysfunction. Severe acute COVID-19 is associated with hyperactivation and increased inflammation, which may be an underlying cause of long COVID in a subset of individuals. However, the immunologic mechanisms driving long COVID development are still under investigation. Early in the pandemic, our group and others observed immune dysregulation persisted into convalescence after acute COVID-19. We subsequently observed persistent immune dysregulation in a cohort of individuals experiencing long COVID. We demonstrated increased SARS-CoV-2-specific CD4+ and CD8+ T-cell responses and antibody affinity in patients experiencing long COVID symptoms. These data suggest a portion of long COVID symptoms may be due to chronic immune activation and the presence of persistent SARS-CoV-2 antigen. This review summarizes the COVID-19 literature to date detailing acute COVID-19 and convalescence and how these observations relate to the development of long COVID. In addition, we discuss recent findings in support of persistent antigen and the evidence that this phenomenon contributes to local and systemic inflammation and the heterogeneous nature of clinical manifestations seen in long COVID.


Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Humans , Convalescence , SARS-CoV-2 , Inflammation
6.
Eur Respir J ; 61(5)2023 05.
Article in English | MEDLINE | ID: covidwho-2280327

ABSTRACT

BACKGROUND: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID). METHODS: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury. RESULTS: Monocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (p<0.001), confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A convalescence. CONCLUSIONS: Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.


Subject(s)
COVID-19 , Influenza, Human , Lung Injury , Humans , Monocytes/metabolism , Chemokines, CXC/metabolism , Receptors, Virus/metabolism , Receptors, CXCR6 , Receptors, Chemokine/metabolism , Post-Acute COVID-19 Syndrome , Ligands , Convalescence , Receptors, Scavenger/metabolism , Chemokine CXCL16 , Patient Acuity
7.
J Korean Med Sci ; 38(8): e55, 2023 Feb 27.
Article in English | MEDLINE | ID: covidwho-2286010

ABSTRACT

BACKGROUND: The emergence of the severe acute respiratory syndrome coronavirus 2 omicron variant has been triggering the new wave of coronavirus disease 2019 (COVID-19) globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after diagnosis) of omicron infected patients are still unknown. METHODS: Patients were retrospectively enrolled if they were admitted to the hospital due to COVID-19. The chest computed tomography (CT) images and clinical data obtained at baseline (at the time of the first CT image that showed abnormalities after diagnosis) and 1 month after diagnosis were longitudinally analyzed. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at baseline and residual pulmonary abnormalities after 1 month. RESULTS: We assessed 316 COVID-19 patients, including 47% with radiological abnormalities at baseline and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21 × 10-9/L, interleukin-6 (IL-6) ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at baseline. The age ≥ 47 years, presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up. For residual abnormalities group, the patients with less consolidations and more parenchymal bands at baseline could progress on CT score after 1 month. There were no significant changes in the number of involved lung lobes and total CT score during the early convalescent stage. CONCLUSION: The higher IL-6 level was a common independent risk factor for CT abnormalities at baseline and residual pulmonary abnormalities at 1-month follow-up. There were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Middle Aged , Follow-Up Studies , Retrospective Studies , Convalescence , Interleukin-6
8.
Int J Environ Res Public Health ; 20(5)2023 02 21.
Article in English | MEDLINE | ID: covidwho-2247832

ABSTRACT

High rates of psychological distress among COVID-19 survivors and stigmatisation have been reported in both early and late convalescence. This study aimed to compare the severity of psychological distress and to determine the associations among sociodemographic and clinical characteristics, stigma, and psychological distress among COVID-19 survivors across two different cohorts at two different time points. Data were collected cross-sectionally in two groups at one month and six months post-hospitalisation among COVID-19 patient from three hospitals in Malaysia. This study assessed psychological distress and the level of stigma using the Kessler Screening Scale for Psychological Distress (K6) and the Explanatory Model Interview Catalogue (EMIC) stigma scale, respectively. At one month after discharge, significantly lower psychological distress was found among retirees (B = -2.207, 95% confidence interval [95% CI] = -4.139 to -0.068, p = 0.034), those who received up to primary education (B = -2.474, 95% CI = -4.500 to -0.521, p = 0.014), and those who had an income of more than RM 10,000 per month (B = -1.576, 95% CI = -2.714 to -0.505, p = 0.006). Moreover, those with a history of psychiatric illness [one month: (B = 6.363, 95% CI = 2.599 to 9.676, p = 0.002), six months: (B = 2.887, CI = 0.469-6.437, p = 0.038)] and sought counselling services [one month: (B = 1.737, 95% CI = 0.385 to 3.117, p = 0.016), six months: (B = 1.480, CI = 0.173-2.618, p = 0.032)] had a significantly higher severity of psychological distress at one month and six months after discharge from the hospital. The perceived stigma of being infected with COVID-19 contributed to greater severity of psychological distress. (B = 0.197, CI = 0.089-0.300, p = 0.002). Different factors may affect psychological distress at different periods of convalescence after a COVID-19 infection. A persistent stigma contributed to psychological distress later in the convalescence period.


Subject(s)
COVID-19 , Psychological Distress , Humans , Convalescence , Malaysia , Sociodemographic Factors , Stress, Psychological/psychology , Survivors/psychology
9.
Front Immunol ; 14: 1127352, 2023.
Article in English | MEDLINE | ID: covidwho-2247730

ABSTRACT

Introduction: Severe COVID-19 originates a myriad of alterations in the immune system during active disease, especially in the T and NK cell compartments, but several studies in the last year have unveiled some alterations that persist in convalescence. Although most of the studies follow the participants for a short recovery time, studies following patients up to three or six months still find alterations. We aimed at evaluating changes in the NK, T and B cell compartments after severe COVID-19 in participants with a median recovery time of eleven months. Methods: Eighteen convalescent of severe COVID-19 (CSC), 14 convalescent of mild COVID-19 (CMC) and nine controls were recruited. NKG2A, NKG2C, NKG2D and the activating receptor NKp44 were evaluated in NKbright, NKdim and NKT subpopulations. In addition, CD3 and CD19 were measured and a basic biochemistry with IL-6 levels was obtained. Results: CSC participants showed lower NKbright/NKdim ratio, higher NKp44 expression in NKbright subpopulations, higher levels of serum IL-6, lower levels of NKG2A+ T lymphocytes and a trend to a lower expression of CD19 in B lymphocytes compared to controls. CMC participants showed no significant alterations in the immune system compared to controls. Conclusions: These results are concordant with previous studies, which find alterations in CSC weeks or months after resolution of the symptoms, and point to the possibility of these alterations lasting one year or more after COVID-19 resolution.


Subject(s)
COVID-19 , Convalescence , Humans , Interleukin-6 , Adaptor Proteins, Signal Transducing , Killer Cells, Natural
10.
Curr Opin Crit Care ; 29(2): 101-107, 2023 04 01.
Article in English | MEDLINE | ID: covidwho-2241430

ABSTRACT

PURPOSE OF REVIEW: To summarize recent research on critical care nutrition focusing on the optimal composition, timing, and monitoring of enteral feeding strategies for (post)-ICU patients. We provide new insights on energy and protein recommendations, feeding intolerance, and describe nutritional practices for coronavirus disease 2019 ICU patients. RECENT FINDINGS: The use of indirect calorimetry to establish individual energy requirements for ICU patients is considered the gold standard. The limited research on optimal feeding targets in the early phase of critical illness suggests avoiding overfeeding. Protein provision based upon the absolute lean body mass is rational. Therefore, body composition measurements should be considered. Body impedance analysis and muscle ultrasound seem reliable, affordable, and accessible methods to assess body composition at the bedside. There is inadequate evidence to change our practice of continuous enteral feeding into intermittent feeding. Finally, severe acute respiratory syndrome coronavirus 2 patients are prone to underfeeding due to hypermetabolism and should be closely monitored. SUMMARY: Nutritional therapy should be adapted to the patient's characteristics, diagnosis, and state of metabolism during ICU stay and convalescence. A personalized nutrition plan may prevent harmful over- or underfeeding and attenuate muscle loss. Despite novel insights, more research is warranted into tailored nutrition strategies during critical illness and convalescence.


Subject(s)
COVID-19 , Critical Illness , Humans , Critical Illness/therapy , Convalescence , COVID-19/prevention & control , Enteral Nutrition/methods , Critical Care/methods , Nutritional Requirements , Intensive Care Units , Energy Intake
11.
Viruses ; 15(2)2023 02 06.
Article in English | MEDLINE | ID: covidwho-2230305

ABSTRACT

BACKGROUND: The duration of anti-SARS-CoV-2-antibody detectability up to 12 months was examined in individuals after either single convalescence or convalescence and vaccination. Moreover, variables that might influence an anti-RBD/S1 antibody decline and the existence of a post-COVID-syndrome (PCS) were addressed. METHODS: Forty-nine SARS-CoV-2-qRT-PCR-confirmed participants completed a 12-month examination of anti-SARS-CoV-2-antibody levels and PCS-associated long-term sequelae. Overall, 324 samples were collected. Cell-free DNA (cfDNA) was isolated and quantified from EDTA-plasma. As cfDNA is released into the bloodstream from dying cells, it might provide information on organ damage in the late recovery of COIVD-19. Therefore, we evaluated cfDNA concentrations as a biomarker for a PCS. In the context of antibody dynamics, a random forest-based logistic regression with antibody decline as the target was performed and internally validated. RESULTS: The mean percentage dynamic related to the maximum measured value was 96 (±38)% for anti-RBD/S1 antibodies and 30 (±26)% for anti-N antibodies. Anti-RBD/S1 antibodies decreased in 37%, whereas anti-SARS-CoV-2-anti-N antibodies decreased in 86% of the subjects. Clinical anti-RBD/S1 antibody decline prediction models, including vascular and other diseases, were cross-validated (highest AUC 0.74). Long-term follow-up revealed no significant reduction in PCS prevalence but an increase in cognitive impairment, with no indication for cfDNA as a marker for a PCS. CONCLUSION: Long-term anti-RBD/S1-antibody positivity was confirmed, and clinical parameters associated with declining titers were presented. A fulminant decrease in anti-SARS-CoV-2-anti-N antibodies was observed (mean change to maximum value 30 (±26)%). Anti-RBD/S1 antibody titers of SARS-CoV-2 recovered subjects boosted with a vaccine exceeded the maximum values measured after single infection by 235 ± 382-fold, with no influence on preexisting PCS. PCS long-term prevalence was 38.6%, with an increase in cognitive impairment compromising the quality of life. Quantified cfDNA measured in the early post-COVID-19 phase might not be an effective marker for PCS identification.


Subject(s)
COVID-19 , Cell-Free Nucleic Acids , Humans , Antibodies, Viral , Convalescence , COVID-19/complications , Immunity, Humoral , Quality of Life , SARS-CoV-2 , COVID-19 Vaccines , Post-Acute COVID-19 Syndrome/etiology
12.
Front Cell Infect Microbiol ; 12: 953750, 2022.
Article in English | MEDLINE | ID: covidwho-2198702

ABSTRACT

Introduction: Recently, India witnessed an unprecedented surge of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) cases. In addition to patient management issues, environmental Mucorales contamination possibly contributed to the outbreak. A recent study evaluated environment contamination by Mucorales in the hospital setting. However, a considerable number of CAM patients were never admitted to a hospital before the development of the disease. The present study, therefore, planned to evaluate Mucorales contamination of patients' residences. Methods: The residential environment of 25 patients with CAM living in north India was surveyed. Air samples were collected from indoor and immediate outdoor vicinity of the patients' residence and cultured on Dichloran Rose-Bengal Chloramphenicol (DRBC) agar with benomyl for selective isolation of Mucorales. Surface swab samples were also collected from the air coolers fitted in those residences and cultured on DRBC agar. The isolates were identified by phenotypic and genotypic methods. Amplified fragment length polymorphism (AFLP) was employed to evaluate the genetic relatedness of the environmental and patients' clinical isolates. Results: The median spore count (mean ± SD, cfu/m3) of Mucorales in the air of patients' bedrooms was significantly higher than in the air in other rooms in those residences (3.55 versus 1.5, p = 0.003) or the air collected directly from the front of the air cooler (p < 0.0001). The Mucorales spore count in the environment did not correlate with either ventilation of the room or hygiene level of the patients' residences. Rhizopus arrhizus was isolated from the environment of all patients' residences (n = 25); other Mucorales species isolated were Cunninghamella bertholletiae (n = 14), Rhizopus microsporus (n = 6), Rhizopus delemar (n = 6), Syncephalastrum racemosum (n = 1), Lichtheimia corymbifera (n = 1), and Mucor racemosus (n = 1). Genetic relatedness was observed between 11 environmental isolates from the patients' bedrooms and respective clinical isolates from patients. Discussion: The study supported the view that the patients might have acquired Mucorales from the home environment during the post-COVID-19 convalescence period. Universal masking at home during patients' convalescence period and environmental decontamination could minimize exposure in those susceptible patients.


Subject(s)
COVID-19 , Mucorales , Mucormycosis , Agar , Amplified Fragment Length Polymorphism Analysis , Benomyl , Chloramphenicol , Convalescence , Humans , Mucorales/genetics , Mucormycosis/epidemiology
13.
Sci Rep ; 12(1): 22471, 2022 12 28.
Article in English | MEDLINE | ID: covidwho-2186060

ABSTRACT

The associations between clinical phenotypes of coronavirus disease 2019 (COVID-19) and the host inflammatory response during the transition from peak illness to convalescence are not yet well understood. Blood plasma samples were collected from 129 adult SARS-CoV-2 positive inpatient and outpatient participants between April 2020 and January 2021, in a multi-center prospective cohort study at 8 military hospitals across the United States. Plasma inflammatory protein biomarkers were measured in samples from 15 to 28 days post symptom onset. Topological Data Analysis (TDA) was used to identify patterns of inflammation, and associations with peak severity (outpatient, hospitalized, ICU admission or death), Charlson Comorbidity Index (CCI), and body mass index (BMI) were evaluated using logistic regression. The study population (n = 129, 33.3% female, median 41.3 years of age) included 77 outpatient, 31 inpatient, 16 ICU-level, and 5 fatal cases. Three distinct inflammatory biomarker clusters were identified and were associated with significant differences in peak disease severity (p < 0.001), age (p < 0.001), BMI (p < 0.001), and CCI (p = 0.001). Host-biomarker profiles stratified a heterogeneous population of COVID-19 patients during the transition from peak illness to convalescence, and these distinct inflammatory patterns were associated with comorbid disease and severe illness due to COVID-19.


Subject(s)
COVID-19 , Humans , Female , United States/epidemiology , Male , SARS-CoV-2 , Prospective Studies , Convalescence , Biomarkers , Phenotype , Severity of Illness Index , Hospitalization
14.
Microbiol Spectr ; 11(1): e0251622, 2023 02 14.
Article in English | MEDLINE | ID: covidwho-2193556

ABSTRACT

SARS-CoV-2 infection is known to trigger an important inflammatory response, which has a major role in COVID-19 pathogenesis. In infectious and inflammatory contexts, the modulation of human endogenous retroviruses (HERV) has been broadly reported, being able to further sustain innate immune responses due to the expression of immunogenic viral transcripts, including double-stranded DNA (dsRNA), and eventually, immunogenic proteins. To gain insights on this poorly characterized interplay, we performed a high-throughput expression analysis of ~3,300 specific HERV loci in the peripheral blood mononuclear cells (PBMCs) of 10 healthy controls and 16 individuals being either convalescent after the infection (6) or retesting positive after convalescence (10) (Gene Expression Onmibus [GEO] data set GSE166253). Results showed that the exposure to SARS-CoV-2 infection modulates HERV expression according to the disease stage and reflecting COVID-19 immune signatures. The differential expression analysis between healthy control (HC) and COVID-19 patients allowed us to identify a total of 282 differentially expressed HERV loci (deHERV) in the individuals exposed to SARS-CoV-2 infection, independently from the clinical form. In addition, 278 and 60 deHERV loci that were specifically modulated in individuals convalescent after COVID19 infection (C) and patients that retested positive to SARS-CoV-2 after convalescence (RTP) as individually compared to HC, respectively, as well as 164 deHERV loci between C and RTP patients were identified. The identified HERV loci belonged to 36 different HERV groups, including members of all three classes. The present study provides an exhaustive picture of the HERV transcriptome in PBMCs and its dynamic variation in the presence of COVID-19, revealing specific modulation patterns according to the infection stage that can be relevant to the disease clinical manifestation and outcome. IMPORTANCE We report here the first high-throughput analysis of HERV loci expression along SARS-CoV-2 infection, as performed with peripheral blood mononuclear cells (PBMCs). Such cells are not directly infected by the virus but have a crucial role in the plethora of inflammatory and immune events that constitute a major hallmark of COVID-19 pathogenesis. Results provide a novel and exhaustive picture of HERV expression in PBMCs, revealing specific modulation patterns according to the disease condition and the concomitant immune activation. To our knowledge, this is the first set of deHERVs whose expression is dynamically modulated across COVID-19 stages, confirming a tight interplay between HERV and cellular immunity and revealing specific transcriptional signatures that can have an impact on the disease clinical manifestation and outcome.


Subject(s)
COVID-19 , Endogenous Retroviruses , Humans , Endogenous Retroviruses/genetics , Transcriptome , Leukocytes, Mononuclear , Convalescence , COVID-19/genetics , SARS-CoV-2/genetics
15.
Nat Commun ; 13(1): 7775, 2022 12 15.
Article in English | MEDLINE | ID: covidwho-2160213

ABSTRACT

Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.


Subject(s)
COVID-19 , Convalescence , Thrombosis , Humans , Multiomics , SARS-CoV-2 , Leukocytes, Mononuclear , Proteomics , Membrane Proteins
16.
Allergy ; 77(12): 3704-3705, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2136628
17.
Front Immunol ; 13: 1031254, 2022.
Article in English | MEDLINE | ID: covidwho-2119769

ABSTRACT

Emerging variants of concern (VOC) raise obstacles in shaping vaccination strategies and ending the pandemic. Vaccinated SARS-CoV-2 convalescence shapes the current immune dynamics. We analyzed the SARS-CoV-2 VOC-specific cellular and humoral response of 57 adults: 42 convalescent mRNA vaccinated patients (C+V+), 8 uninfected mRNA vaccinated (C-V+) and 7 unvaccinated convalescent individuals (C+V-). While C+V+ demonstrated a superior humoral SARS-CoV-2 response against all analyzed VOC (alpha, delta, omicron) compared to C-V+ and C+V-, SARS-CoV-2 reactive CD4+ and CD8+ T cells, which can cross-recognize the alpha, delta and omicron VOC after infection and/or vaccination were observed in all there groups without significant differences between the groups. We observed a preserved cross-reactive C+V+ and C-V+ T cell memory. An inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C+V+ was observed, as well as an inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C-V+. Adaptive immunity generated after SARS-CoV-2 infection and vaccination leads to superior humoral immune response against VOC compared to isolated infection or vaccination. Despite the apparent loss of neutralization potential caused by viral evolution, a preserved SARS-CoV-2 reactive T cell response with a robust potential for cross-recognition of the alpha, delta and omicron VOC was detected in all studied cohorts. Our results may have implications on current vaccination strategies.


Subject(s)
COVID-19 , Immunity, Humoral , Adult , Humans , SARS-CoV-2 , Convalescence , COVID-19/prevention & control , Antibodies, Viral , Vaccination , RNA, Messenger
18.
J Leukoc Biol ; 112(1): 201-212, 2022 07.
Article in English | MEDLINE | ID: covidwho-2075041

ABSTRACT

T cells are thought to be an important correlates of protection against SARS-CoV2 infection. However, the composition of T cell subsets in convalescent individuals of SARS-CoV2 infection has not been well studied. The authors determined the lymphocyte absolute counts, the frequency of memory T cell subsets, and the plasma levels of common γ-chain in 7 groups of COVID-19 individuals, based on days since RT-PCR confirmation of SARS-CoV-2 infection. The data show that both absolute counts and frequencies of lymphocytes as well as, the frequencies of CD4+ central and effector memory cells increased, and the frequencies of CD4+ naïve T cells, transitional memory, stem cell memory T cells, and regulatory cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. In addition, the frequencies of CD8+ central memory, effector, and terminal effector memory T cells increased, and the frequencies of CD8+ naïve cells, transitional memory, and stem cell memory T cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. The plasma levels of IL-2, IL-7, IL-15, and IL-21-common γc cytokines started decreasing from Days 15-30 till Days 151-180. Severe COVID-19 patients exhibit decreased levels of lymphocyte counts and frequencies, higher frequencies of naïve cells, regulatory T cells, lower frequencies of central memory, effector memory, and stem cell memory, and elevated plasma levels of IL-2, IL-7, IL-15, and IL-21. Finally, there was a significant correlation between memory T cell subsets and common γc cytokines. Thus, the study provides evidence of alterations in lymphocyte counts, memory T cell subset frequencies, and common γ-chain cytokines in convalescent COVID-19 individuals.


Subject(s)
COVID-19 , Cytokines , Memory T Cells , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/blood , COVID-19/immunology , Convalescence , Cytokines/blood , Humans , Immunologic Memory/immunology , Interleukin-15/blood , Interleukin-2/blood , Interleukin-7/blood , Memory T Cells/immunology , RNA, Viral , SARS-CoV-2 , T-Lymphocyte Subsets/immunology
19.
JCI Insight ; 7(19)2022 10 10.
Article in English | MEDLINE | ID: covidwho-2064378

ABSTRACT

Protective immunity against SARS-CoV-2 infection after COVID-19 vaccination may differ by variant. We enrolled vaccinated (n = 39) and unvaccinated (n = 11) individuals with acute, symptomatic SARS-CoV-2 Delta or Omicron infection and performed SARS-CoV-2 viral load quantification, whole-genome sequencing, and variant-specific antibody characterization at the time of acute illness and convalescence. Viral load at the time of infection was inversely correlated with antibody binding and neutralizing antibody responses. Across all variants tested, convalescent neutralization titers in unvaccinated individuals were markedly lower than in vaccinated individuals. Increases in antibody titers and neutralizing activity occurred at convalescence in a variant-specific manner. For example, among individuals infected with the Delta variant, neutralizing antibody responses were weakest against BA.2, whereas infection with Omicron BA.1 variant generated a broader response against all tested variants, including BA.2.


Subject(s)
AIDS Vaccines , COVID-19 , Influenza Vaccines , Papillomavirus Vaccines , Respiratory Syncytial Virus Vaccines , SAIDS Vaccines , Antibodies, Neutralizing , Antibodies, Viral , BCG Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Convalescence , Diphtheria-Tetanus-Pertussis Vaccine , Humans , Measles-Mumps-Rubella Vaccine , Neutralization Tests , SARS-CoV-2
20.
Can J Cardiol ; 38(11): 1676-1683, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2035864

ABSTRACT

BACKGROUND: Acute myocarditis is a rare complication of mRNA-based COVID-19 vaccination. Little is known about the natural history of this complication. METHODS: Baseline and convalescent (≥ 90 days) cardiac magnetic resonance (CMR) imaging assessments were performed in 20 consecutive patients meeting Updated Lake Louise Criteria for acute myocarditis within 10 days of mRNA-based vaccination. CMR-based changes in left ventricular volumes, mass, ejection fraction (LVEF), markers of tissue inflammation (native T1 and T2 mapping), and fibrosis (late gadolinium enhancement [LGE] and extracellular volume [ECV]) were assessed between baseline and convalescence. Cardiac symptoms and clinical outcomes were captured. RESULTS: Median age was 23.1 years (range 18-39 years), and 17 (85%) were male. Convalescent evaluations were performed at a median (IQR) 3.7 (3.3-6.2) months. The LVEF showed a mean 3% absolute improvement, accompanied by a 7% reduction in LV end-diastolic volume and 5% reduction in LV mass (all P < 0.015). Global LGE burden was reduced by 66% (P < 0.001). Absolute reductions in global T2, native T1, and ECV of 2.1 ms, 58 ms, and 2.9%, repectively, were documented (all P ≤ 0.001). Of 5 patients demonstrating LVEF ≤ 50% at baseline, all recovered to above this threshold in convalescence. A total of 18 (90%) patients showed persistence of abnormal LGE although mean fibrosis burden was < 5% of LV mass in 85% of cases. No patient experienced major clinical outcomes. CONCLUSIONS: COVID-19 mRNA vaccine-associated myocarditis showed rapid improvements in CMR-based markers of edema, contractile function, and global LGE burden beyond 3 months of recovery in this young patient cohort. However, regional fibrosis following edema resolution was commonly observed, justifying need for ongoing surveillance.


Subject(s)
COVID-19 , Heart Injuries , Myocarditis , Humans , Male , Adolescent , Young Adult , Adult , Female , Myocarditis/diagnosis , Myocarditis/etiology , Myocarditis/pathology , COVID-19 Vaccines/adverse effects , Contrast Media , Gadolinium , COVID-19/epidemiology , COVID-19/prevention & control , Convalescence , Ventricular Function, Left , Stroke Volume , Predictive Value of Tests , Fibrosis , RNA, Messenger , Magnetic Resonance Imaging, Cine , Myocardium/pathology
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